recently , the detection of cystic lesions in the pancreas has greatly increased because of the wide use of high - resolution diagnostic imaging techniques.1 in contrast to solid tumors which are usually ductal adenocarcinomas , which have a very poor prognosis , most cystic lesions of the pancreas are either benign or low - grade malignancies ; thus , it is relatively easy to perform curative resection for them.2 therefore , cystic and intraductal tumors of the pancreas consist of an essential category with a challenging differential diagnosis.3 pancreatic squamoid cyst is defined as a lesion with cyst - like dilated ducts that are lined by non - keratinized squamous epithelium , and it is a recently recognized type of cystic lesion of the pancreas.2 we herein present a case of a patient with a pancreatic squamoid cyst who underwent laparoscopic resection .
a 60-year - old woman who underwent abdominal computed tomography ( ct ) for a routine health check - up was found to have a 1.8-cm cystic lesion in the tail of the pancreas .
her abdomen was soft and flat , and no tenderness or rebound tenderness was observed .
there was no evidence of pancreatitis . both the serum carcinoembryonic antigen ( cea ) and carbohydrate antigen 19 - 9 ( ca19 - 9 ) levels were normal .
a dynamic ct of the pancreas showed multiple cystic lesions in the tail of the pancreas and the largest cystic lesion showed a lobulated contour without communication with the pancreatic duct .
there were no indications of invasion into the surrounding tissues or dilatation of the main pancreatic duct ( fig .
magnetic resonance cholangiopancreatography revealed a 2.2-cm round cystic lesion in the tail of the pancreas which had no communication with the main pancreatic duct .
endoscopic ultrasonography revealed a 2.21.3 cm - sized cystic lesion and a 52.5 mm - sized mural nodule ; the septation within the cyst and the cyst wall was thin ; and the cyst was well - demarcated from the surrounding tissues .
the pancreas showed normal parenchymal echogenicity and the main pancreatic duct had a normal caliber ( fig .
we diagnosed the cystic lesion as an intraductal papillary mucinous neoplasm . to treat this lesion
, we performed laparoscopic spleen - saving distal pancreatectomy . during the operation , the cystic lesion , approximately 3 cm in diameter ,
was found arising from the border between the body and tail of the pancreas without any infiltration into the surrounding tissues .
most of the lesion was located within the pancreatic tissue , and its border was well - defined .
the patient showed the usual routine postoperative course and was discharged 10 days after surgery .
the patient quickly returned to her normal activities . on examination of the resected specimen ,
the cystic lesion of the pancreas ( 21.81.5 cm ) was multi - locular with thin septa ( fig .
a well - defined , oligo - locular cystic mass was in the pancreatic tail without a solid portion .
inner surface of the cyst was smooth and glistening and the cyst contained serous fluid .
histologic examination revealed that the cysts had linings ranging from flat squamoid cells to transitional cells with non - keratinization ( fig .
the epithelia of the cysts reacted negatively with muc 1 and muc 6 ( a marker for intercalated duct centroacinar cells ) , and positively with ck7 and p63 , and negatively with inhibin .
in 2007 , othman et al reported on 6 cases of cystic lesions with distinctive morphologic , immunophenotypic , and clinical characteristics , and proposed the term squamoid cyst of the pancreatic ducts to refer to these types of lesions.2 they mentioned that this type of cystic lesion typically resulted from uni - locular cystic dilatation of the ducts and had variable linings ranging from attenuated , flat , non - stratified squamous to transitional and stratified squamous epithelium , without a cornified layer or parakeratosis.2 however , no tall - columnar mucinous cells or acinar cells are evident in a squamoid cyst.1 the squamoid cyst of the pancreas is characterized by a flat , transitional , or squamous epithelium , and a p63 expressing basal and parabasal cell component .
kurahara et al mentioned that the microscopic version of this lesion is a relatively common incidental finding in the pancreas , and these , along with the expression of muc 1 and muc 6 , suggest that the process originates from the entroacinar / intercalated ductal system.1 however , the surface cells were negative for muc1 and muc6 in our case .
so we suggest that the immunophenotyping of the squamoid cyst should be studied further , especially from the point of view of the expression of muc1 and muc6 .
the expression of p63 in the cells forming the basal region is essential because p63 is a transitional / squamous cell marker and is not detected in the normal pancreas or in non - squamous neoplasms .
the surface cells were negative for muc1 and muc6 ( markers present in intercalated duct cells ) in this case .
thus , we were able to determine that squamoid cysts can be diagnosed without muc1 or muc6 being expressed .
there are other types of squamous - lined cysts of the pancreas , such as lymphoepithelial cysts , epidermoid cysts within an intrapancreatic accessory spleen , and dermoid cysts.4 lymphoepithelial cysts are lined by well - differentiated stratified squamous epithelium surrounded by a band of dense lymphoid tissue.4 epidermoid cysts within the intrapancreatic accessory spleen are lined by attenuated squamous cells , usually non - stratified , surrounded by normal - appearing splenic tissue.5 dermoid cysts are morphologically similar to teratomas seen in other sites .
the presence of adnexa - type elements ( sebaceous glands , hair , etc ) is more typical of dermoid cysts.6,7 these cystic lesions of the pancreas are thought to be all benign .
clinically , it is important to distinguish squamoid cysts of the pancreatic ducts from mucinous cyst - forming neoplasias , especially mucinous cystic neoplasms and intraductal papillary mucinous neoplasms.2 in contrast to squamoid cyst of the pancreatic ducts , which appears to be a benign lesion , these mucinous lesions have the risk of malignant transformation and have the potential to progress to invasive adenocarcinoma .
however , the differential diagnosis of pancreatic cystic lesions is not easy because the radiologic and clinical findings are not specific .
kurahara et al mentioned that tumor markers ( cea and ca19 - 9 ) may be high in squamoid cysts of the pancreas.1 we investigated 5588 patients who underwent a pancreatic biopsy or pancreatic resection from 2009 to 2012 in our institution , and found 7 cases of squamoid cysts of the pancreas . there were no connections to the main pancreatic duct and no solid portion in any of the cases .
the levels of cea , ca19 - 9 and ca72 - 4 were 1.860.91 ng / ml , 19.5526.9 u / ml , 2.570.23 , respectively .
there was one patient whose ca 19 - 9 was 76.6 u / ml , but this was not a specific finding because a pancreatic intraepithelial neoplasia was also found in her pancreas biopsy report.8 thus , we suggest that tumor markers can be an important method to use in the differential diagnosis .
cea is a very accurate tumor marker for diagnosing mucinous pancreatic cystic neoplasms , although the accuracy of this marker and the cut - off level vary among laboratories.9,10 in conclusion , squamoid cyst of the pancreas is a very rare disease , and it has been proposed only recently as a distinct pathologic lesion .
however , the diagnosis of squamoid cyst will increase due to improvements in imaging techniques such as ct scanning and magnetic resonance imaging .
this lesion is regarded as a benign entity , thus an extended operation should be avoided and resection of the lesion can be performed minimally .

 squamoid cyst of the pancreas is a very rare disease and it has been proposed only recently as a distinct pathologic lesion .
 we herein present a case of pancreatic squamoid cyst in a patient who underwent laparoscopic resection .
 a 60-year - old woman had an abdominal computed tomography ( ct ) scan for a routine check - up , and a multi - cystic lesion of 1.8-cm in size was incidentally found in the tail of the pancreas .
 biochemical laboratory tests were within normal limits .
 at first , we presumed that the most likely diagnosis of the cystic lesion was an intraductal papillary mucinous neoplasm . to treat this lesion
 , we performed laparoscopic spleen - saving distal pancreatectomy .
 the patient showed the usual routine postoperative course and she was discharged 10 days after surgery . on examination of the resected specimen , a well - defined
 , oligolocular cystic mass was found in the pancreatic tail , without a solid portion .
 histologic examination revealed that the cysts had linings ranging from flat squamoid cells to transitional cells with non - keratinization .
 after immunohistochemical staining , the final diagnosis was confirmed to be squamoid cyst of the pancreas .
 this lesion appears to be regarded as a benign entity , thus an extended operation should be avoided and resection of the lesion can be performed minimally .


