What Factors Predict Conversion to THA After Arthroscopy?
Failure of hip preservation to alleviate symptoms potentially subjects the patient to reoperation or conversion surgery to THA, adding recovery time, risk, and cost. A risk calculator using an algorithm that can predict the likelihood that a patient who undergoes arthroscopic hip surgery will undergo THA within 2 years would be helpful, but to our knowledge, no such tool exists. (1) Are there preoperative and intraoperative variables at the time of hip arthroscopy associated with subsequent conversion to THA? (2) Can these variables be used to develop a predictive tool for conversion to THA? All patients undergoing arthroscopy from January 2009 through December 2011 were registered in our longitudinal database. Inclusion criteria for the study group were patients undergoing hip arthroscopy for a labral tear, who eventually had conversion surgery to THA. Patients were compared with a control group of patients who underwent hip arthroscopy for a labral tear but who did not undergo conversion surgery to THA during the same study period. Of the 893 who underwent surgery during that time, 792 (88.7%) were available for followup at a minimum of 2 years (mean, 31.1 ± 8.1 years) and so were considered in this analysis. Multivariate regression analyses of 41 preoperative and intraoperative variables were performed. Using the results of the multivariate regression, we developed a simplified calculator that may be helpful in counseling a patient regarding the risk of conversion to THA after hip arthroscopy. Variables simultaneously associated with conversion to THA in this model were older age (rate ratio, 1.06; 95% CI, 1.03-1.08; p < 0.0001), lower preoperative modified Harris hip score (rate ratio [RR], 0.98; 95% CI, 0.96-0.99; p = 0.0003), decreased femoral anteversion (RR, 0.97; 95% CI, 0.94-0.99; p = 0.0111), revision surgery (RR, 2.4; 95% CI, 1.15-5.01; p = 0.0193), femoral Outerbridge Grades II to IV (Grade II: RR, 2.23 [95% CI, 1.11-4.46], p = 0.023; Grade III: RR, 2.17, [95% CI, 1.11-4.23], p = 0.024; Grade IV: RR, 2.96 [95% CI, 1.34-6.52], p = 0.007), performance of acetabuloplasty (RR, 1.83; 95% CI, 1.03-3.24; p = 0.038), and lack of performance of femoral osteoplasty (RR, 0.62; 95% CI, 0.36-1.06; p = 0.081). Using the results of the multivariate regression, we developed a simplified calculator that may be helpful in counseling a patient regarding the risk of conversion surgery to THA after hip arthroscopy. Multiple risk factors have been identified as possible risk factors for conversion to THA after hip arthroscopy. A weighted calculator based on our data is presented here and may be useful for predicting failure after hip arthroscopy for labral treatment. Determining the best candidates for hip preservation remains challenging; careful attention to long-term followup and identifying characteristics associated with successful outcomes should be the focus of further study. Level III, therapeutic study.


Macrophages are crucial for epithelial cell death and adipocyte repopulation during mammary gland involution.
Mammary gland development is dependent on macrophages, as demonstrated by their requirement during the expansion phases of puberty and pregnancy. Equally dramatic tissue restructuring occurs following lactation, when the gland regresses to a state that histologically resembles pre-pregnancy through massive programmed epithelial cell death and stromal repopulation. Postpartum involution is characterized by wound healing-like events, including an influx of macrophages with M2 characteristics. Macrophage levels peak after the initial wave of epithelial cell death, suggesting that initiation and execution of cell death are macrophage independent. To address the role of macrophages during weaning-induced mammary gland involution, conditional systemic deletion of macrophages expressing colony stimulating factor 1 receptor (CSF1R) was initiated just prior to weaning in the Mafia mouse model. Depletion of CSF1R(+) macrophages resulted in delayed mammary involution as evidenced by loss of lysosomal-mediated and apoptotic epithelial cell death, lack of alveolar regression and absence of adipocyte repopulation 7 days post-weaning. Failure to execute involution occurred in the presence of milk stasis and STAT3 activation, indicating that neither is sufficient to initiate involution in the absence of CSF1R(+) macrophages. Injection of wild-type bone marrow-derived macrophages (BMDMs) or M2-differentiated macrophages into macrophage-depleted mammary glands was sufficient to rescue involution, including apoptosis, alveolar regression and adipocyte repopulation. BMDMs exposed to the postpartum mammary involution environment upregulated the M2 markers arginase 1 and mannose receptor. These data demonstrate the necessity of macrophages, and implicate M2-polarized macrophages, for epithelial cell death during normal postpartum mammary gland involution.


Maintenance of Weight Loss After Initiation of Nutrition Training: A Randomized Trial.
Weight regain after successful weight loss interventions is common. To establish the efficacy of a weight loss maintenance program compared with usual care in obese adults. 2-group, parallel, randomized trial stratified by initial weight loss (<10 kg vs. ≥10 kg), conducted from 20 August 2012 to 18 December 2015. Outcome assessors were blinded to treatment assignment. (ClinicalTrials.gov: NCT01357551). 3 primary care clinics at the Veterans Affairs Medical Center in Durham and Raleigh, North Carolina. Obese outpatients (body mass index ≥30 kg/m2) who lost 4 kg or more of body weight during a 16-week, group-based weight loss program. The maintenance intervention, delivered primarily by telephone, addressed satisfaction with outcomes, relapse-prevention planning, self-monitoring, and social support. Usual care involved no contact except for study measurements. Primary outcome was mean weight regain at week 56. Secondary outcomes included self-reported caloric intake, walking, and moderate physical activity. Of 504 patients in the initial program, 222 lost at least 4 kg of body weight and were randomly assigned to maintenance (n = 110) or usual care (n = 112). Retention was 85%. Most patients were middle-aged white men. Mean weight loss during initiation was 7.2 kg (SD, 3.1); mean weight at randomization was 103.6 kg (SD, 20.4). Estimated mean weight regain was statistically significantly lower in the intervention (0.75 kg) than the usual care (2.36 kg) group (estimated mean difference, 1.60 kg [95% CI, 0.07 to 3.13 kg]; P = 0.040). No statistically significant differences in secondary outcomes were seen at 56 weeks. No adverse events directly attributable to the intervention were observed. Results may not generalize to other settings or populations. Dietary intake and physical activity were self-reported. Duration was limited to 56 weeks. An intervention focused on maintenance-specific strategies and delivered in a resource-conserving way modestly slowed the rate of weight regain in obese adults. Veterans Affairs Health Services Research and Development Service.


Training and credentialing in vascular laboratory diagnosis.
Physicians interpreting vascular laboratory studies require proper training and credentialing. It is suggested minimal training requirements include but, may not be limited to, the following: a medical license and knowledge of the fundamental concepts of vascular physiology, anatomy, and ultrasound physics. In addition, there should be evidence of training in vascular diagnostics beyond medical school, clinical experience in the treatment of vascular disease, supervised experience with specific numbers of vascular laboratory interpretations in the areas in which the physician wishes to interpret, and evidence of ongoing continuing medical education (CME) in noninvasive vascular diagnostics. Credentialing requirements are determined locally, but it is suggested that successful completion of the American Registry of Diagnostic Medical Sonographers' Registered Physician in Vascular Interpretation (RPVI) examination will provide evidence of core knowledge of vascular laboratory topics that is independent of medical or surgical specialty. Completion of the RPVI exam, completion of core training requirements, along with ongoing CME, is a basis for establishing minimal requirements for interpretation of vascular laboratory studies.


[Toward cultural assessment of grief and grief-related psychopathology].
Ways of dealing with bereavement and grief are influenced by the norms of one's cultural identity. Cultural assessment of bereavement and grief is therefore needed for a comprehensive evaluation of grief-related psychopathology and for negotiating appropriate treatment. Cultural aspects of bereavement and grief include cultural traditions related to death, bereavement, and mourning as well as help seeking and coping. To facilitate clinical exploration of cultural aspects of bereavement and grief, the authors propose a set of brief, person-centered, and open-ended questions as a draft supplementary module to the DSM-5 Cultural Formulation Interview. Three case vignettes show how cultural assessment of bereavement and grief may contribute to diagnosis, treatment, and enhancing rapport in patients who seek help following the loss of loved ones.


Production of freeze-dried human antihaemophilic cryoprecipitate.
Concentration of factor VIII from fresh plasma by cryoprecipitation remains the basis for preparation of products used to treat haemophilia A. This paper describes the preparation of a factor VIII concentrate from small plasma pools in transfusion centres with drying facilities. The dried concentrate from one litre of plasma dissolves very well in 50 or 100 ml of distilled water and contains around 500 IU per bottle. The specific activity per mg protein is 0.19 IU and the fibrinogen concentration is half that in frozen cryoprecipitate. This method of drying causes no appreciable loss in the factor VIIIC activity and little denaturation as shown by the factor-VIII-related antigen/factor VIIIC ratio of 1.7.


Predicting response to epigenetic therapy.
Drugs targeting the epigenome are new promising cancer treatment modalities; however, not all patients receive the same benefit from these drugs. In contrast to conventional chemotherapy, responses may take several months after the initiation of treatment to occur. Accordingly, identification of good pretreatment predictors of response is of great value. Many clinical parameters and molecular targets have been tested in preclinical and clinical studies with varying results, leaving room for optimization. Here we provide an overview of markers that may predict the efficacy of FDA- and EMA-approved epigenetic drugs.


