Group A comprised 45 H-HCAs, 44 IHCAs, and 9 β-catenin-activated IHCAs (b-IHCA), and group B, 16 b-HCA and unclassified HCA (UHCA). Steatosis was the hallmark of H-HCA. IHCA and b-IHCA were mainly characterized by inflammation, thick arteries, and sinusoidal dilatation; b-IHCA could not be differentiated from IHCA by routine histology. Group B was identified by default. A control set (91 cases) was analyzed using routine and GS stainings . Among the 45 H-HCAs and 27 IHCAs, 40 and 24 were correctly classified, respectively. Among the 10 b-IHCAs, 4 were identified as such using additional GS. Eight of the 9 HCAs that were neither H-HCA nor IHCA were correctly classified. Conclusion. Routine histology allows to diagnose >85% of the 2 major HCA subtypes. GS is essential to identify b-HCA. This study demonstrates that a “palliative” diagnostic approach can be proposed, when the panel of specific antibodies is not available.Immunohistochemistry is a valid method to classify hepatocellular adenoma (HCA). The aim was to test the performance of routine histology combined to glutamine synthetase (GS) staining to identify the 2 major HCA subtypes: HNF1 The remaining HCAs are the β-catenin-mutated HCA  [Hepatocellular adenomas (HCAs) are rare benign tumors. Molecular data have brought new insight in the characterization of this disease. They allow the distinction of focal nodular hyperplasia (FNH) from HCA and the identification of 2 major HCA subtypes which represent more than 80% of all HCAs, namely, HNF1A-mutated HCA H-HCA, 35–40%) [5–40% [β-β-catenin, it is possible to identify all HCA subgroups with good confidence. Among these markers, GS is of major importance to identify patients at high risk of malignant transformation. Indeed, abnormal GS staining [β-catenin activation. Unfortunately, the rarity of these tumors in routine practice leads to the low availability of the specific IHC markers. To overcome this problem, the possibility to identify the 2 major HCA subtypes using standard histological techniques has not been tested. The immunohistochemical (IHC) classification of HCA subtypes was derived from the above-mentioned molecular characterization and showed a good correlation with the molecular data . Using sstaining  is a strThe aim of this study was (1) to test routine histology in the diagnosis of HCA subtypes and (2) to appreciate the contribution of GS combined with routine histology in the diagnosis of HCA subtypes. All surgically removed HCA cases were retrieved from our files from January 2000 to November 2011. We excluded cases with specific etiologies such as glycogenosis, male hormone administration (since they are very particular and rare conditions), cases of obvious hepatocellular carcinoma (HCC) possibly related to HCA  and cases with massive hemorrhage or necrosis (but without sufficient nonnecrotic tissue available). clinical data: sex, age, body mass index (BMI), oral contraception (OC), and imaging data (number and size of nodules), as well as liver enzymes  and CRP in blood, routine stainings on paraffin sections in tissue areas devoid or with minimal necrosis or hemorrhage, IHC stainings. Since 2007, IHC has been performed prospectively; prior this date, it had been performed retrospectively in all cases, according to previous published studies [Briefly, taking into account our own experience previously published in pathology textbooks showing the very good correlation between molecular analysis and IHC for H-HCA and IHCA [β-catenin, was studied in all cases. GS staining was quoted as negative in the absence of abnormal expression; and in this situation, β-catenin staining was not mandatory. GS staining in T always differed from the normal distribution of GS which is limited to a few rows of centrilobular hepatocytes in the NTL. In T, GS could be either totally absent or restricted to the border between T and NTL and/or around some persistent veins within T. Abnormal expression of GS characterized in the whole nodule by a strong positive staining diffuse or patchy is easy to interpret but is more difficult to interpret when the staining is faint or focal, limited to individual or groups of positive hepatocytes irregularly distributed within the tumor. In any case, abnormal GS staining was considered as a strong argument to suggest β-catenin activation [β-catenin nuclear labelling allowed the final diagnosis of b-HCA or b-IHCA. However, the absence of labelled nuclei on the section did not rule out this diagnosis because the number of labelled nuclei can be heterogeneously distributed, extremely limited, or even absent on the section. When all the specific IHC markers were negative, the HCA was termed UHCA. For all patients 114 cases), the following data were available:and IHCA , 6: LFABtivation , 4. In t cases, tAnother cohort of 91 HCAs was analyzed for external validation. It corresponded to cases not included in the above series and concerning cases from our center (prior 2000) or from cases sent for advice. For each case, 2 slides of H&E and GS  were available. β-catenin and non β-catenin activated) cases. Group B included all other cases. For each group and subgroup, we analysed the clinical, imaging, and biological data. Routine stainings  as well as CD34, keratin (K)7 immunostainings of the 2 groups were reviewed (T and NTL) according to a flowchart  filled out by an experienced liver pathologist (PBS). Different pathological items were checked such as steatosis, sinusoidal dilatation, congestion, inflammation, thick arteries, ductular reaction. Steatosis and sinusoidal dilatation were graded semiquantitatively as indicated in supplemental Table 1. In the NTL, the liver was considered as normal or steatotic (with or without NASH).Cases were divided into 2 groups. Group A included H-HCA cases and IHCA , without knowing IHC results obtained previously. For each case the following diagnosis based on standard features was: H-HCA, IHCA, and b-IHCA with 3 possibilities: yes, no, and possibly for each. For each case the pathological items had to be filled . If the features were obvious, the diagnosis was certain: H-HCA, IHCA (group A) or another type (group B). The diagnosis of H-HCA was uncertain when the result of the reading was H-HCA “possibly,” IHCA “no;” the same was true for IHCA. IHCA cases could be also t-test. Abnormal liver enzyme and CRP levels in each group were compared using ANOVA test. Fisher's exact test was used to compare different types of pathological abnormalities . P values lower than 0.05 were considered as significant. Kappa statistic was used to measure the level of agreement between the standard histological including GS versus the complete set of immunohistochemical techniques to estimate proportions of HCA subtypes.Disparities between groups according to age, BMI score, size, and the number of nodules were analyzed with unpaired Amongst the 114 cases analysed by standard morphology and IHC, there were 98 cases in group A: 45 H-HCAs, 53 IHCAs (9 were b-IHCAs) and 16 cases in group B: 4 b-HCAs and 12 UHCAs. The relevant clinical, biological, and pathological data are shown in Figures H-HCA. This subgroup included 45 patients, all women; 84.4% were under OC; the median age was 40. The median size of the largest nodule was 5.6 cm, and nodules were multiple in 62.2%. 75% of the patients had normal BMI; CRP and AP were rarely elevated, and 22.2% had mild elevation of GGT. Interestingly enough, in 8 patients, micro/small H-HCA (<1 cm) were incidentally discovered on the surgical specimen removed for large tumor(s) of different types including focal nodular hyperplasia (4 cases), 1 angiomyolipoma, 1 HCC; in other 2 cases, there was a past history of melanoma, and the small nodules were suspected to be metastases. Steatosis was the hallmark of H-HCA, which usually exhibited a very characteristic aspect with lobulated contours Figures . SteatosIHCA. This group included 44 patients (39 women and 5 men) . CRP and GGT were raised in 68.2 and 75%, respectively; AP, GGT, and CRP were higher than in the other HCA groups (H-HCA/b-HCA/UHCA (P < 0.01). The hallmark of IHCA was the inflammation  and pseudoportal tracts  present in 97.7 and 90.9%, respectively, (P < 0.001).  Figures . The medctively, , as wellctively, . Steatosctively, . Micro-IP < 0.05, Comparison between the H-HCA and IHCA groups showed that multiple nodules were more frequently observed in the H-HCA group than in the IHCA group .In summary, considering standard histological features, steatosis (frequency and area) and sinusoidal dilatation (frequency and area) may represent the hallmark of H-HCA and IHCA, respectively, (b-IHCA. This group included 9 patients (3 men) and represented 17% of all IHCAs. Clinical abnormalities similar to that observed in IHCA were found . b-HCA subtype was more frequently detected in young patients . 50% were overweight/obese. UHCAs were detected often during complications (hemorrhage and necrosis) associated with large tumors. No specific pathological features usually existed , but focAmong the 45 H-HCA, 40 were classified correctly (H-HCA positive and IHCA negative). There were 3 false negative readings . In 3 cases correctly classified H-HCA, GS was abnormal, with mild and patchy staining irregularly distributed within the tumor.Among the 27 IHCAs, 24 were correctly classified, as well as 4 out of the 10 b-IHCAs. Interestingly enough, none of the b-IHCAs were identified without GS. There were 3 false negative readings: 1 in the IHCA and 2 in the b-IHCA. There were 6 cases with no formal diagnosis  for H-HCA, IHCA/b-IHCA, and b-HCA/UHCA respectively, indicating a good agreement between them.The agreement between routine technics combined to GS compared to the all sets of IHC markers for the identification of the 2 major HCA subtypes gave a kappa index of 0.89, 0.91/0.54 (group A), and 0.92 (group B) . First, in H-HCA, steatosis can be mild, focal, or rarely absent, and furthermore areas of sinusoidal dilatation can exist. On the other hand, in IHCA and b-IHCA, sinusoidal dilatation can be mild, focal, or absent; inflammation limited to few portal tracts-like and steatosis—generally focal—could be severe. In addition, in these 2 main subgroups, as well as in all cases of HCA, necrotic areas may lead to remodeling and more or less misleading features. In IHCA particularly, fibrotic bands associated with inflammation and ductular reaction may mimic FNH on routine histology. Additional IHC is mandatory to assess the right diagnosis. The fact that in the control set, we missed 6 out of 10 b-IHCAs based on IHCA criteria raises the question of the similarity between the 2 entities. The number of b-IHCA was, however, too small to be entirely sure to draw any firm conclusion.β-catenin-activated HCA (inflammatory or not), particularly when the staining is strong, diffuse, or patchy, even in the absence of aberrant β-catenin nuclear staining. However, GS reading is not always easy as underlined above, particularly when GS staining is faint and focal; in these cases, the distinction between a truly abnormal staining and, a few positive cells around veins in the nodule is hard to make. Indeed, this was the case in rare H-HCA. Cases of β-catenin activation could be observed in H-HCA, but this seems extremely rare. Therefore, the main issue remains the differential diagnosis between IHCA and b-IHCA. In these difficult cases, if there is no nuclear β-catenin staining, the issue can be solved only by molecular biology. If routine histology represents a reasonable means to identify the 2 major subtypes for pathologists with no access to specific IHC, the lack of identification of b-IHCA remains a serious limitation. Interestingly enough, this study demonstrates the impossibility to identify b-IHCA using standard histology. Surprisingly, none of the b-IHCA in our series  had cytological or architectural abnormalities such as rosette formation as previously mentioned in b-HCA . AbnormaMore generally speaking, in the absence of specific complete set of IHC stainings, routine histology combined with GS can be considered as a reasonable surrogate approach for the identification of the 2 major HCA subgroups. In addition, clinical, biological, and radiological data can help to make the right diagnosis of HCA subtype , 18. We have to remember that the very peculiar pattern of GS immunostaining in FNH is particularly helpful for their diagnosis mainly when different types of nodules are associated with the same liver. Finally, in the present work, we acknowledged that the H-HCA and IHCA/b-IHCA subtypes using routine histology were obtained on surgical specimens. In a recent article, we demonstrate that typical H-HCA can be recognized on biopsy on H&E staining; this is also possible for IHCA, but the % of correct diagnosis is lower . Therefoβ-catenin-activated HCA (inflammatory or not) that is particularly important to detect patient with higher risk of malignant transformation.The diagnosis of HCA may be difficult particularly for the pathologists are not familiar with these rare tumors. Characteristic features may exist which can be recognized by general pathologists on routine histology, allowing a good estimation of the 2 major HCA subtypes (>80%). Therefore, a “palliative” diagnosis approach can be proposed, when the panel of the antibodies is not available. However, in absence of these features, IHC remains the gold standard to assess the diagnosis of HCA and its subtype. GS is essential to identify Supplementary Table 1: Pathological analysis of resected hepatocellular adenoma.Supplementary Table 2: Clinical data of hepatocellular adenoma subtypes.Click here for additional data file.Click here for additional data file.