hundreds of thousands of avoidable deaths are caused each year by parasitic infections , particularly the intestinal helminthes , and these infectious diseases affect the nutritional status of most children under the age of five . it has been estimated to affect about 3.5 billion people globally and caused morbidity in approximately 450 million people .
developing countries are the most affected , majority being school children because of their typical hand - mouth activity , uncontrolled fecal activity and their immature immune systems . the climatic conditions in this part of the world favor the development and survival of these parasites , the high prevalence in a region results to infection and diseases that are the immediate causes of malnutrition and death in young children .
records show that a global estimate of 162 million under - five years old children are documented to be stunted , 99 million underweight and 51 million wasted .
a silent emergency already exists in nigeria , as the country has extremely poor nutritional indices : stunting 37% , underweight 29% and wasting 18% .
diarrhea is the second leading cause of death among children under five in nigeria after malaria .
e. histolytica , g. lamblia , n. americanus , a. doudenale , hookworm , ascariasis and trichuriasis are the other common intestinal parasitic infections in benue state , nigeria . the incidence of the disease varies greatly with seasons and a child s age ; the youngest children are most vulnerable , due to poor environmental sanitation and contamination of water .
these parasitic infections have detrimental impact on host nutritional status in several ways , they can depress appetite and food intake , compete for micronutrients , or blood loss resulting in the loss of iron , diarrhea , vomiting , dehydration , weight loss and growth retardation , fever , school attendance , physical activity and cognitive performance of school age children.[8 - 11 ] thus , the objective of this study was to determine the prevalence of intestinal helminthic infections and assess the nutritional status of pre - school aged children in communities of gboko local government area of benue state in nigeria s middle belt region .
the present research was a cross sectional study conducted from january - june 2016 , among 418 school children under the age of five living in gboko .
the area covers a land mass of 2,264 square kilometers with a population of 361,325 people according to 2006 nigeria census . on the geo - political map of nigeria
, the area is located between latitude 630 and 810 north of the equator and longitudes 8 and 10 east of the greenwich meridian .
the 17 council wards in gboko local government area ( lga ) were clustered into districts .
a list of certified primary schools was obtained from benue state ministry of education , the schools in the randomly selected council ward ( gboko - north , igorov , mbadim , ukpekper , mbankur ) were further clustered into urban and rural primary schools .
these schools were further clustered into private and public schools in both urban and rural areas . in all , 4 schools were selected from a council ward ( a private & a public school in both rural and urban areas of each council ward ) , making a total of 20 schools . entirely , 422 pupils both boys and girls ranging from ages of 2 - 5 years were randomly selected .
the actual size of those that participated in the research were 418 with 208 children from rural areas and 210 children from urban areas . before the commencement of the research
, permission was obtained from the headmasters of all the schools including the pupil s parents / guardian .
the study protocol was approved by the benue state ministry of health s ethical committee with the reference number med/156/vol.1/56 .
anthropometric measurements such as height and weight were taken by a set of trained investigators following the internationally accepted standard techniques .
height and weight measurements were recorded to the nearest 0.1 cm and 0.5 kg respectively .
weight - for - height ( whz ) , which was used to identify wasting in children , was computed for all boys and girls of ages 2 - 5 years .
height - for - age ( haz ) and weight - for - age ( waz ) ratios were used to diagnose children with stunted and underweight growth ( < -2sd ) respectively .
stool samples were collected in labeled screw capped plastic containers for parasitological examination within one hour of collection .
all stool samples were re - examined microscopically using the formal ether concentration technique which is considered to be the most - sensitive method for most intestinal helminthes .
anthropometry indices were computed using the calculator mode of anthropometry calculating software program epi info version 6 .
wasting , stunting and underweight were defined as z score values of less than -2sd ( standard deviation ) .
the significance of the differences in frequency distribution was tested by using chi - square analyses .
the present research was a cross sectional study conducted from january - june 2016 , among 418 school children under the age of five living in gboko .
the area covers a land mass of 2,264 square kilometers with a population of 361,325 people according to 2006 nigeria census . on the geo - political map of nigeria
, the area is located between latitude 630 and 810 north of the equator and longitudes 8 and 10 east of the greenwich meridian .
the 17 council wards in gboko local government area ( lga ) were clustered into districts .
a list of certified primary schools was obtained from benue state ministry of education , the schools in the randomly selected council ward ( gboko - north , igorov , mbadim , ukpekper , mbankur ) were further clustered into urban and rural primary schools .
these schools were further clustered into private and public schools in both urban and rural areas . in all , 4 schools were selected from a council ward ( a private & a public school in both rural and urban areas of each council ward ) , making a total of 20 schools . entirely ,
422 pupils both boys and girls ranging from ages of 2 - 5 years were randomly selected .
the actual size of those that participated in the research were 418 with 208 children from rural areas and 210 children from urban areas .
before the commencement of the research , permission was obtained from the headmasters of all the schools including the pupil s parents / guardian .
the study protocol was approved by the benue state ministry of health s ethical committee with the reference number med/156/vol.1/56 .
anthropometric measurements such as height and weight were taken by a set of trained investigators following the internationally accepted standard techniques .
height and weight measurements were recorded to the nearest 0.1 cm and 0.5 kg respectively .
weight - for - height ( whz ) , which was used to identify wasting in children , was computed for all boys and girls of ages 2 - 5 years .
height - for - age ( haz ) and weight - for - age ( waz ) ratios were used to diagnose children with stunted and underweight growth ( < -2sd ) respectively .
stool samples were collected in labeled screw capped plastic containers for parasitological examination within one hour of collection .
all stool samples were re - examined microscopically using the formal ether concentration technique which is considered to be the most - sensitive method for most intestinal helminthes .
anthropometry indices were computed using the calculator mode of anthropometry calculating software program epi info version 6 .
wasting , stunting and underweight were defined as z score values of less than -2sd ( standard deviation ) .
the significance of the differences in frequency distribution was tested by using chi - square analyses .
the result presented below is the data for 418 pupils ( 208 rural and 210 urban ) who returned stool sample and their anthropometric data were obtained .
there were 103 males and 105 females for rural areas and 106 males and 104 females for urban areas .
the subjects were grouped between 2 - 5 years with a mean age of 4.22  0.81 years .
prevalence of infection was significantly ( p<0.05 ) higher among the rural pupils than among the urban pupils .
prevalence of e. histolytica was higher in both rural ( 51.0% ) and urban areas ( 29.0% ) than all other parasites encountered in the study areas ( p<0.05 ) .
other parasites found in both rural and urban areas were hookworm ( 46.2% and 24.8% ) ; g. lamblia ( 11.5% and 8.6% ) ; and t. trichiura ( 2.4% and 5.2% ) .
the subjects co - infected with mixed species of parasites were ( 63.5% and 40.0% ) in rural and urban pupils respectively ( figure 1 ) .
prevalence of intestinal parasites among children in rural and urban communities prevalence of intestinal parasites among children in rural and urban communities there were significant relationships between intestinal parasitic infection and school types as well as the community ( table 2 ) .
the public school pupils were more infected with the parasites than the private school pupils ( 66.4% and 36.2% ) and the pupils from the rural settings were more infected than those from the urban settings ( 63.5% and 39.5% ) .
prevalence of intestinal parasitic infection according to sex and school type in rural and urban communities p<0.05 statistically significant table 3 shows associations between the various risk factors and intestinal parasitic infections among the school pupils . among all the potential risk factors
explored , pupils from rural communities had the highest level of some risk factors that could easily result to infection .
a total of 64.4% use well as their source of drinking water as against 29.0% in urban , 41.8% pupils in rural settings use pit latrine whereas only 14.3% in urban uses pit latrine , 38.0% pupil live in a house with sand as their type of floor as against 0.0% in urban areas and more importantly only 13.0% of the pupils in the rural area had been de - wormed in the 6 months preceding the study , 42.8% were not , while the remaining 44.2% had never been de - wormed .
but in urban setting , 44.8% had been dewormed , 30.0% had not , and only 25.2% were never dewormed . the habit of washing hands after toilet use posed a problem in both rural and urban settings , 15.4% in rural settings still wash their hands while only 26.7% in urban settings do wash their hands after toilet use .
risk factors for intestinal parasitic infections the overall prevalence of nutritional indicators below -2sd is presented in table 4 , the prevalance of stunting in rural and urban pupils were 43.8% and 32.9% ; 64.4% and 39.0% rural and urban pupils were underweight while 30.3% and 24.3% were wasted .
only e. histolytica , hookworm and g. lamblia were significantly ( p<0.05 ) associated with low height - for - age ( stunting ) , weight - for - height ( wasting ) and weight - for - age ( underweight ) .
generally intestinal parasitic infection are dangerous disease causing agents among school children ultimately resulting to malnutrition .
the prevalence of intestinal parasitic infection in this study ( 63.5% ) in rural and ( 40.0% ) in urban is lower ( 80.9% rural and 51.4% urban ) than what was found by opara et al in eastern nigeria , and also the 75.7% found by wosu et al in south eastern nigeria , but higher than the 30.6% as reported by adekunle et al , 45.5% that was reported by emeka , and the 52.0% reported by adefioye et al .
these results evidently showed a high level of intestinal parasitic infection especially among the rural dwellers .
such prevalence has been attributed to ignorance , poverty , poor environmental and personal hygiene , shortages of clean potable water and indiscriminate defecation as most vegetable farmers use excreta as manure which is a veritable source of infection since children and their mothers often go to the farm to tender to the vegetables . despite all these factors ,
the relatively high prevalence connotes continuous infection , re - infection and transmission of intestinal parasites .
the commonest was the co - infection of e. histolytica , hookworm and g. lamblia .
this present study recorded a high degree of malnutrition among the children investigated for intestinal parasitic infections .
64.4% of pupils in rural areas were found to be underweight whereas 39.0% in urban were underweight .
this rate is similar to what was reported by goon et al , he reported 43% to be underweight in benue state and emeka who reported 57.9% .
higher rates of underweight were however reported by adekunle et al , in rural and semi - urban communities of osun state who reported 70.0% and 54.7% in the year 2015 .
these findings agree with the publication of other researchers.[8 , 10 ] the high rate ( > = 30% ) of stunting and underweight recorded in this study was due to high prevalence of e. histolytica , hookworm , g. lamblia and t. trichiura .
it has been documented by crompton and neisheimthat growth and development during childhood could be diminished by ascariasis , trichiuriasis and hookworm infection .
intestinal parasitic infections can cause vomiting , diarrhea , anorexia , abdominal pain and nausea that may result in reduced food intake , thereby further reducing nutrient availability hence contributing to undernutrition therefore the government and other non - governmental organizations ( ngos ) involved in development should introduce adequate strategies to crisscross on personal and environmental hygiene , especially for the rural dwellers .
there is also need for regular deworming of school - age children , especially those living in the rural communities .
they should also design relevant policies or review existing ones in order to savage the situation because a greater proportion of the population still live in rural communities .
the prevalence of intestinal helminthic infection in this study was high and was significantly associated with the nutritional status of the respondents . it was such that children with intestinal parasitic infections were more malnourished when compared with those with no infection .
there is need for regular de - worming of preschool - age children , especially those living in the rural communities . reducing the prevalence of parasitic infections in school children ,
compliance with ethical standards
 intestinal parasitic infections prominently detected in benue were e.histolytica , hookworm , g.lamblia , t.trichiura and the prevalence of infection was significantly higher in rural than urban areas.public school pupils were more infected with the parasites than the private school pupils.among all the potential risk factors explored , pupils from rural communities had the highest level of some risk factors that could easily result to infections.the rural children were significantly more malnourished than urban children
. only e.histolytica , hookworm , g.lamblia were significantly associated with stunting , underweight and wasting .

intestinal parasitic infections prominently detected in benue were e.histolytica , hookworm , g.lamblia , t.trichiura and the prevalence of infection was significantly higher in rural than urban areas .
public school pupils were more infected with the parasites than the private school pupils . among all the potential risk factors explored , pupils from rural communities had the highest level of some risk factors that could easily result to infections .
. only e.histolytica , hookworm , g.lamblia were significantly associated with stunting , underweight and wasting .

 background and objectives : intestinal parasitic infections are highly prevalent in developing countries , contributing to high incidence of malnutrition and morbidity . this study aimed to find the prevalence of intestinal parasitic infections and their association with nutritional status of children in benue state , nigeria.methods:a cross sectional study conducted from january - june 2016 , among 418 school children under-5 years of age .
 anthropometric data , height - for - age , weight - for - height , and weight - for - age z - scores from each child and fecal samples were collected and screened for intestinal parasites using standard laboratory methods.results:among the intestinal parasitic infections detected , the prevalence of e. histolytica was higher ( 51.0% and 29.0% ) than all other parasites encountered in rural and urban pupils ( p<0.05 ) .
 other parasites were hookworm ( 46.2% and 24.8% ) ; g. lamblia ( 11.5% and 8.6% ) ; and t. trichiura ( 2.4% and 5.2% ) .
 the prevalence of stunting ( haz<-2 ) , in rural and urban pupils were 43.8% and 32.9% ; 64.4% and 39.0% rural and urban pupils were underweight ( waz<-2 ) , while 30.3% and 24.3% were wasted ( whz<-2 ) .
 infected children had significantly ( p<0.05 ) higher z - scores than the uninfected children.conclusion and global health implications : benue state is among the nigerian states with the highest burden of tropical diseases with a current plan of elimination implemented through mass drug administration .
 this study identify / evaluate some essential information that will support the planning and implementation of the state s ongoing efforts .