Climatic controls of decomposition drive the global biogeography of forest-tree symbioses.
The identity of the dominant root-associated microbial symbionts in a forest determines the ability of trees to access limiting nutrients from atmospheric or soil pools1,2, sequester carbon3,4 and withstand the effects of climate change5,6. Characterizing the global distribution of these symbioses and identifying the factors that control this distribution are thus integral to understanding the present and future functioning of forest ecosystems. Here we generate a spatially explicit global map of the symbiotic status of forests, using a database of over 1.1 million forest inventory plots that collectively contain over 28,000 tree species. Our analyses indicate that climate variables-in particular, climatically controlled variation in the rate of decomposition-are the primary drivers of the global distribution of major symbioses. We estimate that ectomycorrhizal trees, which represent only 2% of all plant species7, constitute approximately 60% of tree stems on Earth. Ectomycorrhizal symbiosis dominates forests in which seasonally cold and dry climates inhibit decomposition, and is the predominant form of symbiosis at high latitudes and elevation. By contrast, arbuscular mycorrhizal trees dominate in aseasonal, warm tropical forests, and occur with ectomycorrhizal trees in temperate biomes in which seasonally warm-and-wet climates enhance decomposition. Continental transitions between forests dominated by ectomycorrhizal or arbuscular mycorrhizal trees occur relatively abruptly along climate-driven decomposition gradients; these transitions are probably caused by positive feedback effects between plants and microorganisms. Symbiotic nitrogen fixers-which are insensitive to climatic controls on decomposition (compared with mycorrhizal fungi)-are most abundant in arid biomes with alkaline soils and high maximum temperatures. The climatically driven global symbiosis gradient that we document provides a spatially explicit quantitative understanding of microbial symbioses at the global scale, and demonstrates the critical role of microbial mutualisms in shaping the distribution of plant species.


Alcohol use by pedestrians who are struck by motor vehicles: how drinking influences behaviors, medical management, and outcomes.
Injuries to pedestrians struck by motor vehicles represent a significant public health hazard in large cities. The purpose of this study is to investigate the demographics of alcohol users who are struck by motor vehicles and to assess the effects of alcohol on pedestrian crossing patterns, medical management, and outcomes. Data were prospectively collected between December 2008 to September 2010 on all pedestrians who presented to a Level I trauma center after being struck by a motor vehicle. Variables were obtained by interviewing patients, scene witnesses, first responders, and medical records. Pedestrians who used alcohol were less likely to cross the street in the crosswalk with the signal (22.6% vs. 64.7%) and more likely to cross either in the crosswalk against the signal (22.6% vs. 12.4%) or midblock (54.8% vs. 22.8%). Alcohol use was associated with more initial computed tomography imaging studies compared with no alcohol involvement. Alcohol use was associated with a higher Injury Severity Score (8.82 vs. 4.85; p < 0.001) and hospital length of stay (3.89 days vs. 1.82 days; p < 0.001) compared with those with no alcohol involvement. Patients who used alcohol had a lower average Glasgow Coma Scale score (13.80 vs. 14.76; p < 0.001) and a higher rate of head and neck, face, chest, abdomen, and extremity/pelvic girdle injuries (based on Abbreviated Injury Scale) than those with no alcohol involvement. Alcohol use is a significant risk factor for pedestrians who are struck by motor vehicles. These patients are more likely to cross the street in an unsafe manner and sustain more serious injuries. Traffic safety and injury prevention programs must address irresponsible alcohol use by pedestrians.


Do All Switches Cost the Same? Reliability of Language Switching and Mixing Costs.
The current study examined the reliability and consistency of switching and mixing costs in the language and the color-shape tasks in three pre-existing data sets, to assess whether they are equally well suited for the study of individual differences. Specifically, we considered if the language task is as reliable as the color-shape task - an important question given the wide use of language switching tasks but little information available to address this question. Switching costs had low to moderate reliability and internal consistency, and these were similar for the language and the color-shape tasks. Mixing costs were more reliable in the language task than in the color-shape task when tested twice on the same day and trended in the same direction when tested a week apart. In addition, mixing costs were larger and more consistent than switching costs in all data sets and they were also were more reliable than switching costs in the language task when tested on the same day. These results reveal the language task to be as good as the color-shape task for measuring switching and mixing ability. Low variability of switching costs may decrease their reliability and consistency, in turn interfering with the chance of detecting cross task correlations. We advocate for exploring procedures to increase the variability of switching costs, which might increase reliability and consistency of these measures, and improve the ability to determine if bilingual language use relies on cognitive mechanisms that overlap with those underlying nonlinguistic multi-tasking.


A new basal sauropod dinosaur from the middle Jurassic of Niger and the early evolution of sauropoda.
The early evolution of sauropod dinosaurs is poorly understood because of a highly incomplete fossil record. New discoveries of Early and Middle Jurassic sauropods have a great potential to lead to a better understanding of early sauropod evolution and to reevaluate the patterns of sauropod diversification. A new sauropod from the Middle Jurassic of Niger, Spinophorosaurus nigerensis n. gen. et sp., is the most complete basal sauropod currently known. The taxon shares many anatomical characters with Middle Jurassic East Asian sauropods, while it is strongly dissimilar to Lower and Middle Jurassic South American and Indian forms. A possible explanation for this pattern is a separation of Laurasian and South Gondwanan Middle Jurassic sauropod faunas by geographic barriers. Integration of phylogenetic analyses and paleogeographic data reveals congruence between early sauropod evolution and hypotheses about Jurassic paleoclimate and phytogeography. Spinophorosaurus demonstrates that many putatively derived characters of Middle Jurassic East Asian sauropods are plesiomorphic for eusauropods, while South Gondwanan eusauropods may represent a specialized line. The anatomy of Spinophorosaurus indicates that key innovations in Jurassic sauropod evolution might have taken place in North Africa, an area close to the equator with summer-wet climate at that time. Jurassic climatic zones and phytogeography possibly controlled early sauropod diversification.


Ferroportin is a manganese-responsive protein that decreases manganese cytotoxicity and accumulation.
Although manganese (Mn) is an essential trace element for human development and growth, chronic exposure to excessive Mn levels can result in psychiatric and motor disturbances, referred to as manganism. However, there are no known mechanism(s) for efflux of excess Mn from mammalian cells. Here, we test the hypothesis that the cytoplasmic iron (Fe) exporter ferroportin (Fpn) may also function as a Mn exporter to attenuate Mn toxicity. Using an inducible human embryonic kidney (HEK293T) cell model, we examined the influence of Fpn expression on Mn-induced cytotoxicity and intracellular Mn concentrations. We found that induction of an Fpn-green fluorescent protein fusion protein in HEK293T cells was cytoprotective against several measures of Mn toxicity, including Mn-induced cell membrane leakage and Mn-induced reductions in glutamate uptake. Fpn-green fluorescent protein mediated cytoprotection correlated with decreased Mn accumulation following Mn exposure. Thus, Fpn expression reduces Mn toxicity concomitant with reduced Mn accumulation. To determine if mammalian cells may utilize Fpn in response to increased intracellular Mn concentrations and toxicity, we assessed endogenous Fpn levels in Mn-exposed HEK293T cells and in mouse brain in vivo. We find that 6 h of Mn exposure in HEK293T cells is associated with a significant increase in Fpn levels. Furthermore, mice exposed to Mn showed an increase in Fpn levels in both the cerebellum and cortex. Collectively, these results indicate that (i) Mn exposure promotes Fpn protein expression, (ii) Fpn expression reduces net Mn accumulation, and (iii) reduces cytotoxicity associated with exposure to this metal.


Spore Trapping and Pathogenicity of Fungi in the Botryosphaeriaceae and Diaporthaceae Associated with Avocado Branch Canker in California.
Avocado branch canker in California is caused by a complex of fungal species in the families Botryosphaeriaceae and Diaporthaceae. As the popularity of avocado fruit increases, California growers are under pressure to increase their productivity in order to compete with imports. One way to increase production is through high-density planting, which entails intense canopy management, possibly leaving the trees vulnerable to infection through pruning wounds. A spore trap study was undertaken to determine the seasonal spore discharge of Botryosphaeriaceous and Diaporthaceous fungi. Based on colony counts, the highest population of Botryosphaeriaceous fungi (68%) occurred during or soon after precipitation events, which coincided with the winter months of December, January, and February. The spring and fall seasons had lower numbers of spores trapped (at 13 and 17%, respectively), with few spores trapped in the summer season. For members of the Diaporthaceae family, spores trapped were almost evenly split between winter and fall seasons (50 and 49%, respectively), with few to no spores trapped in the spring and summer seasons. A pathogenicity test of six fungi of Botryosphaeriaceae and one fungus of Diaporthaceae was conducted in the greenhouse. Internal plant vascular lesion lengths resulting from inoculation with any of the seven fungal species differed significantly from the noninoculated control. These studies suggest that pruning during the drier parts of the year would minimize infection by fungi in the Botryosphaeriaceae and Diaporthaceae families.


Analysis of Risk Factors for Severe Acute Respiratory Infection and Pneumonia and among Adult Patients with Acute Respiratory Illness during 2011-2014 Influenza Seasons in Korea.
The World Health Organization recommends the surveillance of influenza-like illness (ILI) and severe acute respiratory infection (SARI) to respond effectively to both seasonal influenza epidemics and pandemics. In Korea, the "Hospital-based Influenza Morbidity and Mortality (HIMM)" surveillance system has been operated to monitor ILI and SARI occurrences. A multi-center prospective observational study was conducted. Adult patients with acute respiratory infection (ARI) were enrolled during the 2011-12, 2012-2013, and 2013-2014 influenza seasons at the 10 university hospitals using the HIMM surveillance system. With respect to SARI and pneumonia development, risk profiles were analyzed in patients with ARI in Korea. A total of 5,459 cases were eligible for this analysis. Among 5,459 cases with ARI, 2,887 cases (52.9%) were identified that they had influenza infection. Among enrolled cases, 750 cases belonged to the SARI group, while 4,709 cases belonged to the non-SARI group. With respect to pneumonia development, 317 cases were accompanied by pneumonia, and 5,142 cases were not. Multivariate analyses revealed that the following factors were associated with an increased risk of SARI: Old age (≥65 years) (odds ratio [OR] 2.69, 95% confidence interval [CI] 2.2-3.32), chronic heart disease (CHD) (OR 2.24, 95% CI 1.68-2.98), cerebrovascular disease (CVD) (OR 1.49, 95% CI 1.05-2.10), chronic obstructive pulmonary disease (COPD) (OR 2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62-3.36), chronic kidney disease (CKD) (OR 2.62, 95% CI 1.73-3.99), chronic liver disease (OR 1.71, 95% CI 1.04-2.81), and autoimmune diseases (OR 2.53, 1.57-4.08). Multivariate analyses revealed that the following factors were independent risk factors for pneumonia development: Old age (≥65 years) (OR 5.71, 95% CI 4.10-7.94), CHD (OR 1.54, 95% CI 1.07-2.22), COPD (OR 2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62-3.36), CKD (OR 2.62, 95% CI 1.73-3.99), immunocompromised conditions (OR 3.12, 95% CI 1.47-6.62), and autoimmune diseases (OR 3.35, 95% CI 1.79-6.27). The risk of SARI and pneumonia was increased by the number of concurrent chronic medical conditions. The risk of SARI and pneumonia development among adult patient with ARI was significantly increased by the presence or number of concurrent chronic medical conditions in Korea.


