Investigating the genetic and causal relationship between initiation or use of alcohol, caffeine, cannabis and nicotine.
Caffeine, alcohol, nicotine and cannabis are commonly used psychoactive substances. While the use of these substances has been previously shown to be genetically correlated, causality between these substance use traits remains unclear. We aimed to revisit the genetic relationships among different measures of SU using genome-wide association study (GWAS) summary statistics from the UK Biobank, International Cannabis Consortium, and GWAS & Sequencing Consortium of Alcohol and Nicotine use. We obtained GWAS summary statistics from the aforementioned consortia for ten substance use traits including various measures of alcohol consumption, caffeine consumption, cannabis initiation and smoking behaviours. We then conducted SNP-heritability (h2) estimation for individual SU traits, followed by genetic correlation analyses and two-sample Mendelian randomisation (MR) studies between substance use trait pairs. SNP h2 of the ten traits ranged from 0.03 to 0.11. After multiple testing correction, 29 of the 45 trait pairs showed evidence of being genetically correlated. MR analyses revealed that most SU traits were not causally associated with each other. However, we found evidence for an MR association between regular smoking initiation and caffeine consumption 40.17 mg; 95 % CI: [24.01, 56.33] increase in caffeine intake per doubling of odds in smoking initiation). Our findings were robust against horizontal pleiotropy, SNP-outliers, and the direction of causality was consistent in all MR analyses. Most of the substance traits were genetically correlated but there is little evidence to establish causality apart from the relationship between smoking initiation and caffeine consumption.


Patient-assisted incident reporting: including the patient in patient safety.
Patient Safety Reporting Systems are a commonly used method for capturing information about adverse events and near misses in the acute care setting. These event reports are almost exclusively submitted by the frontline care provider, and the patient perspective of the event is rarely captured. The authors present a case which illustrates the use of eliciting the patient's perspective to provide a complementary perspective to the provider's description of the event. The methodology for obtaining and using this information to enhance understanding of the event and to inform prevention strategies is described.


Sleep telemedicine: patient satisfaction and treatment adherence.
Obstructive sleep apnea is common, but access to diagnosis remains limited. Telemedicine may allow greater access to care; however, its effect on patient satisfaction and treatment adherence is unknown. This study compares patient satisfaction and continuous positive airway pressure (CPAP) adherence of patients seen by videoconference with those seen in person. New patients seen via video or in person at a sleep center completed a survey, with three questions pertaining to satisfaction with the provider. Questions were scored 1-5; the sum was the patient satisfaction score. CPAP adherence was retrospectively analyzed in patients who met the physician via video or in person. Percentage of nights CPAP was used for ≥4 h and average minutes of CPAP use per night over 2 consecutive weeks were compared. A Mann-Whitney test compared patient satisfaction of the 90 subjects (of whom, 56 met physician in person and 34 via video). Mean scores (in person, 14.82; video, 14.91; p=0.851) did not differ between groups. Mann-Whitney tests compared CPAP adherence in the 172 subjects (of whom, 111 met physician in person and 61 via video). Mean percentage of nights CPAP was used ≥4 h (in person, 71%; video, 65%; p=0.198) and the average minutes per night of CPAP use (in person, 340.55; video, 305.31; p=0.153) did not differ between groups. The findings indicate that patients were equally satisfied with their provider and adherent to CPAP treatment whether they were seen in person or via video. Videoconferencing may improve access to patient care without reducing patient satisfaction or treatment adherence.


Shiftwork and environment as interactive predictors of work perceptions.
Evidence suggests that the work environment may play a role in the elevated risk of adverse health outcomes among shiftworkers compared with dayworkers. Perceived work environment measures (physical stressors, job demand, job control, skill discretion, supervisor support, and safety perceptions) from UK oil industry personnel (N=1,867) were analyzed in relation to shiftwork (day/night rotation vs daywork) and objective work environment (onshore vs offshore). Age, education, job type, and negative affectivity were also included. The Environment * Shiftwork interaction was significant in multivariate tests and in 5 of the 6 univariate analyses. Onshore, shiftworkers perceived their environment significantly less favorably than dayworkers, but differences were less marked offshore. Results are discussed in relation to the demand-control-support model of work stress.


Local and transient expression of E-cadherin involved in mouse embryonic brain morphogenesis.
We found that E-cadherin (uvomorulin) is transiently expressed in restricted regions of the metencephalon, mesencephalon and diencephalon of mouse embryonic brain. This expression first occurred in parts of the mesencephalon and diencephalon at around E9.5, and subsequently extended to the primordia of cerebellum, the dorsal midline of mesencephalon and some other regions of the embryonic brain. These E-cadherin expressions ceased by E15 except at the dorsal midline. Immunohistological analyses showed that E-cadherin-positive cells are radially arranged in the neural tube and the E-cadherin-positive regions are sharply demarcated from E-cadherin-negative regions. Axons extending from some of the E-cadherin-positive regions also expressed this molecule. When embryonic brains were dissociated into single cells and cultured as monolayers, E-cadherin-positive cells formed clusters that were segregated from E-cadherin-negative cells. E9.5 brain fragments containing metencephalon and mesencephalon were isolated, explanted on Nucleopore filters and cultured in the absence or presence of antibodies to E-cadherin. This antibody treatment removed most of the E-cadherin molecules from the explants and consequently affected their growth pattern. To analyze cellular events induced by the antibody treatment, we stained these explants with an antiserum to En whose distribution was found to overlap in part with that of E-cadherin and found that the pattern of En staining was altered by the anti-E-cadherin antibody treatment. These results suggest that the local and transient expression of E-cadherin in embryonic brain is involved in regional pattern formation in this organ.


Adults' food skills and use of gardens are not associated with household food insecurity in Canada.
To determine the extent to which Canadian adults' food preparation and cooking skills and use of home or community gardens relate to their household food insecurity status; and to compare the food shopping and cooking behaviours of adults in food-secure and food-insecure households. Data were drawn from two Rapid Response Modules appended to the Canadian Community Health Survey in 2012 and 2013. The analytic sample comprised 16,496 respondents 18 years and older. Multivariable logistic regression analyses were conducted to determine the association between food insecurity and adults' self-rated cooking abilities, food preparation skills score, use of gardens, food shopping behaviours, and cooking behaviours, while adjusting for socio-demographic characteristics. Adults in food-insecure households did not differ significantly from others with respect to their food preparation skills or cooking ability, and neither variable predicted the odds of household food insecurity when socio-demographic characteristics were taken into account. Adults in food-insecure households were less likely to use a garden for food, but gardening was unrelated to the odds of food insecurity. Shopping with a budget was more common among adults in food-insecure households, but no other differences in food shopping behaviours were observed after adjustment for socio-demographic characteristics. Adults in food-insecure households were as likely as others to adjust recipes to make them healthier, but they had higher odds of adjusting recipes to reduce their fat content. Our findings suggest that household food insecurity in Canada is not a problem of insufficient food skills.


Broad spectrum aminoglycoside phosphotransferase type III from Enterococcus: overexpression, purification, and substrate specificity.
The aminoglycoside phosphotransferases (APHs) are responsible for the bacterial inactivation of many clinically useful aminoglycoside antibiotics. We report the characterization of an enterococcal enzyme, APH(3')-IIIa, which inactivates a broad spectrum of aminoglycosides by ATP-dependent O-phosphorylation. Overproduction of APH(3')-IIIa has permitted the isolation of 30-40 mg of pure protein/(L of cell culture). Purified APH(3')-IIIa is a mixture of monomer and dimer which is slowly converted to dimer only over time. Dimer could be dissociated into monomer by incubation with 2-mercaptoethanol, suggesting that dimerization is mediated by formation of disulfide bond(s). Both monomer and dimer show Km values in the low micromolar range for good substrates such as kanamycin and neomycin, and kcat values of 1-4 s-1. All aminoglycosides show substrate inhibition except amikacin and kanamycin B. Determination of minimum inhibitory concentrations indicates a positive correlation between antibiotic activity and kcat/Km, but not with Km or kcat. NMR analysis of phosphorylated kanamycin A has directly demonstrated regiospecific phosphoryl transfer to the 3'-hydroxyl of the 6-aminohexose ring of the antibiotic. Analysis of structure-activity relationships with a variety of aminoglycosides has revealed that the deoxystreptamine aminocyclitol ring plays a critical role in substrate binding. This information will form the basis for future design of inhibitors of APH(3')-IIIa.


Magnesium and cell cycle control: an update.
Accumulating evidence, from bacteria to human cells, points to a universal role for magnesium in controlling the cell cycle. In microorganisms, the co-ordinate sequence of events which culminate in biomass doubling and cell division may be modulated through expression of differential magnesium effects during the cell cycle. For example, it has been suggested in bacteria that growth and cell division may possess different affinities for magnesium; whilst in yeast, cell cycle-dependent fluxes in intracellular magnesium are postulated to regulate cell proliferation. In mammalian cells, magnesium is important in governing key rate-limiting steps in the cell cycle, particularly at the onset of DNA synthesis and at mitosis. Furthermore, it has been demonstrated that cell transformation may cause selective loss of this regulatory role for magnesium, implying that magnesium is important in oncogenesis and perhaps in the expression of malignancy.


Boron modifications produced in an induction-coupled argon plasma.
Most of the small particles (50 to 100 micrometers in diameter) of microcrystalline beta-rhombohedral boron that quickly transit an argon plasma maintained within a radio-frequency induction-coupled torch emerge as better crystallized spheroids of the same crystalline form and nearly the same size as the starting material. A few crystals of each of four distinctive, well-faceted habits are formed along with the general product. Three of these types are monocrystals of the beta-rhombohedral polymorph, of the tetragonal-III modification, and of an unreported cubic form of boron. Specimens of the fourth type are polycrystals of another unreported form of boron, apparently consisting of many hexagonal platelets stacked in an imprecise fashion.