breast cancer is one of the major causes of mortality in middle - aged women , especially in developed countries . at present , there are no effective ways to prevent breast cancer since its cause remains unknown . therefore , early detection becomes the key to improving the breast cancer prognosis and reducing the mortality rates .
mammography has been widely recognized as being one of the most effective imaging modalities for early detection of breast cancer .
however , it is a hard work for radiologists to provide both accurate and uniform evaluation for the enormous number of mammograms generated in widespread screening .
a computer - aided detection or diagnosis ( cad ) system , which uses computer technologies to detect the typical signs of breast cancer , has been developed to provide a  second opinion  for radiologists and to improve the accuracy and stability of diagnosis . in general
, there are three signs of breast cancer in a mammogram : microcalcification clusters ( mcs ) , architectural distortions , and masses . in this paper
, we particularly focus on the detection of mcs since they appear in 3050% of mammographic diagnosed cases and show a high correlation with breast cancer .
according to the breast image reporting and data system ( bi - rads ) lexicon , mcs are tiny calcium deposits that appear as small bright spots in mammograms . as an example , figure 1 shows an mc in a mediolateral - oblique ( mlo ) mammogram .
it is often hard for radiologists to find individual mcs in mammograms because they are very small ( typically , 0.051  mm ) in the size and the contrast between the mcs and the surrounding breast tissue is not high enough .
over the past two decades , there has been extensive research focused on developing the cad tools for automatic detection of mcs in mammograms .
several review papers have also been published on this topic [ 2 , 48 ] .
as described in , mc detection can be classified into four categories : ( 1 ) image enhancement methods [ 913 ] ; ( 2 ) multiscale decomposition methods [ 1417 ] ; ( 3 ) stochastic modeling methods [ 18 , 19 ] ; and ( 4 ) machine learning methods [ 2028 ] . in , a performance evaluation was summarized using free - response receiver operating characteristic ( froc ) in which a support vector machine ( svm ) approach   is found to be superior to conventional methods and is capable of achieving a true positive rate of approximately 90% when the false - positive ( fp ) rate is on average of 1.1 fp clusters per image .
however , such fp is not low enough for clinical application .   in this paper
, we present a new method based on a hybrid method which combines a morphological technique   and wavelet decomposition processing for detecting the mcs in mammograms .
compared with previous methods , the proposed method can achieve not only a high sensitivity but also a lower fp . in the proposed method , we first use a multistructuring - elements ( ses- ) based top - hat transform to enhance the intensity of microcalcification .
subsequently , we employ a wavelet decomposition to refine the enhanced results for removing the false enhanced microcalcifications .
then , based on the feature of malignant mcs , threshold processing is used to segment the mcs from mammograms .
the rest of paper is organized as follows : section 2 presents a morphological processing technique to enhance the mcs in mammogram . in section 3
section 4 presents the detection of the mcs and gives the experimental results by using the proposed method .
as mentioned in section 1 , the mcs appear as small bright spots in mammograms . in this sense , mcs can be directly segmented by using a threshold process . however , since most mammograms have a low dynamical rang and the intensity contrast between mcs and surrounding tissue is quite low , selection of a threshold for the whole image is not an easy task . as a solution ,
the difference of gaussian ( dog- ) based method which approximates the individual microcalcification as a two - dimensional ( 2d ) gaussian kernel has been reported in , but this method only is suitable for detecting the microcalcifications with approximate circle shape .   in this section
, we propose a new method which is based on a morphological filtering technique   to enhance the individual microcalcifications for mc detection .
the basic idea of the method is to use a set of top - hat transforms based on multi - structuring elements ( ses ) of which sizes and shapes are fitted to the individual microcalcifications to enhance them .
the top - hat transform of a gray - scale image f is defined as f minus its opening by structuring element b :
 ( 1)t = f(f  b ) ,
 where  denotes the opening operation ; the difference operation yields an image in which only the components fitting to the se remain .
figure 2 illustrates the concept of the top - hat transform in one dimension .
in the top - hat transform , selection of an appropriate se fitting to the target objects is the key . since
individual microcalcifications in mammograms frequently vary both in size and shape , it is imposable to use a single se to remove all of them . to solve this problem
, we use a multi - ses - based method which uses eight different flat ses , denoted as bi  ( i = 1,2 ,  , 8) to remove the individual microcalcifications in the opening processing . in this paper
, the ses are a set of lines revolving around its center in a 15  15 array . for a mammogram image with resolution 0.05  mm / pixel
, the 15  15 array indicates that the objects whose size are larger than 0.75  0.75  mm will be removed in the opening operation .
figure 3 shows the flat ses used in the top - hat transform where the dots denote the centers of the ses .   for each se bi ,  i = 1,2 ,  , 8
, the opening operation yields an image , denoted by ( f  bi ) , in which the individual microcalcifications fitting to the se are removed .
then , in order to enhance these individual microcalcifications removed by the opening operation , we use a subtraction between the original image and the maximum of the opening results to obtain an image , given by
 ( 2)e = fargmax(f    bi ) .
figure 4 shows an original mammogram and an enhanced image obtained from ( 2 ) . comparing figure 4(b ) with figure 4(a )
, we can see that individual microcalcifications appearing on a complex background were enhanced successfully .
these results indicate that the microcalcifications can be easily segmented by using a threshold process .
however , the top - hat transform also enhances some undesired objects in the mammograms , such as mammary glands , vessels , and so on .
therefore , a refinement processing is required to remove these undesirable objects from the enhanced mammogram images .
as mentioned above , although the top - hat transform is capable of enhancing microcalcifications varying in size and shape , a side effect is that the undesirable objects are also enhanced .
based on an investigation , we found that these unwanted objects are mainly caused by the soft tissues , such as mammary glands and vessels .
the typical feature of them is that they have a relatively higher intensity compared with their surrounding area as well as an inner nonhomogeneous intensity .
figure 5 shows a comparison between the microcalcification and the mammary gland after the top - hat transform . comparing figures 5(c ) and 5(g ) , we find that the intensity of microcalcification in the enhanced image approximately equals that of the mammary glands .
however , since the individual microcalcification has almost homogeneous intensity , the size of the enhanced microcalcification is generally larger than that of the mammary gland . figures 5(d ) and 5(e ) show the expanded view of the dashed rectangles in figures 5(c ) and 5(g ) , respectively . we can find that the size of the microcalcification is almost twice as large as the size of the mammary gland .
therefore , the enhanced mammary glands can be treated as noise that can be removed according to their size . in this paper
, we employ a wavelet denoising method to remove the mammary glands because the wavelet decomposition can easily separate them according to their particular size .
the wavelet - based procedure for denoising the image consists of the following four steps .

a four - scale wavelet transform is used to decompose the image obtained from the top - hat transform .
symlet-2 ,  as the decomposition filters since they have the least asymmetry and highest number of vanishing moments .
figures 6(a ) and 6(b ) show the scaling function and wavelet function used in the decomposition filtering .
figure 7 shows the decomposition results in which w(4 , m , n ) ,  w(4 , m , n ) ,  and w(4 , m , n ) denote the detail coefficients at level 4 size of half the original image .

a four - scale wavelet transform is used to decompose the image obtained from the top - hat transform .
symlet-2 ,  as the decomposition filters since they have the least asymmetry and highest number of vanishing moments .
figures 6(a ) and 6(b ) show the scaling function and wavelet function used in the decomposition filtering .
figure 7 shows the decomposition results in which w(4 , m , n ) ,  w(4 , m , n ) ,  and w(4 , m , n ) denote the detail coefficients at level 4 size of half the original image .

since the size of the microcalcification is almost twice as large as the size of the mammary gland , the noise caused by the mammary gland can be decomposed in level 4 .
therefore , we set the detail coefficients at level 4 as well as the approximation coefficients at level 1 to zeros .
figure 7 shows the result of the four - scale wavelet transform in which the shaded coefficients marked are set to zero .
  thresholding the approximation and detail coefficients .
since the size of the microcalcification is almost twice as large as the size of the mammary gland , the noise caused by the mammary gland can be decomposed in level 4 .
therefore , we set the detail coefficients at level 4 as well as the approximation coefficients at level 1 to zeros .
figure 7 shows the result of the four - scale wavelet transform in which the shaded coefficients marked are set to zero .

figures 8(a ) and 8(b ) show the results of the inverse wavelet transform of the microcalcification and mammary gland in figures 5(d ) and 5(h ) .
we see that the intensity of the mammary gland is clearly reduced so that the microcalcifications and mammary glands can be easily separated using a threshold .

figures 8(a ) and 8(b ) show the results of the inverse wavelet transform of the microcalcification and mammary gland in figures 5(d ) and 5(h ) .
we see that the intensity of the mammary gland is clearly reduced so that the microcalcifications and mammary glands can be easily separated using a threshold .