Mie light scattering calculations for an Indian age-related nuclear cataract with a high density of multilamellar bodies.
Multilamellar bodies (MLBs) are lipid-coated spheres (1-4 microm in diameter) found with greater frequency in the nuclear region of human age-related cataracts compared with human transparent lenses. Mie light scattering calculations have demonstrated that MLBs are potential sources of forward light scattering in human age-related nuclear cataracts due to their shape, size, frequency, and cytoplasmic contents, which often differ in refractive index from their surroundings. Previous studies have used data from several non-serial tissue sections viewed by light microscopy to extrapolate a volume and have assumed that MLBs are random in distribution. Currently, confocal microscopy is being used to examine actual tissue volumes from age-related nuclear cataracts and transparent lenses collected in India to confirm MLB shape, size, frequency, and randomness. These data allow Mie scattering calculations to be done with directly observed MLBs in intact tissue. Whole Indian donor lenses and Indian lens nuclei after extracapsular cataract extraction were immersion-fixed in 10% formalin for 24 h and in 4% paraformaldehyde for 24 h before sectioning with a Vibratome. The 160 microm thick sections were stained for 24 h in the lipid dye DiI (1,1'-dilinoleyl-3,3,3',3' tetramethylindocarbocyanine, 4-chlorobenzenesulfonate), washed, stabilized in Permount under coverslips and examined with a Zeiss LSM 510 confocal microscope. Individual volumes of tissue (each typically 500,000 microm(3)) were examined using a plan-apochromat 63X oil (NA=1.4) lens. Other lenses were prepared for electron microscopy and histological examination using previously described procedures. Analysis of tissue volumes within Indian age-related nuclear cataracts and transparent lenses has confirmed that most MLBs are 1-4 microm in diameter and typically spherical with some occurring as doublets or in clusters. Most Indian cataracts and transparent lenses are similar to samples obtained in the United States. One cataract contained as many as 400,000 MLBs per mm(3) -100 times more than in cataracts collected in the United States. Pairwise distribution analysis has revealed that MLBs even in this exceptional case are found with a distribution that appears to be random. Mie calculations indicate that more than 90% of the incident light could be scattered by the high density of MLBs. An important finding was that one advanced Indian cataract contained many more MLBs than cataracts examined from India and previously from the United States. This indicates that specific conditions or susceptibilities may exist that promote the formation of excessive MLBs. Based on the extremely high frequency, as well as their spherical shape, large size, and apparent random distribution, the MLBs are predicted according to Mie light scattering calculations to cause high amounts of forward scattering sufficient to produce nuclear opacity.


Dissociable cortical pathways for qualitative and quantitative mechanisms in the face inversion effect.
Humans' ability to recognize objects is remarkably robust across a variety of views unless faces are presented upside-down. Whether this face inversion effect (FIE) results from qualitative (distinct mechanisms) or quantitative processing differences (a matter of degree within common mechanisms) between upright and inverted faces has been intensely debated. Studies have focused on preferential responses to faces in face-specific brain areas, although face recognition also involves nonpreferential responses in non-face-specific brain areas. By using dynamic causal modeling with Bayesian model selection, here we show that dissociable cortical pathways are responsible for qualitative and quantitative mechanisms in the FIE in the distributed network for face recognition. When faces were upright, the early visual cortex (VC) and occipital and fusiform face areas (OFA, FFA) suppressed couplings to the lateral occipital cortex (LO), a primary locus of object processing. In contrast, they did not inhibit the LO when faces were inverted but increased couplings to the intraparietal sulcus, which has been associated with visual working memory. Furthermore, we found that upright and inverted face processing together involved the face network consisting of the VC, OFA, FFA, and inferior frontal gyrus. Specifically, modulatory connectivity within the common pathways (VC-OFA), implicated in the parts-based processing of faces, strongly correlated with behavioral FIE performance. The orientation-dependent dynamic reorganization of effective connectivity indicates that the FIE is mediated by both qualitative and quantitative differences in upright and inverted face processing, helping to resolve a central debate over the mechanisms of the FIE.


Scanning holographic microscopy with spatially incoherent sources: reconciling the holographic advantage with the sectioning advantage.
A new mode of operation of scanning holographic microscopy that combines the two seemingly incompatible holographic advantage and axial sectioning advantage is proposed and demonstrated. Temporally modulated Fabry-Perot fringes are scanned in a two-dimensional raster over the specimen. With a spatially coherent (point) source, the fringes are spatially nonlocalized and encode the entire three-dimensional volume of the specimen in the form of a single-sideband in-line Fresnel hologram. With an extended spatially incoherent source the fringes are axially localized and select the modulated information from a specific axial plane only. The holographic advantage and the sectioning advantage can thus be achieved with the same scanning holographic setup using different source sizes.


Can we use a functional trait to construct a generalized model for ungulate populations?
Ecologists have long desired predictive models that allow inference on population dynamics, where detailed demographic data are unavailable. Integral projection models (IPMs) allow both demographic and phenotypic outcomes at the level of the population to be predicted from the distribution of a functional trait, like body mass. In species where body mass markedly influences demographic rates, as is the rule among mammals, then IPMs provide not only opportunity to assess the population responses to a given environment, but also improve our understanding of the complex interplay between traits and demographic outcomes. Here, we develop a body-mass-based approach to constructing generalized, predictive IPMs for species of ungulates covering a broad range of body size (25-400 kg). Despite our best efforts, we found that a reliable and general, functional, trait-based model for ungulates was unattainable even after accounting for among-species variation in both age at first reproduction and litter size. We attribute this to the diversity of reproductive tactics among similar-sized species of ungulates, and to the interplay between density-dependent and environmental factors that shape demographic parameters independent of mass at the local scale. These processes thus drive population dynamics and cannot be ignored. Environmental context generally matters in population ecology, and our study shows this may be the case for functional traits in vertebrate populations.


Resistance vs resilience to Alzheimer disease: Clarifying terminology for preclinical studies.
Preventing or delaying Alzheimer disease (AD) through lifestyle interventions will come from a better understanding of the mechanistic underpinnings of (1) why a significant proportion of elderly remain cognitively normal with AD pathologies (ADP), i.e., amyloid or tau; and (2) why some elderly individuals do not have significant ADP. In the last decades, concepts such as brain reserve, cognitive reserve, and more recently brain maintenance have been proposed along with more general notions such as (neuro)protection and compensation. It is currently unclear how to effectively apply these concepts in the new field of preclinical AD specifically separating the 2 distinct mechanisms of coping with pathology vs avoiding pathology. We propose a simplistic conceptual framework that builds on existing concepts using the nomenclature of resistance in the context of avoiding pathology, i.e., remaining cognitively normal without significant ADP, and resilience in the context of coping with pathology, i.e., remaining cognitively normal despite significant ADP. In the context of preclinical AD studies, we (1) define these concepts and provide recommendations (and common scenarios) for their use; (2) discuss how to employ this terminology in the context of investigating mechanisms and factors; (3) highlight the complementarity and clarity they provide to existing concepts; and (4) discuss different study designs and methodologies. The application of the proposed framework for framing hypotheses, study design, and interpretation of results and mechanisms can provide a consistent framework and nomenclature for researchers to reach consensus on identifying factors that may prevent ADP or delay the onset of cognitive impairment.


Evolution of restraint in a structured rock-paper-scissors community.
It is not immediately clear how costly behavior that benefits others evolves by natural selection. By saving on inherent costs, individuals that do not contribute socially have a selective advantage over altruists if both types receive equal benefits. Restrained consumption of a common resource is a form of altruism. The cost of this kind of prudent behavior is that restrained individuals give up resources to less-restrained individuals. The benefit of restraint is that better resource management may prolong the persistence of the group. One way to dodge the problem of defection is for altruists to interact disproportionately with other altruists. With limited dispersal, restrained individuals persist because of interaction with like types, whereas it is the unrestrained individuals that must face the negative long-term consequences of their rapacity. Here, we study the evolution of restraint in a community of three competitors exhibiting a nontransitive (rock-paper-scissors) relationship. The nontransitivity ensures a form of negative feedback, whereby improvement in growth of one competitor has the counterintuitive consequence of lowering the density of that improved player. This negative feedback generates detrimental long-term consequences for unrestrained growth. Using both computer simulations and evolution experiments with a nontransitive community of Escherichia coli, we find that restrained growth can evolve under conditions of limited dispersal in which negative feedback is present. This research, thus, highlights a set of ecological conditions sufficient for the evolution of one form of altruism.