Clinical predictors of silent but substantial liver fibrosis in primary Sjogren's syndrome.
To investigate the prevalence and the predictors of silent but substantial liver fibrosis in patients with primary Sjogren's syndrome (pSS). We enrolled 101 pSS patients with normal liver function and structures, and without significant liver diseases or other conditions affecting liver fibrosis. The European league against rheumatism (EULAR) SS patients reported index (ESSPRI) and the EULAR SS disease activity index (ESSDAI) were analyzed. Liver stiffness (LS) was measured using transient elastography and 7.4 kPa was determined as the cutoff value for significant liver fibrosis. The median age of patients (91women) was 53 years and the median LS value was 4.7 kPa. The median ESSPRI and ESSDAI showed no correlation with LS values. Twelve patients (11.9%) had significant liver fibrosis. In multivariate logistic regression, white blood cells count ≤4000.0/mm(3) (Odds ratio [OR] 9.821), serum albumin ≤3.8 mg/dL (OR 16.770) and aspartate aminotransferase (AST) ≥ 27.0 IU/L (OR 20.858) independently predicted silent but substantial liver fibrosis in pSS patients. The prevalence of silent but substantial liver fibrosis was 11.9% in pSS and its predictors were leukopenia, decreased serum albumin and increased AST levels.


Clarifying the relationship between impulsive delay discounting and nicotine dependence.
Impulsive delayed reward discounting (DRD) has been linked to nicotine dependence, but with some inconsistency. This may be related to the considerable variability in the literature with regard to the DRD assessments used, particularly in the case of the reward magnitudes assessed. In addition, previous studies have often not considered concurrent substance use when examining the relationship between DRD and nicotine dependence. The current study sought to further clarify the relationship between DRD and nicotine dependence by characterizing DRD across diverse reward magnitudes and incorporating other substance use. Daily smokers (N = 933) were assessed for DRD preferences across nine reward magnitudes (delayed reward range: $2.50-$850), comorbid substance use, and relevant demographic variables (age, education, income). A significant large effect size magnitude effect was found for DRD, reflecting steeper discounting for smaller delayed rewards, but significant correlations across magnitudes also suggested similar relative levels of discounting. Principal components analysis (PCA) was used to generate a single latent index of discounting across all magnitudes that accounted for 69% of the total variance. In correlation and regression analyses, steeper composite DRD was significantly associated with nicotine dependence severity. This relationship remained statistically significant after incorporating demographic variables and alcohol and illicit drug use. These findings provide evidence of a specific link between impulsive DRD and nicotine dependence and reveal that this association is robust across a broad range of monetary rewards. The study also demonstrates the utility of using PCA to generate latent indices of delay discounting across multiple magnitudes of delayed reward.


Cellulose Nanofiber Alignment Using Evaporation-Induced Droplet-Casting, and Cell Alignment on Aligned Nanocellulose Surfaces.
This work investigates droplet-evaporated cellulose nanofiber (CNF) alignment and cell responses on CNF surfaces. Surfaces of unmodified (u-), anionic (a-), and cationic (c-) CNFs were fabricated using an evaporation-induced droplet-casting method and characterized in terms of degree of orientation. Circular variance (CV) values obtained using Cytospectre software to analyze the degree of orientation from AFM images showed a significantly higher degree of orientation on c- and u-CNF surfaces (average CV 0.27 and 0.24, respectively) compared to a-CNF surfaces (average CV 0.76). Quantitative analysis of surface roughness plots obtained from AFM images confirmed the difference between the direction of alignment versus the direction perpendicular to alignment. AFM images as well as observations during droplet evaporation indicated c-CNF alignment parallel to a dry-boundary line during droplet evaporation. Fibroblasts were cultured on the u-, a-, and c-CNF surfaces with or without a fibronectin (FN) coating for 48 h, and the cell response was evaluated in terms of cell viability, proliferation, morphology, and degree of orientation. Cell viability and proliferation were comparable to that on a control surface on the a-CNF and c-CNF surfaces. Although an FN coating slightly enhanced cell growth on the studied surfaces, uncoated a-CNF and c-CNF surfaces were able to support cell growth as well. The results showed cell orientation on aligned c-CNF surfaces, a finding that could be further utilized when guiding the growth of cells. We also showed that the alignment direction of c-CNFs and thus the cell orientation direction can be controlled with a contact-dispensing technique.


Dissimilar effects of L and D amino acids on the growth of Tetrahymena.
Of the L and D configurations of four amino acids (phenylalanine, valine, tryptophan, tyrosine) tested for influence on the growth rate of Tetrahymena, only L-tyrosine was able to induce imprinting in Tetrahymena pyriformis Zeuthen. D-valine stimulated the division of T. pyriformis NT-1, but failed to induce imprinting. The experiments have substantiated the selectivity of the amino acid receptors of T. pyriformis, and the extraordinary imprinting potential of tyrosine as well, as judged by its influence on the growth rate.


Coordination of pincer grasp and transport after mechanical perturbation of the index finger.
Our understanding of reach-to-grasp movements has evolved from the original formulation of the movement as two semi-independent visuomotor channels to one of interdependence. Despite a number of important contributions involving perturbations of the reach or the grasp, some of the features of the movement, such as the presence or absence of coordination between the digits during the pincer grasp and the extent of spatio-temporal interdependence between the transport and the grasp, are still unclear. In this study, we physically perturbed the index finger into extension during grasping closure on a minority of trials to test whether modifying the movement of one digit would affect the movement of the opposite digit, suggestive of an overarching coordinative process. Furthermore, we tested whether disruption of the grasp results in the modification of kinematic parameters of the transport. Our results showed that a continuous perturbation to the index finger affected wrist velocity but not lateral displacement. Moreover, we found that the typical flexion of the thumb observed in nonperturbed trials was delayed until the index finger counteracted the extension force. These results suggest that physically perturbing the grasp modifies the kinematics of the transport component, indicating a two-way interdependence of the reach and the grasp. Furthermore, a perturbation to one digit affects the kinematics of the other, supporting a model of grasping in which the digits are coordinated by a higher-level process rather than being independently controlled.NEW & NOTEWORTHY A current debate concerning the neural control of prehension centers on the question of whether the digits in a pincer grasp are controlled individually or together. Employing a novel approach that perturbs mechanically the grasp component during a natural reach-to-grasp movement, this work is the first to test a key hypothesis: whether perturbing one of the digits during the movement affects the other. Our results support the idea that the digits are not independently controlled.


Plk1- and beta-TrCP-dependent degradation of Bora controls mitotic progression.
Through a convergence of functional genomic and proteomic studies, we identify Bora as a previously unknown cell cycle protein that interacts with the Plk1 kinase and the SCF-beta-TrCP ubiquitin ligase. We show that the Bora protein peaks in G2 and is degraded by proteasomes in mitosis. Proteolysis of Bora requires the Plk1 kinase activity and is mediated by SCF-beta-TrCP. Plk1 phosphorylates a conserved DSGxxT degron in Bora and promotes its interaction with beta-TrCP. Mutations in this degron stabilize Bora. Expression of a nondegradable Bora variant prolongs the metaphase and delays anaphase onset, indicating a physiological requirement of Bora degradation. Interestingly, the activity of Bora is also required for normal mitotic progression, as knockdown of Bora activates the spindle checkpoint and delays sister chromatid segregation. Mechanistically, Bora regulates spindle stability and microtubule polymerization and promotes tension across sister kinetochores during mitosis. We conclude that tight regulation of the Bora protein by its synthesis and degradation is critical for cell cycle progression.


Volumetric imaging of shark tail hydrodynamics reveals a three-dimensional dual-ring vortex wake structure.
Understanding how moving organisms generate locomotor forces is fundamental to the analysis of aerodynamic and hydrodynamic flow patterns that are generated during body and appendage oscillation. In the past, this has been accomplished using two-dimensional planar techniques that require reconstruction of three-dimensional flow patterns. We have applied a new, fully three-dimensional, volumetric imaging technique that allows instantaneous capture of wake flow patterns, to a classic problem in functional vertebrate biology: the function of the asymmetrical (heterocercal) tail of swimming sharks to capture the vorticity field within the volume swept by the tail. These data were used to test a previous three-dimensional reconstruction of the shark vortex wake estimated from two-dimensional flow analyses, and show that the volumetric approach reveals a different vortex wake not previously reconstructed from two-dimensional slices. The hydrodynamic wake consists of one set of dual-linked vortex rings produced per half tail beat. In addition, we use a simple passive shark-tail model under robotic control to show that the three-dimensional wake flows of the robotic tail differ from the active tail motion of a live shark, suggesting that active control of kinematics and tail stiffness plays a substantial role in the production of wake vortical patterns.


