Many efforts to prevent alcohol-related harm are aimed at reducing risk drinking. This article outlines the many conceptual and methodological challenges to defining risk drinking. It summarizes recent evidence regarding associations of various aspects of alcohol consumption with chronic and acute alcohol-related harms, including mortality, morbidity, injury, and alcohol use disorders, and summarizes the study designs most appropriate to defining risk thresholds for these types of harm. In addition, it presents an international overview of low-risk drinking guidelines from more than 20 countries, illustrating the wide range of interpretations of the scientific evidence related to risk drinking. This article also explores the impact of drink size on defining risk drinking and describes variation in what is considered to be a standard drink across populations. Actual and standard drink sizes differ in the United States, and this discrepancy affects definitions of risk drinking and prevention efforts. Preventing alcohol-related harm does not necessarily require that risk drinking be defined. At the population level, harm reduction can be achieved through numerous broad measures that determine the price or availability of beverage alcohol . MeasurePerhaps the most essential challenge lies in determining the threshold that discriminates “low-risk” and “risk” drinking. Is risk drinking any consumption that corresponds to a significantly higher level of harm than that experienced by lifetime abstainers, or does the harm have to be of a specified magnitude? Given a linear relationship between consumption and harm, where is the appropriate cutoff point? Beyond this basic question, one must also ask what types of harms should be considered. Excessive use of alcohol is associated with a wide range of harmful outcomes, including alcohol use disorders; mortality and morbidity from chronic medical conditions, such as alcoholic liver disease, and acute causes, such as vehicular crashes and accidental and intentional injury; and a host of social and legal problems. Should risk-drinking definitions be keyed more closely to those types of harm most strongly attributable to alcohol use, or to the most severe harms  regardless of the strength of their association with drinking?What aspects of alcohol consumption should be used to define risk drinking? Should these vary according to the type of harm ? Should risk drinking be defined in terms of consumption that reflects current alcohol-related problems, as is the case with screening for alcohol use disorders and emergency-department studies of drinking in relation to the risk of injury? Or should it be defined in terms of consumption that increases the risk of developing alcohol-related harm in the long term, as is the case with prospective studies of alcohol-related mortality and morbidity?What types of studies are most appropriate for assessing associations between different aspects of alcohol consumption and alcohol-related harm? To what extent should we account for the quality of the consumption data upon which evidence of alcohol-related harm is based? Many of the large prospective studies used to assess mortality risk collect data on numerous putative risk factors, and they often contain too few questions on alcohol use to yield estimates of consumption that fully capture the contribution of heavy drinking days or multiple beverage types. If it is likely that associations of consumption with the risk of harm are based on underestimates of consumption, how should we account for that fact when using the data to inform definitions of risk drinking?Finally, what is the appropriate cutoff between enough information and too much? Should definitions of risk drinking, or, conversely, low-risk drinking guidelines, be complex enough to include volume- and pattern-related risks and their variation across population subgroups or should they be simple enough so that drinkers can easily recall them and clinicians can easily identify risk drinkers based on a single metric? Many guidelines contain different limits for men and women; others stipulate lower limits for the youngest and oldest drinkers. In addition, some guidelines explicitly mention groups of individuals for whom any drinking is inadvisable . These exceptions to the general guidelines might also include individuals with former alcohol problems or those with a history of treatment for alcohol use disorders. Is it appropriate to use the same definition of risk drinking for all prevention efforts, or should the context determine the relative emphasis on different aspects of risk drinking? How should we account for variation across beverages and drinkers in drink size and alcohol content when defining risk drinking?These questions provide some notion of the complex challenges posed in defining risk drinking and illustrate why there is no absolute consensus on the most appropriate definition. The following sections describe the evidence for associations of drinking volume and pattern with alcohol-related harm, issues surrounding standard drink size, and the conclusions drawn by selected countries in defining risk drinking in their national drinking guidelines.Drinking volume, generally characterized in terms of average daily volume (ADV) of alcohol intake, has been widely studied in association with mortality and chronic disease morbidity in large prospective cohort studies. Because a full review of this extensive literature lies beyond the scope of this article, this section will summarize the findings of selected meta-analyses conducted in 2000 or more recently. The focus will be on studies with dose-response curves that can be used to inform risk-drinking definitions, rather than studies that summarize associations by means of alcohol-attributable fractions  or years of life lost e.g., , 2009. MIn terms of disease-specific morbidity and mortality, much of the literature concerning coronary heart disease (CHD), stroke, and type 2 diabetes has centered on the debate concerning possible protective effects of moderate volumes of intake, but some meta-analyses have reported increased risks of these diseases at heavy volumes of consumption. A meta-analysis of 28 CHD studies by In a meta-analysis of six studies of pancreatitis, Finally, in terms of neoplastic conditions, For some types of alcohol-related harm, notably those that reflect acute consequences of heavy-drinking occasions, average volume of intake is a less relevant risk factor than measures of alcohol use directly associated with the event  or of heavy episodic drinking patterns. Drinking in the event is typically measured by means of a positive blood alcohol content (BAC) result or self-report of drinking in the 6 hours preceding an injury or medical problem. Heavy episodic drinking (HED), sometimes called risky single-occasion drinking RSOD;  or bingeEmergency-department studies have been a major source of data on the association between drinking and the likelihood of injury severe enough to warrant treatment at an emergency department , have shown three- to fourfold increases in the risk of injury in association with drinking in the event a. One stBecause deaths from external causes generally reflect drinking in the event of a fatal injury, analyses of the role of alcohol in such deaths have focused more strongly on drinking pattern than average volume of ethanol intake. In a prospective study of Russian men aged 25 to 64 years, with an average follow-up of 9.5 years, usual consumption of at least 160 g of alcohol per occasion increased the risk of death from external causes by a factor of 2.08 compared with a usual consumption of less than 80 g among individuals who drank at least once a month. A similar prospective study of Finnish men found that those who usually drank six or more bottles of beer per drinking occasion had a far higher risk of death from external causes than those who usually consumed less than three bottles (RR: 7.10), even after adjusting for total consumption . No signAlthough most studies of chronic disease and all-cause mortality have focused on the association with volume of ethanol intake, as described previously, a limited number of studies have examined associations with drinking pattern measures, primarily HED. In a meta-analysis of six studies that included drinking pattern and volume measures, Among the other types of alcohol-related harm that have been associated with HED or high BAC concentrations in experimental, cross-sectional, and prospective surveys are violence , includiAssociations of drinking volume and pattern with alcohol use disorders (AUDs) have been established in both cross-sectional and prospective designs. Studies of general-population samples have shown that both the average volume of consumption and the absolute or relative frequency of heavy drinking are independently associated with the risk of alcohol abuse and dependence .Perhaps the best illustration of the complexity of defining risk drinking can be obtained by comparing international drinking guidelines. A number of countries have systematically formulated low-risk drinking guidelines with the input of expert committees of researchers who have conducted extensive reviews of the scientific literature. By providing the upper limits of low-risk drinking, these guidelines implicitly reveal various countries’ definitions of risk drinking . Two reports describing recent changes to the Australian and Canadian drinking guidelines provide the rationales used for setting the guidelines in those countries. They illustrate the broad range of evidence typically considered in establishing these guidelines and the diverse approaches  that may be applied to the interpretation of this evidence . The various guidelines differ among countries not only in terms of the maximum permissible numbers of drinks but also in terms of what types of limits are included  and whether there are different guidelines for men and women  is almost twice as large as the standard drink size of 8 g used by the United Kingdom. A standard drink size of 10 g is used in Australia and most of Europe other than the United Kingdom; the Canadian standard drink size is 13.45 g. Japan lies at the upper extreme, with a standard drink size of 19.75 g. For a full description of international variation in standard drink size, see Australia, Canada, France, Italy, Romania, Singapore, Spain , Sweden, and Switzerland have identical low-risk drinking guidelines for men and women, although Italy also has a set of Nutritional Guidelines with complex moderate drinking recommendations based on total body weight that generally would yield higher limits for men than women. The Canadian guidelines from the Center for Addiction and Mental Health have identical daily limits for men and women but lower weekly limits for women. Japan has guidelines for men only. The remaining countries for which guidelines are available—Austria, Canada , the Czech Republic, Denmark, Finland, Germany, Ireland, the Netherlands, Poland, Portugal, Slovenia, South Africa, the United Kingdom, and the United States) have different drinking limits for men and women in all components of their low-risk drinking guidelines. Typically, the gender differences in the daily limits are proportionately smaller than those in the weekly limits.There have been surprisingly few attempts to validate individual countries’ drinking guidelines against specific outcomes. In a cross-sectional analysis of the U.S. drinking guidelines among past-year drinkers, http://rethinkingdrinking.niaaa.nih.gov/). They also provide information on the number of standard drinks in commonly sold container sizes such as a 40-oz can of malt liquor, a 750-mL bottle of table wine, and a fifth of spirits.Despite the abundant evidence of chronic and acute alcohol-related harm at various levels of average daily or per-occasion ethanol intake, converting risk thresholds into a comprehensible definition of risk drinking must ultimately confront the issue of drink size. The amount of ethanol contained in an alcoholic drink varies considerably depending on the type of alcohol  and on the size of the drink. Within the major categories of alcoholic beverages, there are significant variations according to beverage subtype. Malt liquor, with a