Oxidative stress in rat testis and epididymis under intermittent hypobaric hypoxia: protective role of ascorbate supplementation.
Hypobaric hypoxia (HH), an environmental condition of high altitude encountered by mountaineers, miners, and observatory, rural health, border patrol, and rural education workers, jeopardizes normal physiologic functions in humans. The present study was conducted to evaluate the effects of intermittent HH (IHH; equivalent to 4600 m above mean sea level) on oxidative stress and the protective role of dietary ascorbic acid on rat testis and epididymis. Ten-week-old male Wistar rats were assigned to 1 of 6 groups: 1) normobaric (Nx), 2) Nx + physiologic solution (Nx + PS), 3) Nx + ascorbic acid (Nx + AA), 4) IHH, 5) IHH + PS, or 6) IHH + AA. Animals subjected to IHH were exposed for 96 hours followed by normobaric conditions for 96 hours for a total of 32 days. The control groups (2 and 5) were injected with doses of PS, and the treated groups (3 and 6) were injected with doses of AA (10 mg x kg(-1) body weight) at an interval of 96 hours. Rats were sacrificed on day 32 after initiation of the protocol. The testis and epididymis were collected to determine the activity and expression of glutathione reductase and the levels of lipid peroxide formation. An epididymal sperm count was also performed in each animal. The results of this study revealed that IHH induced lipid peroxidation, a reduction in glutathione reductase activity in testis and epididymis, and a significant decrease in epididymal sperm count. Treatment with AA prevented these changes. In conclusion, AA was capable of decreasing oxidative stress in testis and epididymis under IHH. This protection by AA of the IHH-induced lipid peroxidation can be explained in part by the preservation of glutathione reductase activity in these organs.


Effect of topically applied lipids on surfactant-irritated skin.
Moisturizers are used daily by many people to alleviate symptoms of dry skin. All of them contain lipids. It has been suggested that topically applied lipids may interfere with the structure and function of the permeability barrier. The influence of a single application of nine different lipids on normal skin and skin irritated by sodium lauryl sulphate (SLS) was studied in 21 healthy subjects. Parameters assessed were visible signs of irritation, and objectively measured cutaneous blood flow and transepidermal water loss (TEWL). The substances tested were hydrocortisone, petrolatum, fish oil, borage oil, sunflower seed oil, canola oil, shea butter, and fractions of unsaponifiable lipids from canola oil and shea butter. Water was included as a control. On normal skin, no significant differences in the effects of the test substances were found, whereas significant differences were observed when they were applied to SLS-irritated skin. The visible signs of SLS-induced irritation were significantly less pronounced after treatment with the sterol-enriched fraction from canola oil than after treatment with water. This fraction, and hydrocortisone, reduced cutaneous blood flow. Furthermore, application of hydrocortisone, canola oil, and its sterol-enriched fraction, resulted in significantly lower TEWL than with water. The other lipids had no effect on the degree of irritation. In conclusion, lipids commonly used in moisturizers may reduce skin reactions to irritants. Previous studies have shown that, in barrier perturbed skin, the synthesis of sterols is increased. The observed effects of canola oil and its fraction of unsaponifiable lipids on SLS-induced irritation suggest the possibility that they assisted the skin in supplying the damaged barrier with adequate lipids.


Gradual release of sperm bound sex-peptide controls female postmating behavior in Drosophila.
In many female insects, peptides transferred in the seminal fluid induce postmating responses (PMR), such as a drastic increase of egg laying and reduction of receptivity (readiness to mate). In Drosophila melanogaster, sex-peptide (SP) elicits short- and long-term PMR, but only the latter in the presence of stored sperm (sperm effect). Here, we elucidate the interaction between SP and sperm by immunofluorescence microscopy. Transgenic males were used to study the effects of SP modification on the PMR of females in vivo. We report that SP binds to sperm with its N-terminal end. In females, the C-terminal part of SP known to be essential to induce the PMR is gradually released from stored sperm by cleavage at a trypsin cleavage site, thus prolonging the PMR. These findings are confirmed by analyzing the PMR elicited by males containing transgenes encoding modified SPs. SP lacking the N-terminal end cannot bind, and SP without the trypsin cleavage site binds permanently to sperm. By binding to sperm tails, SP prolongs the PMR. Thus, besides a carrier for genetic information, sperm is also the carrier for SP. Binding to sperm may protect the peptide from degradation by proteases in the hemolymph and, thus, prolong its half-life. Longer sperm tails may transfer more SP and thus increase the reproductive fitness of the male. We suggest that this could explain the excessive length of sperm tails in some Drosophila species.


Importance and feasibility of an adapted set of implementation strategies in schools.
Implementation strategies are methods or techniques used to enhance the adoption, implementation, and sustainment of a new program or practice. Recent studies have facilitated implementation strategy prioritization by mapping strategies based on their feasibility and importance, but these efforts have not been replicated across distinct service delivery contexts. The aim of the current project was to evaluate the feasibility and importance of an education-adapted taxonomy of implementation strategies and to directly compare feasibility and importance ratings to the original Expert Recommendations for Implementing Change (ERIC) taxonomy, the leading compilation of implementation strategies in healthcare. A sample of 200 school-based consultants who support social, emotional, and mental health services provided ratings of feasibility and importance for each of the 75 strategies included in the adapted School Implementation Strategies, Translating ERIC Resources (SISTER) compilation. Results identified strategies rated as: (a) both feasible and important, (b) important but not feasible, (c) feasible but not important, and (d) neither feasible nor important. When mapped onto scatterplots using feasibility and importance ratings, comparison of ERIC and SISTER ratings indicated that approximately one third of the strategies shifted from one quadrant of the feasibility and importance axis to another. Findings demonstrate the value of efforts to adapt and generalize existing implementation products to novel service settings, such as schools. Additionally, findings assist implementation researchers and practitioners in prioritizing the selection of actionable and practically relevant implementation strategies to advance the quality of school mental health services.


The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-Cell leukemia/lymphoma.
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with dismal prognosis, and no optimal therapy has been developed. We tested the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, KM2760, to develop a novel immunotherapy for this refractory tumor. In the presence of peripheral blood mononuclear cells (PBMCs) from healthy adult donors, KM2760 induced CCR4-specific antibody-dependent cellular cytotoxicity (ADCC) against CCR4-positive ATLL cell lines and primary tumor cells obtained from ATLL patients. We next examined the KM2760-induced ADCC against primary ATLL cells in an autologous setting. Antibody-dependent cellular cytotoxicity mediated by autologous effector cells was generally lower than that mediated by allogeneic control effector cells. However, a robust ADCC activity was induced in some cases, which was comparable with that mediated by allogeneic effector cells. It suggests that the ATLL patients' PBMCs retain substantial ADCC-effector function, although the optimal conditions for maximal effect have not yet been determined. In addition, we also found a high expression of FoxP3 mRNA and protein, a hallmark of regulatory T cells, in ATLL cells, indicating the possibility that ATLL cells originated from regulatory T cells. KM2760 reduced FoxP3 mRNA expression in normal PBMCs along with CCR4 mRNA by lysis of CCR4+ T cells in vitro. Our data suggest not only that the CCR4 molecule could be a suitable target for the novel antibody-based therapy for patients with ATLL but also that KM2760 may induce effective tumor immunity by reducing the number of regulatory T cells.


[Genetic neuroimaging].
Both genetics and neuroimaging have developed rapidly in the past few years. Recently the two methods have been combined in a new technique called genetic neuroimaging. To provide an overview of the backgrounds and the possibilities of genetic neuroimaging. In this review we first discuss genetic and neuroimaging research methods that are currently in use and then discuss their synergistic combination. Finally we analyse two recent cases in which genetic neuroimaging was used to study an individual's vulnerability to affective and psychotic symptoms. results Results are very promising, particularly with regard to research into vulnerability to psychiatric disorders. It is expected that the use of genetic neuroimaging procedures will increase. Genetic and neuroimaging methods are often exceedingly complex, which means they cannot be easily accessed by the general public. Genetic neuroimaging is an important method to study the relation between candidate genes and variations in cognitive and emotional functioning and the vulnerability to psychiatric disorders.


Finding stationary subspaces in multivariate time series.
Identifying temporally invariant components in complex multivariate time series is key to understanding the underlying dynamical system and predict its future behavior. In this Letter, we propose a novel technique, stationary subspace analysis (SSA), that decomposes a multivariate time series into its stationary and nonstationary part. The method is based on two assumptions: (a) the observed signals are linear superpositions of stationary and nonstationary sources; and (b) the nonstationarity is measurable in the first two moments. We characterize theoretical and practical properties of SSA and study it in simulations and cortical signals measured by electroencephalography. Here, SSA succeeds in finding stationary components that lead to a significantly improved prediction accuracy and meaningful topographic maps which contribute to a better understanding of the underlying nonstationary brain processes.


Superior discrimination of speech pitch and its relationship to verbal ability in autism spectrum disorders.
Whilst hypersensitivity to pitch information appears to be characteristic of many individuals with autism spectrum disorders little is known about the implications of such a tendency for language acquisition and development. Discrimination of systematically varied pitch differences between pairs of words, nonwords, and nonspeech pitch contour analogues was assessed in children with autism spectrum disorders (ASD) and matched controls. The findings revealed superior performance in ASD, although, like controls, discrimination of pitch in speech stimuli was poorer in this group than for nonspeech stimuli. Whilst it was hypothesized that enhanced processing of speech pitch would correlate negatively with receptive language skills in ASD, the findings did not fully support this, and enhanced discrimination skills were observed in individuals without significant language impairment. The implications of these findings for understanding heterogeneity of language ability in ASD are discussed.


The application of monolayer studies in the understanding of liposomal formulations.
The study of surfactant monolayers is certainly not a new technique, but the application of monolayer studies to elucidate controlling factors in liposome design remains an underutilised resource. Using a Langmuir-Blodgett trough, pure and mixed lipid monolayers can be investigated, both for their interactions within the monolayer, and for interfacial interactions with drugs in the aqueous sub-phase. Despite these monolayers effectively being only half a bilayer, with a flat rather than curved structure, information from these studies can be effectively translated into liposomal systems. Here we outline the background, general protocols and application of Langmuir studies with a focus on their application in liposomal systems. A range of case studies are discussed which show how the system can be used to support its application in the development of liposome drug delivery. Examples include investigations into the effect of cholesterol within the liposome bilayer, understanding effective lipid packaging within the bilayer to promote water soluble and poorly soluble drug retention, the effect of alkyl chain length on lipid packaging, and drug-monolayer electrostatic interactions that promote bilayer repackaging.