, we use a thresholding processing to obtain a binary image in which each microcalcification is segmented as connected components .

we use a thresholding processing to obtain a binary image in which each microcalcification is segmented as connected components .
in this section , we introduce a procedure that segments the mcs from the mammogram image obtained from the above sections and give some experimental results by using the proposed method .
as mentioned in section 1 , the mcs are tiny calcium deposits clustering together in the mammogram images . based on an investigation on the bi - rads
, we found that a typical mc generally has the following two features:(1)an mc usually consists of four or more individual microcalcifications;(2)an mc generally appears within a limited area of size 10  10  mm in mammogram images .
an mc usually consists of four or more individual microcalcifications ; an mc generally appears within a limited area of size 10  10  mm in mammogram images .
 according to these two features , we use the following two steps to detect the mcs .
first , the binary image is subdivided into blocks that overlap their neighbors both horizontally and vertically .
the blocks are of size 200  200 pixels ; for each pair of overlapping blocks , the overlapping boundary region is of size 100  100 pixels .
second , for each block , if the total number of the connected components is larger than three , this block will be labeled as an mc .
we developed and tested the proposed method using a database collected by the tohoku university school of medicine .
these mammograms are of size 4740  3540 pixels , with a spatial resolution of 0.05  mm / pixel and 16-bit grayscale .
the performance of the proposed method is summarized by the true positive rate and false positive cluster per image .
table 1 summarizes the experimental results of the proposed method comparing with several previous methods [ 8 , 9 , 13 , 14 , 32 , 33 ] .
the proposed method is capable of detecting 92.9% of true microcalcification clusters with an average of 0.08 false microcalcification clusters detected per image . to our best knowledge
, this performance is better than most state - of - the - art methods in mc detection [ 2 , 34 ] . in the experiments
, we found that the fps are mainly caused by the linear - structure tissues interlacing with each other or benign calcifications with nonhomogenous intensity .
since the characteristics of linear - structure tissues are quite different with that of the mcs , we consider that fps can still be reduced by using a statistic classifier , such as a support vector machine ( svm ) .
in this paper , we presented a high - accuracy method for the detection of mcs in mammograms .
the proposed method combined a multi - ses top - hat transform and a wavelet - based denoising approach to enhance the individual microcalcifications in mammograms .
experimental results demonstrated that the proposed method is capable of detecting the mcs in mammograms with high accuracy .   in further work
, we will conduct more experiments on a wider database and improve its performance both in accuracy and computational cost .

 the presence of microcalcification clusters ( mcs ) in mammogram is a major indicator of breast cancer .
 detection of an mc is one of the key issues for breast cancer control . in this paper
 , we present a highly accurate method based on a morphological image processing and wavelet transform technique to detect the mcs in mammograms .
 the microcalcifications are firstly enhanced by using multistructure elements morphological processing .
 then , the candidates of microcalcifications are refined by a multilevel wavelet reconstruction approach . finally , mcs are detected based on their distributions feature .
 experiments are performed on 138 clinical mammograms .
 the proposed method is capable of detecting 92.9% of true microcalcification clusters with an average of 0.08 false microcalcification clusters detected per image .


vitamin d deficiency ( vdd ) is defined as serum 25-hydroxy vitamin d ( 25ohd ) levels < 20 ng / ml .
vdd has been documented in more than 90% across all age groups and both sexes from india .
classical manifestations of vdd is described as rickets / osteomalacia , which manifest as bony deformity / pain , decreased bone mineral density ( bmd ) , increased risk of fracture and is associated with raised alkaline phosphatase and parathormone ( pth ) . however , secondary hyperparathyroidism ( shpt ) is observed in < 50% of subjects in indian and us population .
subjects with same levels of serum 25ohd have varied clinical and biochemical abnormalities including some showing no abnormalities .
this raises logical question  do all subjects with vdd have clinical disease according to this definition ?  the main physiological function of vitamin d is maintenance of calcium homeostasis by its effect on calcium absorption and bone health in association with parathyroid gland .
calcium is absorbed actively in the duodenum through transcellular ( active transport-80% ) process , which is vitamin d dependent , whereas passive absorption is a paracellular ( passive diffusion-20% ) process , which occurs throughout intestine independent of vitamin d and is dependent on concentration of calcium in the intestinal tract .
total fraction of calcium absorbed from total intake can vary from 20 to 80% . in the event of decreased calcium availability from intake ,
calcium is released from bone under the effect of vitamin d - pth system to maintain its homeostasis .
as per the recent institute of medicine ( iom ) statement  the data currently suggest that fractional calcium absorption ( fca ) reaches a maximum between 12 and 20 ng / ml in both children and adults .
 in most of the studies reviewed by iom , the baseline serum 25ohd was > 10 ng / ml and there was no correlation of serum 25ohd levels with calcium absorption .
when we have plotted mean basal serum 25ohd levels in various studies and mean fca , there was a significant inverse correlation ( r = 0.75 , p = 0.001 ) .
there is only one study among elderly that has assessed the relation of calcium absorption and base line serum 25ohd levels ranging from 4 to 20 ng / ml .
this study has clearly shown that calcium absorption decreases in the ranges from 4 to 8 ng / ml and not > 8 ng / ml .
similarly , in the most studies related to vitamin d supplementation , basal serum 25ohd levels were > 8 ng / ml .
only one study carried out in subjects with 25ohd level of 4 ng / ml showed an increase of 21% with change in 25ohd
level to 24 ng / ml , whereas in those with the increase in 25ohd level from 8 to 28 ng / ml only 3% increase of calcium absorption occurred
. there is no correlation of mean change in fca ( increase or decrease ) with either mean basal serum 25ohd levels ( r = 0.122 , p = 0.754 ) or increment in serum 25ohd levels .
these data clearly shows that the maximum calcium absorption capacity is reached when serum 25ohd levels are > 8 ng / ml . logically to maintain calcium homeostasis in the face of vdd , the first body will try to absorb maximum available calcium , rather than affecting bone .
hence , calcium absorption is the first most important adaptive mechanism in patients with vdd .
high fca ( 54 - 63% ) has been reported from the region of china with low calcium intake ( < 500 mg ) compared with 25 - 34% in us children with high intake of calcium ( > 900 mg ) .
this suggests that the body tries to adapt to the calcium availability to bodies requirement by adjusting fca .
the conventional explanation of homeostasis is by systemic adaptation , in which decreased calcium intake results in decreased calcium absorption , which leads to increase in pth levels .
the pth up regulates the 1- hydroxylase enzyme , leading to increase generation of 1,25-dihydroxyvitamin d ( 1,25(oh ) 2d ) levels and increased calcium absorption and bone resorption .
however , as deduced from the above discussion , the body has a tremendous reserve to increase the fca in the face of decrease in calcium intake .
this suggests that calcium absorption can be kept static over a wide range of calcium intake and serum 25ohd levels by local intestinal adaptation .
we hypothesize that the first adaptive mechanism in calcium homeostasis is local rather than systemic .
it consists of calcium sensing receptor ( casr ) on intestinal brush border , which senses calcium in intestinal cells and negatively affect vitamin d system in intestinal cells to decrease active transcellular calcium transport .
it also facilitates passive paracellular diffusion of calcium in the intestine , which is less efficient process . on the contrary , when there is decreased calcium intake , this feedback inhibition is removed and vitamin d dependent active calcium absorption will increase , maintaining calcium homeostasis .
furthermore , there may be some genetic or epigenetic alteration in genes of 1- hydroxylase enzyme , which decreases efficiency of active vitamin d generation or vitamin d receptor ( vdr ) genotype affecting calcium absorption . in subjects with efficient vdr genotype for calcium absorption , local adaptation
will be maintained at lower levels of serum 25ohd and vice versa will also be true .
the interaction between casr and vitamin d system in intestinal cells (  intestinal calcistat  ) will decide the level of serum 25ohd at which calcium absorption can be maintained according to the need of the body or becomes suboptimal in a given individual indicating failure of local adaptation .
firstly , decrease in calcium intake < 250 mg , which can not be overcome by increasing fca .
this will manifest as calcium deficiency rickets on the face of normal vitamin d levels .
secondly , mutation in casr , if  activating ,  may lead to decreased calcium absorption and if  inactivating ,  increased calcium absorption .
thirdly , decreased supply of substrate below critical levels ( serum 25ohd < 8 ng / ml ) will lead to vdd rickets .
however , this level can vary according to interaction between casr and vitamin d system in an individual-intestinal calcistat .  finally , genetic mutation in 1- hydroxylase [ vitamin d resistant rickets - i ( vdrr - i ) ] or vdr ( vdrr - ii ) will also lead to failure of local adaptive response .
this will also explain the observation in vdrr - i and ii , where high intake of calcium can overcome most of the clinical manifestation of the disease .
with very high intake , casrs will get saturated and will enhance passive ( paracellular ) calcium absorption , which will be able to fulfill the requirement of body . with increasing severity of vdd , there will be decrease in calcium absorption .
the calcium levels will now be maintained by bone resorption , rather than increasing calcium absorption , which is currently believed .
hence , generally held belief that increase in pth will increase calcium absorption through generation of active vitamin d metabolites , is wrong .
this puts pth as a marker for systemic vdd or failure of local adaptation by the  intestinal calcistat .
the above hypothesis of the  intestinal calcistat  explains the vide variation observed in literature about relation between serum 25ohd , pth , calcium absorption and bmd . according to this hypothesis , subjects with low serum 25ohd who have normal  intestinal calcistat
will absorb required amount of calcium and will not mount systemic adaptive response in the form of increase in pth and 1,25(oh ) 2d levels , hence will have lower 1,25(oh ) 2d levels than those with failure of adaptation and bmd will not be affected .
subjects with adaptive failure will have higher 1,25(oh ) 2d levels and will have lower bmd .
this is further supported by observation that patients with similar low serum 25ohd levels ( < 10 ng / ml ) , bmd was lower in subjects with shpt .
this will also explain the observation that about 50% of subjects with vdd do nt mount pth response because they have adequate local adaptation in  intestinal calcistat .
 this will also explains that why there is no substantial increase in calcium absorption in with vitamin d supplementation because basal level of serum 25ohd is sufficient to supple enough substrate for generation of active vitamin d metabolites .
this brings us to question that should we define vdd with a value of serum 25ohd in isolation ? it is obvious from the above discussion that there are adaptive mechanisms to overcome low vitamin d levels , which can be operative over a wide range of serum 25ohd levels .
failure of adaptive mechanism will lead to clinical and biochemical evidence of vdd . among them
hence , the subjects with vdd defined by low vitamin d levels ( < 20 ng / ml or < 30 ng / ml ) according to the current definition with normal pth and bmd will not have any clinical and biochemical consequence of low vitamin d levels and vice versa subjects with similar levels of serum 25ohd with raised pth or low bmd are likely to be vdd . what should we call subjects with low serum 25ohd levels without evidence of shpt or low bmd ?
should we call them subclinical vdd , compensated vdd , asymptomatic vdd or not call them vdd at all .
further studies are required to define adverse biological consequences of vdd in this group and effects of vitamin d supplementation and comparing them with the population who already had adverse biological effects of vdd .