The minimum legal drinking age (MLDA) was increased in the U.S. in the late 1980s in an effort to reduce intoxication-associated injuries, especially those related to motor vehicle accidents. This paper explores distal (secondary) effects of changing MLDA on indices of infant health, and whether changes in drinking behaviors or birth composition contributed to these effects.State- and year-fixed-effects models are used to analyze the relationship between MLDA, drinking behaviors, and birth outcomes. We studied the effects of different MLDA  when potential mothers were 14 years old by merging two population-based datasets, the Natality Detailed Files and the Behavioral Risk Factor Surveillance System between 1985 and 2002.A MLDA of 18 years old  increased the prevalence of low birth weight, low Apgar scores, and premature births. Effects were stronger among children born to black women compared with white women. Moreover, a younger MLDA was associated with an increasing proportion of very young and high school dropouts for black women. Furthermore, older MLDA laws at age 14 years decreased the prevalence of binge drinking among black women.Increasing the MLDA had longer term, distal impacts beyond the initially intended outcomes, specifically on birth outcomes (particularly among infants born to black women) as well as school drop-outs and binge drinking patterns among black young females. The older MLDA, intended initially to reduce problematic drinking behaviors, appeared to alter broader social contexts that influenced young women during their early childbearing years. Broadly applied changes in social or public health policies may yield unintended consequences, in addition to initially targeted changes . A majori.e., decreasing youth alcohol consumption and drunk driving, and unintended social and health benefits, such as decreasing high school dropouts, teen births, and the prevalence of sexually transmitted diseases . This effect was mainly associated with MLDA-21 laws, under which the proportion of mothers with less than a high school education dropped by 1.1 percentage point . The age-specific legal access to alcohol had little impact on the composition of white mothers. While compositional shift is one possible explanation for the change in birth outcomes, results suggest that this shift only contributes to a very modest degree of improvement in birth outcomes for black mothers. No such effects are found among white mothers.How could the changes in MLDA laws affect birth outcomes? i.e., current survey-year age) with 0.15 percentage points , and age-19 and age-21 partly explained these changes.Using the individual-level data from BRFSS, χ2 = 3,169, df = 70). Moreover, MLDA differences during early teenage years predicted differences in binge drinking between young white and black women, with the younger MDLA associated with more binging among blacks. Those who lived in a state where the MLDA was age-18 were 2.2 percentage points  more likely to binge than those who lived in states with an older MLDA. Exposure to age-20 or -21 MLDA reduced the binge drinking by about 6.6 percentage points .The stepwise change in MLDA laws had little effect on drinking among white women as the MLDA of age 21 years decreased the probability of alcohol drinking up to one percentage point, and had no significant effects on reducing binge drinking. In contrast, establishing the MLDA at age 21 years decreased the probability of alcohol drinking among black women by 2–8% points  can benefit the health of the next generation. It also offers an additional perspective to the recent debate whether the US should lower the age for alcohol consumption, prompted by current levels of under-age drinking among college-students [Future work is needed to clarify how and why MLDA laws had different impacts among black and white young women. In addition, this study reflects a lack of data that simultaneously include reliable information regarding an infant’s health and his/her mother’s drinking behaviors. If such ideal data had existed, we could find whether the MLDA has a causal impact on birth outcomes through drinking behaviors, using two-stage least square models. This current study is unable to draw out this causality claim. Moreover, not all policies, such as expansion of Medicaid for pregnant women, were accounted for in this study. In addition, some other factors like insurance status, utilization and frequency of pre-natal care may influence infant health, but were not included in the analysis. Some of these variables are not available in the Natality data. Hence, the omitted variable bias may still exist. Despite these limitations, this study suggests that measures to improve the social context (students ,31. Our


This paper elaborates a novel hypothesis regarding the observed predictive relation between finger gnosis and mathematical ability. In brief, we suggest that these two cognitive phenomena have overlapping neural substrates, as the result of the re-use (“redeployment”) of part of the finger gnosis circuit for the purpose of representing numbers. We offer some background on the relation and current explanations for it; an outline of our alternate hypothesis; some evidence supporting redeployment over current views; and a plan for further research. Finger gnosis, alternatively called finger recognition or finger localization, is the presence of an intact finger schema or “finger sense” . A variePerhaps surprisingly, recent research is demonstrating links between finger gnosis and mathematics ability in neuropsychologically normal children. For instance, Though a clear relation has been demonstrated between finger gnosis and math, what remains unclear is what the true nature of the relation is. It is possible that the true underlying relation is correlational, as proposed by In the following sub-sections we first outline the two prevailing views, termed localizationist and functionalist  should also predict math ability. This is in part because on the functionalist view there is a direct causal link between finger gnosis and math ability and, moreover, this link is formed experientially in the course of normal development. The precise motor control required to use the fingers to represent quantities and perform counting and arithmetic procedures is vital for the development of numeracy  are frequently exapted for later uses when they perform a low-level function, or cognitive working that is useful in multiple task contexts. Cognitive workings are low-level operations that are performed by small, typically local anatomical circuits  is both a theory about the functional topography of the cortex, and an account of how it got that way. According to MRH, neural circuits evolved for one cognitive or behavioral task . Second, differences in domain uses will be accounted for primarily by differences in the way brain areas cooperate with one another, rather than by differences in which brain areas are used in each domain. Third, more recently evolved cognitive uses will utilize more, and more widely scattered brain areas. And fourth, evolutionarily older brain areas will be deployed in more cognitive uses. See Anderson , 2010 anFigure 1). The comorbidity of finger agnosia and acalculia as well as the relation between finger gnosis and math in normally developing children arise from the shared neural circuit used for both representations.In line with the general findings of MRH, we propose that one of the neural circuits integrated into the functional complex supporting finger gnosis is also part of the functional complex supporting the representation of number. That is, one of the functional circuits originally evolved for finger representation has since been redeployed to support the representation of number and now serves both uses. Alternatively, the functional circuit may have originally evolved for a third use and been redeployed for both finger and number representation. Regardless, on the redeployment view, finger gnosis is related to math ability because part of the functional complex for number representation overlaps with the functional complex for finger representation. Thus, finger and number share a common neural circuit – a circuit that performs a shared working that supports both sorts of representation . For now, we hope that this brief outline offers the reader some idea of the kinds of things workings can be, both in general, and in this particular case.At this point, some readers will surely be wondering: exactly what cognitive/computational working might account for the deployment of the shared circuit in these ostensibly very different uses? Exploring this specific question with the care it deserves would take us very far afield, for in fact the circuit in question is used not just in finger and number representation, but in a large number of other tasks, including word generation e.g., , task-swFinally, it should be noted that If the relation between finger gnosis and math arises because part of the neural circuit responsible for the representation of fingers has been redeployed in support of the representation of number and now supports both uses then the following predictions should be borne out:(1) Brain regions associated with the representation of fingers should be activated during tasks requiring the representation of number.(2) Damage/disruption of the neural substrate should affect both finger gnosis and tasks requiring the representation of number.(3) There should be measurable interference between tasks involving finger gnosis and tasks involving number representation, insofar as these would be competing for the same neural resource.(4) Individuals with intact finger gnosis, who could not or did not use their fingers to represent quantities during development, should nevertheless show activation in the finger circuit during tasks requiring the representation of number.Brain regions associated with the representation of fingers are activated during tasks requiring the representation of number. Prediction 1 would differentiate redeployment from localization, given adequate precision; however, it does not differentiate the redeployment view from the functionalist view, except in very young children. On both the functionalist and redeployment views, the representation of fingers and numbers are linked, with the key difference being the experiential requirement in the functionalist view.There is strong empirical support for Prediction 1. Regions associated with finger representation within the left parietal lobe are activated during a variety of mathematical tasks: a region in the premotor strip  or direct cortical stimulation provide converging evidence that disruption in the left angular gyrus affects both finger gnosis and tasks requiring the representation of number.Prediction 3 is that there should be measurable interference between tasks involving finger gnosis and tasks involving number representation, as these would be competing for the same neural resource. Two methods would allow for the testing of this hypothesis: a dual task paradigm or injection of noise into the system. As an example of noise injection, electrical stimulation of the fingers (but not of various locations on the forearm) might impact performance on mathematical tasks.A recent study by 3Not only does this demonstrate the predicted cross-talk between finger and number circuits, the result is somewhat awkward to explain on the functionalist view. Given the important role of experience in setting up the finger–number associations, the functionalist view would presumably predict fairly strong associations between individual fingers and specific numbers, induced by the particular counting procedures typically employed. In this case, participants all employed a counting procedure starting with the thumb for “1,” and continuing in order down the hand to the little finger (“5”). On the functionalist view, one would