The Assessment of Hepatosteatosis in Living-Donor Liver Transplant: Comparison of Liver Attenuation Index and Histopathologic Results.
The purpose of the study was to determine the diagnostic value of computed tomography densitometry in the quantification of hepatosteatosis. Fifty-one potential liver donors, ranging in age from 19 to 52 years (mean age: 32.4 years ± 10.2), participated in the study. The mean hepatic attenuation and mean splenic attenuation were determined using regions of interest measurements. The difference between the mean hepatic attenuation and mean splenic attenuation (or liver attenuation index), with liver attenuation index = mean hepatic attenuation - mean splenic attenuation were calculated. Computed tomography densitometric parameters were correlated with histopathologic results. From the histopathologic analysis, the degree of macrovesicular hepatosteatosis was 0% to 8% (mean: 1.1% ± 2%). Seven donors (13.7%) had a degree of macrovesicular steatosis of > 5%, and 12 donors (23.5%) had ≥ 2%. Of the 29 normal donors with histopathologic verification, computed tomography densitometry predicted ≤ 5% of the hepatosteatosis in 27 donors, and ≤ 2% hepatosteatosis in 2 subjects. The liver attenuation index was significantly correlated to the histopathologic results. The mathematical relation between liver attenuation index and the degree of histopathologic hepatosteatosis was calculated using the least-squares methods, which provided quadratic polynomials. Computed tomography densitometry is a rapid, robust, noninvasive technique for the assessment of hepatosteatosis. When used in conjunction with clinically stable reference measurements of spleen, the density measurements of liver correctly predicted the presence of fatty infiltration with significant sensitivity (77%) and specificity (75%). This technique, which was refined during the course of our liver transplant program, minimizes the need for highly invasive percutaneous liver biopsies.


On the formation and structure of nanometric polyhedral foams: toward the dry limit.
High surface area, high porosity, nanometric polygonal silica foams with hierarchically connected and uniformly sized pore systems are reported here. We observe a remarkable increase in foam cell sizes from mesoscopic to macroscopic dimensions upon swelling the self-assembled template with oil. The resultant structures resemble classical macroscopic soap foams and display, among other features, Plateau borders and volume fractions approaching the dry limit of 100%. In well-developed foams of this kind, dimensionally isometric polyhedral cells are connected by relatively short, flat cylindrical mesopores through polyhedral faces and micropores through the walls. For one sample, with approximately 75 nm diameter primary foam cells, we infer three separate sets of cell-connecting mesopores puncturing tetragonal, pentagonal, and hexagonal faces of the component polyhedra. A multiple step model of foam formation is discussed where an organic silica precursor progressively hydrolyzes and condenses as a growing flexible shell from the core-corona interface of oil-swollen triblock copolymer micelles or microemulsion droplets, inducing a clouding phenomena in the otherwise stabilizing poly(ethylene oxide) chains, leading to aggregation, deformation, and jamming to high volume fractions.


Stress-activated protein kinases are negatively regulated by cell density.
Stimulation by UV irradiation, TNFalpha, as well as PDGF or EGF activates the JNK/SAPK signalling pathway in mouse fibroblasts. This results in the phosphorylation of the N-terminal domain of c-Jun, increasing its transactivation potency. Using an antibody that specifically recognizes c-Jun phosphorylated at Ser63, we show that culture confluency drastically inhibited c-Jun N-terminal phosphorylation due to the inhibition of the JNK/SAPK pathway. Transfection experiments demonstrate that the inhibition occurs at the same level as, or upstream of, the small G-proteins cdc42 and Rac1. In contrast, the classical MAPK pathway was insensitive to confluency. The inhibition of JNK/SAPK activation depended on the integrity of the actin microfilament network. These results were confirmed and extended in monolayer wounding experiments. After PDGF, EGF or UV stimulation, c-Jun was predominantly phosphorylated in cells bordering the wound, which are the cells that move to occupy the wounded area. Thus, modulation of the stress-dependent signal cascade by confluency will restrict c-Jun N-terminal phosphorylation in response to mitogenic or chemotactic agents to cells that border a wounded area.


The application of systems thinking in health: why use systems thinking?
This paper explores the question of what systems thinking adds to the field of global health. Observing that elements of systems thinking are already common in public health research, the article discusses which of the large body of theories, methods, and tools associated with systems thinking are more useful. The paper reviews the origins of systems thinking, describing a range of the theories, methods, and tools. A common thread is the idea that the behavior of systems is governed by common principles that can be discovered and expressed. They each address problems of complexity, which is a frequent challenge in global health. The different methods and tools are suited to different types of inquiry and involve both qualitative and quantitative techniques. The paper concludes by emphasizing that explicit models used in systems thinking provide new opportunities to understand and continuously test and revise our understanding of the nature of things, including how to intervene to improve people's health.


The cyclohedron test for finding periodic genes in time course expression studies.
The problem of finding periodically expressed genes from time course microarray experiments is at the center of numerous efforts to identify the molecular components of biological clocks. We present a new approach to this problem based on the cyclohedron test, which is a rank test inspired by recent advances in algebraic combinatorics. The test has the advantage of being robust to measurement errors, and can be used to ascertain the significance of top-ranked genes. We apply the test to recently published measurements of gene expression during mouse somitogenesis and find 32 genes that collectively are significant. Among these are previously identified periodic genes involved in the Notch/FGF and Wnt signaling pathways, as well as novel candidate genes that may play a role in regulating the segmentation clock. These results confirm that there are an abundance of exceptionally periodic genes expressed during somitogenesis. The emphasis of this paper is on the statistics and combinatorics that underlie the cyclohedron test and its implementation within a multiple testing framework.


Association of fibrinogen and coagulation factors VII and VIII with cardiovascular risk factors in the elderly: the Cardiovascular Health Study. Cardiovascular Health Study Investigators.
The cross-sectional correlates of three hemostatic factors--fibrinogen, factor VII, and factor VIII--were examined in the Cardiovascular Health Study, a population-based cohort study of 5,201 subjects over age 65 years. Subjects were recruited in 1989-1990 in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. In multivariate linear regression models, cardiac risk factors significantly associated with fibrinogen were current smoking, race, lipids, and white blood count. In women, alcohol use, obesity, physical activity, and insulin level were also significant, while in men hypertension was correlated. The significant correlates of factor VII were lipids and white blood count in men and estrogen use, alcohol use, race, lipids, insulin level, white blood count, and obesity in women. The independent correlates of factor VIII were insulin, glucose, and race in both sexes; low density lipoprotein cholesterol, white blood count, and diuretic use in men; and alcohol use in women. In multivariate models, factors known to be modifiable risk factors for cardiovascular disease accounted for more of the population variance of these hemostatic factors in women than in men, especially for factor VII. The hemostatic factors may mediate some effects of risk factors on disease, and this should be considered in longitudinal studies.


Viral host jumps: moving toward a predictive framework.
In order to predict pathogen emergence, we must distinguish between emergence phenomena that occur via different processes. Focusing on the appearance of viral pathogens in new host species, I outline a framework that uses specific molecular characteristics to rank virus families by their expected a priori ability to complete each of three steps in the emergence process (encounter, infection, and propagation). I then discuss the degree to which the patterns expected, based solely on molecular-level structural characteristics, agree with observations regarding the ability of animal viruses to infect humans. This approach yields predictions consistent with empirical observations regarding the ability of specific viral families to infect novel host species but highlights the need for consideration of other factors, such as the ecology of host interactions and the determinants of cellular susceptibility and permissivity to specific virus groups, when trying to predict the frequency with which a virus will encounter a novel host species or the probability of propagation within a novel host species once infection has occurred.


Impaired fear recognition and attentional set-shifting is associated with brain structural changes in alcoholic patients.
Alcoholic patients with multiple detoxifications/relapses show cognitive and emotional deficits. We performed structural magnetic resonance imaging and examined performance on a cognitive flexibility task (intra-extradimensional set shift and reversal; IED). We also presented subjects with fearful, disgust and anger facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n = 12) or singly detoxified patients (SDTx; n = 17) and social drinker controls (n = 31). Alcoholic patients were less able than controls to change their behavior in accordance with the changing of the rules in the IED and they were less accurate in recognizing fearful expressions in particular. They also showed lower gray matter volume compared with controls in frontal brain areas, including inferior frontal cortex (IFC) and insula that mediate emotional processing, inferior parietal lobule and medial frontal cortex that mediate attentional and motor planning processes, respectively. Impairments in performance and some of the regional decreases in gray matter were greater in MDTx. Gray matter volume in IFC in patients was negatively correlated with the number of detoxifications, whereas inferior parietal lobule was negatively correlated with the control over drinking score (impaired control over drinking questionnaire). Performance in IED was also negatively correlated with gray matter volume in IFC/BA47, whereas recognition of fearful faces was positively correlated with the IFC gray matter. Repeated episodes of detoxification from alcohol, related to severity of dependency, are coupled with altered brain structure in areas of emotional regulation, attention and motor planning. Such changes may confer increased inability to switch behavior according to environmental demands and social incompetence, contributing to relapse.


