Factors influencing hospital conveyance following ambulance attendance for people with diabetes: A retrospective observational study.

AIM: To assess variables contributing to hospital conveyance for people with diabetes and the interactions between them. A secondary aim was to generate hypotheses for further research into interventions that might reduce avoidable hospital admissions. METHODS: A national retrospective data set including 30 999 diabetes-related callouts from the Scottish Ambulance Service was utilized covering a 5-year period between 2013 and 2017. The relationship between diabetes-related hospital conveyance and seven potential risk factors was analysed. Independent variables included: age, gender, deprivation, paramedic attendance, treatment at the scene, first blood glucose measurement and day of the week. RESULTS: In Scotland, hyperglycaemia was associated with a higher number of people being conveyed to hospital than hypoglycaemia (49.8% with high blood glucose vs. 39.3% with low glucose, P ≤ 0.0001). Treatment provided in pre-hospital care was associated with reduced conveyance rates (47.3% vs. 58.2% where treatment was not administered, P ≤ 0.0001). Paramedic attendance was also associated with reduced conveyance to hospital (51.4% vs. 59.5% where paramedic was not present, P ≤ 0.0001). Paramedic attendance in hyperglycaemic cases was associated with significantly reduced odds of conveyance (odds ratio 0.52, P ≤ 0.001). CONCLUSIONS: A higher rate of conveyance associated with hyperglycaemic cases indicates a need for more resources, education and training in this area. Higher conveyance rates were also associated with no paramedic being present and no treatment being administered. This suggests that paramedic attendance may be crucial in reducing avoidable admissions. Developing and validating protocols for pre-hospital services and treatment may help to reduce hospital conveyance rates.

Cardiovascular risk prevalence in South Africans with drug-resistant tuberculosis: a cross-sectional study.

In South Africa, the risk factors for cardiovascular disease (CVD) are increasing, thereby impacting patients with drug-resistant tuberculosis (DR-TB). To determine the prevalence of traditional CVD risk factors (diabetes mellitus [DM], smoking, hypertension, increased body mass index [BMI]) and a total risk score for CVD among patients with DR-TB. This cross-sectional study was nested within an ongoing cluster-randomized trial in 10 DR-TB hospitals in South Africa. The data for the present study were collected between November 2014 and July 2016. Of 900 participants aged 18 years, 75.1% were co-infected with the human immunodeficiency virus (HIV), and 52.3% had one or more CVD risk factors. The prevalence of CVD risk factors was hypertension (16.7%), increased BMI (16.6%), DM (5.2%), and smoking (31.4%). Among patients with DM or hypertension, 58.8-95.5% had additional comorbid CVD risk factors. Of 398 participants eligible for the CVD risk score (age 35 years), 23.4% had a moderate or high CVD risk score. Patients with multiple diseases, including DR-TB and HIV, with traditional CVD risk factors, may have higher risks for negative outcomes during treatment for DR-TB. TB providers should identify people at risk to initiate primary and secondary prevention to improve outcomes. .

Effectiveness of psychoeducational interventions for the treatment of diabetes-specific emotional distress and glycaemic control in people with type 2 diabetes: A systematic review and meta-analysis.

AIMS: Psychological comorbidity, such as depression and/or diabetes-specific emotional distress (DSD), is highly prevalent in people with type 2 diabetes (T2DM) and associated with poorer treatment outcomes. While treatments for depression are well established, interventions specifically designed for DSD are sparse. The aim of this study was to determine interventions that successfully address DSD and HbA1c in people with T2DM. METHODS: Seven databases were searched to identify potentially relevant studies. Eligible studies were selected and appraised independently by two reviewers. Multiple meta-analyses and meta-regression analyses were performed to synthesise the data; the primary analyses determined the effect of interventions on DSD, with secondary analyses assessing the effect on HbA1c. RESULTS: Thirty-two studies (n = 5206) provided sufficient DSD data, of which 23 (n = 3818) reported data for HbA1c. Meta-analyses demonstrated that interventions significantly reduced DSD (p = 0.034) and HbA1c (p = 0.006) compared to controls, although subgroup meta-analyses and meta-regression to explore specific intervention characteristics that might mediate this effect yielded non-significant findings. CONCLUSIONS: The findings demonstrate that existing interventions successfully reduce DSD and HbA1c in people with T2DM. While promising, deductions should be interpreted tentatively, highlighting a stark need for further focused exploration of how best to treat psychological comorbidity in people with T2DM.