not expect these associations to be modulated by hand orientation.In contrast, the finding is compatible with  the redeployment view. This is because on the redeployment view, there need be no strong association between individual fingers and specific numbers. The entwinement of finger and number representations is not established by experience, but is the result of the fact that the two functional complexes share a neural circuit that does something useful for both. Even if what is being shared is a particular representational storage resource such as an array – as was proposed by 4 It could conceivably also have alphabetic, numerological, or iconographic content, or be an instruction set for a Turing machine. The point is: on the redeployment view, the meaning of whatever representation might be stored in that resource would depend on the representation consumer, and this meaning could vary greatly depending on the needs of the functional complexes incorporating the resource.Because on the redeployment view any given neural resource is being utilized by potentially many different functional complexes, understanding the functional relationship requires a strong distinction between the representation itself – what is being stored – and the representation consumer that is using the thing stored . The conare using the same representational resource, they will interfere with one another only when the representation for one use is incongruent with the representation for the other concurrent use. Thus if by chance a finger stimulus produced activation consistent with the standing number representation, there would be no interference. This is relevant because counting on the fingers, during which process one successively stimulates  fingers, is a real-world instance of a finger stimulation task that by design produces representations in the shared representational resource that can provide accurate information to consumers in both complexes: I know I have reached 7 because I have just touched this finger. This suggests a further implication. Although the details of the procedure one can use to count on one’s fingers – which fingers are touched in which order with what meaning – are highly various . They then showed the participants numbers on a computer screen, and asked them to press the key underneath the matching finger.That participants were able to do this task with very little training suggests that it is indeed possible to teach alternate systems in a short time. However, there were significant differences in the number of errors participants made with different mappings. Naturally, mapping 7 – identical to mapping from the participants’ primary counting procedure – showed very few errors, but interestingly, there were no significant differences in the number of errors made for mappings 1, 7, and 8, even though mapping 1 has no overlap with 7, and a five digit overlap with 8. Even more interesting, mappings 2–6 induced significantly more errors than did 1, 7, and 8, even though some of them  have a five digit overlap with 7, and others . Thus, it does not appear that any strong associations induced by the familiar counting procedure are responsible for making mappings 2–6 harder than the rest. There must be some other explanation, and limits imposed by existing representation consumers – as predicted by redeployment – offer one plausible option.This evidence is more suggestive than definitive, but it certainly seems an intriguing line of research that could push both models in new directions. For instance, the discovery of a counting procedure or finger–number mapping that did not just reduce performance, but resulted in systematic errors consistent with the mismatch between the procedure and the inferred properties of a representation consumer could be strong evidence for the redeployment view.In general, which outcomes in interference experiments would, and would not, be consistent with the functionalist view might depend in part on the nature and timeline of the hypothesized intertwining of representations that occurs during development. The strongest interpretation of intertwining is that number representations and the finger sense become inextricably linked, even coming to share the same neural resources. If this is the hypothesis, then perhaps redeployment and functionalism cannot be distinguished based on interference studies, since they would then posit the same underlying neural relationship, and differ only with respect to the account of how that relationship came about. However, there are weaker versions of intertwining that are consistent with the original model. For instance, one might expect that number representations would come to depend on the finger sense, but not the reverse. Such a model might be somewhat more plausible developmentally speaking, as although it may be typical to use the fingers whenever one is doing mathematics, it would certainly be atypical to think of mathematics whenever one is using the fingers. At the very least, the various possibilities to be entertained in designing interference experiments suggest the need for a clarification of the functionalist model.Prediction 4 is that individuals with intact finger gnosis, who could not or did not use their fingers to represent quantities during development, will nevertheless show activation in the finger circuit during tasks requiring the representation of number. Prediction 4 is the key in distinguishing the redeployment view from the functionalist view. Special populations may play a crucial role in testing this prediction.If the relation between fingers and number is a functional one, then the use of ones’ fingers to represent numerosities and perform counting and arithmetic procedures would be a necessary element in the development of numeracy. We have already found that finger gnosis in a sample of normally achieving children is more highly correlated with numeracy and calculation skills than is finger agility. This finding is apparently at odds with the functionalist view, but is consistent with the redeployment view that the connection between fingers and number does not rest on the experiential use of fingers to represent number.One possible route for further investigation would involve imaging experiments using participants from cultures without the practice of using fingers in mathematical contexts. It has been reported, for instance, that various populations including the Amazonian Pirahã and children in Australia’s Northern Territory do not use their fingers in support of mathematical tasks . The redAnother route would involve investigations using children presenting specific developmental disorders. Children with spina bifida have both finger agnosia and poor finger agility co-morbid with significant mathematical difficulties . This fiIn contrast, children with developmental coordination disorder (DCD) have poor finger agility, but most have preserved finger gnosis . Thus, cAs a first indication of support for the redeployment view, DCD is not generally comorbid with mathematical difficulties . Thus, dIn summary, two of the four predictions that arise from the redeployment view are well supported by empirical evidence: (1) brain regions associated with the representation of fingers are activated during tasks requiring the representation of number and (2) damage/disruption of the neural substrate affects both finger gnosis and tasks requiring the representation of number. Prediction 3, that there should be measureable interference between tasks involving finger gnosis and tasks involving number representation has yet to be systematically investigated, although we review some existing evidence that appears to point in that direction. There is also suggestive evidence for Prediction 4, that individuals with intact finger gnosis, who could not or did not use their fingers to represent quantities during development, will nevertheless show activation in the finger circuit during tasks requiring the representation of number.The data reviewed above strongly favors the first two predictions, which are inconsistent with the localizationist view. Even so, supporters of localization might question the strength of the results, since the spatial resolution of the imaging methods employed in some of those studies is poor enough that it is theoretically possible for circuits that are in fact segregated to appear to overlap. Thus, experiments using methods with greater ability to differentiate between local circuits may be called for. For instance, in investigating the hypothesized overlap between motor control and language processing, Although the localizationist view appears to be ruled out, pending further evidence to the contrary, support for the redeployment view could not be conclusively distinguished from that for the functionalist view on the basis of evidence for Predictions 1–3. Thus, support for Prediction 4 would be the crucial evidence to conclude that the relation between fingers and number is not functional. We provided evidence consistent with Prediction 4 and outlined further empirical tests of the redeployment view. That said, the redeployment and functionalist views need not ultimately be in conflict – it is likely that there is both a developmental and an evolutionary story to tell about the overall relation between fingers and mathematical ability.This paper elaborated a novel hypothesis regarding the observed predictive relation between finger gnosis and mathematical ability. In brief, we suggested that these two cognitive capacities have overlapping neural substrates, as the result of the re-use (“redeployment”) of part of the finger gnosis circuit for the purpose of representing number. On balance, the evidence seems to favor the redeployment account of the relation, over the functionalist and localizationist accounts. Of course, more research will be needed, and we have indicated some of the paths such research might follow.one part of the functional complex necessary for number representation. In MRH, existing neural circuits are redeployed for new uses and combined to support new capacities. Along with the neural circuit shared with finger gnosis, additional neural circuits  are expected to combine in support of the capacity for number representation.It is important to reiterate that on the redeployment view, the neural circuitry shared between finger gnosis and number representation forms only doing for each of these apparently quite different domains? An important implication of the redeployment view is that such questions should be approached using a cross-domain structure-function mapping methodology, as discussed above. Using this methodology, we have examined 2164 imaging experiments from the BrainMap and NICAM databases (If redeployment is the right framework for understanding the relation between finger gnosis and math, the natural next question is: what could the brain region in question be atabases  to guideThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Brief intervention (BI) has the potential to reduce heavy drinking in young adults that present to the emergency department (ED) but require time and resources that are rarely available. Text-messaging (TM) may provide an effective way to collect drinking data from young adults after ED discharge as well as to provide ongoing support for behavior change. Young adults in three urban EDs identified as hazardous drinkers based on Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) score were randomly assigned to weekly TM feedback with goal setting (intervention group), weekly TM drinking assessments without feedback (assessment group), or a control group. Participants in the intervention group who reported drinking ≥5 drinks during any 24-hour period (≥4 drinks for women) were asked whether they would set a goal to reduce their drinking the following week. We assessed the interaction between TM and goal-setting as well as heavy drinking days (HDD), and drinks per drinking day (DPDD) using the timeline follow-back procedure at baseline and three months. Forty-five young adults  met inclusion criteria and were randomized to one of the three study conditions. Of these, six  did not complete the three-month web-based follow-up. Eighty-eight percent  of weekly TM drinking assessments were answered, with 77%  of participants responding on all 12 weeks. Agreeing to set a goal was associated with a repeat HDD 36% of the time  compared with 63% of the time  when participants were not willing to set a goal. At three months, participants exposed to the TM intervention had 3.4 fewer past-month HDD  and 2.1 fewer DPDD  compared with baseline. Interventions delivered via text message have the potential to reduce heavy drinking among young adults but larger studies are needed to establish efficacy.