The health sector gap in the southern Africa crisis in 2002/2003.
The southern Africa crisis represents the first widespread emergency in a region with a mature HIV/AIDS epidemic. It provides a steep learning curve for the international humanitarian system in understanding and responding to the complex interactions between the epidemic and the causes and the effects of this crisis. It also provoked much debate about the severity and causes of this emergency, and the appropriateness of the response by the humanitarian community. The authors argue that the over-emphasis on food aid delivery occurred at the expense of other public health interventions, particularly preventative and curative health services. Health service needs were not sufficiently addressed despite the early recognition that ill-health related to HIV/AIDS was a major vulnerability factor. This neglect occurred because analytical frameworks were too narrowly focused on food security, and large-scale support to health service delivery was seen as a long-term developmental issue that could not easily be dealt with by short-term humanitarian action. Furthermore, there were insufficient countrywide data on acute malnutrition, mortality rates and performance of the public health system to make better-balanced evidence-based decisions. In this crisis, humanitarian organisations providing health services could not assume their traditional roles of short-term assistance in a limited geographical area until the governing authorities resume their responsibilities. However, relegating health service delivery as a long-term developmental issue is not acceptable. Improved multisectoral analytical frameworks that include a multidisciplinary team are needed to ensure all aspects of public health are dealt with in similar future emergencies. Humanitarian organisations must advocate for improved delivery and access to health services in this region. They can target limited geographical areas with high mortality and acute malnutrition rates to deliver their services. Finally, to address the underlying problem of the health sector gap, a long-term strategy to ensure improved and sustainable health sector performance can only be accomplished with truly adequate resources. This will require renewed efforts on part of governments, donors and the international community. Public health interventions, complementing those addressing food insecurity, were and are still needed to reduce the impact of the crisis, and to allow people to re-establish their livelihoods. These will increase the population's resilience to prevent or mitigate future disasters.


Reading and doing arithmetic nonconsciously.
The modal view in the cognitive and neural sciences holds that consciousness is necessary for abstract, symbolic, and rule-following computations. Hence, semantic processing of multiple-word expressions, and performing of abstract mathematical computations, are widely believed to require consciousness. We report a series of experiments in which we show that multiple-word verbal expressions can be processed outside conscious awareness and that multistep, effortful arithmetic equations can be solved unconsciously. All experiments used Continuous Flash Suppression to render stimuli invisible for relatively long durations (up to 2,000 ms). Where appropriate, unawareness was verified using both objective and subjective measures. The results show that novel word combinations, in the form of expressions that contain semantic violations, become conscious before expressions that do not contain semantic violations, that the more negative a verbal expression is, the more quickly it becomes conscious, and that subliminal arithmetic equations prime their results. These findings call for a significant update of our view of conscious and unconscious processes.


Direct observation of the rise of delayed fluorescence in dithienylbenzothiadiazole and its role in the excited state dynamics of a donor-acceptor-donor molecule.
Dithienylbenzothiadiazole (DTBT) is used as a building block in several molecules having application in organic light emitting devices (OLED) and organic photovoltaic (OPV) devices. Delayed fluorescence (DF) is the preferred design principle employed currently in OLED research. DTBT has excellent delayed fluorescence properties which makes this moiety a potentially viable OLED material. Here, the dynamics of intersystem crossing (ISC) and reverse intersystem crossing (RISC) have been explored using fluorescence, phosphorescence, fluorescence lifetime and transient absorption measurements. Experimentally it is demonstrated that singlet and triplet states of DTBT are close lying or degenerate and after a certain time the molecules can stay in the singlet or the triplet state forming an equilibrium between the two states which hinders the identification of these two states that could be characterized by routine steady state fluorescence and phosphorescence studies. Similarly in OPV material research, DTBT is coupled with strong donors to form push-pull molecules to produce a prolonged charge separated state. In this study DTBT appended with carbazole at both ends (CDTBT) was used to study the dynamics of DTBT within a donor-acceptor-donor system. The study reveals similar kinds of ISC and RISC in CDTBT along with a competitive deactivation pathway of the singlet state and it was concluded to be through the formation of a charge separated species in CDTBT.


Characterization of Aerosols Generated During Patient Care Activities.
Questions remain about the degree to which aerosols are generated during routine patient care activities and whether such aerosols could transmit viable pathogens to healthcare personnel (HCP). The objective of this study was to measure aerosol production during multiple patient care activities and to examine the samples for bacterial pathogens. Five aerosol characterization instruments were used to measure aerosols during 7 patient care activities: patient bathing, changing bed linens, pouring and flushing liquid waste, bronchoscopy, noninvasive ventilation, and nebulized medication administration (NMA). Each procedure was sampled 5 times. An SKC BioSampler was used for pathogen recovery. Bacterial cultures were performed on the sampling solution. Patients on contact precautions for drug-resistant organisms were selected for most activity sampling. Any patient undergoing bronchoscopy was eligible. Of 35 sampling episodes, only 2 procedures showed a significant increase in particle concentrations over baseline: NMA and bronchoscopy with NMA. Bronchoscopy without NMA and noninvasive ventilation did not generate significant aerosols. Of 78 cultures from the impinger samples, 6 of 28 baseline samples (21.4%) and 14 of 50 procedure samples (28.0%) were positive. In this study, significant aerosol generation was only observed during NMA, both alone and during bronchoscopy. Minimal viable bacteria were recovered, mostly common environmental organisms. Although more research is needed, these data suggest that some of the procedures considered to be aerosol-generating may pose little infection risk to HCP.


Novel synthetic inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity that inhibit tumor cell proliferation and are structurally unrelated to existing statins.
Pilot-scale libraries of eight-membered medium ring lactams (MRLs) and related tricyclic compounds (either seven-membered lactams, thiolactams or amines) were screened for their ability to inhibit the catalytic activity of human recombinant 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in vitro. A dozen of the synthetic compounds mimic the inhibition of purified HMG-CoA reductase activity caused by pravastatin, fluvastatin and sodium salts of lovastatin, mevastatin and simvastatin in this cell-free assay, suggesting direct interaction with the rate-limiting enzyme of cholesterol biosynthesis. Moreover, several MRLs inhibit the metabolic activity of L1210 tumor cells in vitro to a greater degree than fluvastatin, lovastatin, mevastatin and simvastatin, whereas pravastatin is inactive. Although the correlation between the concentration-dependent inhibitions of HMG-CoA reductase activity over 10 min in the cell-free assay and L1210 tumor cell proliferation over 4 days in culture is unclear, some bioactive MRLs elicit interesting combinations of statin-like (IC50: 7.4-8.0 microM) and anti-tumor (IC50: 1.4-2.3 microM) activities. The HMG-CoA reductase-inhibiting activities of pravastatin and an MRL persist in the presence of increasing concentrations of NADPH. But increasing concentrations of HMG-CoA block the HMG-CoA reductase-inhibiting activity of pravastatin without altering that of an MRL, suggesting that MRLs and existing statins may have different mechanisms of enzyme interaction and inhibition. When tested together, suboptimal concentrations of synthetic MRLs and existing statins have additive inhibitory effects on HMG-CoA reductase activity. Preliminary molecular docking studies with MRL-based inhibitors indicate that these ligands fit sterically well into the HMG-CoA reductase statin-binding receptor model and, in contrast to mevastatin, may occupy a narrow channel housing the pyridinium moiety on NADP+.


Low percolation transitions in carbon nanotube networks dispersed in a polymer matrix: dielectric properties, simulations and experiments.
The low concentration behaviour and the increase of the dielectric constant in carbon nanotubes/polymer nanocomposites near the percolation threshold are still not well understood. In this work, a numerical model has been developed which focuses on the effect of the inclusion of conductive fillers in a dielectric polymer matrix on the dielectric constant and the dielectric strength. Experiments have been carried out in carbon nanotubes/poly(vinylidene fluoride) nanocomposites in order to compare to the simulation results. This work shows how the critical concentration is related to the formation of capacitor networks and that these networks give rise to high variations in the electrical properties of the composites. Based on numerical studies, the dependence of the percolation transition on the preparation of the nanocomposite is discussed. Finally, based on numerical and experimental results, both ours and from other authors, the causes of anomalous percolation behaviour of the dielectric constant are identified.


Mechanisms of murine cranial suture patency mediated by a dominant negative transforming growth factor-beta receptor adenovirus.
Using a physiologic model of mouse cranial suture fusion, the authors' laboratory has previously demonstrated that transforming growth factor (TGF)-betas appear to be more abundantly expressed in the suture complex of the fusing posterior frontal compared with the patent sagittal suture. Furthermore, the authors have shown that by blocking TGF-beta signaling with a replication-deficient adenovirus encoding a defective, dominant negative type II TGF-beta receptor (AdDN-TbetaRII), posterior frontal suture fusion was inhibited. In this study, the authors attempt to further elucidate the role of TGF-beta in cranial suture fusion by investigating possible mechanisms of AdDN-TbetaRII-mediated cranial suture patency using both an established organ culture model and a novel in vitro co-culture system that recapitulates the in vivo anatomic dura mater/cranial suture relationship. In this article, the authors demonstrate that blocking TGF-beta signaling with the AdDN-TbetaRII construct led to inhibition of cellular proliferation in the suture mesenchyme and subjacent dura mater during the early period of predicted posterior frontal suture fusion. Interestingly, co-culture experiments revealed that transfecting osteoblasts with AdDN-TbetaRII led to alterations in the gene expression levels of two important bone-related molecules (Msx2 and osteopontin). Inhibiting TGF-beta signaling prevented time-dependent suppression of Msx2 and prevented induction of osteopontin, thereby retarding osteoblast differentiation. Furthermore, the authors demonstrated that the AdDN-TbetaRII construct was capable of blocking TGF-beta -mediated up-regulation of collagen IalphaI, an extracellular matrix molecule important for bone formation. Collectively, these data strongly suggest that AdDN-TbetaRII maintains posterior frontal patency, in part by altering early events in de novo bone formation, including cellular proliferation and early extracellular matrix production.