 the main physiological function of vitamin d is maintenance of calcium homeostasis by its effect on calcium absorption , and bone health in association with parathyroid gland .
 vitamin d deficiency ( vdd ) is defined as serum 25-hydroxy vitamin d ( 25ohd ) levels < 20 ng / ml .
 do all subjects with vdd have clinical disease according to this definition ?
 we hypothesize that there exist an intestinal calcistat , which controls the calcium absorption independent of pth levels .
 it consists of calcium sensing receptor ( casr ) on intestinal brush border , which senses calcium in intestinal cells and vitamin d system in intestinal cells .
 casr dampens the generation of active vitamin d metabolite in intestinal cells and decrease active transcellular calcium transport .
 it also facilitates passive paracellular diffusion of calcium in intestine .
 this local adaptation adjusts the fractional calcium absorption according the body requirement .
 failure of local adaptation due to decreased calcium intake , decreased supply of 25ohd , mutation in casr or vitamin d system decreases systemic calcium levels and systemic adaptations comes into the play .
 systemic adaptations consist of rise in pth and increase in active vitamin d metabolites .
 these adaptations lead to bone resorption and maintenance of calcium homeostasis .
 not all subjects with varying levels of vdd manifest with secondary hyperparathyroidism and decreased in bone mineral density .
 we suggest that rise in pth is first indicator of vdd along with decrease in bmd depending on duration of vdd .
 hence , subjects with any degree of vdd with normal pth and bmd should not be labeled as vitamin d deficient .
 these subjects can be called subclinical vdd , and further studies are required to assess beneficial effect of vitamin d supplementation in this subset of population .


tricyclic alkaloids represented by cylindricines , lepadiformine ( 3 )   and fasicularin   are unique metabolites of ascidians .
cylindricines a and b isolated from clavelina cylindrical   were the first members of the family based on the perhydropyrrolo[2,1-j]quinoline and the perhydropyrido[2,1-j]quinoline ring systems , respectively .
the structures and relative stereochemistries were unambiguously established by x - ray crystallography of their corresponding picrates . moreover ,
these two compounds were reported to interconvert through aziridinium intermediate forming 3:2 equilibrium mixture upon standing in a solution .
compound 3 exhibited cytotoxicity against several tumor cell lines   and in vivo and in vitro cardiovascular activity .
more recently , fasicularin , isolated from nephteis fasicularis , was reported as a cytotoxin to vero cells and was found to act as a dna - damaging agent in the assay using a dna repair - deficient yeast strain . as a part of collaborative investigation of biologically active compounds from indonesian marine organisms , we herein report the isolation and structures of two new tricyclic alkaloids polycitorols a ( 1 ) and b ( 2 ) together with known lepadiformine ( 3 ) from a marine ascidian .
specimens ( 65.0 g , wet ) of the ascidian of the family polycitoridae were collected by scuba ( 25 m ) off flores , indonesia in august 2001 and were stored in ethanol after its collection . the sample was exhaustively extracted with meoh and the resulting extract was chromatographed on a silica gel column followed by reversed - phase hplc to give polycitorol a ( 1 ) , b ( 2 ) , and lepadiformine ( 3 ) .
polycitorol a ( 1 ) , colorless oil , [ ]d + 15 ( c 0.2 , chcl3 ) , was shown to have a molecular formula of c17h31no by hreims ( m / z 265.2410 , m ,  + 0.4 mmu ) .
strong absorption bands at 3384 and 1671 cm in the ir spectrum suggested that 1 contain hydroxyl and amine functionalities .
the h nmr spectrum contained a number of unresolved multiplets in the high field region (  1.212.24 ) , while no olefinic signals were observed .
the c nmr spectrum revealed the presence of a quaternary carbon (  77.9 ) , two heteroatom bearing methines (  67.0 , 71.9 ) , one methine (  44.2 ) , one ch2oh (  65.0 ) , one methyl , and eleven methylenes .
therefore , alkaloid 1 is tricyclic , and the nitrogen atom was suggested as a tertiary amine .
the c nmr spectrum of 1 displayed 17 carbon signals indicating that 1 has two less carbons than 3 .
a mass fragment ion at m / z 208 was formed by the cleavage of c4h9 , thus , differing in the length of the alkyl side chain from 3 .
cosy correlations revealed that a methine proton at  2.97 ( c 67.0 ) correlated with two methylene protons at  1.58 and 2.05 confirming the c2/c15 linkage .
further 2d nmr analysis ( table 1 ) allowed us to elucidate the planar structure of 1 .
enhancement of h-2 at  2.97 and h-4ax at  1.57 upon irradiation of h-9ax at  2.15 suggested a cisfusion between rings a and b. the alkyl side chain at c-2 occupied  equatorial position on the basis of mutual noe enhancements between h-2 and h-5 .
noe between one of h-12 protons and h-13 may indicate the primary hydroxyl group as shown .
polycitorol b ( 2 ) , [ ]d 10.3 ( c 0.6 , chcl3 ) , was isolated as a colorless oil .
the molecular formula c17h31no was determined by hreims , indicating that it was isomeric to 1 .
comparison of nmr data of 1 and 2 revealed that considerable higher field shifts were observed for a methine at  58.3 and a quaternary carbon at  66.5 in the c spectrum of 2 .
furthermore , additional methine signal at  4.06 ( c 60.5 ) suggested that 2 had a secondary rather than a primary alcohol .
the cosy spectrum indicated that this proton coupled to two nitrogenattached methylene protons (  3.53 , 3.36 ) and two other protons (  1.78 , 2.11 ) .
thus , the aforementioned data indicated that the pyrrolidine ring was rearranged to a piperidine ring .
the relative stereochemistry of a / b rings was shown to be identical to that in 1 with a c-2 butyl side chain based on similar noe data , particularly a set of mutual noe enhancements between h-2 , h-4ax and h-9ax .
a trans fusion between rings a and c was suggested by noe between h-13/h-2 , h-14ax / h-2 and h-5/h-2 .
thus , rings a and c of 2 adopted a much more rigid trans 1-azadecalin system and the c-13 hydroxyl group occupied  equatorial position .
two new tricyclic alkaloids , polycitorols a ( 1 ) and b ( 2 ) , have been isolated along with the known lepadiformine ( 3 ) from a marine ascidian .
the new compounds contain a butyl side chain instead of a hexyl group observed more commonly in known related compounds .
nmr spectra were taken on a jeol  500 ft nmr spectrometer and referenced to chcl3 solvent signal at  7.26 for h nmr and  77.0 for c nmr spectra in cdcl3 as a solvent and also referenced to tms signal at  0.00 for h nmr and  49.0 for c nmr spectra in cd3od as a solvent .
hplc separations were carried out on a hitachi l-6000 or shimadzu lc 9a pumps equipped with waters 486 or hitachi l-4000 uv detector and waters r401 differential refractometer .
columns used for hplc were reverse phase nacalai 5c18-ar ii ( 10  250 mm ) .
tlc was carried out on precoated silica 60f254 plates and visualized with vanillin - etoh-1% h2so4 .
the specimens ( 65.0 g , wet wt . ) of the ascidian ( family polycitoridae ) were collected by hand using scuba ( 25 m ) at misa is .
, labuhanbajo , flores , indonesia in august 2001 and were stored in ethanol after its collection .
adrian gittenberger , national museum of natural history naturalis , leiden , the netherlands . a voucher specimen ( 0117j78 )
is deposited at department of chemistry , biology , and marine science , university of the ryukyus .
a photo of the specimen can be viewed at http://www.ascidians.com/families/polycitoridae/polycitoridae_blue/polycitoridaeblue.htm a sample of tunicate ( 65.0 g wet weight ) was cut into small pieces and soaked in acetone ( 300 ml ) for 7 hr .
after decantation , fresh solvent was added , and the procedure was repeated three times .
the oil was chromatographed on silica gel by eluting with step gradient of hexane / ch2cl2/etoac / meoh .
fraction v was selected for further purification using hplc ( rp-18 , meoh / h2o / tfa ) to afford compounds 1 , 2 and 3 .
polycitorol a ( 1 ) : colorless oil ; [ ]d + 15.3 ( c 0.2 , chcl3 ) ; ir ( film ) 3384 , 2937 , 2867 , 1671 , 1455 , 1201 , 1132 cmh and c nmr see table 1 ; eims m / z 265 ( 25 , m ) , 234 ( 100 ) , 222 ( 97 ) , 208 ( 45 ) , 194 ( 5 ) , 178 ( 5 ) ; hreims found m / z 265.2410 ( calcd for c17h31no , 265.2406 ) .
polycitorol b ( 2 ) : colorless oil ; [ ]d 10.3 ( c 0.6 , chcl3 ) ; ir ( film ) 3384 , 2937 , 2869 , 1670 , 1457 , 1201 , 1132 cmh and c nmr see table 1 ; eims m / z 265 ( 6 , m ) , 222 ( 29 ) , 208 ( 100 ) , 193 ( 7 ) , 150 ( 5 ) ; hreims found m / z 265.2406 ( calcd for c17h31no , 265.2406 ) .
nmr spectra were taken on a jeol  500 ft nmr spectrometer and referenced to chcl3 solvent signal at  7.26 for h nmr and  77.0 for c nmr spectra in cdcl3 as a solvent and also referenced to tms signal at  0.00 for h nmr and  49.0 for c nmr spectra in cd3od as a solvent .
hplc separations were carried out on a hitachi l-6000 or shimadzu lc 9a pumps equipped with waters 486 or hitachi l-4000 uv detector and waters r401 differential refractometer .
columns used for hplc were reverse phase nacalai 5c18-ar ii ( 10  250 mm ) .
tlc was carried out on precoated silica 60f254 plates and visualized with vanillin - etoh-1% h2so4 .
the specimens ( 65.0 g , wet wt . ) of the ascidian ( family polycitoridae ) were collected by hand using scuba ( 25 m ) at misa is . , labuhanbajo , flores , indonesia in august 2001 and were stored in ethanol after its collection .
adrian gittenberger , national museum of natural history naturalis , leiden , the netherlands . a voucher specimen ( 0117j78 )
is deposited at department of chemistry , biology , and marine science , university of the ryukyus .
a sample of tunicate ( 65.0 g wet weight ) was cut into small pieces and soaked in acetone ( 300 ml ) for 7 hr .
after decantation , fresh solvent was added , and the procedure was repeated three times .
the oil was chromatographed on silica gel by eluting with step gradient of hexane / ch2cl2/etoac / meoh .
fraction v was selected for further purification using hplc ( rp-18 , meoh / h2o / tfa ) to afford compounds 1 , 2 and 3 .
polycitorol a ( 1 ) : colorless oil ; [ ]d + 15.3 ( c 0.2 , chcl3 ) ; ir ( film ) 3384 , 2937 , 2867 , 1671 , 1455 , 1201 , 1132 cmh and c nmr see table 1 ; eims m / z 265 ( 25 , m ) , 234 ( 100 ) , 222 ( 97 ) , 208 ( 45 ) , 194 ( 5 ) , 178 ( 5 ) ; hreims found m / z 265.2410 ( calcd for c17h31no , 265.2406 ) .
polycitorol b ( 2 ) : colorless oil ; [ ]d 10.3 ( c 0.6 , chcl3 ) ; ir ( film ) 3384 , 2937 , 2869 , 1670 , 1457 , 1201 , 1132 cmh and c nmr see table 1 ; eims m / z 265 ( 6 , m ) , 222 ( 29 ) , 208 ( 100 ) , 193 ( 7 ) , 150 ( 5 ) ; hreims found m / z 265.2406 ( calcd for c17h31no , 265.2406 ) .

 two new tricyclic alkaloids , polycitorols a ( 1 ) and b ( 2 ) have been isolated along with the known lepadiformine ( 3 ) from a marine ascidian of the family polycitoridae .
 the structures of the new compounds were elucidated by analysis of nmr data and comparison with those of 3 and other related compounds [ 15 ] .
 compounds 1 and 2 are closely related to cylindricines a and b , lacking c-4 oxygenation found in cylindricines and having a butyl instead of a hexyl appendage .
 noe experiments on compounds 1 and 2 suggested the a / b ring fusion to be cis .