The extraordinary progress experienced by sequencing technologies and bioinformatics has made the development of omic studies virtually ubiquitous in all fields of life sciences nowadays. However, scientific attention has been quite unevenly distributed throughout the different branches of the tree of life, leaving molluscs, one of the most diverse animal groups, relatively unexplored and without representation within the narrow collection of well established model organisms. Within this Phylum, bivalve molluscs play a fundamental role in the functioning of the marine ecosystem, constitute very valuable commercial resources in aquaculture, and have been widely used as sentinel organisms in the biomonitoring of marine pollution. Yet, it has only been very recently that this complex group of organisms became a preferential subject for omic studies, posing new challenges for their integrative characterization. The present contribution aims to give a detailed insight into the state of the art of the omic studies and functional information analysis of bivalve molluscs, providing a timely perspective on the available data resources and on the current and prospective applications for the biomonitoring of harmful marine compounds. Next Generation Sequencing (NGS) platforms have been implemented, most notably de novo 454-pyrosequencing of transcriptomes pyrene pyrene . Additioasiliana  whereas asiliana ,22 or caasiliana . Similarstradiol . Interesstradiol  has alsoincialis .Pinctada maxima (BioProject PRJNA114601). Similarly, the expression profile of the digestive gland of the manila clam Ruditapes philippinarum was studied by using an Agilent Oligo Microarray platform (BioProject PRJNA135933) during four seasons in four different areas of the Venice Lagoon. Finally, pharmaceuticals also constitute a new emerging class of environmental contaminants continuously released in aquatic environments. Among them, the effect of exposure to ibuprofen has been already tested on R. philippinarum using microarrays, revealing an alteration of several molecular pathways, including arachidonic acid metabolism, apoptosis, peroxisomal proliferator-activated receptors, and nuclear factor-kappa B, helping elucidate the putative mechanisms of action of ibuprofen in non-model species [Other examples of transcriptomic approaches to the study of anthropic compounds include microarray-based studies of Tributyltin, a chemical biocide used in marine antifouling paints that, in addition to causing shell abnormalities, also affects biomineralization pathways in the oyster Crassostrea hongkongensis, supporting their potential application as diagnostic tools for the assessment of metal pollution in environmental monitoring programs [M. galloprovincialis [Mytilus species [Geukensia demissa [Proteomic approaches are a valuable complement of transcriptomic studies in bivalves and can support the identification of new biomarkers of xenobiotic toxicity . For insprograms . Moreoveincialis . The pro species ,113,114  demissa . OverallThe great relevance of marine invertebrates makes the lack of bivalve model organisms puzzling. Still, the information reviewed throughout this work supports two bivalve molluscs, the Pacific oyster and the blue mussel, as upcoming model organisms. This notion is sustained by progressive omic characterizations of these organisms during the last decade, unleashing many potential applications most notably for pollution biomonitoring. Yet, the implications of bivalve omics for other research fields are still unexplored. Given the high bioaccumulation rates associated with the filtering capacity of bivalves and their relative tolerance to xenobiotics, it would not be surprising if new useful marine compounds, proteins or whole metabolic pathways could be discovered as a result of the omic analysis of these organisms. Although the possibilities promise to be endless, the development of further applications is still hampered by the early stage of development of omic technologies and associated computational methods of data analysis in bivalve molluscs, definitely far behind traditional model organisms. In such a scenario, and given the nature of the omic data, the advance in the integrative knowledge of bivalves will require coordination and transfer of knowledge across researchers sharing complementary goals. Indeed, the release of web accessible databases containing processed and reviewed results (not simply raw data) seems the best way to consolidate the omic characterization of bivalve molluscs. Altogether, great expectations are placed on future bivalve omics as it pertains to life sciences, environmental sciences and aquaculture livestock managing. Nonetheless, there is undoubtedly a long road ahead to obtain a truly holistic understanding of the basic features displayed by the different bivalve omes.


Evidence on the link between income inequality and alcohol-related problems is scarce, inconclusive and dominated by studies from the developed world. The use of income as a proxy measure for wealth is also questionable, particularly in developing countries. The goal of the present study is to explore the contextual influence of asset-based wealth inequality on problem drinking among Thai older adults. A population-based cohort study with a one-year follow-up was nested in a Demographic Surveillance System (DSS) of 100 villages in western Thailand. Data were drawn from a random sample of 1104 older residents, aged 60 or over (one per household) drawn from all 100 villages, of whom 982 (89%) provided problem drinking data at follow-up. The primary outcome measure was a validated Thai version of the Alcohol-Used Disorder Identification Test for problem drinking. Living in areas of high wealth inequality was prospectively associated with a greater risk for problem drinking among older people , after adjusting for individual-level and village-level factors. A rise in wealth inequality over the year was also independently associated with an increased risk of problem drinking . The associations were not explained by the social capital, status anxiety or psychosocial stress variables. The data suggest that wealth inequality and an increase in inequality across time lead to a greater risk of problem drinking. Efforts should be directed towards reducing gaps and preventing large jumps in inequality in the communities. Further research should investigate the effect of asset-based inequality on various health risk behaviors and its specific mediating pathways. •Evidence on inequality and alcohol-related outcomes is inconclusive.•Assets may be more reliable for measuring inequality in developing countries.•The findings suggested that wealth disparity increased the risk of problem drinking.•Widening disparity across time also increased the risk.•To address problem drinking may need to target areas with high wealth inequalities. Alcohol-related problems are a major global public health concern being associated with a wide range of social and economic challenges . AlcoholThe notion that the distribution of wealth within societies could be a health determinant has attracted a great deal of attention in public health research. Thailand is a developing country which has seen significant growth in Gross Domestic Product (GDP) over the past few decades. However, this economic growth has been unequal across groups of populations with greater increases for the rich, thereby contributing to greater disparity . ThailanA number of theories have been put forward to explain the association between wealth inequality and health. For instance, the ‘social capital’ theory holds that higher levels of wealth inequality increase status differentials between individuals, thereby reducing levels of interpersonal trust . The ‘stWealth inequality can be measured in a number of ways, but is most often measured through the GINI coefficient of income inequality in the field of health research . The useIn measuring inequality, it is recommended that choosing a unit of analysis to capture the right level of differentiation should be on the basis of the processes through which inequality may influence specific health outcomes . In prevTo date, studies examining the link between wealth inequality and alcohol-related problems, all carried out in the United States and Europe, have shown inconsistent findings . A studyKanchanaburi's Demographic Surveillance System (DSS) presents a unique opportunity to study the prospective relationship of wealth inequality and health outcomes. Kanchanaburi is a large province in western Thailand and the only one in the country which has a DSS, comprising a longitudinal census for monitoring population changes. DSS is especially suited for studies on older people because they rarely migrate and are less likely to be lost during follow-up compared to younger people. In 2007, about 11% of those aged 60 years or over in Kanchanaburi had reported drinking alcohol .Our goal in the present study was to examine the prospective relationship between asset-based wealth inequality at baseline, its one-year change and risk for individual problem drinking among older people aged 60 or over at one year follow-up, accounting for individual- and village-level potential confounders. We also sought to examine the possible mediating effect of individual-level perceived social capital, social anxiety and psychological stress variables.We obtained information from a data source originally designed to investigate out-migration of children and its impact on mental health of the older parents left behind in rural Thailand , nested The sampling strategy had been developed for the main study , based oThe tension reduction model, a widely known model of drinking and alcoholism , was useEducational attainment was categorized in years; 0 (no education), 1–3 (not completing compulsory education), 4 (completing compulsory education), 5–13 (higher than compulsory education).Household wealth index: The heads of household were asked to report the presence of household assets on the list provided (up to 24). We used principal component analysis to develop a household wealth index comprising 15 household assets  and interviewer's global rating of household quality. Scoring factors of the first principal component was used to construct the asset index of each household. The mean value of the index is zero by construction. Household asset index has been validated and widely used in many developing countries as proxy for wealth .Problem drinking was assessed using the Alcohol Use Disorder Identification Test (AUDIT), a structured and standardized instrument which provides valid and reliable detection of hazardous and harmful use of alcohol in a general population  is a 14-item instrument designed to measure anxiety and depression symptomatology . A household has an average of 4 residents . These vy is the first principal component of the listed assets, relative measure of inequality for community c is calculated by the following formula.