Neurochemistry study of spinal cord in non-human primate (Sapajus spp.).
The spinal cord is involved in local, ascending and descending neural pathways. Few studies analyzed the distribution of neuromediators in the laminae of non-human primates along all segments. The present study described the classic neuromediators in the spinal cord of the non-human primate Sapajus spp. through histochemical and immunohistochemical methods. Nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) method showed neuronal somata in the intermediolateral column (IML), central cervical nucleus (CCN), laminae I, II, III, IV, V, VI, VII, VIII and X, besides dense presence of nerve fibers in laminae II and IX. Acetylcholinesterase (AChE) activity was evident in the neuronal somata in laminae V, VI, VII, VIII, IX, CCN, IML and in the Clarke's column (CC). Immunohistochemistry data revealed neuronal nitric oxide synthase (nNOS) immunoreactivity in neuronal somata and in fibers of laminae I, II, III, VII, VIII, X and IML; choline acetyltransferase (ChAT) in neuronal somata and in fibers of laminae VII, VIII and IX; calcitonin gene-related peptide (CGRP) was noticed in neuronal somata of lamina IX and in nerve fibers of laminae I, II, III, IV, V, VI and VII; substance P (SP) in nerve fibers of laminae I, II, III, IV, V, VI, VII, VIII, IX, X, CCN, CC and IML; serotonin (5-HT) and vesicular glutamate transporter-1 (VGLUT1) was noticed in nerve fibers of all laminae; somatostatin (SOM) in neuronal somata of laminae III, IV, V, VI, VII, VIII and IX and nerve fibers in laminae I, II, V, VI, VII, X and IML; calbindin (Cb) in neuronal somata of laminae I, II, VI, VII, IX and X; parvalbumin (PV) was found in neuronal somata and in nerve fibers of laminae III, IV, V, VI, VII, VIII, IX and CC; finally, gamma-amino butyric acid (GABA) was present in neuronal somata of laminae V, VI, VII, VIII, IX and X. This study revealed interesting results concerning the chemoarchitecture of the Sapajus spp. spinal cord with a distribution pattern mostly similar to other mammals. The data corroborate the result described in literature, except for some differences in CGRP, SP, Cb, PV and GABA immunoreactivities present in neuronal somata and in nerve fibers. This could suggest certain specificity for the neurochemistry distribution in this non-human primate species, besides adding relevant data to support further studies related to processes involving spinal cord components.


Health survey of professional drivers.
A cross-sectional health survey comprising 633 male drivers showed that the frequencies of some complaints, for instance, pain in the shoulders and in the back of the neck, increased in older age groups. The frequencies of elevated blood pressure and electrocardiographic findings, on the other hand, tended to decrease among the older drivers. The percentage of drivers who had met with some kind of accident decreased among drivers aged 45-54 years. It was assumed that the results point toward health-based selection. The rate of turnover and its causes were studied in a cohort of 1,597 drivers. The results of the turnover study supported the findings of the health survey.


Universal health outcome measures for older persons with multiple chronic conditions.
Older adults with multiple chronic conditions (MCCs) require considerable health services and complex care. Because the persistence and progression of diseases and courses of treatments affect health status in multiple dimensions, well-validated universal outcome measures across diseases are needed for research, clinical care, and administrative purposes. An expert panel meeting held by the National Institute on Aging in September 2011 recommends that older persons with MCCs complete a brief initial composite measure that includes general health; pain; fatigue; and physical health, mental health, and social role function, along with gait speed measurement. Suitable composite measures include the Medical Outcomes Study 8 (SF-8) and 36 (SF-36) -item Short-Form Survey and the Patient Reported Outcomes Measurement Information System 29-item Health Profile. Based on responses to items in the initial measure, short follow-on measures should be selectively targeted to symptom burden, depression, anxiety, and daily activities. Persons unable to walk a short distance to assess gait speed should be assessed using a physical function scale. Remaining gaps to be considered for measure development include disease burden, cognitive function, and caregiver burden. Routine outcome assessment of individuals with MCCs could facilitate system-based care improvement and clinical effectiveness research.


Flight thermogenesis and energy conservation in hovering hummingbirds
As the smallest homeotherms, hummingbirds suffer from low thermal inertia and high heat loss. Flapping flight is energetically expensive, and convective cooling due to wing and air movements could further exacerbate energy drain. Energy conservation during flight is thus profoundly important for hummingbirds. The present study demonstrates that heat produced by flight activity can contribute to thermoregulatory requirements in hovering hummingbirds. The rate of oxygen consumption, as an indicator of metabolic cost, was measured during hover-feeding and compared with that during perch-feeding. In hover-feeding, oxygen consumption increased only moderately between 35 and 5 degreesC in contrast to the sharp increase during perch-feeding over the same temperature range. This result suggests that heat produced by contraction of the flight muscles substituted for regulatory thermogenesis to accommodate for heat loss during exposure to low temperature. With declining air temperatures, the mechanical power requirements of hovering decreased slightly, but metabolic costs increased moderately. As a result, the mechanical efficiency of the muscle in converting metabolic power to mechanical power was reduced. Changes in wingbeat kinematics also accompanied the reduction in muscle efficiency. Wingbeat frequency increased but stroke amplitude decreased when hovering in the cold, suggesting thermoregulatory roles for the flight muscles. Hovering hummingbirds modulated their wingbeat frequency within a narrow range, reflecting the physical constraints of tuning to a natural resonant frequency with an elastic restoring force. We hypothesize that, by forcing the resonant system of the wings and thorax to oscillate at different frequencies, muscle contraction in the cold generates more heat at the expense of mechanical efficiency. This mechanism of modulating the efficiency of muscle contraction and heat production allows flying hummingbirds to achieve energy conservation at low air temperatures.


Radiotherapy of pituitary tumours in five cats.
Five cats tentatively diagnosed with pituitary adenoma (four cases) or pituitary carcinoma (one case), based on computed tomography (CT) or magnetic resonance imaging, were treated with radiotherapy. Electrons were applied in four cats and electrons and photons in the fifth. Ten to 12 fractions of 3.5 to 4.0 Gy each were delivered on a Monday/Wednesday/Friday schedule. The mean total dose applied was 39 Gy. No severe acute side effects to treatment were seen. Follow-up CT examination was performed in four cats; the mass had disappeared in one cat and remained stable or slightly decreased in size in the other three. The survival times were 5.5, 8.0, 15.0, 18.0 and 20.5 months, with two cats dying of causes unrelated to the tumour. Based on these cases, radiotherapy appears to be a valuable treatment option for feline pituitary tumours.


Use of stream width for determining the dosage rates of Bacillus thuringiensis var. israelensis for larval black fly (Diptera: Simuliidae) control.
Data from several operational black fly abatement programs using Bacillus thuringiensis var. israelensis (B.t.i.) in New York State's Adirondack Mountains were analyzed to determine what the concentration of formulation in the stream might have been if application rates were determined by a stream's width rather than its discharge. There was a high correlation (magnitude of R = 0.87) between discharge and width measured at 315 treatment sites. Had the applications been based upon the stream width, 96% of the actual concentrations in the streams would have been within plus or minus a factor of 5 and none exceeding a factor of 10, a range in which B.t.i. remains environmentally safe and effective.


Short-term activity cycles impede information transmission in ant colonies.
Rhythmical activity patterns are ubiquitous in nature. We study an oscillatory biological system: collective activity cycles in ant colonies. Ant colonies have become model systems for research on biological networks because the interactions between the component parts are visible to the naked eye, and because the time-ordered contact network formed by these interactions serves as the substrate for the distribution of information and other resources throughout the colony. To understand how the collective activity cycles influence the contact network transport properties, we used an automated tracking system to record the movement of all the individuals within nine different ant colonies. From these trajectories we extracted over two million ant-to-ant interactions. Time-series analysis of the temporal fluctuations of the overall colony interaction and movement rates revealed that both the period and amplitude of the activity cycles exhibit a diurnal cycle, in which daytime cycles are faster and of greater amplitude than night cycles. Using epidemiology-derived models of transmission over networks, we compared the transmission properties of the observed periodic contact networks with those of synthetic aperiodic networks. These simulations revealed that contrary to some predictions, regularly-oscillating contact networks should impede information transmission. Further, we provide a mechanistic explanation for this effect, and present evidence in support of it.


Converging action of alcohol consumption and cannabinoid receptor activation on adult hippocampal neurogenesis.
Alcoholism is characterized by successive periods of abstinence and relapse, resulting from long-lasting changes in various circuits of the central nervous system. Accumulating evidence points to the endocannabinoid system as one of the most relevant biochemical systems mediating alcohol addiction. The endocannabinoid system regulates adult neurogenesis, a form of long-lasting adult plasticity that occurs in a few areas of the brain, including the dentate gyrus. Because exposure to psychotropic drugs regulates adult neurogenesis, it is possible that neurogenesis might be implicated in the pathophysiology, and hence treatment, of neurobiological illnesses related to drugs of abuse. Here, we investigated the sensitivity of adult hippocampal neurogenesis to alcohol and the cannabinoid receptor agonist WIN 55,212-2 (WIN). Specifically, we analysed the potential link between alcohol relapse, cannabinoid receptor activation, and adult neurogenesis. Adult rats were exposed to subchronic alcohol binge intoxication and received the cannabinoid receptor agonist WIN. Another group of rats were subjected to an alcohol operant self-administration task. Half of these latter animals had continuous access to alcohol, while the other half were subjected to alcohol deprivation, with or without WIN administration. WIN treatment, when administered during alcohol deprivation, resulted in the greatest increase in alcohol consumption during relapse. Together, forced alcohol binge intoxication and WIN administration dramatically reduced hippocampal neurogenesis. Furthermore, adult neurogenesis inversely correlated with voluntary consumption of alcohol. These findings suggest that adult hippocampal neurogenesis is a key factor involved in drug abuse and that it may provide a new strategy for the treatment of alcohol addiction and dependence.


Iteratively-reweighted local model fitting method for adaptive and accurate single-shot surface profiling.
The local model fitting (LMF) method is one of the useful single-shot surface profiling algorithms. The measurement principle of the LMF method relies on the assumption that the target surface is locally flat. Based on this assumption, the height of the surface at each pixel is estimated from pixel values in its vicinity. Therefore, we can estimate flat areas of the target surface precisely, whereas the measurement accuracy could be degraded in areas where the assumption is violated, because of a curved surface or sharp steps. In this paper, we propose to overcome this problem by weighting the contribution of the pixels according to the degree of satisfaction of the locally flat assumption. However, since we have no information on the surface profile beforehand, we iteratively estimate it and use this estimation result to determine the weights. This algorithm is named the iteratively-reweighted LMF (IRLMF) method. Experimental results show that the proposed algorithm works excellently.