Managing the matrix: decadal responses of eucalypt-dominated savanna to ambient fire regimes.
Much of our understanding of the response of savanna systems to fire disturbance relies on observations derived from manipulative fire plot studies. Equivocal findings from both recent Australian and African savanna fire plot assessments have significant implications for informing conservation management and reliable estimation of biomass stocks and dynamics. Influential northern Australian replicated fire plot studies include the 24-year plot-scale Munmarlary and the five-year catchment-scale Kapalga, mesic savanna (> 1000 mm/yr of rainfall) experiments in present-day Kakadu National Park. At Munmarlary, under low-to-moderate-intensity fire treatments, woody vegetation dominated by mature eucalypts was found to be structurally stable. At Kapalga, substantial declines in woody biomass were observed under more intense fire treatments, and modeling assessments implicate early-season fires as having adverse effects on longer-term tree recruitment. Given these contrasting perspectives, here we take advantage of a landscape-scale fire response monitoring program established on three major northern Australian conservation reserves (Kakadu, Litchfield, and Nitmiluk National Parks). Using statistical modeling we assess the decadal effects of ambient fire regime parameters (fire frequency, severity, seasonality, time since fire) on 32 vegetation structure components and abundance of 21 tree and 16 grass species from 122 monitoring plots. Over the study period the mean annual frequency of burning of plots was 0.53, comprising mostly early-dry-season, low-severity fires. Structural and species responses were variable but often substantial, notably resulting in stem recruitment and declines in juveniles, but only weakly explained by fire regime and habitat variables. Modeling of these observations under three realistic scenarios (increased fire severity under projected worsening climate change; modest and significant reductions in fire frequency to meet conservation criteria) indicates that all scenarios have positive and negative structural implications. Effecting significant regional fire regime change (e.g., reduction in frequency and size of severe fires) is demonstrably feasible, but it incurs risks and potentially some undesirable structural consequences. Given recent Australian and African experience, the generality and application of landscape-scale implications derived from manipulative fire assessments (including variable grazing and browsing regimes) in savanna require more critical assessment.


Trends in the Prevalence of Severe Obesity and Bariatric Surgery Access: A State-Level Analysis from 2011 to 2014.
Understanding what proportion of the eligible population is undergoing bariatric surgery at the state level provides critical insight into characterizing bariatric surgery access. We sought to describe statewide trends in severe obesity demographics and report bariatric surgery volume in Wisconsin from 2011 to 2014. Self-reported data from the Behavioral Risk Factor Surveillance System (BRFSS) were used to calculate prevalence rates of severe obesity (class II and III) in Wisconsin. Bariatric surgery volume data were analyzed from the Wisconsin Hospital Association. A survey was sent to all American Society for Metabolic and Bariatric Surgery member bariatric surgeons in Wisconsin to assess perspectives on bariatric surgery access, insurance coverage, and referral processes. The prevalence of severe obesity in Wisconsin increased by 30% from 2011 to 2014 (10.4%-13.2%; P = .035); the odds of severe obesity nearly doubled for adults age 20-39 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.3-3.0). During this time, the volume of bariatric surgery declined by 4.2%; (1432 to 1372; P < .001), whereas the rates of bariatric surgery per 1000 persons with severe obesity declined by 25.7% (3.5 to 2.6/1000). A majority (72%) of bariatric surgeon respondents felt bariatric surgery access either worsened or remained the same over the last 4 years. Severe obesity increased significantly in Wisconsin over a 4-year period, whereas bariatric surgery rates among severely obese persons have remained largely unchanged and are substantially below the national average. Combining the state-level obesity survey data and bariatric surgery administrative data may be a useful approach for tracking bariatric surgery access throughout the United States.


Fish Ecology and Evolution in the World's Oxygen Minimum Zones and Implications of Ocean Deoxygenation.
Oxygen minimum zones (OMZs) and oxygen limited zones (OLZs) are important oceanographic features in the Pacific, Atlantic, and Indian Ocean, and are characterized by hypoxic conditions that are physiologically challenging for demersal fish. Thickness, depth of the upper boundary, minimum oxygen levels, local temperatures, and diurnal, seasonal, and interannual oxycline variability differ regionally, with the thickest and shallowest OMZs occurring in the subtropics and tropics. Although most fish are not hypoxia-tolerant, at least 77 demersal fish species from 16 orders have evolved physiological, behavioural, and morphological adaptations that allow them to live under the severely hypoxic, hypercapnic, and at times sulphidic conditions found in OMZs. Tolerance to OMZ conditions has evolved multiple times in multiple groups with no single fish family or genus exploiting all OMZs globally. Severely hypoxic conditions in OMZs lead to decreased demersal fish diversity, but fish density trends are variable and dependent on region-specific thresholds. Some OMZ-adapted fish species are more hypoxia-tolerant than most megafaunal invertebrates and are present even when most invertebrates are excluded. Expansions and contractions of OMZs in the past have affected fish evolution and diversity. Current patterns of ocean warming are leading to ocean deoxygenation, causing the expansion and shoaling of OMZs, which is expected to decrease demersal fish diversity and alter trophic pathways on affected margins. Habitat compression is expected for hypoxia-intolerant species, causing increased susceptibility to overfishing for fisheries species. Demersal fisheries are likely to be negatively impacted overall by the expansion of OMZs in a warming world.


Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology.
Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types.


Asthma-chronic obstructive pulmonary disease overlap syndrome - Literature review and contributions towards a Portuguese consensus.
Phenotypic overlap between the two main chronic airway pulmonary diseases, asthma and chronic obstructive pulmonary disease (COPD), has been the subject of debate for decades, and recently the nomenclature of asthma-COPD overlap syndrome (ACOS) was adopted for this condition. The definition of this entity in the literature is, however, very heterogeneous, it is therefore important to define how it applies to Portugal. A literature review of ACOS was made in a first phase resulting in the drawing up of a document that was later submitted for discussion among a panel of chronic lung diseases experts, resulting in reflexions about diagnosis, treatment and clinical guidance for ACOS patients. There was a consensus among the experts that the diagnosis of ACOS should be considered in the concomitant presence of: clinical manifestations characteristic of both asthma and COPD, persistent airway obstruction (post-bronchodilator FEV1/FVC<0.7), positive response to bronchodilator test (increase in FEV1 of ≥200mL and ≥12% from baseline) and current or past history of smoking or biomass exposure. In reaching diagnosis, the presence of peripheral eosinophilia (>300eosinophils/μL or >5% of leukocytes) and previous history of atopy should also be considered. The recommended first line pharmacological treatment in these patients is the ICS/LABA association; if symptomatic control is not achieved or in case of clinical severity, triple therapy with ICS/LABA/LAMA may be used. An effective control of the exposure to risk factors, vaccination, respiratory rehabilitation and treatment of comorbidities is also important. The creation of initial guidelines on ACOS, which can be applied in the Portuguese context, has an important role in the generation of a broad nationwide consensus. This will give, in the near future, a far better clinical, functional and epidemiological characterization of ACOS patients, with the ultimate goal of achieving better therapeutic guidance.


Automated analysis of heidelberg retina tomograph optic disc images by glaucoma probability score.
To compare the diagnostic performance of the Heidelberg Retinal Tomograph's (HRT; Heidelberg Engineering GmbH, Dossenheim, Germany) glaucoma probability score (GPS), an automated, contour line-independent method of optic disc analysis with that of the Moorfields regression analysis (MRA). HRT images were obtained from one eye of 121 patients with glaucoma (median age, 70.2 years; median mean deviation [MD], -3.6 dB, range, +2.0 to -9.9 dB) and 95 healthy control subjects (median age, 59.7 years; median MD -0.1 dB, range +2.5 to -3.7). The diagnostic performances of GPS and MRA were evaluated by including borderline classifications, either as test negatives (most specific criteria) or as test positives (least specific criteria). Agreement between global and sectoral data of both analyses was established. Logistic regression analyses were performed to evaluate the effect of covariates such as optic disc size and age on the classification outcomes of both the GPS and the MRA. In 8 (7%) patients with glaucoma and 10 (11%) control subjects, the GPS failed to provide a complete global and sectoral optic disc classification. Although we could not identify a single distinct cause of this failure in the glaucoma group, failures in the control subjects occurred most often (7/10) with small and crowded optic discs. In subjects who were successfully classified at least globally by the GPS (117 patients with glaucoma, 88 control subjects), the diagnostic performances of GPS and MRA were similar (areas under the receiver operating characteristic [ROC] curve of 0.78 and 0.77, respectively; P > 0.1). With the GPS, sensitivity and specificity were 59% and 91% (most specific criteria) and 78% and 63% (least specific criteria), respectively. Combining GPS and MRA did not increase diagnostic performance significantly (ROC area of combined classifiers, 0.81). Both GPS and MRA were affected by disc size. In patients with glaucoma as well as healthy control subjects, the odds of a positive GPS classification (borderline or outside normal limits) increased by 21% (95% confidence interval [CI], 12%-30%) for each 0.1 mm2 increase in optic disc area. With the MRA, the corresponding increase was 15% (95% CI, 7%-23%). Optic disc area alone accounted for approximately 30% and 22% of the explained variance with the GPS and MRA, respectively (P < 0.001). The proportional-odds logistic regression confirmed that optic disc size affected mainly the tradeoff between true- and false-positive classifications (criterion) rather than the absolute performance of the analyses (area under the ROC curve). There was some evidence of an age effect with the MRA, which showed a 53% (95% CI, 16%-102%) increase in the odds of a positive test (borderline or outside normal limits) associated with each decade of age (P = 0.002), but no age effects were observed with the GPS (P > 0.1). The diagnostic performance of the contour line-independent GPS analysis is similar to that of the MRA. However, clinicians should be aware of the strong size dependence of both GPS and MRA. In large optic discs, both GPS and MRA are likely to produce many false-positive classifications. Correspondingly, the sensitivity to early damage is likely to be low in small optic discs. There is a need for automated classification systems that explicitly address the size dependence of current analyses.