σc is the sample standard deviation of the yi across households in community c, and λ is both the eigenvalue corresponding to the first principal component, and also the variance of yi over the whole sample. Ic will be greater than one if community c displays more inequality within it than does the sample population as a whole. In the present study, the sample villages were simply equally divided into 2 groups according to their level of wealth inequality: villages of high and low inequality.Our main predictor variables were village wealth, wealth inequality and their one-year changes. These were measured for each village where a respondent resided at the times of the interview from baseline to follow-up. Village wealth was simply the median of the household asset scores among the sampled households in each village. It was classified for analysis into high and low levels of wealth based on the median cut-off. We used the relative measure of inequality as the measure of wealth inequality on the basis that data from on household infrastructure, building materials, and ownership of certain durable assets can be used to measure inequality in living standards . The meaThere were eight interviewers, all trained and supervised by the research team in Thailand. All the interviews were conducted in Thai and informed consent was obtained from all participants. If the selected older adults and the head of household gave consent, the interviewer first interviewed the head of household with the household questionnaire and then the older adult with the individual questionnaire. Quality control included checking on data completeness and consistency. Interviewers had to return to the participants if the data were incomplete. We gained ethical approval from King's College Ethics Committee (No. 05/05-68) and from Mahidol University Institutional Review Board.t test and Mann–Whitney U test were used to evaluate statistically significant differences in continuous variables where appropriate. We then used multilevel logistic regression models, to analyze the prospective relationship between wealth inequality, as well as its one-year change, in village of residence and individual AUDIT outcome as the dependent variable. Because individuals were clustered within villages and villages within strata, three-level models with variances at the level of individual, village and strata were used. The model was a random intercepts model in which the regression coefficients of the independent variables were assumed to be the same for all areas (fixed effects), but the intercepts were allowed to vary across areas (random effects) i.e., village and strata in the present study. The analysis was not extended to random slope models. All risk estimates, represented by odds ratios (OR), and their 95% confidence intervals (CI) were calculated using STATA version 10 for Windows  or unavailable at follow-up (n = 3). The median number of participants in each village was 9 (range 3–31).Out of the 1300 eligible older people at baseline, 153 (11.8%) were non-responders of whom 110 were unavailable for an interview (despite up to ten visits to the household), 21 refused to take part and 22 were too unwell. Those unavailable were mostly away visiting their children. Of the 1147 (88.2%) who agreed to participate, data were complete for 1104 and incomplete for 43 because the older adults were unwell or cognitively impaired. Of 1104 respondents who formed the baseline sample, 982 (89%) provided complete data on AUDIT and on other key variables at one-year follow-up. The main reasons for not completing any follow-up measures were absence 39 (32%) despite up to 3 visits, illness 14 (11.5%) and death 34 (27.9%), 28 (23%) had moved and could not be traced and only 7 (5.7%) refused to take part. Although several characteristics were individually associated with missing follow-up, older age, cognitive impairment and disability remained significant predictors in multiple regression. In the end, a total of 96 villages were used for analyses. People in the remaining 4 villages were too few (The mean age of the study participants at baseline was 69.4 years (sd 6.86). The majority of the sample was female, married, currently in work, and completed four years of education . Charactt-statistic = 2.151, p = 0.0159). Those with and without problem drinking had no significant differences in level of village wealth  and level of inequality at baseline . All the mediating variables including social capital, status anxiety and psychological stress were not significantly associated with problem drinking.Problem drinking at follow up was significantly associated with many of the baseline characteristics, including younger age, male gender, married or single/divorced/separated status and being currently in work . Those wp = 0.141). However, there was a significant trend towards greater risk of problem drinking among those experiencing varying changes, from a decrease to a rise, in inequality (p = 0.009). The multilevel logistic regression analyses showed that at the individual level, problem drinking at baseline, younger age and male gender remained significantly associated with risk for problem drinking at follow-up. Village-level wealth at baseline was not significantly associated with increased risk for problem drinking at follow-up, both before and after adjustment for the individual-level and village-level confounders . HoweverOur findings demonstrate a contextual effect of village wealth inequality on risk for individual problem drinking among older people at one-year follow-up after controlling for a set of potential individual- and village-level confounders. In addition, a strong prospective relationship between one-year growth in inequality and problem drinking was observed. This finding was further strengthened with the presence of a gradient in risk for problem drinking among those exposed to varying changes, from a decrease to a rise, in inequality. In other words, older adults living in areas of high and/or growing wealth inequality had a significantly greater risk for problem drinking. Wealth at the household and village levels, on the other hand, was not found to be associated with problem drinking. Previous studies examining the contextual effect of income inequality on individual drinking outcomes have reached different conclusions, although they are not exactly comparable due to differences in age groups under study, alcohol outcomes and unit of analysis . Our stuOur findings showed that the hypothesized perceived social capital, status anxiety and psychological stress pathways were not supported by our data. Along a similar line, a recent study investigating the neighborhood effect on hazardous alcohol use found that the relationship between high neighborhood disorder and more hazardous alcohol use was not mediated by individual psychological distress . The queThe present study was the first, to our knowledge, to provide evidence of a prospective relationship between asset-based wealth inequality and individual problem drinking. The particular strength of our study lay in the utilization of the fact that high wealth inequality and the continuing rise in wealth inequality were particularly prominent in many developing nations. Another advantage was that the older populations in the present study were largely local and rarely migrated, as opposed to younger adults, hence loss to follow up due to migration was negligible. The contextual effects observed were also therefore likely to be due to having been exposed to social environment in their neighborhood and less likely to be due to the effect of selective migration, a kind of bias where migrants with certain characteristics choose to live in a particular place and influence their environment, rather than vice versa. The results of the study, however, should be interpreted with caution. The overall sample was relatively small and the prevalence of problem drinking rather low. All these may contribute to the marginally significant contextual effect of high inequality at baseline on problem drinking, which came out as such only after controlling for the full set of potential confounders. Thus, the role of chance as a possible explanation for the observed finding could not be totally excluded. However, this was unlikely because the size of the association changed very little after adjusting for a series of potential confounders, from the basic model controlling for age, gender and baseline problem drinking only (OR 1.9) (data is not shown), to Model I (OR 2.00) and to Model II (OR 2.03). Only when controlling for changes in wealth from baseline to follow up did the association slightly strengthen (OR 2.3) and became significant. In other words, controlling for more variables did little in strengthening the association. The likelihood of chance was reduced further still by the fact that strong contextual effect with changes in inequality was also observed in the present study. Nevertheless, future studies should benefit from additional data collected from a larger sample size, which may include younger age groups, because they are more likely to have a high prevalence of problem drinking by comparison. A more accurate picture of such contextual effect can also be obtained from young problem drinkers, who have only recently developed such behavior. It is possible that that current problem drinking among older people, like many mental illnesses or chronic diseases, runs a remitting and relapsing course, and may also be determined more by earlier characteristics of the life course, and less by recent exposure to a certain environment.Consideration should be taken into account when considering whether the current findings can be generalized to other settings. On the other hand, including only older adults in the sample should not limit the validity of the study findings. It could be argued that findings that are replicated in any specific age group can be seen as further evidence that supports the general theory on inequality and health.It should be noted that the manner in which the mediators are operationalized in this article are far from ideal. There may be better candidates for the variables we used to represent the hypothesized pathways in the present study, particularly the relatively complicated social capital concept. To address this issue, a priori and validated measures of such pathway mediators should be used.Measuring inequality based on a wide variety of assets may be more appropriate than income inequality in developing countries. To reduce problem drinking, policy makers may need to be concerned more about households' access to assets and the associated opportunities. Long-term strategies to curb problem drinking should also target those in areas where inequalities are high and focus on efforts to reduce gaps and prevent large jumps in asset inequality in the communities. The findings also suggest that interventions to address psychological stress may help little to reduce problem drinking among older people.