typical ethanol content of at least 6.0 percent alcohol by volume (ABV), is far stronger than light beer, with a typical ABV of about 4.2 percent. Likewise, fortified wines have an ABV that is about 50 percent greater than that of regular table wine or champagne, approximately 18 percent versus 12 percent a. MoreovDoes this ensure that drinkers understand the concept of a standard drink and know how many standard drinks they typically consume? Unfortunately, all evidence suggests that this is not the case. In an exhaustive review of 32 studies related to drink size published through 2007, Definitions of risk drinking, as implied by the low-risk drinking guidelines of the United States and other countries, are generally in line with levels of risk observed in the scientific literature. Although estimated associations of alcohol consumption with all-cause mortality and chronic disease vary as a function of level of adjustment and reference group, the ADV at which an increased risk of mortality is apparent generally lies in the range of 35 g to 45 g, or 245 g to 315 g per week, and the risk of many chronic medical conditions is significantly increased  at ADVs as low as 25 g, or 175 g per week. The weekly drinking limits for the majority of countries lie within this range. Evidence for gender differences in the association of drinking volume and chronic harm is both sparse and inconsistent but suggests that risk thresholds may be somewhat lower for women than men, at least for some conditions. The quite substantial differences in men’s and women’s weekly drinking guidelines in a number of countries, including the United States, with limits of 196 g and 98 g, respectively, are not fully supported by the existing data. They are more consistent with an influential early analysis of alcohol and all-cause mortality conducted by Acute alcohol-related harm generally shows a linear increase with drinking in the event and frequency of HED, sometimes with a threshold effect . Linear risk curves provide no obvious basis for determining the cutoff corresponding to risk drinking, which may help to explain the wide range of daily drinking limits in international low-risk drinking guidelines. Moreover, the data as related to gender differences in the association of acute alcohol-related harm and drinking are highly inconsistent across studies. In part, these inconsistencies may reflect gender differences in the underlying probability of the type of acute harm being studied, . This raises questions as to whether risk-drinking definitions for men and women should reflect gender differences in the underlying harm probabilities themselves or rather in the extent to which these probabilities are modified by drinking . One solQuestions about how best to convey the definition of risk drinking to the public remain even after evidence-based risk-drinking limits have been established. As is evident from a review of international drinking guidelines, the United States is among a minority of countries that define risk drinking both in terms of daily and weekly consumption. It is arguable that daily limits alone would be sufficient. The logic for such an argument is that most U.S. drinkers are not daily drinkers but rather consume alcohol primarily on weekends and special occasions . Given sRegarding the perplexing and challenging issue of drinkers’ inability to accurately gauge their consumption in standard drinks, the most obvious solution lies in the approach that has been adopted by a number of Western countries, in which alcoholic beverage containers explicitly state how many standard drinks (“units”) they contain. Even in the absence of such labeling, it has been argued that if risks attributed to drinking five or more drinks are based on scientific evidence relying on actual as opposed to standard drink sizes, coupled with other sources of consumption underreporting, then drinking less than five drinks, irrespective of how closely they correspond to standard drink size, will reduce harm in the aggregate. That is, if one assumes that relative risks associated with various consumption levels are overstated because of underreporting of consumption, then adherence to low-risk drinking limits should prove effective even for individuals whose actual drink sizes are larger than standard. Hence, publicizing low-risk drinking limits should play an important role in any activities aimed at preventing alcohol-related harm.


Despite extensive research on face perception, few studies have investigated individuals’ knowledge about the physical features of their own face. In this study, 50 participants indicated the location of key features of their own face, relative to an anchor point corresponding to the tip of the nose, and the results were compared to the true location of the same individual’s features from a standardised photograph. Horizontal and vertical errors were analysed separately. An overall bias to underestimate vertical distances revealed a distorted face representation, with reduced face height. Factor analyses were used to identify separable subconfigurations of facial features with correlated localisation errors. Independent representations of upper and lower facial features emerged from the data pattern. The major source of variation across individuals was in representation of face shape, with a spectrum from tall/thin to short/wide representation. Visual identification of one’s own face is excellent, and facial features are routinely used for establishing personal identity. However, our results show that spatial knowledge of one’s own face is remarkably poor, suggesting that face representation may not contribute strongly to self-awareness. Face perception is a central topic in modern psychology. The field has overwhelmingly used visual stimuli and focussed on face recognition, even when considering perception of one’s own face . People In general, the self-face visual recognition literature cannot readily distinguish between self-face processing based on familiarity with a visual image of one’s own face suitable for template matching, or based on structural knowledge about what one’s face is like , and stored models of one’s own body ,11. ThesAll participants gave informed written consent. All experiments were approved by the local ethics committee at University College London.Participants were seated in front of a computer screen in portrait orientation  which displayed only a small central dot. The position of the dot on the screen was randomised across trials. Participants were instructed to imagine their own face projected frontally, life-size on the screen, with the tip of the nose located at the dot. They used a mouse to indicate the locations corresponding to 11 landmark facial features The figure reproduced as left and right in the context of the task. By analysing the pattern of errors, we aimed to investigate the internal stored representation of one’s own face.Fifty participants  took part. The x data from left-sided landmarks  was reflected in the midline, and averaged with the corresponding right-sided landmark. This imposed an assumption of facial symmetry, but reduced the number of dependent variables and avoided possible confusion regarding the terms Finally, a subset of 10 participants were asked to attend for a second session, in which the screen was rotated to landscape mode.overall pattern of biases: for example, the compression of face height may appear to be a regression of judgement towards the mean defined by the anchor point on the nose tip. However, eye and ear vertical positions appear to be unaffected by this bias, and the bias is absent in the horizontal dimension, suggesting it is not simply a matter of eccentricity. Moreover, Bonferroni-corrected testing showed significant biases for some facial features close to the anchor point, but not for those farther away .structure of the face representation shown in To investigate the underlying 2, X3 for convenience, corresponding to the principal, independent sources of variability in horizontal judgement errors for facial features. The first factor (X1) suggested a tendency to expand facial width outward from the midline. It loaded strongly and roughly equally on all lateralised structures , but not on midline structures . The second factor (X2) suggested lateral distortion of the upper face. It loaded largely on the hairline and nose bridge. The third factor (X3) suggested lateral distortion of the lower face, loading almost exclusively on the chin. For analysis of vertical errors, only two factors were retained. The first (Y1) loaded strongly on upper face structures (eyes), including midline structures , but with some modest negative loading on the chin. This factor suggested a vertical expansion of the face from its centre. The loadings of the second factor (Y2) on lower face structures  suggest a vertical shift confined to the lower face.For horizontal errors, we identified three retainable factors, which we label X1, XWe investigated the relation between the factors underlying face representation and our participants’ actual facial features, as measured from photos. Since factor X1 was interpreted as the width of the face, we correlated scores on this factor with the actual ear-to-ear distance. Since factor Y1 was interpreted as the vertical height of the face, we correlated it with the actual hairline-to-chin distance. We found no associations between represented and actual facial dimensions .2, Y1 and Y2 all loaded on more than one facial feature. The loading patterns suggest complexes of two or more individual features that group together, and which covary across the face representations of different individuals. By this means, we could identify separable representations of lateral and midline horizontal facial features, and separable representations of upper and lower face vertical structure. The effects of varying each factor on an average face are shown as vectors in These factor solutions carry important information about the internal structure of horizontal and vertical face representation. Factors X1, X2) and vertical factors .We also investigated the overall geometry of face representation by seeking an inter-domain association between factors affecting horizontal and vertical errors. We used canonical correlation to identify the principal associations between our horizontal factors , suggesting that it constituted an independent aspect of facial structure. The combination of weightings in the first canonical variate is readily interpretable as face aspect ratio, or 2D shape. The lateral shift of eyes, mouth edges, ears and nose captured by factor X1 was associated with a downward shift of the hairline and nose-bridge (captured by Y1), and some upward shift of the mouth, nose edges and chin (captured by Y2). That is, the lateral expansion of the face was strongly associated with a vertical compression of towards the face centre, suggesting that the face aspect ratio is the major structural principle of face representation. The second canonical variate explained only 1.7% of the shared variance between factors, and was far from significant (p=0.37). Factor X3 was excluded from the inter-domain analysis, as its loading was largely confined to a single feature. However, re-running the analysis with this factor included had only small effects on weightings of inter-domain association and did not change the pattern of inference. The first canonical variate accounted for 48.5% of the variance between the horizontal and vertical factors and was highly significant =9.34, p<.001). The standardised weights showed that the canonical variate related X1 (weighting 0.99) negatively to Y1 (-0.85) and positively, though less strongly, to Y2 (0.53). In contrast, factor XWe have developed a new method to investigated stored knowledge about the “face image”, or structural arrangement of one’s own facial features. Importantly, this method allows the structural description of the face to be investigated independent of visual recognition.Analyses of errors in locating facial landmarks relative to the tip of the nose suggested an internal representation or model of one’s own face, with characteristic structure. We first showed an overall bias to represent face shape as shorter than it really is. This