Passive transfer of virus-specific antibodies confers protection against reproductive failure induced by a virulent strain of porcine reproductive and respiratory syndrome virus and establishes sterilizing immunity.
Immune mechanisms mediating protective immunity against porcine reproductive and respiratory syndrome virus (PRRSV) are not well understood. The PRRSV-specific humoral immune response has been dismissed as being ineffective and perhaps deleterious for the host. The function of PRRSV antibodies in protective immunity against infection with a highly abortifacient strain of this virus was examined by passive transfer experiments in pregnant swine. All of a group of pregnant gilts (n = 6) that received PRRSV immunoglobulin (Ig) from PRRSV-convalescent, hyperimmune animals were fully protected from reproductive failure as judged by 95% viability of offspring at weaning (15 days of age). On the other hand, the totality of animals in a matched control group (n = 6) receiving anti-pseudorabies virus (PRV) Ig exhibited marked reproductive failure with 4% survival at weaning. Besides protecting the pregnant females from clinical reproductive disease, the passive transfer of PRRSV Ig prevented the challenge virus from infecting the dams and precluded its vertical transmission, as evidenced by the complete absence of infectious PRRSV from the tissues of the dams and lack of infection in their offspring. In summary, these results indicate that PRRSV-Igs are capable of conferring protective immunity against PRRSV and furthermore that these Igs can provide sterilizing immunity in vivo.


Foot and Ankle Injuries in Soccer.
The ankle is one of the most commonly injured joints in soccer and represents a significant cost to the healthcare system. The ligaments that stabilize the ankle joint determine its biomechanics-alterations of which result from various soccer-related injuries. Acute sprains are among the most common injury in soccer players and are generally treated conservatively, with emphasis placed on secondary prevention to reduce the risk for future sprains and progression to chronic ankle instability. Repetitive ankle injuries in soccer players may cause chronic ankle instability, which includes both mechanical ligamentous laxity and functional changes. Chronic ankle pathology often requires surgery to repair ligamentous damage and remove soft-tissue or osseous impingement. Proper initial treatment, rehabilitation, and secondary prevention of ankle injuries can limit the amount of time lost from play and avoid negative long-term sequelae (eg, osteochondral lesions, arthritis). On the other hand, high ankle sprains portend a poorer prognosis and a longer recovery. These injuries will typically require surgical stabilization. Impingement-like syndromes of the ankle can undergo an initial trial of conservative treatment; when this fails, however, soccer players respond favorably to arthroscopic debridement of the lesions causing impingement. Finally, other pathologies (eg, stress fractures) are highly encouraged to be treated with surgical stabilization in elite soccer players.


The chorioallantoic placenta of the spotted hyena (Crocuta crocuta Erxleben): an electron microscopic study.
The histology and ultrastructure of the chorioallantoic placenta of the spotted hyena have been studied in three specimens obtained in the field and fixed promptly with glutaraldehyde. Observations revealed that the interhemal membrane at its minimal thickness is hemomonochorial, consisting of a continuous layer of syncytial trophoblast, a basal lamina, and fetal capillary endothelium. Cytotrophoblastic cells form a discontinuous layer beneath the syncytial trophoblast and are distinguished by the presence of numerous extracted lipid droplets in their cytoplasm. A network of extracellular spaces, incorrectly identified as cisternae of endoplasmic reticulum by earlier investigators, occurs beneath the maternal surface of the syncytial trophoblast. These spaces contain moderately dense, nonfibrillar material resembling the intrasyncytial lamina previously described only in the hemochorial placenta of certain bats. Hence, these spaces may contain remnants of maternal capillary basal lamina following displacement of the endothelium by extensions of syncytial trophoblast at an early stage of placental development.


Functional brain imaging of episodic memory decline in ageing.
The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation.


Beta-glucans in higher fungi and their health effects.
Together with chitin, the beta-glucans are components of mycetes' cell walls. A high level of biological efficiency has been found in beta-glucans, especially beta-1,3-D-glucans and beta-1,6-D-glucans isolated from some basidiomycetes. (Biological efficiency refers to the relative ability of beta-glucans to promote a desired response, for example to induce leukocyte activation and to produce inflammatory mediators.) These polysaccharides increase the number of Th1 lymphocytes, which help protect organisms against allergic reactions. A number of beta-glucans, for example pleuran from Oyster (Pleurotus spp.) mushrooms or lentinan from Shiitake (Lentinus edodes) mushrooms, have shown marked anticarcinogenic activity. In addition to having an immunity-stimulating effect, beta-glucans may participate in physiological processes related to the metabolism of fats in the human body. Their application results in a decrease in the total cholesterol content in blood and may also contribute to reductions in body weight.


Esthesioneuroblastoma - a clinicopathologic study and role of DNA topoisomerase alpha.
Esthesioneuroblastoma (ENB) differs from adrenal neuroblastomas in its histopathologic and biologic characteristics. Hyams grading and Kadish staging have shown correlation with survival. Scant data are available on proliferation indices and prognosis. We retrospectively reviewed the clinicopathologic characteristics of ENB. Both Kadish and UCLA staging systems were used. Hyams grading was simplified into low and high grade. DNA topoisomerase II alpha labeling index (T2alpha LI) was obtained in 8 cases using immunohistochemistry. Of the 19 cases studied, 14 were males and 5 females. Age range was 2 to 62 years (average 27 years). The mass primarily involved the nose in 12 (63%) and paranasal sinuses in 7 cases (37%). Patients presented with nose block in 19 (100%), epistaxis in 10 (53%), proptosis in 9 (47%) and loss of vision in 6 cases (32%). Bony involvement was seen in 7 cases (37%), and intracranial spread in one case (5%). Thirteen (68%) were low-grade tumors and 6 were (32%) high-grade. There was no statistically significant difference between the low- and high-grade ENB in age (years) (p=0.2882), duration of symptoms (months) (p=0.5636), and either in the Kadish (p=0.5456) or the UCLA staging system (p=0.7771). The difference in DNA topoisomerase alpha labeling index between the low- and highgrade ENB (medians: 10.4 and 22.3, respectively) was not statistically significant (p=0.0714), but it was suggestive of a positive association. The results of this study should be interpreted with caution, because of the limited sample size. Three cases recurred locally, one each stage A, B and C, but all low-grade. This preliminary study suggests the need to combine a simplified histologic grading with accurate staging in a reasonable attempt to assess local progression in esthesioneuroblastoma. Larger studies may clarify the role of T2alpha LI in improving histologic grading.


A community study of factors related to poorly controlled asthma among Brazilian urban children.
Asthma constitutes a serious public health problem in many regions of the world, including the city of Salvador, State of Bahia-Brazil. The purpose of this study was to analyse the factors associated with poor asthma control. Two definitions were used for asthma: 1) wheezing in the last 12 months; 2) wheezing in the last 12 months plus other asthma symptoms or asthma diagnosis ever. The definition of poorly controlled asthma was: at least one reported hospitalisation due to asthma and/or high frequency of symptoms, in the last year. Children with poorly controlled asthma (N = 187/374) were compared with wheezing children with controlled asthma regarding age, gender, atopy, parental asthma, rhinitis, eczema, exposure to second hand tobacco smoke, presence of moulds, pets and pests in the house, helminth infections and body mass index. Crude and logistic regression adjusted odds ratios were used as measures of association. There was a higher proportion of poorly controlled asthma among children with eczema (OR = 1.55; 95% CI 1.02; 2.37). The strength of the association was greater among children with eczema and rhinitis (42.6%, 53.4% and 57.7%, respectively, in children who had no rhinitis nor eczema, had only one of those, and had both (p = 0.02 for trend test). The presence of mould in the houses was inversely associated with poorly controlled asthma (OR = 0.54; 95% CI 0.34; 0.87). Our results indicate an association between eczema and poor asthma control in this environment, but emphasize the role of various other individual and environmental factors as determinants of poor control.


Glucose Gel as a Treatment Strategy for Transient Neonatal Hypoglycemia.
Transient asymptomatic neonatal hypoglycemia (TANH) is common as infants transition from their mother's energy stores to their own. There is little evidence supporting the blood glucose threshold that indicates a need for treatment although sustained hypoglycemia has been correlated with negative neurodevelopmental consequences. Treatment of TANH includes a stepwise approach from supplemental enteral feedings, buccal glucose gel, intravenous dextrose infusion, and/or transfer to special care units including neonatal intensive care units. The purpose of this evidence-based practice brief is to review current evidence on 40% buccal glucose gel administration as a treatment strategy for TANH. CINAHL, Cochrane, Google Scholar, and PubMed were searched using the key words and restricted to English language over the last 7 years. The use of buccal dextrose gel for TANH may reduce neonatal intensive care unit admissions, reduce hospital length of stay and cost, support the mother-infant dyad through reduced separation, support exclusive breastfeeding, and improve parental satisfaction without adverse neurodevelopmental consequences. Timely collection of blood glucose levels following intervention is critical to support clinical decisions. Clinicians should offer family education regarding the rationale for serial glucose monitoring and treatment indications including buccal glucose administration. Clinical protocols can be revised to include use of buccal dextrose gel. There is a need for rigorous long-term studies comparing treatment thresholds and neurodevelopmental outcomes among various treatment strategies for TANH.