The surgical correction of kyphosis in patients with myelomeningocele is associated with a high complication rate , ranging from 78% to 90% in some series [11, 17, 19]. Most complications appear to be related to the surgical wound, but they also result from instrumentation failure, junctional kyphosis, cerebrospinal fluid fistulae, infections, thromboembolic events, ventriculoperitoneal shunt failure, rhabdomyolysis, meningitis, pneumonia, and urinary tract infections, and can lead to death. Despite the high complication rate, to the best of our knowledge, no prior studies have directly measured the impact of kyphectomy on the quality of life (QOL) of these patients. The objective of this study was to report the health-related QOL (HRQOL) and the results and complications observed in the treatment of kyphosis associated with myelomeningocele in a consecutive series of patients treated using the same surgical technique.


Patients with a ventriculoperitoneal shunt only underwent surgery if the shunt was permeable and their hydrocephalus was compensated for surgery. Urine cultures were used to guide the treatment of possible infections with at least 3 days of antibiogram-guided antibiotic therapy before surgery. Antibiotic prophylaxis was administered in the form of first-generation cephalosporin. All patients were tested for a latex allergy, which is common in patients with myelomeningocele [13, 18]. In patients whose test result was positive, a 100% latex-free environment was prepared in the surgical center.


The surgical technique used was a modified Dunn-McCarthy technique ; fixation of the thoracic spine was performed using pedicle screws instead of sublaminar wires. Screws (USS 1 titanium pedicle screws [DePuy Synthes Spine, Raynham, MA, USA]) were inserted proximally into the normal thoracic spine. The number of fixation points for the interface between the screw and bone was determined subjectively by the surgeon. Six screws in three vertebrae were frequently used.


Osteosynthesis was then performed following the principles of the Dunn-McCarthy technique . The rods were bent into the shape of a bayonet (S-shaped), and the short arms of the rods were passed through the foramina of S1 so they were anterior to the sacrum . By orienting the rods horizontally, a lever was created that reduced lumbar kyphosis and restored the sacrum to its original position. The upper portions of the rods were then fixed to the thoracic spine using pedicle screws. The resected body provides a good amount of bone graft material (Fig. 2C). Postoperative immobilization was not used.


The MCID considered for the generic core scale was 5, as established previously in the evidence for the generic core scale using distribution-based methods (that is, standard error of measurement) [7, 28]. We found no previous studies establishing the MCID for the neuromuscular module.


C ongressional employees are retained to perform public duties that include assisting Members in official responsibilities in personal, committee, leadership, or administrative office settings. The roles, duties, and activities of congressional staff are matters of ongoing interest to Members of Congress, congressional staff, groups, and individuals, including those who raise concerns about congressional operations. Most observers recognize that Congress does not function without staff, but there is little systematic attention to what staff do, or what Members expect of them. In congressional offices, there may be interest in identifying Member expectations of congressional staff duties by position from multiple perspectives, including assessment of staffing needs in Member offices; guidance in setting position expectations, qualifications, and experience when offices choose to hire staff; and informing current and potential congressional employees of position expectations. Members of the House and Senate generally establish their own employment policies and practices for their personal offices. It is arguably the case that within Member offices, a common group of activities is executed for which staff with relevant skillsets and other qualifications are necessary. A body of publicly available job advertisements for staff positions from a number of different offices can shed light on the expectations Members have for position duties, as well as staff skills, characteristics, experience, and other expectations. For 33 commonly used congressional staff position titles, this report describes the most frequently listed job duties, applicant skills, characteristics, prior experiences, and other expectations found in a sample of job advertisements placed by Members of Congress between approximately December 2014 and September 2019 seeking staff in their offices. Table 1 lists the position titles and the frequency with which advertisements for them appeared in the sample. Identifying Job Advertisements for Congressional Staff Positions Data used in developing sample position expectations were taken from several publicly available sources, including the following, over the periods specified: The House Employment Bulletin, published weekly by the House Vacancy Announcement and Placement Service (HVAPS) in the Human Resources Office of the House Chief Administrative Officer (CAO). Data were collected from ads published between approximately January 2015 and September 2019. The Employment Bulletin, published online by the Senate "as a service to Senate offices choosing to advertise staff vacancies." Data were collected from ads, which were not dated, appearing from approximately July 2016 to July 2019. The House GOP Job and Resume Bank, which posts ads on behalf of the House Republican Conference on Facebook. Ads were collected between approximately January and June 2017. Other ads were collected from the period between approximately December 2014 and January 2017 from the House GOP Job Bank web page on the website of Representative Virginia Foxx during part of her tenure as the House Republican Conference Secretary. The Job Announcements Board hosted by Representative Steny Hoyer during part of his tenure as House Minority Whip. Data were collected from ads posted between approximately January 2016 and December 2017. Categorizing and Coding Job Advertisements More than 1,800 ads were collected from all sources. Duplicate ads resulting from posts to more than one source, and ads that appear to have been frequently reposted, were removed, as were ads for positions in congressional settings other than personal offices, yielding 880 ads for positions in Member personal offices. Substantially similar position titles (e.g., deputy scheduler and state deputy scheduler) for which there were five or more ads were identified and grouped together, as were related job titles (e.g., positions designated as district, field, or regional representative that had essentially similar job duties and expectations) for which there were five or more substantially similar ads, yielding a total of 704 ads. Ads for the 33 identified position titles were further categorized if there were five or more ads that specified the advertised position as "not entry level" or other signifier of presumptive advanced status. The 704 ads were coded against a variety of variables within eight categories, including ad tracking information; ad details; position responsibilities and responsibility areas; expected job skills, qualifications, and credentials; application materials; and office type. The distribution of ads by job title and level is provided in Table 1 . Solicitations of applicants for congressional staff appear to originate in a highly decentralized manner. Means of identifying appropriate candidates might potentially include reassigning staff within offices, placing ads in services that make them available by subscription, word of mouth, and other nonpublic means of identifying potential applicants for congressional staff positions. Consequently, it cannot be determined whether the dataset of ads analyzed in this report is representative of all congressional employment solicitations. In addition, the process by which candidates for some Member office senior staff positions are identified may not be public-facing. Based on information specified within the ads, most position titles were identified by one of the following four primary responsibility areas (some positions were identified by up to three responsibility areas): Legislative, Policy, and Oversight, Media, Messaging, and Speeches, Constituent Communications, Outreach, and Service, and Office Administration and Support. For each position, at least one sample position description was created based on the coded data. Information includes the most frequently occurring of the following: primary responsibility areas; widely expected duties, typically up to six of the most frequently occurring duties specified in all ads for that position; other potential duties, typically up to six other duties mentioned in more than one ad; applicant information, including characteristics, skills, and knowledge and prior experience; and other expectations. Concluding Observations Categorizing congressional staff positions by position title relies on an assumption that similarly titled positions in House and Senate personal offices carry out the same tasks under essentially similar circumstances. While personal offices may carry out similar activities, the assumption might be questionable given the differences in staff resources in House and Senate offices, as well as potential differences within offices of each chamber. Generalizations about staff roles and duties may also be limited in some ways due to the broad discretion Members have with regard to running their office activities. Variations from office to office, which might include differences in job duties, work schedules, office emphases, and other factors, may limit the extent to which sample position expectations provided here match operational practices in all congressional offices. Sample Position Expectations Caseworker18 Communications Director19 Communications Director, "Senior Level" or "Not Entry Level"20 Constituent Services Representative21 Correspondence Manager22 Deputy Press Secretary23 Deputy Scheduler24 Deputy Scheduler/Assistant to Chief of Staff25 Digital Director/Press Assistant26 Digital Media Director27 District Director28 Executive Assistant29 Executive Assistant/Scheduler30 Executive Assistant/Scheduler, "Not Entry Level"31 Field, District, or Regional Representative32 Field Representative/Caseworker33 Legislative Aide34 Legislative Assistant35 Legislative Assistant, "Not Entry Level"36 Legislative Correspondent37 Legislative Correspondent/Press Assistant38 Legislative Correspondent/Staff Assistant39 Legislative Counsel40 Legislative Director, House41 Legislative Director "Senior Level," or "Not Entry Level"42 Legislative Director, Senate43 Military Legislative Assistant44 Press Assistant45 Press Secretary46 Regional Coordinator47 Scheduler48 Scheduler, "Not Entry Level"49 Scheduler/Office Manager50 Senior Legislative Assistant51 Speechwriter52 Staff Assistant53 Staff Assistant/Driver54 Staff Assistant/Press Assistant55 Systems Administrator56

The roles, duties, and activities of congressional staff are matters of ongoing interest to Members of Congress, congressional staff, and observers of Congress. Members of the House and Senate establish their own employment policies and practices for their personal offices. It is arguably the case that within Member offices, a common group of activities is executed for which staff are necessary. Accordingly, a group of job advertisements for those positions from a number of different offices can shed light on the expectations Members have for position duties, as well as staff skills, characteristics, experience, and other expectations. This report provides a set of 39 widely expected job duties, applicant skills, characteristics, prior experiences, and other expectations based on a sample of ads placed by Members of Congress between approximately December 2014 and September 2019 seeking staff in their offices for 33 position titles: Sample position expectations might assist Congress from multiple perspectives, including assessment of staffing needs in Member offices; guidance in setting position expectations, qualifications, and experience when offices need to hire staff; and informing current and potential congressional employees of position expectations. At the same time, categorizing congressional staff positions by position title relies on an assumption that similarly titled positions in House and Senate personal offices carry out the same tasks under essentially similar circumstances. Although personal offices may carry out similar activities, the assumption might be questionable given the differences in staff resources in House and Senate offices, as well as potential differences among offices of each chamber, particularly the Senate. Genera lizations about staff roles and duties may also be limited in some ways due to the broad discretion Members have with regard to running their office activities. Variations from office to office, which might include differences in job duties, work schedules, office emphases, and other factors, may limit the extent to which sample position expectations might match operational practices in all congressional offices. This is one of several CRS products on congressional staff. To access those products, see CRS Report R44688, Congressional Staff: CRS Products on Size, Pay, and Job Tenure .