bias was unrelated to the actual height and width of an individual’s face. Second, we showed that the most prominent signature of different individuals’ overall face representations is the extent to which they express a set of associated factors that code for tall/thin vs short/wide face representation. This recalls similar shape distortions for the position sense of the hand , and forOne striking component of this structure was the aspect ratio defined by facial features. We investigated horizontal and vertical structure of face representation in two independent analyses. We next investigated the association of these dimensions, and found that facial aspect ratio emerged as a prominent feature of the data pattern. Our data therefore provides strong and independent convergent evidence that aspect ratio is a major source of variation in face representation. Not only are people poor at estimating the shape of their own face , but thevice versa. This dissociation could reflect innervation by different branches of the trigeminal nerve, or it could reflect different functions of the upper face  and lower face . In any case, our data confirm a fundamental division in face representation, as opposed to face perception, between upper and lower face.A second clear component of face structure was the separation between upper and lower facial features. For most of the factors we extracted, we found that high loadings on the upper face were accompanied by low loadings on the lower face, or 2) and lower face (factor X3), providing further strong evidence for independent representation of upper and lower face, but this time from the orthogonal, horizontal dimension of representation. We note that factor X3 requires a more cautious interpretation, given the marginal eigenvalue and loading on a single feature (the chin). The two midline shift factors could be interpreted as forehead and mandibular asymmetry, respectively. The importance of symmetry in developmental and evolutionary biology is widely accepted [Third, we found important misrepresentations of the lateral position of midline structures. Interestingly, these midline shifts occurred independently for the upper face . We suggest that such feature grouping may underlie configural face processing, and could provide a useful data-driven method for identifying what structural information is actually stored in the hypothesised configural representation. Configural processing might reflect precise representation of the spatial relations of features representation of the face is strongly and systematically distorted, but we have no difficulty in recognising much smaller distortions when viewing faces . Our reng faces . This poIn addition, our results offer a dramatic example of the asymmetry between fluent, automatic, stimulus-driven access to object representation, and the limited accessibility of such object representations to the kind of deliberate controlled processing involved in our task. Even our own face appears to be impenetrable to controlled cognition. It is well-known from memory research that recognition is superior to recall. In contrast, the everyday concept of self-awareness implies an opposite pattern. We do not need to recognise our thoughts and mental states as ours. Rather, a stable, persistent core self is held to be directly known, and to provide an origin for mental states, attitudes and actions. This account of the self has recently been questioned . Our appprocesses, reflecting the difficulty of comparing the content of information represented [It is unclear whether the distortions reported here are specific to representing one’s own face, or indeed to faces as a category. Identifying suitable objects for a control task is problematic. The quality and quantity of experience we have with other people’s faces, and with non-face objects, is entirely different from the experience of our own face. Controlling for modality, familiarity, prototypicality and other relevant factors is therefore difficult. Further, the features of non-face objects cannot match those of faces in number, salience and configuration, almost by definition. Thus, the representation of information about faces cannot easily be compared to representation of other objects. Many perceptual studies suggest a specialised brain system for face processing , consistresented .For these reasons, it remains unclear if our effects are specific to representations of one’s own face. However, the bias towards short and wide face representation recalls similar biases for hands  and bodyCould the factor structure we identified arise artefactually, from some process other than face representation? One possibility is a simple rotational error. Any head tilt in the facial photographs we used to measure judgement accuracy, or in the internal representation of the face that participants used to locate features, would produce systematic errors in judging the features of positions. The misrepresentation of face shape cannot be explained in this way because shape is invariant under rotation. However, some of the other distortions we noted could potentially be due to rotation. Tilt of the head (canting) is particularly likely , and is A second alternative explanation would involve the spatial distribution of pointing errors around the fixation/anchor point. For example, regression to the mean might cause people to judge all facial features as closer to the nose-tip anchor point than their true location. On this account, errors should vary strictly geometrically with each feature’s position in the face, but we found several aspects of face representation that were feature-specific and independent of position in the face or on the screen. For example, we found that errors in localising the bridge of the nose were lower than errors in localising the edges of the mouth , even thbetween individuals may influence their face representation, due to limited sample size. In particular, an individual’s face representation might depend on their actual facial structure, on their gender, or on cultural factors such as a desire to play down unusual or “unattractive” features.Finally, we acknowledge several limitations of our study. First, the number of participants is small, though it meets standards for exploratory factor analysis based on detailed simulation studies . Second,Table S1Correlation matrix for horizontal errors in feature localisation.(DOCX)Click here for additional data file.Table S2Correlation matrix for vertical errors in feature localisation.(DOCX)Click here for additional data file.Figure S1Results of factor analysis of the face image task reveal principal factors of horizontal and vertical distortion in face representation, rendered on an average female face. Vector show the principal feature loadings (>0.4 or <-0.4) of each factor. The vector lengths are shown at 4x the actual values for visual clarity. The percentage variance and tentative interpretation of each factor are given.(TIF)Click here for additional data file.Figure S2Pictorial representation of the principal factors of horizontal and vertical distortion. For each factor, the upper row shows an average male face distorted by a positive score of 1 standard deviation, and the bottom row shows the same face distorted by a negative unit score. Only features with high (>0.4 or <-0.4) loadings on the relevant factor were used to render the distortions.(TIF)Click here for additional data file.


We reviewed retrospectively our surgical HCA series to learn how to recognize the different subtypes histopathologically and how to interpret adequately their immunohistochemical staining. From January 1992 to January 2012, 37 patients underwent surgical resection for HCA in our institution. Nine had H-HCA (25%) characterized by steatosis and loss of L-FABP expression; 20 had IHCA (55.5%) showing CRP and/or SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient had both H-HCA and IHCA. In 5 patients (14%), b-HCA with GS and β-catenin nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two cases (5.5%) remained unclassified. One of the b-HCA showed also the H-HCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/αHNF1-inactivated HCA, another b-HCA exhibited the IHCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/inflammatory HCA. Interestingly, three patients had underlying vascular abnormalities. Using the recently published criteria enabled us to classify histopathologically our retrospective HCA surgical series with accurate recognition of b-HCA for which we confirm the higher risk of malignant transformation. We also underlined the association between HCA and vascular abnormalities.Light has been shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA) recognizing  Hepatocellular adenomas (HCA) are rare benign tumors most frequently observed in women on oral contraception , 2. HCA The existence of four different categories of HCA was recently recognized, and the clinical relevance of subtyping these liver lesions according to histological and immunohistochemical features and to molecular alterations was demonstrated –15.αHNF1-inactivated HCA (H-HCA) are associated with αHNF1 inhibiting mutations leading to the loss of expression of liver fatty acid binding protein (L-FABP) within the lesion as compared with the surrounding liver parenchyma by immunohistochemistry (IHC). These HCA are histologically associated with marked liver steatosis and do not show cytological abnormalities. The second group, the more frequent, is the inflammatory type of HCA (IHCA) associated with the activation of inflammatory pathways, and showing expression of serum amyloid A (SAA) and C-reactive protein (CRP) by IHC. Histologically, IHCA exhibit variable amounts of sinusoidal dilation, inflammation, and ductular reaction. The third subgroup is related to activating mutation of the β-catenin pathway (b-HCA) and carries a higher risk of transformation in hepatocellular carcinoma (HCC). The b-HCA can be identified on IHC by a nuclear accumulation of β-catenin and by the presence of a strong cytoplasmic staining for glutamine synthetase (GS). The last group corresponds to the unclassified and less-well understood HCA.Our aim was to review our series of HCA in light of the new histological and immunohistochemical criteria –13, 15 iA retrospective study of our surgical series of HCA was performed with the help of the Bordeaux group on thirty-one cases retrieved from the archives of our department of pathology. Six additional HCA surgically removed in our institution were then similarly studied, leading to a total number of 37 cases from January 1992 to January 2012.Clinical data including age, sex, body mass index (BMI), and oral contraceptive (OC) use, number of lesions, and clinical presentation which led to HCA diagnosis were retrieved from the clinical files.β-catenin  were performed according to the recommendations of the Bordeaux group. In cases suspicious of transformation into HCC, immunohistochemical staining of glypican-3  was also carried out. HE and IHC staining of 31 cases was analyzed as a training set, with the help of the Bordeaux group. Based on this training, one pathologist (CS) examined subsequently the next 6 cases.Formalin-fixed paraffin-embedded liver specimens were routinely stained with Hematoxylin Eosine (HE) to identify the histopathological characteristics of each one of the HCA. Liver adenomatosis was defined when more than 10 HCA were present within the liver , 15, 16.The clinical data of the 37 patients are given in The majority of the patients in our series were women (89%). The mean age at diagnosis was 40.9 years with a range from 17 to 68 years of age. In addition, there was one case of HCA surgically removed at 11 years of age in a boy with congenital absence of the portal vein. Twenty of the 33 female patients (66.7%) were on OC. Fifteen patients (44.1%) had a BMI higher than or equal to 25 and none of the patients had diabetes. Fifteen patients (42.9%) presented with symptoms related to intrahepatic hemorrhage of HCA. The other patients were diagnosed either incidentally or during the workup for other nonrelated symptoms. The young boy was followed since several years for portal vein agenesis. HCA was single in 22 patients (59.5%), whereas 3 patients (8.1%) had liver adenomatosis.The histological and immunohistochemical analyses allowed us to classify the HCA of our series of 37 patients into the four recently described categories .