Responses to Systemic Nitrogen Signaling in Arabidopsis Roots Involve trans-Zeatin in Shoots.
Plants face temporal and spatial variation in nitrogen (N) availability. This includes heterogeneity in soil nitrate (NO3-) content. To overcome these constraints, plants modify their gene expression and physiological processes to optimize N acquisition. This plasticity relies on a complex long-distance root-shoot-root signaling network that remains poorly understood. We previously showed that cytokinin (CK) biosynthesis is required to trigger systemic N signaling. Here, we performed split-root experiments and used a combination of CK-related mutant analyses, hormone profiling, transcriptomic analysis, NO3- uptake assays, and root growth measurements to gain insight into systemic N signaling in Arabidopsis thaliana By comparing wild-type plants and mutants affected in CK biosynthesis and ABCG14-dependent root-to-shoot translocation of CK, we revealed an important role for active trans-zeatin (tZ) in systemic N signaling. Both rapid sentinel gene regulation and long-term functional acclimation to heterogeneous NO3- supply, including NO3- transport and root growth regulation, are likely mediated by the integration of tZ content in shoots. Furthermore, shoot transcriptome profiling revealed that glutamate/glutamine metabolism is likely a target of tZ root-to-shoot translocation, prompting an interesting hypothesis regarding shoot-to-root communication. Finally, this study highlights tZ-independent pathways regulating gene expression in shoots as well as NO3- uptake activity in response to total N deprivation.


Obesity enhances the recruitment of mesenchymal stem cells to visceral adipose tissue.
In obesity, high levels of TNF-α in the bone marrow microenvironment induce the bone marrow-mesenchymal stem cells (BM-MSCs) towards a pro-adipogenic phenotype. Here, we investigated the effect of obesity on the migratory potential of BM-MSCs and their fate towards the adipose tissues. BM-MSCs were isolated from male C57Bl/06 mice with high-fat diet-induced obesity. The migratory potential of the BM-MSCs, their presence in the subcutaneous (SAT) and the visceral adipose tissues (VAT), and the possible mechanisms involved were investigated. Obesity did not affect MSC content in the bone marrow but increased the frequency of MSCs in blood, SAT, and VAT. In these animals, the SAT adipocytes presented a larger area, without any changes in adipokine production or the Sdf-1α gene expression. In contrast, in VAT, obesity increased leptin and IL-10 levels but did not modify the size of the adipocytes. The BM-MSCs from obese animals presented increased spontaneous migratory activity. Despite the augmented expression of Cxcr4, these cells exhibited decreased migratory response towards SDF-1α, compared to that of BM-MSCs from lean mice. The PI3K-AKT pathway activation seems to mediate the migration of BM-MSCs from lean mice, but not from obese mice. Additionally, we observed an increase in the spontaneous migration of BM-MSCs from lean mice when they were co-cultured with BM-HCs from obese animals, suggesting a paracrine effect. We concluded that obesity increased the migratory potential of the BM-MSCs and induced their accumulation in VAT, which may represent an adaptive mechanism in response to chronic nutrient overload.


Asynchronous spawning in sympatric populations of a hard coral reveals cryptic species and ancient genetic lineages.
Genetic subdivision within a species is a vital component of the evolution of biodiversity. In some species of Acropora corals in Western Australia, conspecific individuals spawn in two seasons 6 months apart, which has the potential to impede gene flow and result in genetic divergence. Genetic comparison of sympatric spring and autumn spawners of Acropora samoensis was conducted to assess the level of reproductive isolation and genetic divergence between the spawning groups based on multiple loci (13 microsatellite loci, the mitochondrial control region and two nuclear introns). Bayesian clustering and principal coordinate analysis of the microsatellite loci showed a high level of genetic differentiation between the spawning groups (F'ST = 0.30; P < 0.001), as did the sequence data from PaxC and Calmodulin (ΦST = 0.97 and 0.31, respectively). At the PaxC locus, the autumn and spring spawners were associated with two divergent lineages that were separated by an evolutionary distance of 1.7% and statistical tests indicate divergent selection in PaxC, suggesting this gene may play a role in coral spawning. This study indicates that the autumn and spring spawners represent two cryptic species, and highlights the importance of asynchronous spawning as a mechanism influencing speciation in corals.


Molecular survey for foot-and-mouth disease virus in livestock in Tanzania, 2008-2013.
Phylogeography data are of paramount importance in studying the molecular epidemiology dynamics of foot-and-mouth disease virus (FMDV). In this study, epithelial samples and oesophageal-pharyngeal fluids were collected from 361 convalescent animals (cattle and buffaloes) in the field throughout Tanzania between 2009 and 2013. The single plex real-time RT-PCR (qRT-PCR) assay for rapid and accurate diagnosis of FMDV employing the Callahan 3DF-2, 3DF-R primers and Callahan 3DP-1 probe were used. Preparation of the samples was performed according to the OIE manual, with a Kenya O serotype obtained from the attenuated vaccine serving as a positive control and samples collected from healthy animals serving as true negatives. The results indicated that 53.49% of samples (n = 176) were positive for FMDV genome by qRT-PCR, with Ct values ranging from 14 to 32. In addition, molecular typing of the FMDV genome positive samples using serotype specific primers revealed the existence of several serotypes: serotype South Africa Territory 1 (SAT1) (34.25%, n = 60), serotype A (68.92%, n = 98), serotype O (59.20%, n = 98) and SAT2 (54.54%, n = 96). The virus protein 1 sequences analysis for 35 samples was performed and the collective results indicated: 54.28% serotype O, 25.71% serotype A, 14.28% serotype SAT1 and 2.85% serotype SAT2. Therefore in this study, both the phylogenetic trees and spatial distribution of serotypes elucidated the phylodynamics of multiple FMDV field strains in Tanzania and neighbouring countries.


Reflexology for the treatment of pain in people with multiple sclerosis: a double-blind randomised sham-controlled clinical trial.
Multiple sclerosis (MS) results in pain and other symptoms which may be modified by conventional treatment, however, MS is still not curable. Several studies have reported positive effects of reflexology in the treatment of pain, however, no randomised controlled clinical trials for the treatment of pain have been conducted within this population. The objective of this study was to investigate the effectiveness of reflexology on pain in and MS population. We randomly allocated 73 participants to receive either precision or sham reflexology weekly for 10 weeks. Outcome measures were taken pre-and post-treatment with follow-up at 6 and 12 weeks by a researcher blinded to group allocation. The primary outcome measure recorded pain using a Visual Analogue Scale (VAS). A significant (p < 0.0001) and clinically important decrease in pain intensity was observed in both groups compared with baseline. Median VAS scores were reduced by 50% following treatment, and maintained for up to 12 weeks. Significant decreases were also observed for fatigue, depression, disability, spasm and quality of life. In conclusion, precision reflexology was not superior to sham, however, both treatments offer clinically significant improvements for MS symptoms via a possible placebo effect or stimulation of reflex points in the feet using non-specific massage.


Control of type 2 diabetes mellitus among general practitioners in private practice in nine countries of Latin America.
To better understand how diabetes care and control are being administered by general practitioners/nonspecialists in private practice in nine countries of Latin America, and to identify the most significant patient- and physician-related barriers to care. A multicenter, cross-sectional, epidemiological survey was conducted in nine countries in Latin America: Argentina, Brazil, Chile, Costa Rica, Ecuador, Guatemala, Mexico, Peru, and Venezuela. General practitioners in private practice were asked to provide care and control data for patients 18 to 75 years of age with type 2 diabetes mellitus (T2DM), including demographics, medical and medication history, laboratory exams, and information on the challenges of patient management. Of the 3 592 patient questionnaires returned by 377 physicians, 60% of the patients had a family history of diabetes, 58% followed a poor diet, 71% were sedentary, and 79% were obese or overweight. Poor glycemic control (fasting blood glucose >or= 110 mg/dL) was observed in 78% of patients. The number of patients with HbA1c < 7.0% was 43.2%. Glycemic control decreased significantly with increased duration of T2DM. Comorbid conditions associated with T2DM were observed in 86% of patients; insulin use and comorbid conditions, especially those associated with microvascular complications, increased significantly disease duration. Ensuring compliance with recommended diet and exercise plans was the most-cited patient management challenge. Blood glucose levels are undercontrolled in T2DM patients in the private health care system in Latin America, particularly among those who have had the disease the longest (>15 years). Considering the differences between private and public health care in Latin America, especially regarding the quality of care and access to medication, further studies are called for in the public setting. Overall, a more efficient and intensive program of T2DM control is required, including effective patient education programs, adjusted to the realities of Latin America.


Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants.
Extremely premature infants are at high risk of developing invasive candidiasis; fluconazole prophylaxis is safe and effective for reducing invasive candidiasis in this population but further study is needed. We sought to better understand the effect of prophylactic fluconazole on a selection of fluconazole-resistant Candida species. We evaluated the susceptibility to fluconazole of Candida isolates from premature infants (<750 g birth weight) enrolled in a multicentre, randomized, placebo-controlled trial of fluconazole prophylaxis. Candida species were isolated through surveillance cultures at baseline (study day 0-7), period 1 (study day 8-28) and period 2 (study day 29-49). Fluconazole MICs were determined for all Candida isolates. Three hundred and sixty-one infants received fluconazole (n = 188) or placebo (n = 173). After the baseline period, Candida colonization was significantly lower in the fluconazole group compared with placebo during periods 1 (5% versus 27%; P < 0.001) and 2 (3% versus 27%; P < 0.001). After the baseline period, two infants (1%) were colonized with at least one fluconazole-resistant Candida in each group. Median fluconazole MIC was similar in both treatment groups at baseline and period 1. However, in period 2, median MIC was higher in the fluconazole group compared with placebo (1.00 versus 0.50 mg/L, P = 0.01). There was no emergence of resistance observed and no patients developed invasive candidiasis with a resistant Candida isolate. Fluconazole prophylaxis decreased Candida albicans and 'non-albicans' Candida colonization and was associated with a slightly higher fluconazole MIC for colonizing Candida isolates.