The study of cellular cytotoxicity of argireline - an anti-aging peptide.
Argireline is well know, innovative anti-aging product used in the cosmetic market. This short chain peptide is used as active ingredient in dermal ointment and creams. Argireline prevents formation of skin lines and wrinkles in a very similar way to the botulinum toxin (Botox), inhibiting neurotransmitter release at the neuromuscular junction. Argireline does not require under skin muscle injections and it is believed to be relatively safe. However, despite the fact that some toxicity data has been provided by the product manufacturer, there is an evident lack of reliable information about cytotoxicity of argireline in the literature. The aim of the presented study was to estimate the antiproliferation effect of argireline solution in several concentrations. The influence of argireline on cellular proliferation was examined against: human embryonic kidney HEK-293 cell line, human neuroblastoma IMR-32 cell line, and human primary skin fibroblasts. Tests were performed using formazan-based cell proliferation assay: EZ4U, which allows to measure the efficiency of mitochondrial oxidative activity in living cells. The argireline inhibitory concentration, IC50 values were calculated and the results were compared to the IC50 value of the reference compound: doxorubicin. In conclusion, the considered method resulted in dose-dependent argireline anti-proliferation effects. However, the significant cytotoxicity of argireline solution was observed under 18 to 10 000 fold higher concentrations (depending on cells that were examined) in comparison to doxorubicin.


Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum.
The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the in vivo therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of this effect has not been characterized. This study characterized the effects of 'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P. falciparum to anti-malarial drugs. Titres of antibodies against blood stage antigens (mainly the ring-infected erythrocyte surface antigen [RESA]) were measured in plasma samples obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was selected and its effects on in vitro parasite growth and multiplication of the Thai P. falciparum laboratory strain TM267 were assessed by light microscopy. The in vitro susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the 3H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC50 and IC90), of 3H-hypoxanthine uptake. Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. 3H-hypoxanthine incorporation after incubation with 'immune' plasma was decreased significantly compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388 to 5,932] cpm) (p= 0.001). As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range) IC50 6.4 (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (p = 0.02), and also had a borderline effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2 to 2.3) ng/ml (p = 0.08). Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC90 values were not significantly affected; median (range) IC90 448.0 (65 to > 500) ng/ml versus 368.8 (261 to 501) ng/ml for quinine (p > 0.05) and 17.0 (0.1 to 29.5) ng/ml versus 7.6 (2.3 to 19.5) ng/ml for artesunate (p = 0.4). 'Immune' plasma containing anti-malarial antibodies inhibits parasite development and multiplication and increases apparent in vitro anti-malarial drug susceptibility of P. falciparum. The IC90 was much less affected than the IC50 measurement.


Improved Thyroid Hypoechogenicity Following Bariatric-Induced Weight Loss in Euthyroid Adults With Severe Obesity-a Pilot Study.
Background: Obesity may affect both biochemical thyroid function tests; and thyroid morphology, as assessed using ultrasound scans (US). The aim of the present pilot study was to explore whether weight loss achieved by bariatric surgery alters thyroid US morphology including gray-scale measurements; and/or function in euthyroid adults with severe obesity. Methods: Euthyroid adults (>18 years) with body mass index (BMI) ≥40 kg/m2 and negative thyroid peroxidase antibodies were assessed at baseline (pre-surgery) and after achieving at least 5% weight loss of their baseline body weight following bariatric surgery. Anthropometric assessments, biochemical/hormonal measurements (TSH, free-T4, free-T3, reverse-T3, and leptin) and thyroid US with gray-scale histogram analysis were performed at the baseline and post-surgery follow-up. Results: Ten Caucasian, euthyroid patients (women/men: 8/2; age: 48.6 ± 3.1 years; BMI: 51.4 ± 1.8 kg/m2) successfully completed this study with significantly decreased body weight (>5% weight loss), waist circumference and serum leptin levels post-surgery (mean post-surgery follow-up duration: 16.5 ± 2.5 months). In parallel to the observed bariatric-induced weight loss, thyroid US echogenicity increased by 25% (p = 0.03), without significant changes in thyroid volume. No significant changes in thyroid function tests were detected. No significant correlations were observed between the increase in thyroid echogenicity and the decreases in anthropometric parameters and circulating leptin. Conclusion: Our results indicate that in euthyroid adults with severe obesity, marked weight loss achieved by bariatric surgery is associated with a parallel significant increase in the thyroid US echogenicity, suggesting that morphological changes of the thyroid in obesity are reversible with weight loss. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03048708.


Continental-scale footprint of balancing and positive selection in a small rodent (Microtus arvalis).
Genetic adaptation to different environmental conditions is expected to lead to large differences between populations at selected loci, thus providing a signature of positive selection. Whereas balancing selection can maintain polymorphisms over long evolutionary periods and even geographic scale, thus leads to low levels of divergence between populations at selected loci. However, little is known about the relative importance of these two selective forces in shaping genomic diversity, partly due to difficulties in recognizing balancing selection in species showing low levels of differentiation. Here we address this problem by studying genomic diversity in the European common vole (Microtus arvalis) presenting high levels of differentiation between populations (average F ST = 0.31). We studied 3,839 Amplified Fragment Length Polymorphism (AFLP) markers genotyped in 444 individuals from 21 populations distributed across the European continent and hence over different environmental conditions. Our statistical approach to detect markers under selection is based on a Bayesian method specifically developed for AFLP markers, which treats AFLPs as a nearly codominant marker system, and therefore has increased power to detect selection. The high number of screened populations allowed us to detect the signature of balancing selection across a large geographic area. We detected 33 markers potentially under balancing selection, hence strong evidence of stabilizing selection in 21 populations across Europe. However, our analyses identified four-times more markers (138) being under positive selection, and geographical patterns suggest that some of these markers are probably associated with alpine regions, which seem to have environmental conditions that favour adaptation. We conclude that despite favourable conditions in this study for the detection of balancing selection, this evolutionary force seems to play a relatively minor role in shaping the genomic diversity of the common vole, which is more influenced by positive selection and neutral processes like drift and demographic history.


Structure and Function of the T4 Spackle Protein Gp61.3.
The bacteriophage T4 genome contains two genes that code for proteins with lysozyme activity-e and 5. Gene e encodes the well-known T4 lysozyme (commonly called T4L) that functions to break the peptidoglycan layer late in the infection cycle, which is required for liberating newly assembled phage progeny. Gene product 5 (gp5) is the tail-associated lysozyme, a component of the phage particle. It forms a spike at the tip of the tail tube and functions to pierce the outer membrane of the Escherichia coli host cell after the phage has attached to the cell surface. Gp5 contains a T4L-like lysozyme domain that locally digests the peptidoglycan layer upon infection. The T4 Spackle protein (encoded by gene 61.3) has been thought to play a role in the inhibition of gp5 lysozyme activity and, as a consequence, in making cells infected by bacteriophage T4 resistant to later infection by T4 and closely related phages. Here we show that (1) gp61.3 is secreted into the periplasm where its N-terminal periplasm-targeting peptide is cleaved off; (2) gp61.3 forms a 1:1 complex with the lysozyme domain of gp5 (gp5Lys); (3) gp61.3 selectively inhibits the activity of gp5, but not that of T4L; (4) overexpression of gp5 causes cell lysis. We also report a crystal structure of the gp61.3-gp5Lys complex that demonstrates that unlike other known lysozyme inhibitors, gp61.3 does not interact with the active site cleft. Instead, it forms a "wall" that blocks access of an extended polysaccharide substrate to the cleft and, possibly, locks the enzyme in an "open-jaw"-like conformation making catalysis impossible.


Clinical staging of chronic lymphocytic leukemia.
A method of clinical staging of chronic lymphocytic leukemia (CLL) has been proposed which is based on the concept that CLL is a disease of progressive accumulation of nonfunctioning lymphocytes: stage O, bone marrow and blood lymphocytosis only; stage 1, lymphocytosis with enlarged nodes; stage II, lymphocytosis with enlarged spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. Analysis of 125 patients. in the present series showed the following median survival times (in months) from diagnosis: stage 0, is greater than 150; stage I 101; stage II, 71; stage III, 19; stage IV, 19, The median survival for the entire series was 71 mo. The prognostic significance of the stage remained even after adjustment was made for age and sex. However, both sex and age were shown to be poor predictors of survival after adjustment for stage. The method of staging proved to be a reliable predictor of survival whether used at diagnosis or during the course of the disease. The proposed staging system was an equally accurate indicator for survival when applied to two other previously published studies of large series of patients


Comparison between laparoscopic and open radical nephrectomy for the treatment of primary renal tumors in children: single-center experience over a 5-year period.
To compare the outcomes of laparoscopic nephrectomy (LN) with open radical nephrectomy (ORN) in the management of consecutive pediatric neoplasms. Retrospective cohort study of consecutive children treated for primary renal tumors between 2006 and 2011, segregated based on surgical modality (LN/ORN). Pre-, intra- and postoperative data and outcomes were collected. Demographics from the 45 patients (13 LN, 32 ORN) were similar, and tumors in the LN group were smaller [6.59 ± 1.8 cm vs. 10.99 ± 2.99 cm ORN (p < 0.05)]. Six patients had preoperative chemotherapy (two LN, four ORN). No tumor ruptures occurred with either technique. Wilms tumor (seven LN, 24 ORN) was the most common diagnosis, followed by renal cell carcinoma (four LN, four ORN). Procedure length was similar between groups (282 ± 79 LN, 263 ± 81 min ORN). Mean length of stay was significantly shorter for LN (2.9 vs. 5.9 days; p = 0.002). Postoperative narcotic requirements and use of nasogastric tube were higher in the ORN group. After a median follow-up of 18 (LN) and 33 months (ORN), 1 and 4 recurrences occurred, respectively. LN is an attractive alternative to open surgery in carefully selected cases of pediatric renal tumors. Procedure length and incidence of intra-operative rupture were not increased, while post-operative recovery and hospital stay were shorter for LN. Longer follow-up is mandatory to confirm comparable oncological outcomes to ORN.