αHNF1-inactivated HCA (H-HCA), was observed in 9 patients (25%). All patients in this group were women, aged from 27 to 68 years; 55.5% had been on OC and 28% had a high BMI. The first manifestation was bleeding in 44.4%. Four women had a single lesion and 1 had liver adenomatosis. The size of the lesions varied from 30 to 100 mm. Followup, available for 7 patients, ranged from 10 to 129 months with all patients alive, one harboring residual HCA. Lack of L-FABP expression, suggestive of β-catenin suggesting a subgroup of β-catenin-activated/αHNF1-inactivated HCA and was classified within the group of b-HCA  with expression of both CRP and SAA were found in 20 patients (55.5%). They were 18 women and 2 men, aged from 17 to 49 years, and 50% of the women had been on OC. The BMI was high in 45% of the patients and the first manifestation was bleeding in 35%. Twelve patients had a single lesion and 2 had liver adenomatosis. The size of the lesions varied from 27 to 140 mm. Followup, available in 18 patients, ranged from 10 to 200 months. All patients are alive, two with residual HCA. β-catenin suggesting a subgroup of β-catenin-activated/inflammatory HCA (b-IHCA) and was classified within the group of b-HCA . In this group, there were two women on OC and one without, one man who did not take any medication, and one 11-year-old boy. Four patients had a normal BMI and all had a single large lesion (50–180 mm) discovered mostly incidentally in the adults and followed for a few years in the boy because of congenital absence of the portal vein. Imaging techniques revealed absence of the left portal vein in the man. The 5 patients are all alive without recurrence or residual lesion (followup range: 8–120 months).Five patients (14%) were identified as having a β-catenin nuclear staining was easy to find. The center of the b-HCA in these two patients showed transformation in HCC with rosette formation, poor differentiation, vascular invasion, and glypican-3 positivity , inflammatory HCA (IHCA), β-catenin activated HCA (b-HCA), and unclassified HCA [Light has been recently shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA) leading to the identification of four different subtypes: fied HCA –15. Thisfied HCA , 18 and fied HCA . By reviThe clinical characteristics and the frequency of each subtype in our series are similar to what is described in the Western literature , 17, 18.β-catenin nuclear accumulation can be found in otherwise typical IHCA leading to a subgroup of b-IHCA [In our series, as in others , 17, 18,f b-IHCA . Interesβ-catenin nuclear staining can instead be very focal and difficult to find. As exemplified by one of our b-HCA, GS staining can also be patchy within the lesion and this has also to be considered as an abnormal staining suspicious for b-HCA, as shown previously by the Bordeaux group [β-catenin was very focal and required the staining of several slides before identification. Therefore, at least in case of a strong diffuse GS staining, β-catenin IHC has to be performed in several slides to identify a b-HCA. Regarding the patchy GS staining, no clear recommendation can be made so far.In our experience, most of the HCA were easily classified into one of the subtypes using immunohistochemistry. However, interpretation of the staining requires comparison with nontumoral liver tissue and we would like to strongly recommend having this internal control within the same block. Indeed, L-FABP negative staining in H-HCA can be difficult to assess in the absence of adjacent normal liver tissue. By contrast, CRP can be present in scattered normal hepatocytes outside the lesion. Regarding the identification of IHCA, CRP detection was commonly easier to interpret than SAA because of being strong and diffuse, but for some of the cases it was the reverse and so both stainings are probably useful to identify IHCA when starting to study these lesions. HCA borders are not always easy to identify and GS staining is very helpful to allow the recognition of the normal tissue by labeling the perivenular areas. GS staining is also mandatory to recognize b-HCA in which it is commonly strongly and diffusely expressed. This is extremely helpful knowing that ux group , 21. Howβ-catenin positivity that can be very focal [Knowing all these possible pitfalls of immunohistochemistry will help the pathologist confronted to the biopsies that will probably be more and more often done in HCA in the next few years before surgical resection. Indeed, identification of the different types of HCA led to new propositions of management of these lesions, including performing a liver biopsy either because the nature of the lesion is uncertain on imaging techniques or to subtype an HCA prior to decide on the appropriate treatment , 21–24. In our series there were some interesting observations of associations between HCA and a particular clinical context. The most interesting one was the curious coincidence observed in 3 patients. A male child and two adults, one female and one male, were found to have an absence of, respectively, the portal vein in the child and the left branch of the portal vein in the two adults. These findings were also associated with a hyperarterialization of the corresponding branch of the hepatic artery. Both males had a single b-HCA transformed in HCC and the female had multiple H-HCA. Focal liver cell lesions including HCA, HCC, focal nodular hyperplasia, and nodular regenerative hyperplasia have been reported in association with congenital absence of the portal vein, also known as congenital extrahepatic portosystemic shunt or Abernethy malformation –8, 25–27In this series, we also found that one patient had granulomas within her H-HCA leading to a diagnosis of sarcoidosis later on. The presence of granulomas has been described in adenomas , but to β-catenin activated HCA. Our series confirms the higher risk of malignant transformation of this particular subtype and underlines the association between HCA and vascular abnormalities. Based on this learning experience that is reproducible in other series of surgically treated HCA, our recommendations to other pathologists would be (1) to always study in parallel the tumoral and nontumoral liver tissue and (2) to perform GS staining on all cases and rely on strong and diffuse GS staining to identify the potential b-HCA that requires further immunohistochemical and/or molecular confirmation. So far, a patchy GS staining is worrisome, but because it is still poorly understood, it requires further molecular investigations before giving any advice.In conclusion, using the new histological and immunohistochemical criteria enabled us to classify accurately our retrospective surgical series of HCA with recognition of


Video-game play (particularly “action” video-games) holds exciting promise as an activity that may provide generalized enhancement to a wide range of perceptual and cognitive abilities  from non-VGPs. Participants who report playing “action” video-games .Objective measures of video-game expertise are commonly available in the form of skill ratings and ladder rankings (based on the ELO system used in Chess) found in-game or online. For example, While video-game experience is not well suited to assigning expertise, it can highlight the qualitative and quantitative features of video-game engagement that may underlie expertise and its development. For example, Ericsson et al.  used a dOther relevant features of video-game experience include length of experience and the age at which they began gaming , RTS, action RTS, and massively multiplayer online role-playing games (MMORPG). It is important to note that the complexity of these genres is greater than can be highlighted here , which may help shape specific perceptual and cognitive demands. In addition, there are many other “action” video-game sub-genres  with unique demands and potential to provide different sets of enhancements to players.Starcraft II play, players commonly execute up to 250 actions per minute, increasing to over 300 during combat. Other RTS games can have additional layers of complexity through the alternative victory conditions. For example, in Civilization V players can actively obtain victory through science, culture and diplomacy. Given these demands it is unsurprising RTS games may emphasize and enhance executive processes.In RTS games players take control of a race, continually create, and utilize worker units to obtain resources, create, and expand a base, and create and improve combat units. Using combat units, players must destroy opponents or force them to concede. Countless combinations of build orders and unit combinations exist, which must be performed, controlled and adjusted in real-time against opponents. Success is reliant on the ability to assess, update and plan the most efficient series of mechanical responses. During professional Counter Strike: Global Offensive) and include vehicles . However, even with these additions, success is still highly dependent on the speed and accuracy of basic visual and motor processes.The term “action,” when used by researchers, however, has typically referred to FPSs. Players aim a targeting reticule at opponents and click in order to eliminate them. Success is dependent on the ability to make rapid visual judgments and responses. Although the executive demands are lower in FPSs than in RTS games, the demands on speed and accuracy of visual abilities are far higher. Many FPS games are objective and team-based . In a game, two teams of five players fight alongside waves of computer-controlled units in order to destroy the opponent base. Eliminating enemy heroes and units confers experience and currency. Experience allows heroes to gain levels which make them more powerful and grant skill points which are used to learn and improve skills. Currency is spent on items that either make a hero more powerful and provide additional skills, or supports the team by granting map vision, temporary invisibility, or revealing hidden units.Action real-time strategy (ARTS) games arose from RTS games whereby players control a single unit with a handful of unique abilities called a “hero.” Often there are hundreds of unique heroes to choose from , each genre typically has unique perceptual and cognitive demands necessary for success. Specific enhancements may result from these demands. Distinctions between genres are, therefore, of particular importance to researchers conducting training studies and those who wish to target specific abilities.Researchers investigating expert VGPs typically provide lists indicating the “action” video-games participants report playing, with little appreciation given to the breadth of genres shown. Breadth itself may be another characteristic trait of experts, as the unique capabilities trained by specific tasks in a domain are likely to be advantageous to general performance within the domain as a whole. For expert VGPs, the unique capabilities trained by specific genres are likely to benefit video-game performance in general, and those with greater breadth may also tend to show greater expertise. As a result, the genre of video-games played needs to be considered in conjunction with video-game experience (see Assessing video-game experience and expertise).Understanding the extent to which video-game play can shape perceptual and cognitive abilities requires testing expert VGPs. Current research, however, mistakenly classifies participants as expert VGPs using only a limited assessment of recent video-game experience, hindering progress in the field. While knowledge of a participant's video-game experience is incredibly useful, it cannot be used to definitively assign expertise. Proper classification of expertise requires the use of professional attainment, objective performance measures, or both. Once expertise has been correctly assigned, differences in experience between experts and non-experts may highlight factors, or combinations of factors, that promote the development and maintenance of expertise. Perhaps more significantly, it may reveal the key/s to shaping perceptual and cognitive processes.