Premise: A group of kids is playing in a yard and an old man is standing in the background

Hypothesis: A group of boys in a yard is playing and a man is standing in the background


Premise: A group of children is playing in the house and there is no man standing in the background

Hypothesis: A group of kids is playing in a yard and an old man is standing in the background


Premise: The young boys are playing outdoors and the man is smiling nearby

Hypothesis: The kids are playing outdoors near a man with a smile


Premise: The kids are playing outdoors near a man with a smile


Premise: Two dogs are fighting

Hypothesis: Two dogs are wrestling and hugging


Premise: A brown dog is attacking another animal in front of the man in pants

Hypothesis: Two dogs are fighting


Hypothesis: Two dogs are wrestling and hugging


Premise: Nobody is riding the bicycle on one wheel

Hypothesis: A person in a black jacket is doing tricks on a motorbike


Premise: A person is riding the bicycle on one wheel

Hypothesis: A man in a black jacket is doing tricks on a motorbike


France: 10 people dead after shooting at HQ of satirical weekly newspaper #CharlieHebdo, according to witnesses http://t.co/FkYxGmuS58

MT @euronews France: 10 dead after shooting at HQ of satirical weekly #CharlieHebdo. If Zionists/Jews did this they'd be nuking Israel


@nanoSpawn Socialists, Antisemites, anti zionists - usual suspects


@euronews LOL. 5 million Muslims in France, what a disgrace. the french worm president and politicians killed them. tine for croissants now


@j0nathandavis They who? Stupid and partial opinions like this one only add noise to any debate.


@euronews @TradeDesk_Steve A French crime of passion or another heathen moslem atrocity?


BREAKING: 10 reportedly shot dead at Paris HQ of French weekly Charlie Hebdo http://t.co/5F1DOwzoCQ


@Independent why does one feel that this may have something to so with freedom of speech - http://t.co/Uhe5VimATk


BREAKING: At least 10 killed in shooting at French satirical newspaper Charlie Hebdo, Paris prosecutor's office says. http://t.co/mnAeA7j7fY

@cnni actually that wasnt me it was the cats present 2me but it was floping like aflipperedfish so i spatonitandthrewitinthegardenbed


Kelly: Oh! Oh! Can I pick the first question?
Jessica: Sure. Go for it!
Kelly: What's the scariest place you've been to!
Jessica: I'll start: Palermo in Italy.
Mickey: And what's so scary about that? Did you break your nail? :P
Jessica: Shut it, Mickey! No, there are the Capuchin Catacombs with 8000 corpses!
Kelly: Ewwww! Corpses? Rly?
Jessica: Yeah! And you can look at them like museum exhibits. I think they're divided somehow, but have no clue how!
Ollie: That's so cool! Do you get to see the bones or are they covered up?
Jessica: Well, partly. Most of them were exhibited in their clothes. Basically only skulls and hands.
Mickey: I'm writing this one down! That's so precious!
Ollie: Me too!

The scariest place for Jessica was the Capuchin Catacombs in Palermo.


Carrie: Just back from Fantastic Beast :)
Gina: and what do you think?
Carrie: generally good - as usual nice special effect and visuals, an ok plot, a glimpse of the wizarding community in the US.
Alex: Sounds cool. I was thinking of going this weekend with Lane, but I've seen some bad reviews.
Carrie: Depends on what you expect really - I have a lot of sentiment towards Harry Potter so, I'm gonna like everything the do. But seriously the movie was decent. However, if you're expecting to have your mind blown, then no, it's not THAT good.
Gina: I agree. I saw it last week and basically I'm satisfied.
Alex: No spoilers, girls.
Carrie: no worries ;)
Carrie: And Gina, what do you think about Eddie Redmayne as Newt?
Gina: I loved him <3 I loved how introverted and awkward he was and how caring he was towards the animals. And with all that he showed a lot of confidence in his beliefs and was a genuinely compassionate character
Carrie: not your standard protagonist, that's for sure
Gina: and that's what I liked about him
Alex: Maybe I'll go and see it sooner so we can all talk about it.
Carrie: go see it. If' you're not expecting god-knows-what you're going to enjoy it ;)

Carrie and Gina saw "Fantastic Beast" and liked it. Ginna loved Eddie Redmayne as Newt.


Samantha: How are you doing today?
Robyn: better, but I really exaggerated with bier last night
Samantha: was it really only bier?
Robyn: sure, why?
Samantha: I don't know, your eyes, behaviour
Robyn: you want to say I took drugs?
Samantha: I'm only asking, I don't have anything against drugs
Robyn: but I have and I never take them
Samantha: ok, sorry, I didn't intend to offend you
Robyn: I just drank too much, that's eat
Samantha: much too much
Robyn: yes, I lost control a bit
Robyn: I am sorry for that
Samantha: important that you feel better today

Robyn drank too much beer last night and lost control. She is feeling better today.


Peyton: I have been asking you to bring that video game for me
Cameron: Honey, I am not having enough time to come home
Peyton: When would you come home?
Cameron: I will have to stay out of town for another week i guess
Peyton: Cant you just deliver that game through the courier? :P
Cameron: Dont be mean :/
Peyton: Get the job done and come to home then. ASAP :P

Peyton is expecting Cameron to bring the video game. Cameron will probably be out for another week.


Gene: Did you get the package I sent you
Jack: No, when did you send it?
Gene: on Friday
Jack: shit I should have gotten it by now
Jack: send me the tracking umber I;ll check whats up
Gene: 12345678900

Jack has not received yet the package Gene had sent him on Friday. She sent him the tracking number, so he could check the status of the shipment.


Russ: Hi Gurdun, are you feeling better?
Gurdun: Hi Ross, a little bit better, yes, thank you.
Russ: Do you think you'll be back at the uni this week?
Gurdun: Not tomorrow for sure, but I hope Wednesday maybe.
Russ: Oh, that's fine.
Gurdun: Yeah. I'm feeling a bit weak still
Russ: I guess that's pretty normal at this stage.
Gurdun: I believe so. And the muscle pain.
Russ: I know what you mean. I had flu like that three months ago.
Gurdun: Luckily the headache's gone. It was absolutely awful.
Russ: True enough. I had the same.
Gurdun: Anyway, how are things with you?
Russ: Same old, same old, you know. Not much happening in the middle of term.
Gurdun: And the team?
Russ: Oh yeah, we won the last match. It was a good game.
Gurdun: Great. Listen Russ, I need to run. Catch up later.
Russ: OK, talk to you later.

Gurdun has the flu. He is feeling better. Gurdun hopes he'll be back at the uni on Wednesday. Russ and his team won the last match.


Susan: Will you be home tomorrow?
Rob: Why do you ask?
Susan: We could have dinner together if you have time after work
Rob: Sure! Sounds great
Susan: Fantastic! I will cook something special then!

Rob will be home tomorrow. Rob and Susan will have dinner together after Rob's work. Susan will cook something special.


Evan: Hi Dennis, I need to cancel my lesson tomorrow, sorry.
Dennis: Fine, what's up?
Evan: Oh, got the flu, been off college since Tuesday. Should be ok for next Thurs.
Dennis: OK, just tell me in good time if you can't make it. Hope you feel better soon.
Evan: Bye, Den! Thanks.

Evan can't come to his lesson tomorrow, because he's got the flu.


Lorena: Hi, can you help me with something?
Martin: Well, I can try.
Martin: Depends what it is?
Lorena: I got a new desk and it comes with assembly instructions but I give up, I just can't do it.
Lorena: I'm illiterate when it comes to instructions, haha.
Lorena: So I could really use some help...
Martin: Hmm, I can't today, but how about tomorrow? Shouldn't take long anyway.
Lorena: Yeah, it's fine! I just need it for the weekend, but tomorrow's great! Sorry for troubling you again.
Martin: Don't mention it, we've known each other for so long it's almost like we're siblings, haha.
Lorena: Thanks a lot! I should be home by 6, so let me know when you can.

Martin is going to help Lorena assemble a new desk. He is coming to her house tomorrow.


Joanna: They are sending emails about Lewandowska.
Merve: What happened?
Joanna: <file_photo>
Merve: Wooow!
Joanna: She is hospitalized because she has measles.
Merve: She had what?
Joanna: Anyone who had contact with her within the last couple of days must get vaccinated.
Merve: Luckily I didn't see her since the last semester...
Joanna: I did, she is my thesis mentor :(
Merve: What will you do?
Joanna: They are organizing vaccinations in the main building from 17th until 19th.
Merve: You have to go!
Joanna: I know... And I just started working so I really don't have a lot of time.
Merve: Come on, this is really important.
Joanna: I will try to do it before work on 18th, hopefully I won't lose the entire day...

Lewandowska has measles. There are vaccinations in the main building from 17th until 19th for everyone who had contact with her.


Chapter  12

Summary: Mrs. Dashwood and her daughters are busy attending parties and balls. Marianne is in her element. She is overjoyed in the company of Willoughby, who showers much affection and attention on her. Elinor even feels left out at times. Deprived of friends of her own age, she is often thrown in the company of Mrs. Jennings and Lady Middleton. At such times she welcomes the presence of Colonel Brandon. Brandon often talks of Marianne and asks Elinor about her sister's preferences.