Roosting and foraging social structure of the endangered Indiana bat (Myotis sodalis).
Social dynamics are an important but poorly understood aspect of bat ecology. Herein we use a combination of graph theoretic and spatial approaches to describe the roost and social network characteristics and foraging associations of an Indiana bat (Myotis sodalis) maternity colony in an agricultural landscape in Ohio, USA. We tracked 46 bats to 50 roosts (423 total relocations) and collected 2,306 foraging locations for 40 bats during the summers of 2009 and 2010. We found the colony roosting network was highly centralized in both years and that roost and social networks differed significantly from random networks. Roost and social network structure also differed substantially between years. Social network structure appeared to be unrelated to segregation of roosts between age classes. For bats whose individual foraging ranges were calculated, many shared foraging space with at least one other bat. Compared across all possible bat dyads, 47% and 43% of the dyads showed more than expected overlap of foraging areas in 2009 and 2010 respectively. Colony roosting area differed between years, but the roosting area centroid shifted only 332 m. In contrast, whole colony foraging area use was similar between years. Random roost removal simulations suggest that Indiana bat colonies may be robust to loss of a limited number of roosts but may respond differently from year to year. Our study emphasizes the utility of graphic theoretic and spatial approaches for examining the sociality and roosting behavior of bats. Detailed knowledge of the relationships between social and spatial aspects of bat ecology could greatly increase conservation effectiveness by allowing more structured approaches to roost and habitat retention for tree-roosting, socially-aggregating bat species.


Socioeconomic disparities in pain: the role of economic hardship and daily financial worry.
Socioeconomic disparities in pain may be attributable to both greater frequency in stressful financial events as well as greater vulnerability to economic hardship for those at the lower end of the socioeconomic spectrum. This study investigated the effects of economic hardship and daily financial worry on daily pain among women with a chronic musculoskeletal condition. The sample consisted of 250 women with osteoarthritis (N = 105), fibromyalgia (N = 46), or both (N = 99). During an initial assessment, participants' chronic pain diagnosis, level of economic hardship, and demographic information were ascertained. For a period of 30 days, daily diary assessments recorded daily financial worries and daily pain severity. Hypotheses were tested using multilevel modeling for repeated measures in SAS PROC MIXED. Daily pain severity. Conditions of economic hardship and daily ratings of financial worry both had significant detrimental effects on daily pain. Participants with greater levels of economic hardship reported greater pain severity in response to daily financial worries than their counterparts with little or no economic hardship. Further, participants in the sample who were not employed and who reported higher levels of economic hardship exhibited the most pain reactivity in response to daily financial worries. Economic hardship was associated not only with greater exposure to daily financial worries but also with greater vulnerability to pain on days when daily financial worries were experienced.


Segment fusion of ToF-SIMS images.
The imaging capabilities of time-of-flight secondary ion mass spectrometry (ToF-SIMS) have not been used to their full potential in the analysis of polymer and biological samples. Imaging has been limited by the size of the dataset and the chemical complexity of the sample being imaged. Pixel and segment based image fusion algorithms commonly used in remote sensing, ecology, geography, and geology provide a way to improve spatial resolution and classification of biological images. In this study, a sample of Arabidopsis thaliana was treated with silver nanoparticles and imaged with ToF-SIMS. These images provide insight into the uptake mechanism for the silver nanoparticles into the plant tissue, giving new understanding to the mechanism of uptake of heavy metals in the environment. The Munechika algorithm was programmed in-house and applied to achieve pixel based fusion, which improved the spatial resolution of the image obtained. Multispectral and quadtree segment or region based fusion algorithms were performed using ecognition software, a commercially available remote sensing software suite, and used to classify the images. The Munechika fusion improved the spatial resolution for the images containing silver nanoparticles, while the segment fusion allowed classification and fusion based on the tissue types in the sample, suggesting potential pathways for the uptake of the silver nanoparticles.


Drug Induced Liver Injury at a Tertiary Hospital in India: Etiology, Clinical Features and Predictors of Mortality.
Drug-induced liver injury (DILI) is rare; however, it is one of the important causes of acute liver failure which results in significant morbidity or mortality. Patients with suspected DILI were enrolled based on predefined criteria and followed up for at least 6 months or until normalization of liver tests. Causality assessment was done by applying the Roussel Uclaf Causality Assessment Method model. We collected data from 82 individuals diagnosed with DILI at our hospital from 2014 through 2015 (41 men; median age, 38 years). The most commonly implicated drugs were antitubercular therapy (ATT) (49%), antiepileptic drugs (12%), complementary and alternative medicine (CAM) in 10%, antiretroviral drugs (9%) and non-steroidal anti-inflammatory drugs (6%). 8 out of 13 deaths were liver related. Also, liver related mortality was significantly higher for ATT DILI (17.5%) vs. those without (2.4%) (P = 0.02). There was no significant difference in overall as well as liver related mortality in hepatocellular, cholestatic or mixed pattern of injury. Laboratory parameters at one week after discontinuation of drug predicted mortality better than those at the time of DILI recognition. On multivariate logistic regression analysis, jaundice, encephalopathy, MELD (Model for end stage liver disease) score and alkaline phosphatase at one week, independently predicted mortality. DILI results in significant overall mortality (15.85%). ATT, anti-epileptic drugs, CAM and antiretroviral drugs are leading causes of DILI in India. Presence of jaundice, encephalopathy, MELD score and alkaline phosphatase at one week are independent predictors of mortality.


Helping older adults find meaning and purpose through storytelling.
The purpose of this article is to describe a storytelling project that was designed to help community-dwelling older adults find meaning and purpose in their lives through reminiscing about the past. The storytelling project was successful not only for the older adults who participated but also for the nursing students, who were given an opportunity to learn about interviewing and communicating with older adults. The value of life review and storytelling as a nursing intervention became evident from this project. When time is taken to listen to the valuable stories and life lessons of the older population, nurses create a better understanding of their patients while their patients recall special memories and feel proud of their lives.


Relationship Between Assertion and Aggression with Addiction Potential: A Cross-Sectional Study in 2019.
This study aimed to determine the relationship between assertion and aggression with addiction potential among students in Shahroud University of Medical Sciences. In this cross-sectional study conducted in 2019, 500 students of Shahroud University of Medical Sciences, were selected by multistage random sampling, for a study using the Addiction Potential Scale, and Assertion and Aggression Questionnaires. Data were analyzed using ANOVA, Chi-square, t test, Pearson's correlation coefficient, and the linear regression model. The mean scores of addiction potential, aggression, and assertion were 32.7 ± 17.2, 41.5 ± 12.9 and 139.4 ± 22.3, respectively. In this study, 38.8% (N = 194) of students had high aggression and 76.8% (N = 384) had high assertion. In the regression model, aggression, history of drug and addictive substances abuse, history of tobacco use, and history of alcohol abuse were significantly related to addiction potential (p ≤ 0.05). There was a negative relationship between assertion and addiction potential so that with one-unit increase in the assertion score, the addiction potential score decreased by -0.11. Given the direct relationship between aggression and addiction potential, and since more than three-quarters of the students had moderate to high aggression, it is necessary to pay more attention to this issue. Interventions may play an important role in improving the current situation.


Response of Posidonia oceanica seagrass and its epibiont communities to ocean acidification.
The unprecedented rate of CO2 increase in our atmosphere and subsequent ocean acidification (OA) threatens coastal ecosystems. To forecast the functioning of coastal seagrass ecosystems in acidified oceans, more knowledge on the long-term adaptive capacities of seagrass species and their epibionts is needed. Therefore we studied morphological characteristics of Posidonia oceanica and the structure of its epibiont communities at a Mediterranean volcanic CO2 vent off Panarea Island (Italy) and performed a laboratory experiment to test the effect of OA on P. oceanica photosynthesis and its potential buffering capacity. At the study site east of Basiluzzo Islet, venting of CO2 gas was controlled by tides, resulting in an average pH difference of 0.1 between the vent and reference site. P. oceanica shoot and leaf density was unaffected by these levels of OA, although shorter leaves at the vent site suggest increased susceptibility to erosion, potentially by herbivores. The community of sessile epibionts differed in composition and was characterized by a higher species richness at the vent site, though net epiphytic calcium carbonate concentration was similar. These findings suggest a higher ecosystem complexity at the vent site, which may have facilitated the higher diversity of copepods in the otherwise unaffected motile epibiont community. In the laboratory experiment, P. oceanica photosynthesis increased with decreasing pHT (7.6, 6.6, 5.5), which induced an elevated pH at the leaf surfaces of up to 0.5 units compared to the ambient seawater pHT of 6.6. This suggests a temporary pH buffering in the diffusive boundary layer of leaves, which could be favorable for epibiont organisms. The results of this multispecies study contribute to understanding community-level responses and underlying processes in long-term acidified conditions. Increased replication and monitoring of physico-chemical parameters on an annual scale are, however, recommended to assure that the biological responses observed during a short period reflect long-term dynamics of these parameters.


Overview on LFG projects in China.
Since the first landfill gas (LFG) power plant in China was built in 1998, by now more than 10years have passed. In this period the LFG utilization process has progressed greatly in China. An overall review of the process is presented in this paper, which includes the background of policies, the information about the approval procedure of LFG projects, and the theoretical methods used to estimate the amount of LFG's generation. Detailed analysis on the project practice, such as LFG collection techniques, LFG utilization condition in China, is made. According to statistic data, before the end of 2008, 26 LFG power projects have been built and put into operation with total power capacity around 56.8MW, and 2.234 million tons of carbon dioxide equivalent abatement has been achieved annually by all of these LFG projects. The future of LFG industry in China is expected that there is still considerable developing space for LFG utilization in the near coming years, however after 2012, the progress speed may slow down because of some adverse aspects, such as available landfill resource becomes scarce, new laws implemented in China might exclude Chinese landfills from future CDM activities, etc.