An m-health system for real-time wireless communication of medical video based on open-source software is presented. The objective is to deliver a low-cost telemedicine platform which will allow for reliable remote diagnosis m-health applications such as emergency incidents, mass population screening, and medical education purposes. The performance of the proposed system is demonstrated using five atherosclerotic plaque ultrasound videos. The videos are encoded at the clinically acquired resolution, in addition to lower, QCIF, and CIF resolutions, at different bitrates, and four different encoding structures. Commercially available wireless local area network (WLAN) and 3.5G high-speed packet access (HSPA) wireless channels are used to validate the developed platform. Objective video quality assessment is based on PSNR ratings, following calibration using the variable frame delay (VFD) algorithm that removes temporal mismatch between original and received videos. Clinical evaluation is based on atherosclerotic plaque ultrasound video assessment protocol. Experimental results show that adequate diagnostic quality wireless medical video communications are realized using the designed telemedicine platform. HSPA cellular networks provide for ultrasound video transmission at the acquired resolution, while VFD algorithm utilization bridges objective and subjective ratings. Driven by technological advances, especially in the last decade, mobile-health  systems and services have refined access to specialized healthcare delivery –5. AdvanMedical video communication systems aim to meet the demand for emergency telematics, within ambulance care, remote diagnosis and care for frail elderly people and people with mobility problems, mass population screening, especially in developing countries and in disaster incidents and battlefields, and for medical education purposes and second opinion provision see  8]. Med. Med8]. modality-aware (m-aware) systems, where individual properties of different video modalities guide the encoding, transmission, and evaluation process  [The most prevailing research trends in the design of m-health telemedicine systems are summarized next: (a) medical video nterest) –15, (b) nterest) –19, and nterest) –12, 20.In this study, the aim is to develop a low-cost telemedicine platform for the wireless communication of adequate diagnostic quality video using open-source technologies. The aim is to depict that open-source software tools can deliver the acceptable performance required for demanding medical video communications, using commercially available infrastructure. In fact, we aim to bridge the gap between theory and practice, by providing a proof-of-concept study which can accelerate the wider deployment of m-health systems in daily clinical practice. Despite the widespread belief by the research community that such systems and services can provide significant time advantages that can prove vital for the patients' health, the adoption in daily practice is rather limited. This is partly due to the relatively limited studies depicting real-life implementation of medical video streaming systems, attributed to the absence of wireless channels that could support video communications at the in-hospital video resolution. The latter was documented for earlier studies in the literature, where limited upload data rates of 3G channels bounded the successfully communicated medical video to quarter video graphics array (QVGA-320 × 240) resolution –24.Here, we employ top performing open-source software, investigate medical video communications at scalable resolutions, for the most common encoding structures found in the literature today, and evaluate their clinical performance for an overwhelming number of cases. We examine two widely available wireless channels, namely, wireless local area network (WLAN) as the benchmark case and 3.5G high-speed packet access (HSPA) as the default utilization scenario. The objective is to demonstrate that high-resolution medical video communication is possible, approaching the clinical standards of in-hospital examination.Open-source platform for wireless medical video communication: The primary focus of this paper is the development of an open-source platform that will provide for adequate diagnostic quality medical video communications. Such a system will benefit from low-cost development and ease of deployment especially for telemedicine services in developing countries. Moreover, it will serve as a research tool that will accelerate research in m-health video communication systems and facilitate medical education purposes.Coding efficiency: we examine different video resolution transmission for the most widely used coding structures today, employing the most efficient H.264/AVC encoder, namely, x264. The use of higher video resolution such as 560 × 416 resolution suggests that medical video communication at the in-hospital-acquired resolution is possible using open-source technologies. Video communications over HSPA networks: we investigate currently available 3.5G mobile cellular networks performance in Cyprus using Quality of Service (QoS) metrics . The utilization of variable frame delay (VFD) algorithm as a calibration step before computing PSNR aims to bridge the gap between objective and subjective ratings, by removing temporal mismatch between transmitted and received videos.To accomplish this task, we summarize the primary objectives of this paper in three different areas.The rest of the paper is organized as follows: Open-source software is quickly becoming the designated tool for development and evaluation in research and academia, as well as pilots, for potentially commercial applications. This is mainly attributed to the lower costs involved in developing and maintaining open-source applications, source-code availability which enhances reusability and enables customization, and an ever-increasing community which supports and expands available features. Here, the choice of open-source tools aims to develop, evaluate, and disseminate a low-cost telemedicine system, easily deployable, which will provide reliable communication of real-time medical video for remote diagnosis purposes. Such a system can serve as a research tool for the design and development of new m-health systems and services, be used as a medical education tool, and can serve as a telemedicine platform, especially in developing countries. The proposed system's interface is demonstrated in The variable frame delay (VFD)  algorithVariable frame delay algorithm computes the mean square error (MSE) between the normalized processed (received) frame and a predefined window of normalized original frames, for a given region of interest. In this manner, when it comes to computing the objective VQA metric, the algorithm uses for comparison the original frame that minimizes the MSE with the relevant processed frame.Y channel), video sequences for the following formulas will be denoted as Y, where t = 0, 1, 2, …, N − 1, N is the total number of frames parting the video, and i and j correspond to the image's row and column, respectively. A subscript p denotes a processed video , while a subscript o stands for the original, uncompressed video sequence. The procedure for normalizing processed video frames to have zero mean and unit variance appears in  predefined window of frames is estimated using (tuncert). When not all frames are available , only the available frames are used for computing the MSE:Provided that all computations are performed using only the luminance information , compose the dataset used during the experimental evaluation. The investigated encoding setup includes scalable video resolutions that reflect the most common resolutions used in atherosclerotic plaque ultrasound video transmission, different bitrates according to the wireless channel's capacity, and different encoding schemes and profiles for improved efficiency. For the lower QCIF resolution (176 × 144), the videos were encoded at the following bitrates: (a) 128 kbps, (b) 256 kbps, and (c) 324 kbps. These bitrates are well within the typical upload data rates of 3.5G high-speed downlink packet access  wirelesTo investigate the most efficient encoding structure, we examined the most common encoding formats used in real-time video transmission found in the literature today. More specifically, we employed IPPPP, IPBBP, IPBBBBP, and IPBBBBBBBBP schemes. The main H.264/AVC profile was used for all schemes besides the IPPPP case, which was encoded using the baseline profile.The values of the remaining encoding parameters were selected using coarse-to-fine parameter optimization for the parameters appearing in the literature. The maximum slice size is set to 500 bytes, as this value was found to minimize latency and provided for better objective ratings compared to higher values. The packet size was selected accordingly, so that when a packet is lost or corrupted, the error would be limited within slice boundaries. GOP size and intra-update interval is set to fifteen frames. In this manner and in conjunction with a frame rate of 15 fps, error propagation extends to at most one second. This is very important for medical video communications, as it maximizes the probability of error-free cardiac cycles, hence clinical quality.The system's performance is demonstrated based on two typical wireless transmission scenarios. The first scenario examines medical video communications within a wireless local area network (WLAN). This scenario provides for medical video transmission within the hospital facilities. Anticipated integration of such systems in daily clinical practice is expected to reduce in-hospital delays, potentially unsafe for the patient's health movements for routine exams, as well as medical expert's visits to outpatient clinics. Moreover, it can be used for educational purposes in university hospitals. This can be considered as the benchmark scenario.The second scenario investigates wireless communications based on commercially available high speed packet access (HSPA) network in Cyprus. Despite a theoretical upload speed of 5.8 Mbps advertised by the provider, the typical measured upload speed is around 1 Mbps, with an average delay of 135 ms. The sender is connected to the 3.5G network, while the receiver is connected to a WiFi local network. Similarly to the first scenario, the measurements took place in different time periods for a realistic approximation of actual conditions. This scenario simulates medical video transmission in emergency situations to the hospital and/or from remote areas and generally areas where internet access is only available via a cellular network. Likewise, it can be used for mass population screening purposes and most importantly as a gateway of access to specialized care in developing countries with limited resources.To validate the performance of the proposed system, objective and subjective VQA was employed, while