Early infant male circumcision (EIMC) is simpler, safer and more cost-effective than adult circumcision. In sub-Saharan Africa, there are concerns about acceptability of EIMC which could affect uptake. In 2009 a quantitative survey of 2,746 rural Zimbabweans (aged 18–44) indicated that 60% of women and 58% of men would be willing to have their newborn son circumcised. Willingness was associated with knowledge of HIV and male circumcision. This qualitative study was conducted to better understand this issue.In 2010, 24 group discussions were held across Zimbabwe with participants from seven ethnic groups. Additionally, key informant interviews were held with private paediatricians who offer EIMC (n = 2) plus one traditional leader. Discussions were audio-recorded, transcribed, translated into English (where necessary), coded using NVivo 8 and analysed using grounded theory principles.Knowledge of the procedure was poor. Despite this, acceptability of EIMC was high among parents from most ethnic groups. Discussions suggested that fathers would make the ultimate decision regarding EIMC although mothers and extended family can have (often covert) influence. Participants' concerns centred on: safety, motive behind free service provision plus handling and disposal of the discarded foreskin. Older men from the dominant traditionally circumcising population strongly opposed EIMC, arguing that it separates circumcision from adolescent initiation, as well as allowing women (mothers) to nurse the wound, considered taboo.EIMC is likely to be an acceptable HIV prevention intervention for most populations in Zimbabwe, if barriers to uptake are appropriately addressed and fathers are specifically targeted by the programme. Randomised trials suggest that male circumcision (MC) reduces a man's risk of acquiring HIV through heterosexual sex by 51–60% over an 18–24 months period Although EIMC's effects on HIV will take longer to realize, infant circumcision is likely to ultimately be more effective at preventing HIV acquisition than adult MC as the procedure is carried out long before the individual becomes sexually active, negating the risk associated with sex during the healing period Since 2009, Zimbabwe has provided circumcision to adult and adolescent men through a collaborative effort between the government and technical agencies. The programme aims to reach 1.2 million 15–29 year-olds by 2015 In a 2009 representative household survey of 2,746 rural Zimbabweans (aged 18–44), 60% of women and 58% of men reported willingness to have their son circumcised; willingness was associated with increased HIV and MC knowledge The qualitative study was conducted between June and October 2010 with rural and urban participants in five of Zimbabwe's ten provinces: Bulawayo, Harare, Mashonaland West, Masvingo and Matebeleland North. Twenty-four gender-specific focus group discussions (FGDs) were held with expectant mothers (n = 6 groups), expectant fathers (n = 5 groups), grandmothers/mothers-in-law (n = 6 groups) and grandfathers/fathers-in-law (n = 7 groups) from seven ethnicities.Key informant interviews (KIIs) were held with private paediatricians who offer EIMC (n = 2). An additional KII was held with a traditional leader from a traditionally circumcising ethnic group (Shangaan).FGDs were conducted in either Shona or Ndebele, Zimbabwe's dominant indigenous languages, also spoken and understood by smaller ethnic groups. KIIs were conducted in English and Shona. Prior to group discussions, facilitators defined EIMC and presented basic information about the procedure, including the fact that it is quicker and safer than adult MC. Discussions then focused on issues such as perceptions of EIMC, willingness to have son undergo circumcision if it prevented HIV, barriers and motivating factors to EIMC and perceived acceptability of the intervention. Theme saturation - a situation where qualitative data collection reaches a point where no new issues emerge Audio-recorded data were transcribed and translated verbatim into English (where necessary). Names and other personal identifiers were removed from transcripts before they were entered into NVivo 8 , a qualitative data storage and retrieval program. Two researchers (CM and RBT) coded each transcription separately. Discrepancies were resolved by discussion with the senior social scientist (WM), who also independently coded all transcripts. Codes were grouped into categories and emerging themes were then identified iteratively following the general principles of grounded theory Ethics approval was given by the Medical Research Council of Zimbabwe and the ethics board of University College London. Written informed consent was obtained on the day of the interview/discussion.A total of 240 participants took part in FGDs; an additional three key informants were interviewed. EIMC knowledge was generally poor. Despite low knowledge, EIMC acceptability was high among participants from most ethnic groups. Older men from one traditionally circumcising population, who circumcise during adolescence, were strongly opposed to EIMC. Paediatricians reported a recent increase in parents requesting EIMC. Participants raised several concerns that have implications for circumcision roll-out. We present these themes in more depth below.‘It is the removal of the skin on the penis’ . When probed, they did not know how much skin is removed as well as precisely where it is removed from. Additionally, participants from traditionally non-circumcising populations were unaware of MC's benefits. ‘We hear that it [MC] is done among the Shangaan and other people of foreign origin such as the Chewa [from Malawi] but we don't know why they do it’ . The same participants maintained that attempts to learn more about traditional MC have been futile since the procedure is highly secretive.Male circumcision knowledge in general and EIMC knowledge, in particular, is poor among the general population and especially among traditionally non-circumcising groups. Several participants, particularly (and understandably) females, did not know what the procedure involves save to say, ‘It [MC] should be done when they [babies] are about six months old. You can't do it earlier as the organ [penis] will still be too tender’ . Participants generally felt that fragility of the infant penis in the immediate post-partum period would result in unacceptable risk of surgical error. ‘One can easily cut off the head [penile] as well’ . Private paediatricians reported parents requesting infant circumcision often when it is ‘too late’. ‘Mothers are bringing 12 month-old babies for circumcision . Another paediatrician described challenges around circumcising toddlers. ‘As babies grow bigger they become more difficult to sedate because I do it under simple sedation…I know a lot of people want to do it under spinal anaesthesia but that is unduly traumatic to both the family and the baby’ . However, during FGDs, the feeling that it is less-risky to circumcise toddlers, as opposed to infants, was quite pervasive.When asked to give their opinions on timing of EIMC, participants generally felt that it should be done three to six months after birth. ‘Even now as I speak, if I hear that they are now circumcising children at our hospital, I will quickly take my grandchild along. I am currently faced with the burden of looking after AIDS orphans’ . Several participants felt that if circumcision protects one from HIV, infant and adolescent circumcision should be compulsorily offered as part of national HIV prevention efforts. ‘The government should “force” parents to circumcise their sons in the same way it “forces” them to immunise children against measles’ . Overall, participants felt that the impact of HIV on the younger generation is enormous, and were excited to hear that MC is partially protective.Despite low levels of infant MC knowledge, discussions suggested high willingness to have son circumcised in most ethnic groups – providing MC was an effective HIV prevention method. ‘It used to be almost entirely Muslim and Jewish parents [requesting infant MC] and then quite a number of North Africans married to Shona women but we are now getting quite a number of Zimbabweans. So the picture is definitely changing…and people often ask me about male circumcision and HIV’ . Discussions with older men who were collecting their antiretrovirals at one rural hospital corroborated quantitative findings – that HIV positive men are particularly keen to have their sons circumcised; ‘I would not want my son to also go through what I am going through now. Had circumcision come earlier, I would probably be [HIV] negative’ .Paediatricians reported a recent increase in the number of infant circumcisions being conducted privately as well as the number of Zimbabwean parents requesting EIMC, something previously uncommon. ‘The man must make that decision because he is the one who knows whether or not that is practised in his clan; a woman cannot know anything about a clan to which she doesn't belong’ . A female participant concurred, ‘As the mother, I cannot decide whether or not the child should be circumcised. I will need to “sit down” [discuss] with the father and we will have to go by his decision’ . However, subsequent probing suggested that mothers-in-law/grandmothers are likely to have considerable (often covert) influence. A young woman described steps she would take if her husband refused to have their son circumcised. ‘If he [father] refuses, I will talk to his mother and she will then ask his uncles to talk to him’ . EIMC decision-making is therefore likely to involve relations other than the child's parents.Study findings highlighted importance of the father in the decision-making process. ‘For us to be touched [circumcised] by anyone [non-Muslim]…the truth is we don't want but we will be prepared to take our children to Indian [Muslim] doctors .Discussions with traditionally circumcising tribes in Zimbabwe including the Xhosa, Chewa, Venda and Remba suggested that these groups are not opposed to EIMC. However, they felt that they would prefer the procedure to be performed by someone who was themselves circumcised and of the same tribe. Some Muslim participants  preferred it to be done by someone of the same religion. ‘We don't just circumcise. There are “lectures” that we teach those that undergo circumcision. How will we be able to teach infants?’ . Secondly, they noted that if infants were circumcised, their mothers would need to be involved in the process as they would nurse the wound. ‘Infants would need to be nursed by their mothers [after circumcision]. We don't want mothers to know what we do’ . Among the Shangaan, allowing women to see (and nurse) the MC wound is considered taboo.However, older men from the dominant traditionally circumcising population in Zimbabwe, the Shangaan, were strongly opposed to EIMC for two reasons. Firstly, they mentioned that circumcision is just one part of a comprehensive ‘rites of passage’ ritual and should therefore not be undertaken separately. Despite high levels of acceptability, community members raised several key questions discussed below.‘This thing should be done by doctors who really know how to do it and no one else’ . Participants were also concerned about the possibility of excessive bleeding and keloid scarring. ‘What if my child gets swollen like those people who have a large growth from ear piercing…?’ .Community members questioned the safety of EIMC. As previously stated, safety-related concerns were based on the assumption that the newborn infant's penis is too fragile to be circumcised, leading participants to feel that, to maximise safety, the procedure should only be performed by highly-trained doctors. ‘What will happen to the piece [foreskin] that gets removed?’ . Another participant stated, ‘They (HCWs) should ensure that pieces that get removed are carefully disposed of so that they do not end up in the hands of those who could use them as ‘muti’ [traditional charm] .Customarily, Zimbabweans are worried about disposal of body fluids/tissues as they fear that these may be used by ‘witches’ to cause subsequent harm. For example, people burn shaved hair and nail clippings in case these end up in the wrong hands. With infants, disposal of the umbilical stump is a culturally-sensitive issue which involves mothers-in-law/grandmothers. Unilateral disposal of the umbilical stump by a young couple/mother can have serious implications. Community members were therefore anxious about the fate of the amputated foreskin: ‘The foreskin [infant] is just the same as the umbilical cord [stump]; both should be given back to the child's parents’ . Mothers-in-law/grandmothers strongly articulated that should young couples decide to circumcise infants on their own, at a minimum elders need to be involved in foreskin disposal. ‘As is the case with the umbilical cord [stump], I should be the one who decides where and how to dispose the piece that gets removed’ . Overall, older male and female participants alike felt that the infant's removed foreskin should be given to the child's relations.Some participants felt that parents should be given the foreskins in order that they would be able to dispose of them themselves, drawing parallels with the common practice of obtaining the infant umbilical stump from health-care workers. ‘Why is this thing done for free yet operation [caesarean section] on a pregnant woman is costly?’ . These participants felt that caution should be exercised when accepting this service since it is donor-driven and the motive of the countries paying for it are unclear.A few participants questioned why MC in general and EIMC specifically, is being or will be provided free of charge. Data from this qualitative study corroborate some of the quantitative findings from our population-based survey, namely that EIMC was seen as widely acceptable. However, given the very low levels of knowledge or experience of EIMC, it is not clear whether this hypothetical acceptability will translate into actual acceptability once EIMC roll-out begins. It is clear though that participants were very interested in the intervention as described, that is, one that could protect their sons against future HIV.This qualitative study additionally identified new issues which have implications for EIMC implementation. Firstly, given the low levels of knowledge about the procedure, it will be important to provide information at a community level to enhance the procedure's acceptability. These qualitative findings reinforce the need for multi-faceted awareness campaigns  to ensure that everyone in the community is reached and not just those in contact with clinical services directly not just through their wives. As caretakers of their family's health, women often receive information from health-care centres during routine visits. Yet men are notoriously hard to reach via health services Education needs to include both women and men; it should also target multiple generations. While reinforcing the crucial role fathers play in EIMC decision-making shown elsewhere Participants raised concerns around the safety of EIMC. Similar concerns have also been observed in other studies across the region Participants strongly felt that safe EIMC can only be provided by highly-trained doctors. However, in practice, it is likely that EIMC will largely be performed by midwives/nurses since it is an uncomplicated procedure Study findings support the now well-recognised notion that cultural beliefs are integral to successful MC provision These findings have at least three implications for rolling-out circumcision, in general and EIMC, specifically. Firstly, implementers will need to recognise and understand cultural and religious beliefs attached to MC among certain groups This study has several strengths. Firstly, this research was conducted with participants representing the majority of ethnic groups, and in half of Zimbabwe's ten provinces. Secondly, our sample size was large for a qualitative study. The sample was purposively selected to ensure a wide range of views were heard from a diverse population. Thirdly, we managed to achieve theme saturation, an important component of qualitative research.There were some limitations to this study. Firstly, although EIMC was defined prior to group discussions, some participants still discussed neonatal circumcision and had to be reminded that they needed to focus on infant circumcision. Secondly, we explored EIMC acceptability in the absence of widely-available services or any communication campaign that specifically provides information about infant circumcision. Hypothetical acceptability may be quite different from actual acceptance when EIMC is eventually rolled-out In conclusion, this study found that EIMC is a potentially acceptable HIV prevention intervention in Zimbabwe and provided a framework for addressing likely barriers to uptake. Specifically, awareness campaigns that increase knowledge will be crucial to translating hypothetical acceptability into actual uptake. These data suggest that barriers are not insurmountable - which bodes well for achieving high EIMC targets in sub-Saharan Africa, in general and Zimbabwe, specifically.


Forty years have passed since video-games were first made widely available to the public and subsequently playing games has become a favorite past-time for many. Players continuously engage with dynamic visual displays with success contingent on the time-pressured deployment, and flexible allocation, of attention as well as precise bimanual movements. Evidence to date suggests that both brief and extensive exposure to video-game play can result in a broad range of enhancements to various cognitive faculties that generalize beyond the original context. Despite promise, video-game research is host to a number of methodological issues that require addressing before progress can be made in this area. Here an effort is made to consolidate the past 30 years of literature examining the effects of video-game play on cognitive faculties and, more recently, neural systems. Future work is required to identify the mechanism that allows the act of video-game play to generate such a broad range of generalized enhancements. Video-game play has become the past-time of choice for current generations, with entertainment software allowing individuals to engage both socially and competitively with individuals across the globe. Players engage with seamless virtual environments with success contingent on the execution of precise bimanual motor movements in response to complex visual cues. Evidence suggests that extensive video-game play may lead to the enhancement of visual attention and executive control, generalizing beyond the context of the video game, although this is still debated.Magnavox Odyssey. While this new technology was quickly seized upon by the public, it was not without objection. Many saw video-game play as a mindless exercise imparting no real benefit to the player. Ball  than after playing non-spatial games (Conjecture), which may account for at least part of the result  and mental rotation performance have been consistent. Sims and Mayer  differentially improves the performance of females on mental rotation. More convincing changes were observed, however, in a study with children , largely due to the extent of the improved performance of the girls who played Tetris. Overall children who played Tetris improved significantly in comparison to controls who played Carmen Sandiago. While these results may be driven simply by the expectation to improve in mental rotation performance after playing Tetris, this does not account for the differential improvements of the girls who play Tetris.There has been particular interest in the link between spatially-oriented video-games and the reduction of gender disparities in mental rotation performance, although close examination of the findings reveals mixed outcomes. Although De Lisi and Cammarano  concludeThe largest body of video-game literature examines the impact of video-game play on the capacity and spatial distribution of visuospatial attention. Success in many action video-games requires participants to attend to disparate multiple in-game objects all within complex visual environments. Given these demand characteristics, it is perhaps not surprising that most studies report enhancements in these abilities in skilled VGPs.Robotron: 2084 for 5 h, showed results in the same direction as expert VGPs. Unfortunately, there was no control training condition.Greenfield et al.  began thaction video-game play on visual attention has largely been stimulated by the seminal work of Green and Bavelier  but not after playing a non-action video-game (Tetris).Current interest in the effects of Bavelier , who comBavelier ,b replicBavelier . In the Using an enumeration task Green and Bavelier  showed eMany of the performance advantages shown by Green and colleagues in adult expert VGPs have been replicated in child and adolescent VGPs. Dye et al.  found boKuhlman and Beitel  found thWhether anticipatory abilities are related to visual search strategies is a matter of debate. Within the VGP literature, evidence related to enhanced visual search is mixed. Castel et al.  investigContrary to Castel et al. , Hubert-West et al.  comparedThe Sims), showed a significant reduction in backward masking in the same direction as expert VGPs. However, this result could be driven by the expectation of NVGPs trained on the action video-games to improve on backwards masking, especially as the temporal demands of The Sims are low, because players able to control the speed of in-game time and perform actions while the game is paused.Li et al.  showed aThe impact of exogenous cues on the performance of expert VGPs was further examined by West et al.  using a Chisholm et al.  providedUnreal Tournament or puzzle video-game Portal. Participants who played the action video-game showed faster response times but lower accuracy, while participants who played the puzzle video-game showed slower response times but greater accuracy. This provided evidence that cognitive strategies primed by the demands of different video-game genres could possibly generalize beyond the context of the video-game itself.Video-game play has also been found to impact on cognitive task set selection and the higher-order capacity to switch between tasks. For example, Nelson and Strachan  found paColzato et al.  investigTetris) showed no improvement. The inability to produce enhanced visual acuity in NVGPs may mean it is not amenable to short-term training, or instead that it represents a pre-existing characteristic of expert VGPs.Some of the most exciting, diverse and novel findings in the VGP literature have concerned the potential enhancement of fundamental aspects of the visual system. Green and Bavelier  comparedThe Sims 2) showed no improvement.Contrast sensitivity, another fundamental property of vision, has also been found to be superior in expert VGPs. Contrast sensitivity refers to an individual's ability to detect small increments in shades of gray on a uniform background, and like visual acuity, it is a major limiting factor in determining quality of sight  than NVGPs.In addition to increased quality of vision, video-game expertise is also associated with larger central and peripheral visual fields, determined using Goldmann kinetic perimetry , who showed no improvement.Finally, Green et al.  providedVideo-game play was first tested as an intervention to stem cognitive decline in older adults in the mid-1980s. Early results showed promise, with improved performance of older adults on a range of cognitive measures , following video-game play .Haier et al.  conducteGranek et al.  used eveMishra et al.  comparedBavelier et al.  comparedbeyond specific trained skills.To date the small neuroimaging literature on expert VGPs has focused on the functional correlates of enhanced cognitive performance. Substantial evidence in the broader neuroimaging literature indicates that