Renal function as a predictor of outcome in a broad spectrum of patients with heart failure.
Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (< or =40%) or preserved LVEF (>40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 micromol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR <60 mL/min per 1.73 m2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m2 and 1.86 for <45 mL/min per 1.73 m2 for the primary outcome, both P<0.001, and hazard ratio of 1.50, P=0.006, and 1.91, P=0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.


Comparison of lactulose and glucose breath test for diagnosis of small intestinal bacterial overgrowth in patients with irritable bowel syndrome.
Validity of the lactulose breath test (LBT) to diagnose small intestinal bacterial overgrowth (SIBO) has been questioned. Therefore, a study was planned to compare LBT with glucose breath test (GBT) to diagnose SIBO in irritable bowel syndrome (IBS) patients and controls. 175 diarrhea-predominant IBS patients and 150 apparently healthy controls were enrolled. IBS was diagnosed according to Rome II criteria. Breath samples were collected every 10 min up to 180 min. Breath H₂ and CH₄ were measured using an SC MicroLyzer. SIBO was positive with a sustained increase in breath H₂ or CH₄ or both ≥10 ppm over a baseline value within <90 min in case of LBT and within <120 min in GBT. SIBO was positive in 60/175 (34.3%) patients by lactulose and in 11/175 (6.2%) patients by GBT. In controls, LBT was positive for SIBO in 45/150 (30%) patients and in 1/150 (0.66%) patients by GBT. Positive LBT for SIBO was not significantly different in patients and controls; while using GBT, SIBO was significantly higher (p < 0.01) in patients as compared to controls. By using GBT as gold standard for SIBO, sensitivity, specificity, positive predictive value and negative predictive value of LBT in IBS patients was 63.6, 67.7, 11.7 and 96.6% respectively. LBT is not a good test to discriminate SIBO in IBS patients from controls.


5-Azacytidine up regulates the expression of Epstein-Barr virus nuclear antigen 2 (EBNA-2) through EBNA-6 and latent membrane protein in the Burkitt's lymphoma line rael.
Nonproductive infection of B lymphocytes by Epstein-Barr virus (EBV) is associated with a highly restricted expression of viral genes. In growth-transformed lymphoblastoid cell lines, the products of these genes include a complex of at least six EBV nuclear antigens (EBNAs) (EBNA-1 through EBNA-6) and one membrane protein (latent membrane protein [LMP]). EBV-carrying Burkitt's lymphoma (BL) biopsies and derived cell lines that have retained a representative phenotype (group I BL lines) express only EBNA-1 (M. Rowe, D. T. Rowe, C. D. Gregory, L. S. Young, P. J. Farrell, H. Rupani, and A. B. Rickinson, EMBO J. 6:2743-2751, 1987). We have found that EBNA-2 through EBNA-6 and LMP can be up regulated by treating the group I BL line Rael with the DNA-demethylating agent 5-azacytidine (5-AzaC). The drug acted in a time- and dose-dependent manner. EBNA-2-positive cells were detected by anti-complement immunofluorescence staining just 12 h after addition of 4 microM 5-AzaC and reached a maximum number at 72 h, when up to 75% of the population was positive. EBNA-2, EBNA-3, EBNA-4, EBNA-4, EBNA-6, and LMP were demonstrated immunoblots starting at 48 h. The EBV-encoded early antigens and viral capsid antigens were also induced but at a lower level. EBNA-2 and the lytic cycle-associated antigens appeared with a different time course and in largely nonoverlapping cell subpopulations, as demonstrated by double fluorescence staining. Thus, EBNA-2 expression was not restricted to lytically infected cells, nor was EBNA-2 required for entry into the lytic cycle. The coding and regulatory sequences of EBNA-2 and LMP were found to be highly methylated in Rael cells and were, as expected, demethylated after 5-AzaC treatment. These findings suggest that DNA methylation may participate in the regulation of growth transformation-associated viral genes in BL cells.


A Review of Myeloablative vs Reduced Intensity/Non-Myeloablative Regimens in Allogeneic Hematopoietic Stem Cell Transplantations.
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment option for both malignant and some benign hematological diseases. During the last decade, many of the newer high-dose regimens in different intensity have been developed specifically for patients with hematologic malignancies and solid tumors. Today there are three main approaches used prior to allogeneic transplantation: Myeloablative (MA), Reduced Intensity Conditioning (RIC) and Non-MA (NMA) regimens. MA regimens cause irreversible cytopenia and there is a requirement for stem cell support. Patients who receive NMA regimen have minimal cytopenia and this type of regimen can be given without stem cell support. RIC regimens do not fit the criteria of MA and NMA: the cytopenia is reversible and the stem cell support is necessary. NMA/RIC for Allo-HSCT has opened a new era for treating elderly patients and those with comorbidities. The RIC conditioning was used for 40% of all Allo-HSCT and this trend continue to increase. In this paper, we will review these regimens in the setting of especially allogeneic HSCT and our aim is to describe the history, features and impact of these conditioning regimens on specific diseases.


Functional vomiting disorders in infancy: innocent vomiting, nervous vomiting, and infant rumination syndrome.
Pediatric gastroenterologists have tended to view gastroesophageal reflux (GER) as a disease in and of itself--a disease that can be diagnosed "objectively" with use of numerical data from esophageal pH monitoring and cured with pharmacologic or surgical treatment. What is often forgotten is that the data derived from esophageal pH monitoring and other techniques may identify the presence of abnormal GER but tell nothing about its pathogenesis. The usual approach to infants who feed poorly, vomit, or fail to gain weight is to identify the presence of abnormal GER, rule out underlying organic causes of vomiting, and then diagnosis primary GER disease. The baby is then treated with pharmacologic, dietary, or positional therapy and, ultimately, if these therapies fail to eradicate the symptoms attributed to GER, surgical fundoplication, which stops vomiting regardless of its causes. The pediatric literature on infant vomiting and GER is almost devoid of research into the nature and possible relationships among infant stress, vomiting, feeding difficulties, and failure to grow. Clinically, the quality of the maternal-infant relationship is frequently approached superficially, with psychosocial aspects treated as less important in infants considered to have primary organic disease amenable to medical or surgical treatment. Psychosocial factors in the pathogenesis of the infant's symptoms are often not pursued beyond assessment for possible abuse or neglect. It has been known for centuries that stress or excitement affects gastrointestinal function and symptoms. Although the field of infant psychiatry has produced a substantial literature on the nature of stresses that affect both infants and mothers, the pediatric literature on vomiting and failure to thrive seldom acknowledges the existence or importance of these contributions. In clinical practice, failure to explore psychosocial aspects that may contribute to vomiting, feeding difficulties, or failure to thrive may result in missed opportunities for less invasive, more effective therapy at best, and countertherapeutic treatment at worst. This article describes three functional vomiting disorders of infancy, their distinguishing characteristics, hypotheses regarding their pathogenesis, and principles of comprehensive management.


A Finite-Element Study of Metal Backing and Tibial Resection Depth in a Composite Tibia Following Total Knee Arthroplasty.
Prosthetic alignment, patient characteristics, and implant design are all factors in long-term survival of total knee arthroplasty (TKA), yet the level at which each of these factors contribute to implant loosening has not been fully described. Prior clinical and biomechanical studies have indicated tibial overload as a cause of early TKA revision. The purpose of this study was to determine the relationship between tibial component design and bone resection on tibial loading. Finite-element analysis (FEA) was performed after simulated implantation of metal backed (MB) and all-polyethylene (AP) TKA components in 5 and 15 mm of tibial resection into a validated intact tibia model. Proximal tibial strains significantly increased between 13% and 199% when implanted with AP components (p < 0.05). Strain significantly increased between 12% and 209% in the posterior tibial compartment with increased bone resection (p < 0.05). This study indicates elevated strains in AP implanted tibias across the entirety of the proximal tibial cortex, as well as a posterior shift in tibial loading in instances of increased resection depth. These results are consistent with trends observed in prior biomechanical studies and may associate the documented device history of tibial collapse in AP components with increased bone strain and overload beneath the prosthesis.


Supplementation with nutrients modulating insulin-like growth factor-1 negatively correlated with changes in the levels of pro-inflammatory cytokines in community-dwelling elderly people at risk of undernutrition.
Suboptimal nutrition accompanied by chronic low-grade increases in circulating cytokine levels is more common in elderly people. We explored the improvement in nutritional status, especially in the level of insulin-like growth factor-1 (IGF-1) and its relationship with changes in circulating cytokine levels, after providing extra protein and energy content to community-dwelling older adults at risk of undernutrition. Sixty nondiabetic subjects, aged ≥65 years and living independently in a community for elderly people, with a serum pre-albumin level ≤30 mg dL-1 and a body mass index <25 kg m-2 , were recruited. The subjects were followed for a 2-week pre-intervention period, during which they maintained routine dietary habits. This was followed by an intervention period, during which they received oral nutritional supplementation for 2 weeks. Following 2 weeks of intervention, there were significant increases in total lymphocyte count (TLC) and insulin-like growth factor (IGF)-1, pre-albumin and transferrin compared to baseline. Body weight and mid-arm circumference significantly increased without alteration of tricep skinfold thickness at the end of the intervention. There was a significant reduction in interleukin (IL)-6 levels and a trend toward a decrease in the tumor necrosis factor (TNF)-α levels. At baseline, age was negatively correlated with IGF-1 levels and positively correlated with IL-6 and TNF-α levels. The change (▵, from baseline) in IGF-1 level was positively correlated with age and negatively correlated with ▵IL-6 and ▵TNF-α. A 2-week intervention with oral nutritional supplementation improved nutritional status and decreased circulating cytokine levels. Specifically, ▵IGF-1 was negatively correlated with changes in pro-inflammatory cytokine levels in community-dwelling elderly people at risk of undernutrition. (Clinicaltrials.gov: NCT02656186).