quality of service (QoS) measurements assessed network's stability. Objective evaluation was based on the widely used PSNR algorithm. However, as documented in , PSNR ofplaque presence, (b) degree of stenosis, and (c) plaque type and morphology. As documented in [Subjective  ratings were based on the clinically established protocol described in . Using aented in –11, 20, In this section we discuss the experimental evaluation of the proposed medical ultrasound video transmission platform. We present results in terms of investigated coding structures efficiency, performance of real-time medical video transmission over WLAN and HSPA channels, and clinical capacity of the communicated ultrasound videos. Results were obtained using two Lenovo ThinkPad T500 laptops, Intel Core 2 @ 2.53 GHz, 4G RAM, and 32-bit Windows 7 operating system.For the purposes of this study, four coding structures widely used in video streaming applications today were investigated. Denoted by the red-dashed line, is the clinically acceptable threshold for ultrasound video communication described in . For QCIscenario 1 denoted box plots of Figures This is the benchmark scenario. Video packets do not traverse outside the controlled wireless environment, which is not extended beyond the hospital premises. As a result, packet end-to-end delay and packet loss rates are minimal, in the order of 50 ms and ≤1%, respectively, resulting in high diagnostic quality ultrasound video rendering. As evident in the scenario 2).The present scenario resembles a realistic implementation of the developed m-health application. The transmitting end is situated kilometers away from the hospital premises, while varying network conditions affect the quality of the transmitted stream. Figures The objective quality drops abruptly see also , failingDriven by the previously finding and bearing in mind that PSNR often fails to correlate with perceived video quality, led us in considering means of objectively evaluating the instantaneous temporal freeze effect present in the received video. Variable frame delay algorithm was specifically designed to address video pauses during live streaming events, dictated by the high likelihood of such occurrences and the need to evaluate their perceptual impact. As demonstrated in Despite the fact that these ratings are in accordance with the clinical evaluation as detailed later, further tuning is required to accommodate a fair objective evaluation. In the presented results, received frames were compared to the most relative transmitted frames indicated by the VFD algorithm, without addressing erroneous and delayed frames causing the temporal mismatch. As a result, the depicted PSNR ratings are based on fewer frames than the total sequence frames resulting in slightly higher PSNR values. This is a matter of ongoing investigation.  In the context of the clinical evaluation of this work, the physician evaluated a representative sample of the different encoding methods, image analysis, and quality (bitrate). The method used is based on  and illuAs expected, clinical ratings for the first scenario, depicted in Clinical evaluation of the HSPA communicated videos appears in This paper demonstrates the capacity of the proposed open-source-based telemedicine platform to accommodate reliable wireless communication of medical video. Comprehensive experimentation showed that adequate diagnostic quality ultrasound video at the clinically acquired resolution can be realized using both WLAN and commercially available HSPA wireless networks. The former wireless channel can provide for medical education purposes and remote diagnosis within the hospital premises. The latter can be broadly used for remote access to specialized physicians, in emergency incidents, and for mass population screening. Low-cost implementation and ease of deployment can turn out to be a valuable tool for providing m-health solutions in developing countries, as well as for research purposes. Both objective and subjective video quality assessment methods were employed to validate the clinical capacity of the transmitted video. Bidirectional prediction utilization provided for higher objective ratings than single-directional prediction. Using the VFD algorithm to remove the temporal mismatch present in HSPA communicated video, as a calibration step before FR VQA metrics, enabled computing objective scores that correlate with medical experts ratings. Ongoing research includes enhancing the current platform with modality-aware encoding features, investigating mobility aspects in wireless communication for emergency care and extending experiments over long-term evolution (LTE) and LTE-advanced wireless channels. Moreover, mobile devices with limited resources like smart phones and tablets, based on Android and IOS operating systems are currently considered as end-user equipment. Additionally, we also want to investigate how the new high-efficiency video coding (HEVC) standard can lead to more efficient, diagnostically resilient encoding . The pro


Longitudinal studies describing incidence and natural course of malnutrition are scarce. Studies defining malnutrition clinically  rather than anthropometrically are rare. Our aim was to address incidence and course of malnutrition among pre-schoolers and to compare patterns and course of clinically and anthropometrically defined malnutrition.Using a historical, longitudinal study from Bwamanda, DR Congo, we studied incidence of clinical versus anthropometrical malnutrition in 5 657 preschool children followed 3-monthly during 15 months.Incidence rates were highest in the rainy season for all indices except McM. Incidence rates of McM and marasmus tended to be higher for boys than for girls in the dry season. Malnutrition rates increased from the 0–5 to the 6 – 11 months age category. McM and marasmus had in general a higher incidence at all ages than their anthropometrical counterparts, moderate and severe wasting. Shifts back to normal nutritional status within 3 months were more frequent for clinical than for anthropometrical malnutrition (62.2-80.3% compared to 3.4-66.4.5%). Only a minority of moderately stunted (30.9%) and severely stunted children (3.4%) shifted back to normal status. Alteration from severe to mild malnutrition was more characteristic for anthropometrically than for clinically defined malnutrition.Our data on age distribution of incidence and course of malnutrition underline the importance of early life intervention to ward off malnutrition. In principle, looking at incidence may yield different findings from those obtained by looking at prevalence, since incidence and prevalence differ approximately differ by a factor “duration”. Our findings show the occurrence dynamics of general malnutrition, demonstrating that patterns can differ according to nutritional assessment method. They suggest the importance of applying a mix of clinical and anthropometric methods for assessing malnutrition instead of just one method. Functional validity of characterization of aspects of individual nutritional status by single anthropometric scores or by simple clinical classification remain issues for further investigation. While the worldwide prevalence of child malnutrition in the period from 1990 to 2010 declined significantly, there has been only minimal change in sub-Saharan Africa  only oneGiven that clinical assessment of malnutrition is a comparatively inexpensive method suitable for regions with a significant burden of malnutrition, the lack of attention to this method is remarkable.The aim of this paper is to address, in a large population-based study, longitudinal occurrence patterns and course of malnutrition among pre-schoolers and to compare these patterns among clinically and anthropometrically defined malnutrition. Our specific aim was to describe age-, season- and gender- dependent incidence of moderate clinical malnutrition, marasmus and kwashiorkor, and compare these with rates obtained using anthropometrical definitions of malnutrition. We also sought to describe and compare patterns of change and duration of clinically and anthropometrically defined malnutrition.This paper presents a secondary analysis of data from the historical Bwamanda study . The rurThe study included 5 657 children from 16 villages in the Bwamanda area. A sample of 4 238 pre-school children was enrolled at the first contact. During follow-up newborn and immigrated children were added, while some children were lost due to emigration or death. In the last follow up round children who were born in 1984, and had reached six years, were no longer examined. Children were followed in the period 1989–1991. Three-monthly contacts were organised making up 15 months of follow-up and 6 contacts. The area was very homogeneous and there were no significant differences between the villages in nutritional status of the children or socioeconomic status (negligible design effect).Fifteen interviewers holding a secondary school certificate were trained in simple physical examinations and in undertaking interviews in the villages according to an interviewer’s manual. They determined age on the basis of children’s birth date noted on road to health charts or/and on parents’ identity papers. This information was available for about 90% of the children. For the remaining ones, birth dates were determined by a careful interview of the mothers using a local events calendar.Nutritional status of children was assessed by clinical assessment as well as by anthropometrical assessment. The clinical assessment of nutritional status is described by Van den Broeck et al. . With thIncidence rates of the various forms of clinical and anthropometrical malnutrition were calculated for the age categories 0–5, 6–11, 12–23, 24–35 and 36–71 months. Incident cases were defined as malnutrition being present, but absent at the scheduled previous contact. For the calculation of incidence rates, the person-time at risk was defined on the basis of time elapsed from one contact round to the next, normally about 3 months. Incidence rate was expressed as number per 1 000 person months. Direct age standardization was used to compare incidence rates across seasons by using the age distribution in the first follow up round (second contact) as the reference. Season was defined as: dry post-harvest (January – March); beginning of rainy pre-harvest (April – June); rainy (July – September); end of rainy season post-harvest (October –December).To document the natural course of incident malnutrition we examined short-term (3-months) shifts in severity, and short-term (3-months) mortality among children with incident malnutrition. Duration was categorised as 0–3, 3–6, 6–9, 9–12 months, or as censored after end of follow-up. Children with a WHZ and HAZ higher than <-2 were classified as normal, that is “no wasting” and “no stunting”.Ethical approval for the Bwamanda study had been granted by the University of Leuven’s