practice and expertise can induce not only functional but structural changes to neural organization. For example, repetition of simple finger exercises has been shown to lead to increased cortical representation of the fingers  and as a result may not provide evidence of proficiency beyond training. Exceptions showing the generalization of expertise or training to non-computerized tasks do exist . Quaiser-Pohl et al.  examinedCounter Strike: Global Offensive and popular multiplayer online battle area League of Legends use performance ratings. Starcraft II uses a total of seven leagues ranging from the beginners “Bronze” league to the “Grand Master League” which consists of the top 200 players on a server. With the rise of professional video-game play, level of professional attainment  could also serve as a proxy for expertise. While not perfect, future studies may be able to tap into skill metrics, online rankings, and level of professional attainment in order to better assess the expertise of their expert VGP samples.Third, there are difficulties in adequately defining and measuring video-game expertise. Cross-sectional studies often classify video-game players as “experts” if they have played video-games for a small period of time per week over the past 6 months. Unfortunately, there is no guarantee that individuals with these video-gaming characteristics possess expertise, or could even obtain expertise with such a small time commitment. Greenfield et al.  were theLastly, more emphasis is needed on the links between the specific game genres of expert VGPs, video-game training and the cognitive enhancements measured. Throughout this review it is evident the findings of earlier studies (during the 1980's and early 1990's) are typically weaker and less precise than those of more recent studies. While this often reflects study designs, findings were also shaped by the video-games of that era, which were generally extremely simple in nature, requiring only repetitive and distinct patterns of responses to succeed. Overall it appears that training on this sort of game can lead to improved performance, but improvements are generally are restricted to the context in which training occurs and reflect increased task efficacy, rather than more general enhancement of underlying cognitive processes . There are, however, concerns about current research practices that need to be addressed . In addition, all these studies have lacked adequate control conditions making results particularly problematic to interpret. This is particularly surprising as the potential for video-game play to impact on such a broad range of cognitive domains appears to offer many avenues for practical application. Future rigorous research that is capable of determining whether the application of video-game play can stem cognitive decline in older adults is a high priority. Alternatively, researchers could aim to use video-game play as an intervention to ease cognitive deficits in patient populations or further improve cognitive performance in specialist populations.Early neuroimaging studies (see section Neuroimaging and Video-Game Play) have successfully begun examining the functional neural correlates of enhanced cognitive performance in expert VGPs. So far only motor planning, selective attention, and visual search have been assessed. Future neuroimaging research is needed to assess the functional neural correlates of enhanced cognitive performance. There is also a need to investigate the structural changes that accompany video-game expertise. A longitudinal randomized control training trial that also incorporate neuro-imaging study would be a valuable approach. The recommendations to promote best behavioral research practices are equally applicable to neuroimaging.The results in section Fundamental Properties of the Visual System, Visual Perception, and Use of Sensory Evidence are particularly exciting as they suggest fundamental elements of the visual system may be heightened by video-game expertise and play. Changes at this level of the visual system potentially underpin a diverse range of downstream performance enhancements presented in this review, such as spatial visualization , visuospatial attention , visual search  and temporal order judgments . Unfortunately, we still have little understanding as to what about video-game play—other than practice—allows it to shape core elements of the visual system. Answering this question may also elucidate why video-game play has the potential to generate such a broad range of generalized enhancements. Understanding the mechanisms that underlie how video-game expertise gives rise to so many enhancements may lead to the efficient and targeted application of video-game play (and other forms of expertise-related interventions) to both education and clinical settings, and more generally permit individuals to make more informed decisions about the potential uses of their spare time.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.http://www.frontiersin.org/Cognition/10.3389/fpsyg.2013.00629/abstractThe Supplementary Material for this article can be found online at: Click here for additional data file.


Mycobacterium marinum, the cause of chronic systemic infections in fish, occasionally causes granulomatous skin and soft tissue lesions in humans. Cutaneous mycobacterial infection in two patients owing to unusual circumstances is presented in this report. The first patient was infected through improper hygienic behavior, while infection in the second patient was previously misdiagnosed as rheumatoid arthritis and treated with methylprednisolone for a period of three months, which resulted in a rare systemic spread of M. marinum into the bones of the hand, testis, and epididymis. Simultaneously, screening for possible sources of M. marinum infection in patients' aquaria revealed positive fish harboring VNTR profiles identical to those obtained for clinical isolates from patients. M. fortuitum, M. gordonae, M. kansasii, and M. peregrinum are frequently present in the aquatic environment of surface waters in the Moravian region of the Czech Republic. In contrast, the most frequent NTM present in aquaria with ornamental fish were M. marinum [Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and are responsible for several diseases in animals and humans known as mycobacterioses –3. A stu marinum .Mycobacterium marinum is the cause of chronic systemic infections in fish and an occasional cause of granulomatous skin lesions in humans. Infections in humans result in skin and soft tissue infections characterized by their predilection for the upper extremities, often following minor trauma to hands with a history of typical exposure to aquarium tanks [M. marinum if the injury originated from an aquarium or the water environment [um tanks , 6. Diagironment .M. marinum infection in humans , ornamental fish (n = 20), and the aquarium environment . Animal and environmental samples were examined within the framework of an epidemiological study carried out in the aquaria of infected aquarists.A total of 49 samples were taken from two humans , microscopic examination after ZN staining, and sequence analysis of the RNA gene . Subsequ marinum .erp/IS2404 qPCR assay, which enables species-specific detection of M. marinum [DNA isolation from human, fish, and environmental samples was based on a protocol described previously . The iso marinum .M. marinum. The patient was initially treated with clarithromycin. Subcutaneous resistance did not lessen after nine weeks; therefore, treatment was continued with ethambutol for an additional nine weeks.A Twenty-five-year-old male reported cleaning his injured left knee with a brush usually used to clean the aquarium, which resulted in infiltration and subsequently visible crusts together with two subcutaneous resistances caused by M. marinum from the primary site into the joint and bones of the index and ring finger, forearm, testis, and epididymis. The patient was initially treated with a combination of clarithromycin and ethambutol. Because of the insufficient clinical response in the area of the right hand an eight-month-long treatment based on results of sensitivities to a combination of amikacin, ciprofloxacin, ethambutol, cycloserine, and pyrazinamide was administered. Due to the damage to the testis an orchiectomy was also carried out. Because of long-lasting pain and damage the distal part of the ring finger was surgically removed.The second case involved cutaneous infection of a 60-year-old male with a professional interest in fish breeding. He reported injury to the tip of his index finger, which occurred during aquarium clearing. He was misdiagnosed with rheumatoid arthritis and treated with methylprednisolone for a period of 3 months, which resulted in a rare systemic spread of M. marinum infection are distinguished: granulomatous nodular or diffuse inflammation with mixed granulomas; abscesses with mild granulomatous reactions; and subcutaneous (patients 1) or deep dermal granulomatous inflammation [M. marinum infection may have the potential for systemic dissemination in humans as has been reported earlier and was shown in the second patient [Generally, three main histopathological patterns of ammation . Tenosynammation , 15. M.  patient .M. marinum diagnostics are slow and rely solely on phenotypic characteristics, which can be very similar to different causative agents. Clinicians in general have to consider other causes besides M. marinum including deep fungal infection; therefore, a diagnostic ladder is needed in this kind of patients. Delayed diagnosis is the main cause of the patients' serious side effect. Rapid and accurate molecular diagnosis methods are essential. Rapid detection of mycobacteria using conventional broad range PCR assay was previously described in the literature [M. marinum in clinical specimens suitable to overcome this limitation would be beneficial. So far, there have been very few reports on the detection of M. marinum directly from infected tissue without previous culturing [Conventional microbiological methods used for terature . The advterature . Sensitiulturing , 18.M. marinum, in comparison to more time-consuming conventional methods. The protocol used here enabled us to complete the analysis of a sample, including controls, in approximately 6 hrs. The applied qPCR assay enabled the detection of M. marinum in clinical specimens collected from both the infected humans prior to successful cultivation . The number of viable cells in qPCR-positive samples was possibly lower due to the applied decontamination procedure because only one fish from each patient was later culture-positive for M. marinum. As reported earlier, microbiological stains give positive results in less than 25% of cases and do not correlate with the severity of M. marinum infection [M. marinum is described to be present in the water environment, it was detected only in fish.Screening for the presence of nfection . AlthougM. marinum strain isolated from fish had the same VNTR profile as the clinical isolate originating from the fish owner and thus it can be concluded that the aquaria were the source of infection in the case of both aquarists (From the epidemiological aspect it has been proven that the quarists .M. marinum infections. It should be considered as a possible threat to humans reporting close contact with this environment and may be prevented by the use of waterproof gloves by persons with acute or chronic open skin lesions.With regard to health, it is important that many NTM species classified as potentially pathogenic survive not only in the water environment, but also in infected fish. Contact zoonosis may occur particularly in risk groups such as aquaculture and fishery professionals, fish processors, ornamental fish hobbyists, and also consumers. The diagnosis of infections is usually hampered by the unfamiliarity of clinicians with disease agents derived from aquatic species. Fish tank exposure is the source of most cases of cutaneous