Notes Jane Austen paints the picture of an eighteenth-century upper middle-class society. The Dashwoods and Middletons are shown to be busy attending parties and balls. Their main occupation is socializing, and they take pleasure in entertaining people. Every young girl waits for a respectable young man to woo her, and her parents hope for a match between them. They lead a leisurely life, perhaps unusual to the modern reader. Marianne is exhilarated by the looks and manners of her lover. She does not care to understand his essential nature. Obsessed with Willoughby, she ignores Colonel Brandon and unconsciously hurts him. Blinded by her infatuation for Willoughby, she is not able to realize the worth of the Colonel or detect the intensity of his feelings. This chapter again emphasizes the difference in attitudes between Willoughby and Colonel Brandon. Both men are attracted to Marianne. Willoughby displays his affection by wooing Marianne, like a dashing hero would, while Colonel Brandon admires his lady love from a distance and silently hopes to win her favor. Willoughby is interested only in flirting with Marianne, but the Colonel, like a sincere person, looks forward to a lasting relationship. CHAPTER 12 Summary Marianne gets carried away by Willoughby's showy gestures. When he offers her a horse, she accepts it readily and talks about it to her sister. Elinor is shocked to learn this and asks Marianne to decline the offer, as it would prove too costly for them. Elinor observes Willoughby's behavior towards her sister and detects a note of intimacy in it. Margaret tells Elinor about her suspicion of an engagement between Marianne and Willoughby. Later, at Mrs. Jennings' insistence, Margaret gives a hint about Elinor's attachment to Edward, much to Elinor's embarrassment. Notes The chapter hints at the extent of the involvement of Marianne with Willoughby. Willoughby tries to impress Marianne by offering her a horse as a gift, and Marianne foolishly accepts the offer without giving a thought to the expenditure involved. Willoughby's superficiality and Marianne's gullibility are exposed in this episode. Chapter 12 also reveals the character of the youngest of the Dashwood girls. Margaret, one of the minor characters in the novel, is otherwise ignored by Austen. Only a few chapters give a glimpse into her personality. Margaret, like a typical teenager, gets excited over little things and jumps to conclusions easily. She derives pleasure from revealing secrets. She informs Elinor about the impending marriage between Marianne and Willoughby because she saw the young man taking a lock of hair from her sister . At the Park, she gives hints about the relationship between Elinor and Edward to Mrs. Jennings, much to the embarrassment of her sister. Like a reckless teenager, she is always in a hurry to impart information not meant to be disclosed publicly. CHAPTER 13 Summary Everyone is eagerly looking forward to their picnic at Whitewell. However, on the morning of the outing, a letter arrives for Colonel Brandon and alters the situation. The letter disturbs Brandon, and he informs the others about his decision to leave immediately for the town. The picnic is canceled, much to the disappointment of all, since it is not possible to proceed to Whitewell without the assistance of the Colonel. Sir John Middleton suggests that they should go for a ride in the carriage around the countryside. Marianne and Willoughby take a separate carriage. They visit Allenham on the sly. When Elinor learns about their visit, she is angry with Marianne for not observing the rules of propriety. Marianne justifies her action. Notes An element of suspense is introduced in this chapter. After the Colonel reads the letter, he turns grave and decides to leave for the town immediately. He evades the questions of Mrs. Jennings and declines to postpone his visit. After he leaves, Mrs. Jennings hints at the possibility of his visiting his illegitimate daughter, Miss Williams. Through this bit of information, Austen arouses the curiosity of the reader regarding the mysterious past of Colonel Brandon. Marianne and Willoughby are insensitive to the feelings of the Colonel and fail to sympathize with his plight. They criticize Brandon for spoiling the afternoon. Colonel Brandon comes across as a man in control of his emotions. Even though he is disturbed by the contents of the letter, he does not reveal his misery to others. Like a gentleman, he excuses himself from the party and bows to Marianne before taking his leave. His silence speaks volumes. The chapter relates one more incident which creates a clash between the good sense of Elinor and the sensibility of Marianne. Marianne makes a secret visit to Allenham with Willoughby but does not feel guilty about what she has done. Elinor's sense of decorum causes her to condemn her sister's actions, as she does not approve of Marianne's visiting a stranger's house with a man to whom she is not even engaged, at least not openly.

As Elinor and Marianne were walking together the next morning the
latter communicated a piece of news to her sister, which in spite of
all that she knew before of Marianne's imprudence and want of thought,
surprised her by its extravagant testimony of both.  Marianne told her,
with the greatest delight, that Willoughby had given her a horse, one
that he had bred himself on his estate in Somersetshire, and which was
exactly calculated to carry a woman.  Without considering that it was
not in her mother's plan to keep any horse, that if she were to alter
her resolution in favour of this gift, she must buy another for the
servant, and keep a servant to ride it, and after all, build a stable
to receive them, she had accepted the present without hesitation, and
told her sister of it in raptures.

"He intends to send his groom into Somersetshire immediately for it,"
she added, "and when it arrives we will ride every day.  You shall
share its use with me.  Imagine to yourself, my dear Elinor, the
delight of a gallop on some of these downs."

Most unwilling was she to awaken from such a dream of felicity to
comprehend all the unhappy truths which attended the affair; and for
some time she refused to submit to them.  As to an additional servant,
the expense would be a trifle; Mama she was sure would never object to
it; and any horse would do for HIM; he might always get one at the
park; as to a stable, the merest shed would be sufficient.  Elinor then
ventured to doubt the propriety of her receiving such a present from a
man so little, or at least so lately known to her.  This was too much.

"You are mistaken, Elinor," said she warmly, "in supposing I know very
little of Willoughby.  I have not known him long indeed, but I am much
better acquainted with him, than I am with any other creature in the
world, except yourself and mama.  It is not time or opportunity that is
to determine intimacy;--it is disposition alone.  Seven years would be
insufficient to make some people acquainted with each other, and seven
days are more than enough for others.  I should hold myself guilty of
greater impropriety in accepting a horse from my brother, than from
Willoughby.  Of John I know very little, though we have lived together
for years; but of Willoughby my judgment has long been formed."

Elinor thought it wisest to touch that point no more.  She knew her
sister's temper.  Opposition on so tender a subject would only attach
her the more to her own opinion.  But by an appeal to her affection for
her mother, by representing the inconveniences which that indulgent
mother must draw on herself, if (as would probably be the case) she
consented to this increase of establishment, Marianne was shortly
subdued; and she promised not to tempt her mother to such imprudent
kindness by mentioning the offer, and to tell Willoughby when she saw
him next, that it must be declined.

She was faithful to her word; and when Willoughby called at the
cottage, the same day, Elinor heard her express her disappointment to
him in a low voice, on being obliged to forego the acceptance of his
present.  The reasons for this alteration were at the same time
related, and they were such as to make further entreaty on his side
impossible.  His concern however was very apparent; and after
expressing it with earnestness, he added, in the same low voice,--"But,
Marianne, the horse is still yours, though you cannot use it now.  I
shall keep it only till you can claim it.  When you leave Barton to
form your own establishment in a more lasting home, Queen Mab shall
receive you."

This was all overheard by Miss Dashwood; and in the whole of the
sentence, in his manner of pronouncing it, and in his addressing her
sister by her Christian name alone, she instantly saw an intimacy so
decided, a meaning so direct, as marked a perfect agreement between
them.  From that moment she doubted not of their being engaged to each
other; and the belief of it created no other surprise than that she, or
any of their friends, should be left by tempers so frank, to discover
it by accident.

Margaret related something to her the next day, which placed this
matter in a still clearer light.  Willoughby had spent the preceding
evening with them, and Margaret, by being left some time in the parlour
with only him and Marianne, had had opportunity for observations,
which, with a most important face, she communicated to her eldest
sister, when they were next by themselves.

"Oh, Elinor!" she cried, "I have such a secret to tell you about
Marianne.  I am sure she will be married to Mr. Willoughby very soon."

"You have said so," replied Elinor, "almost every day since they first
met on High-church Down; and they had not known each other a week, I
believe, before you were certain that Marianne wore his picture round
her neck; but it turned out to be only the miniature of our great
uncle."

"But indeed this is quite another thing.  I am sure they will be
married very soon, for he has got a lock of her hair."

"Take care, Margaret.  It may be only the hair of some great uncle of
HIS."

"But, indeed, Elinor, it is Marianne's. I am almost sure it is, for I
saw him cut it off.  Last night after tea, when you and mama went out
of the room, they were whispering and talking together as fast as could
be, and he seemed to be begging something of her, and presently he took
up her scissors and cut off a long lock of her hair, for it was all
tumbled down her back; and he kissed it, and folded it up in a piece of
white paper; and put it into his pocket-book."

For such particulars, stated on such authority, Elinor could not
withhold her credit; nor was she disposed to it, for the circumstance
was in perfect unison with what she had heard and seen herself.

Margaret's sagacity was not always displayed in a way so satisfactory
to her sister.  When Mrs. Jennings attacked her one evening at the
park, to give the name of the young man who was Elinor's particular
favourite, which had been long a matter of great curiosity to her,
Margaret answered by looking at her sister, and saying, "I must not
tell, may I, Elinor?"

This of course made every body laugh; and Elinor tried to laugh too.
But the effort was painful.  She was convinced that Margaret had fixed
on a person whose name she could not bear with composure to become a
standing joke with Mrs. Jennings.

Marianne felt for her most sincerely; but she did more harm than good
to the cause, by turning very red and saying in an angry manner to
Margaret,

"Remember that whatever your conjectures may be, you have no right to
repeat them."

"I never had any conjectures about it," replied Margaret; "it was you
who told me of it yourself."

This increased the mirth of the company, and Margaret was eagerly
pressed to say something more.

"Oh! pray, Miss Margaret, let us know all about it," said Mrs.
Jennings.  "What is the gentleman's name?"

"I must not tell, ma'am. But I know very well what it is; and I know
where he is too."

"Yes, yes, we can guess where he is; at his own house at Norland to be
sure.  He is the curate of the parish I dare say."

"No, THAT he is not.  He is of no profession at all."

"Margaret," said Marianne with great warmth, "you know that all this is
an invention of your own, and that there is no such person in
existence."

"Well, then, he is lately dead, Marianne, for I am sure there was such
a man once, and his name begins with an F."

Most grateful did Elinor feel to Lady Middleton for observing, at this
moment, "that it rained very hard," though she believed the
interruption to proceed less from any attention to her, than from her
ladyship's great dislike of all such inelegant subjects of raillery as
delighted her husband and mother.  The idea however started by her, was
immediately pursued by Colonel Brandon, who was on every occasion
mindful of the feelings of others; and much was said on the subject of
rain by both of them.  Willoughby opened the piano-forte, and asked
Marianne to sit down to it; and thus amidst the various endeavours of
different people to quit the topic, it fell to the ground.  But not so
easily did Elinor recover from the alarm into which it had thrown her.

A party was formed this evening for going on the following day to see a
very fine place about twelve miles from Barton, belonging to a
brother-in-law of Colonel Brandon, without whose interest it could not
be seen, as the proprietor, who was then abroad, had left strict orders
on that head.  The grounds were declared to be highly beautiful, and
Sir John, who was particularly warm in their praise, might be allowed
to be a tolerable judge, for he had formed parties to visit them, at
least, twice every summer for the last ten years.  They contained a
noble piece of water; a sail on which was to a form a great part of the
morning's amusement; cold provisions were to be taken, open carriages
only to be employed, and every thing conducted in the usual style of a
complete party of pleasure.

To some few of the company it appeared rather a bold undertaking,
considering the time of year, and that it had rained every day for the
last fortnight;--and Mrs. Dashwood, who had already a cold, was
persuaded by Elinor to stay at home.