Tropical Childcare Health Working Group and funding provided by the Flemish Inter-University Council and the Nutricia Research Foundation.Figure As shown in Table Figure Kwashiorkor was the least frequent type of malnutrition  than in children with severe (severe marasmus and severe wasting) forms of wasting (20.4-25% compared to 9.6-11.5%). As to incident kwashiorkor, 24.3% still presented with kwashiorkor the following round. For stunting, as many as 57.2% of those with moderate forms and 62.5% of those with severe forms had not shifted after 3 months. Alteration from severe to mild forms was more characteristic for anthropometrical than for clinical malnutrition, with the percentage for severe wasting and severe stunting being 27% and 32.1%.Table Earlier studies on malnutrition among preschool children have primarily provided prevalence rates of low anthropometric scores in population cross-sections. To our knowledge the current study is among the first to provide incidence rates according to basic determinants and season, and to compare incidence rates of clinically and anthropometrically defined malnutrition. We have shown that seasonal, gender and age distribution as well as course of malnutrition are different when defining malnutrition clinically instead of anthropometrically. For example, we have shown that clinical forms of malnutrition had in general higher incidence rates than their anthropometric counterparts.The people of Bwamanda are predominantly subsistence farmers and availability of food is strongly influenced by seasonal climatic changes. Our study largely confirmed the findings of other studies showing that the risk of developing malnutrition is especially high in the rainy season -11. We sWe found significant gender inequality in the incidence of McM and Marasmus, with the incidence rate being higher for boys than for girls in the dry season. For other forms, both clinically and anthropometrically defined, we did not find that incidence of malnutrition was higher in boys than in girls. However, in one season we found that the incidence of moderate stunting was higher in girls than in boys. There are other studies that have found associations of gender with malnutrition. For example, in a study using data from 16 DHS  in 10 sub-Saharan countries, Wamani et al. found that boys were more frequently stunted than girls . In compOur study demonstrates that malnutrition incidence at different ages varied according to clinically and anthropometrically defined malnutrition. Still the general pattern for all forms of malnutrition was that incidence was higher at ages 6–36 months than before or after. In a cross sectional study from Uganda Kikafunda et al. found that the risk of older children being stunted relative to younger children were 6 times higher for those in the 12–18 month age range and 10 times higher in the age group above 18 months . While KWe have described the frequency of severity shifts and returns to normal nutritional status after three months. The percentage of children with marasmus or McM who returned to normal was high. It was also noticeable that a large proportion of severely stunted children returned to moderate stunting. Isanaka et al. estimated the duration of untreated acute moderate and severe anthropometrical malnutrition, defined by WHZ and absolute MUAC (mid-upper arm circumference), by a mathematical model and data from a community-based cohort in Niger of children aged 6 to 60 months . Using tOur analysis was based on a large sample of pre-school children, but a weakness is that many children were lost due to emigration and during follow up. This weakness in particular constrained our examination of the duration of malnutrition for severe malnutrition. In order to understand how emigration and lost to follow up might have influenced our findings we compared last nutritional status of children who emigrated or were lost to follow up with children who also were surveyed in the subsequent follow up round. This analysis yielded no evidence that emigration and lost to follow up influenced our findings. Data on incidence and course of malnutrition were obtained from two sequential follow up rounds and thereby dependent on two different measurements. The data on incidence and course of malnutrition were thereby susceptible to measurement errors. We are also aware that we might not have captured some of the shorter episodes of malnutrition which occurred and were resolved between visits.Our data on age distribution of incidence of malnutrition underlines the importance of strengthening interventions before children reaches the age of 2 years to ward off malnutrition. Our findings, especially with regard to course of McM, marasmus and severely stunted children, emphasise the importance of early life intervention.There are few population-based studies that have addressed the occurrence dynamics of clinically and anthropometrically defined malnutrition. Our findings show the occurrence dynamics of general malnutrition in a rural African area, demonstrating that patterns can differ according to nutritional assessment method. None of the assessment methods can be described as superior as they partly measure different aspects of malnutrition. Our findings suggest the importance of applying a mix of clinical and anthropometric methods for assessing malnutrition instead of just one method. Functional validity of aspects of characterization of individual nutritional status by single anthropometric scores or simple clinical classifications remain issues for further investigation.HAZ: Length/height for age Z-score; McM: Moderate clinical malnutrition; NGO: Non-governmental organisation; WHZ: Weight for length/height Z-score.The authors declare that they have no competing interests.HK, CS, MC, MMA, JVdB participated in the conception of the study. H.K. performed data analysis and wrote the paper. All authors participated in the revision of the paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/22/prepub


Plasmodium malariae causes uncommon benign malaria found in the malaria endemic regions mostly of Sub-Saharan Africa. As Plasmodium malariae does not have a continued liver stage in humans the only way to have reinfection without reexposure is through recrudescence. However, reports of its recrudescence after antimalarials are rare with only a handful of case reports in the literature. Research in this field to date has not been able to establish definitively an emergence of resistance in Plasmodium malariae to commonly used antimalarials. In the presented case, patient had a recrudescence of P. malariae after full treatment with quinine and clindamycin. This recrudescence was treated with full course of chloroquine with clearance of parasite from blood immediately after treatment and at two months' follow up. The recrudescence in this case cannot be explained by mechanisms explained in prior articles. We propose that the indolence of some of the Plasmodium malariae trophozoites in the blood can shield them from the effect of the toxic effects of antimalarials and enable them to produce recrudescence later. However, when recrudescence happens, this should not be considered a case of development of resistance and a course of chloroquine should be considered. Plasmodium malariae infections are infrequently found in the malaria endemic regions with majority of them reported from Sub-Saharan Africa and Southeast Asia. There they are commonly found as mixed infections with Plasmodium falciparum [Plasmodium vivax and Plasmodium ovale, Plasmodium malariae is not known to have continued liver cycle with hypnozoites. The only way to have a reinfection without reexposure is from its preexisting erythrocytic forms; this is known as recrudescence. These erythrocytic forms of Plasmodium malariae are known to be the most indolent of all the infective plasmodium species with infections observed decades after exposure. Recrudescence of P. malariae is common if the primary episode of infection goes untreated [Plasmodium malariae even after treatment with different antimalarials [Plasmodium malariae that can explain recrudescence in these cases [lciparum . Unlike ntreated , 2. Howealarials . Till dase cases –7.Plasmodium falciparum trophozoites with very low parasite titer. The patient was readmitted in September of 2012 with complaint of recurrent fever and chills. She had no interval history of travel to any malaria endemic region. Blood smears obtained on the second hospitalization were reported showing Plasmodium malariae trophozoites. The patient's peripheral blood smears from the current and prior hospitalization were reviewed by the hospital's chief pathologist to answer why two different malariae species were identified on the two occasions without any evidence of reexposure. The final pathology report stated that the malaria parasite seen on both occasions was that of Plasmodium malariae and the initial reports of the parasite being Plasmodium falciparum were flawed. After this report the patient was treated with full course of chloroquine with resolution of fever and parasitemia. At 2-month followup a blood smear was obtained which did not show any parasites in her blood.The case is of a 65-year-old migrant from Sierra Leone who has been living in the United States for more than a decade. The patient has had history of multiple episodes of malaria infection in childhood but no reported episode after emigrating to the United States. The patient had last been to the malaria endemic region of Sierra Leone in 2009 and denied any sickness during her trip or immediately after returning to the United States. She had her first episode of malaria in August of 2010 during which she was treated with full course of quinine and clindamycin. Her blood smears examined for parasites were reported as positive for P. malariae after initial antimalarial treatment [P. malariae to the antimalarial medications. Fourthly, it could be a recurrence from prolonged preerythrocytic liver cycle which was not affected by the initial course of antimalarial medications. Lastly, it could be from subtherapeutic plasma level of antimalarials and concomitant immunity. Bearing the last one none of the other theories could explain the reinfection observed in this case as explained here.Reexposure was not possible in this patient as she has not travelled out of the United States in the interval between her hospitalizations and there are zero cases of malaria transmission reported in the United States. All malaria cases reported in the United States were imported .The patient confirmed that she had completed the full course of antimalarials prescribed to her, which were quinine and clindamycin.P. malariae to antimalarials is a compelling theory. Isolated cases of recrudescence of Plasmodium malariae have been reported after almost all types of antimalarial medications like quinine, chloroquine, mefloquine, and artesunates [Plasmodium malariae