Total daily energy expenditure among middle-aged men and women: the OPEN Study.
Few large doubly labeled water (DLW) studies have provided an objective measure of total energy expenditure (TEE) in free-living men and women. The committee that developed the 2002 Dietary Reference Intake (DRI) estimated energy requirements (EER) noted that DLW studies in adults aged 40 to 60 y were limited. We aimed to describe TEE and physical activity energy expenditure in middle-aged men and women by sex, age, menopausal status, and level of obesity, and to compare TEE to the DRI EER. TEE was measured by the DLW method in 450 men and women aged 40-69 y from the Observing Protein and Energy Nutrition Study. Resting metabolic rate was estimated by use of the Mifflin equation. Unadjusted TEE was lower in women than in men (591 kcal/d); however, when the analysis was adjusted for fat-free mass, women had significantly higher TEE than did men (182 kcal/d). This difference appeared to be due to higher physical activity levels in women (physical activity energy expenditure adjusted for FFM was 188 kcal/d greater in women than in men). Mean TEE was lowest in the seventh decade. TEE from DLW was highly correlated (r = 0.93) with EER from the DRI equations. In this population, TEE was higher in women than in men when adjusted for FFM, apparently because of higher physical activity levels in women. There were no significant differences in TEE, FFM, or physical activity levels in women by menopausal status. TEE was inversely associated with age and increased linearly with body mass index. This study corroborates the use of the DRI equations for EER.


The fertilization-induced zinc spark is a novel biomarker of mouse embryo quality and early development.
Upon activation, mammalian eggs release billions of zinc ions in an exocytotic event termed the "zinc spark." The zinc spark is dependent on and occurs coordinately with intracellular calcium transients, which are tightly associated with embryonic development. Thus, we hypothesized that the zinc spark represents an early extracellular physicochemical marker of the developmental potential of the zygote. To test this hypothesis, we monitored zinc exocytosis in individual mouse eggs following parthenogenetic activation or in vitro fertilization (IVF) and tracked their development. Retrospective analysis of zinc spark profiles revealed that parthenotes and zygotes that developed into blastocysts released more zinc than those that failed to develop. Prospective selection of embryos based on their zinc spark profile significantly improved developmental outcomes and more than doubled the percentage of embryos that reached the blastocyst stage. Moreover, the zinc spark profile was also associated with embryo quality as the total cell number in the resulting morulae and blastocysts positively correlated with the zinc spark amplitude (R = 0.9209). Zinc sparks can thus serve as an early biomarker of zygote quality in mouse model.


Beyond the schools of psychology 1: a digital analysis of Psychological Review, 1894-1903.
Traditionally, American psychology at the turn of the twentieth century has been framed as a competition among a number of "schools": structuralism, functionalism, behaviorism, etc. But this is only one way in which the "structure" of the discipline can be conceived. Most psychologists did not belong to a particular school, but they still worked within loose intellectual communities, and so their work was part of an implicit psychological "genre," if not a formalized "school." In this study, we began the process of discovering the underlying genres of American psychology at the turn of the twentieth century by taking the complete corpus of articles from the journal Psychological Review during the first decade of its publication and conducting a statistical analysis of the vocabularies they employed to see what clusters of articles naturally emerged. Although the traditional functionalist school was among the clusters we found, we also found distinct research traditions around the topics of color vision, spatial vision, philosophy/metatheory, and emotion. In addition, momentary clusters corresponding to important debates (e.g., the variability hypothesis) appeared during certain years, but not others.


Conducting research with tribal communities: sovereignty, ethics, and data-sharing issues.
When conducting research with American Indian tribes, informed consent beyond conventional institutional review board (IRB) review is needed because of the potential for adverse consequences at a community or governmental level that are unrecognized by academic researchers. In this article, we review sovereignty, research ethics, and data-sharing considerations when doing community-based participatory health-related or natural-resource-related research with American Indian nations and present a model material and data-sharing agreement that meets tribal and university requirements. Only tribal nations themselves can identify potential adverse outcomes, and they can do this only if they understand the assumptions and methods of the proposed research. Tribes must be truly equal partners in study design, data collection, interpretation, and publication. Advances in protection of intellectual property rights (IPR) are also applicable to IRB reviews, as are principles of sovereignty and indigenous rights, all of which affect data ownership and control. Academic researchers engaged in tribal projects should become familiar with all three areas: sovereignty, ethics and informed consent, and IPR. We recommend developing an agreement with tribal partners that reflects both health-related IRB and natural-resource-related IPR considerations.


Daily Objective Physical Activity and Sedentary Time in Adults with COPD Using Spirometry Data from Canadian Measures Health Survey.
Chronic obstructive pulmonary disease (COPD) is expected to be the third leading cause of premature death and disability in Canada and around the world by the year 2020. The study aims to compare objective physical activity (PA) and sedentary time in a population-based sample of adults with chronic obstructive pulmonary disease (COPD) and compare a group, and to investigate whether these behaviors differ according to COPD severity. From the 2007-2013 Canadian Health Measures Survey dataset, accelerometer and prebronchodilator spirometry data were available for 6441 participants, aged 35 to 79. Two weighted analyses of covariance were performed with adjustments for age, sex, body mass index, accelerometer wearing time, season, work, smoking (cotinine), education level, and income. A set of sensitivity analyses were carried out to examine the possible effect of COPD and type of control group. A cross-sectional weighted analysis indicated that 14.6% of study participants had a measured airflow obstruction consistent with COPD. Time in PA (moderate-vigorous and light PA), number of steps, and sedentary duration were not significantly different in participants with COPD, taken together, compared to controls. However, moderate to severe COPD participants (stages ≥2) had a significantly lower daily time spent in PA of moderate and vigorous intensity level compared to controls. Canadian adults with COPD with all disease severity levels combined did not show lower daily duration of light, moderate, and vigorous PA, and number of steps and higher daily sedentary time than those without airflow obstruction. Both groups are extremely sedentary and have low PA duration. Thus, "move more and sit less" public health strategy could equally target adults with or without COPD.


Predicting skin sensitizers with confidence - Using conformal prediction to determine applicability domain of GARD.
GARD - Genomic Allergen Rapid Detection is a cell based alternative to animal testing for identification of skin sensitizers. The assay is based on a biomarker signature comprising 200 genes measured in an in vitro model of dendritic cells following chemical stimulations, and consistently reports predictive performances ~90% for classification of external test sets. Within the field of in vitro skin sensitization testing, definition of applicability domain is often neglected by test developers, and assays are often considered applicable across the entire chemical space. This study complements previous assessments of model performance with an estimate of confidence in individual classifications, as well as a statistically valid determination of the applicability domain for the GARD assay. Conformal prediction was implemented into current GARD protocols, and a large external test dataset (n = 70) was classified at a confidence level of 85%, to generate a valid model with a balanced accuracy of 88%, with none of the tested chemical reactivity domains identified as outside the applicability domain of the assay. In conclusion, results presented in this study complement previously reported predictive performances of GARD with a statistically valid assessment of uncertainty in each individual prediction, thus allowing for classification of skin sensitizers with confidence.


Febrile convulsions--what do parents do?
To find out about the medical and parental management of children having their first febrile convulsion a hospital-based questionnaire study was carried out in which parents were asked what they did at the time. Fifty-four out of 89 parents brought their child directly to hospital while the remainder attempted to contact their general practitioner, usually successfully, and were then referred to hospital. Whichever course of action the parents chose the outcome was satisfactory. Eighty-seven per cent of convulsions lasted for less than 15 minutes and in only two instances did they last longer than 30 minutes. One child who had convulsions for an hour was given intramuscular phenobarbitone at home without success, and the fit was finally terminated with intravenous diazepam. Parental management of the fit was often widly inappropriate. Only a few parents laid the child on his side and waited for the fit to stop. The parents were bewildered and frightened--30% thought their child was dying or dead. Education of patents of young children is needed. Simply written instructions on how to reduce the temperature of a febrile child and manage a convulsion might help.


Lymphocyte-Rich Classical Hodgkin Lymphoma. A Case with Difficulty in Distinguishing from Nodular Lymphocyte-Predominant Hodgkin Lymphoma.
A 35-year-old man was referred to our hospital because of left supraclavicular and cervical lymphadenopathies. Histopathological examination of the lymph nodes revealed reactive lymphadenopathy. He visited our hospital three years after the initial diagnosis because of enlarged left cervical lymph nodes. Histopathologically, both Hodgkin/Reed-Sternberg (H/RS) and lymphocyte-predominant (LP) cells were found in the lymph node. We first suspected nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), because these cells were CD15(-) and CD30(-). However, the diagnosis of lymphocyte-rich classical Hodgkin lymphoma (LRCHL) was finally confirmed, because these cells were found to be CD20(-), Bob.1(+), Oct.2(-), and BCL6(-) by additional immunostaining. The patient was treated with six cycles of ABVD chemotherapy, and a complete response was achieved. However, he underwent autologous stem-cell transplantation after high-dose chemotherapy owing to a relapse 10 months after primary treatment. Distingushing LRCHL from NLPHL was difficult in this patient, because histopathological examination showed both H/RS and LP cells, and immunostaining revealed these cells to be triple negative (CD15(-), CD30(-) and CD20(-)). Accumulation of such cases are necessary to establish better criteria for the differential diagnosis and assessment of clinical behavior.