to chloroquine in 2 cases which failed to clear the parasite from blood during the 4 days of treatment [Plasmodium malariae take longer time to clear up from the blood compared to other Plasmodium species. In some cases it was up to 16 days [in vivo and in vitro have proved the sensitivity of P. malariae to chloroquine [Plasmodium malariae with chloroquine or quinine.Development of resistance in esunates , 3, 9. Rreatment . However 16 days . Also muoroquine . Hence tPlasmodium malariae is not known to have continuous reproduction of preerythrocytic forms [Reinfection from preerythrocytic forms is not plausible in this case as the episodes of infection were almost 1 year and 3 years from the last presumed exposure to the parasites. Subtherapeutic plasma level could be a possible explanation for treatment failure. Studies have shown subtherapeutic plasma concentration after the regular chloroquine course and plasma levels below MIC levels have been implicated with slow clearance of parasitemia . HoweverA number of theories have been proposed to explain the mechanism of reinfection with reatment , 3. FirsPlasmodium malariae. It is well known that asexual erythrocytic forms of Plasmodium malariae are very indolent and can undergo very slow metabolism and growth for decades [P. malariae can shield it from the toxic effects of chloroquine and hence provide P. malariae an inherent resistance to its action. Though this mechanism is presented for chloroquine, it can be extrapolated to other antimalarial drugs like quinine and mefloquine which are considered to have similar mechanism of action. The indolent erythrocytic schizonts of P. malariae have a low rate of metabolism and hence reduced size and acidity of the food vacuoles which is dependent on their metabolic rates. The acidity in the food vacuoles is important in concentrating the chloroquine and quinines in the food vacuole because of their basic nature. Low metabolic rate can shield these indolent schizonts to survive the initial course of antibiotics. These indolent schizonts then persist in low grade erythrocytic cycle of propagation to produce recrudescence later.The recrudescence in this case and other cases reported before can be attributed to the indolence of the erythrocytic forms of  decades .  FigureP. malariae should not be always counted as a case of resistance to antimalarials and a repeat course of chloroquine should be considered.In conclusion we propose that recrudescence of P. malariae on a blood smear rather than P. falciparum due to low titres of P. malariae's trophozoites in blood. A PCR analysis of patient's blood sample from initial hospitalization could have confirmed if it was a mixed infection or only a P. malariae infection. This was not possible in this case due to lack of blood samples from prior hospitalization of the patient. As a result, all the slides from both hospitalizations were thoroughly examined by the pathologist who reported that only P. malariae parasites were seen on all ten slides.A major critique to this case is that no other confirmatory tests like PCR or antigen testing were obtained. On initial presentation patient could have had a mixed infection which is commonly found in Sub-Saharan Africa. However, in a mixed infection it is difficult to identify


Remote dynamic three-dimensional (3D) scene reconstruction renders the motion structure of a 3D scene remotely by means of both the color video and the corresponding depth maps. It has shown a great potential for telepresence applications like remote monitoring and remote medical imaging. Under this circumstance, video-rate and high resolution are two crucial characteristics for building a good depth map, which however mutually contradict during the depth sensor capturing. Therefore, recent works prefer to only transmit the high-resolution color video to the terminal side, and subsequently the scene depth is reconstructed by estimating the motion vectors from the video, typically using the propagation based methods towards a video-rate depth reconstruction. However, in most of the remote transmission systems, only the compressed color video stream is available. As a result, color video restored from the streams has quality losses, and thus the extracted motion vectors are inaccurate for depth reconstruction. In this paper, we propose a precise and robust scheme for dynamic 3D scene reconstruction by using the compressed color video stream and their inaccurate motion vectors. Our method rectifies the inaccurate motion vectors by analyzing and compensating their quality losses, motion vector absence in spatial prediction, and dislocation in near-boundary region. This rectification ensures the depth maps can be compensated in both video-rate and high resolution at the terminal side towards reducing the system consumption on both the compression and transmission. Our experiments validate that the proposed scheme is robust for depth map and dynamic scene reconstruction on long propagation distance, even with high compression ratio, outperforming the benchmark approaches with at least 3.3950 dB quality gains for remote applications. Depth maps are crucial for three-dimensional (3D) imaging and display, which have been widely deployed in 3D virtual scene perception It is widely recognized that the depth maps with video-rate and high resolution synchronized to the color video are the precondition for high quality of reconstructed dynamic 3D scene Recent years have witnessed a large popularity to directly reconstruct the depth map and dynamic scene at the terminal side However, as shown in Actually, accurate MVs are available in the compressed video stream, for which the MVs are calculated based on the original color video without any compression losses In this section, the compression techniques for video coding are analyzed to be used for both the depth propagation and the dynamic 3D scene reconstruction. Serving as a protocol between the encoder and the decoder, the compression information includes the descriptors for prediction modes , MVs, encoding modes , and block modes  was a good solution that not only improves the prediction accuracy but also avoides the blocking artifacts There are two problems which may occur when applying OBMC for depth reconstruction. First, MVs from neighboring blocks may be not available in decoder when the whole macroblock or several blocks in macroblock are Intra encoded. Originally, in traditional OBMC, the MVs can be predicted by neighboring blocks, or calculated again by motion estimation precisely since the original color frame is available. However, in the perspective of depth reconstruction at terminal side, the neighboring block may be Intra coded without MV for prediction, while no original color frame being available for accurate motion estimation. Second, when the whole macroblock is Inter encoded, MVs for different blocks may point to different direction with different norm. In this case, it is difficult to determine which MV can be involved for prediction. In this case, neighboring MVs for prediction and the weight coefficient window should be modified accordingly.In order to solve the above problem, we improve OBMC adopted in H.264 After all the candidate blocks have been determined, a prediction of MV for each pixel in the current block can be performed based on weight coefficient windows. Traditionally, the weight coefficient windows in OBMC assign more weights on the current block Dynamic 3D scenes contain a video-rate color image sequence that records the motion, color and texture information of this scene. Furthermore, a high-resolution depth map sequence is also captured to record the 3D space information for all visible objects. Note that this high-resolution depth map cannot be captured by RGB-D or ToF cameras in video-rate, as being synchronically with the color image sequence so far. Recently, MPEG released their standard test sequences for dynamic 3D scenes with high resolution (more than standard definition) and high frame-rate, including color images and depth maps Undo Dancer, Lovebird1, and Kendo will be used to testify our proposed algorithm. The captured color images and the calculated depth maps of these materials are selected from The dynamic 3D scene materials named as Since the compression ratio is highly related to the quality of depth reconstruction. we first reconstruct depths via color video bitstream with different compression ratios. Then, we compare: 1. their rate-distortion gains are compared, 2. the bit rate savings on the same reconstruction quality range (measured by BDBR Dancer, Kendo and Lovebird1 from the MPEG 3DV work group Our experiment is carried out on standard test sequences, including In our experiments, we empirically set the thresholds From Based on the analysis in We first show the effectiveness of each step in our scheme to the procedure of depth map reconstruction by Our scheme is a combination of processing steps based on In summary, the proposed scheme is consisted of After the single depth map reconstruction in The results in Based on the reconstructed depth maps, the dynamic 3D scenes can be built. The subject comparisons are given in As shown by the above experimental results, our scheme has better performances on depth map and dynamic scene reconstruction. Based on the results, our scheme has the potential to be applied in remote medical processing and monitoring. In this case, the performance on streaming bandwidth and quality is important for remote applications.The results of streaming bandwidth and quality are given by The results listed in Remote dynamic 3D scene reconstruction is helpful for accurate remote medical processing, and it can be achieved by the combination of 3D scene reconstruction and video streaming. In this combination, the video-rate depth maps are crucial for scene reconstruction, but usually sparse and low resolution depth maps are obtainable. The propagation based depth reconstruction approach has been exploited recently, while it cannot be applied in this application directly since the original color video and accurate motion vectors are not available at the terminal side.In this paper, we propose to reconstruct video-rate and high definition depth map from the color video stream, and then reconstruct the target dynamic 3D scenes. In this scheme, inaccurate temporal propagation caused by motion vector outliers are detected and processed, propagation hole caused by absent motion vectors are predicted by its neighbors, and dislocation caused by block-wise near-boundary motion vectors are processed by modified overlap block motion compensation. The experimental results shown that our scheme has robust performance for depth map and dynamic 3D scene reconstruction on long distance propagation, even with high compression ratio. Furthermore, our scheme has at least 3.3950 dB quality gains and 100.4687 kbps bandwidth gains when comparing to the benchmark in remote applications.