Evaluating the communities care program: best practice for rigorous research to evaluate gender based violence prevention and response programs in humanitarian settings.

BACKGROUND: Gender-based violence (GBV) is a significant issue for women and girls in humanitarian settings. Innovative primary prevention programs are being developed and implemented with existing response programs to change harmful social norms that sustain GBV in humanitarian settings. Social norms are expectations of how women, men, girls and boys should behave, who should have power and control over behavior, and how families and communities value women and girls and support their rights and opportunities. METHODS: The United Nations Children's Fund (UNICEF) led Communities Care program is a primary prevention and response program designed from the understanding that within the context of conflict and displacement, there is an opportunity for positive change in social norms that support gender equity, and decrease GBV. The goal is to support communities in humanitarian settings to create healthy, safe and peaceful environments with quality response services for women and girls by transforming harmful social norms that uphold violence into norms that promote dignity, equity, and non-violence. CONCLUSION: This manuscript will highlight the use of best practices in GBV research to rigorously evaluate the Communities Care program in two diverse in humanitarian settings, Somalia and South Sudan.

Sex-antagonistic genes, XY recombination and feminized Y chromosomes.

The canonical model of sex-chromosome evolution predicts that sex-antagonistic (SA) genes play an instrumental role in the arrest of XY recombination and ensuing Y chromosome degeneration. Although this model might account for the highly differentiated sex chromosomes of birds and mammals, it does not fit the situation of many lineages of fish, amphibians or nonavian reptiles, where sex chromosomes are maintained homomorphic through occasional XY recombination and/or high turnover rates. Such situations call for alternative explanatory frameworks. A crucial issue at stake is the effect of XY recombination on the dynamics of SA genes and deleterious mutations. Using individual-based simulations, we show that a complete arrest of XY recombination actually benefits females, not males. Male fitness is maximized at different XY recombination rates depending on SA selection, but never at zero XY recombination. This should consistently favour some level of XY recombination, which in turn generates a recombination load at sex-linked SA genes. Hill-Robertson interferences with deleterious mutations also impede the differentiation of sex-linked SA genes, to the point that males may actually fix feminized phenotypes when SA selection and XY recombination are low. We argue that sex chromosomes might not be a good localization for SA genes, and sex conflicts seem better solved through the differential expression of autosomal genes.

The prevalence of diabetes-specific emotional distress in people with Type 2 diabetes: a systematic review and meta-analysis.

AIMS: Psychological comorbidity, such as depression and/or diabetes-specific emotional distress (diabetes distress), is widespread in people with Type 2 diabetes and is associated with poorer treatment outcomes. Although extensive research into the prevalence of depression has been conducted, the same attention has not been given to diabetes distress. The aim of this systematic review was to determine the overall prevalence of diabetes distress in people with Type 2 diabetes. METHODS: Seven databases were searched to identify potentially relevant studies; eligible studies (adult population aged > 18 years with Type 2 diabetes and an outcome measure of diabetes distress) were selected and appraised independently by two reviewers. Multiple fixed- and random-effects meta-analyses were performed to synthesize the data; with primary analyses to determine the overall prevalence of diabetes distress in people with Type 2 diabetes, and secondary meta-analyses and meta-regression to explore the prevalence across different variables. RESULTS: Fifty-five studies (n = 36 998) were included in the meta-analysis and demonstrated an overall prevalence of 36% for diabetes distress in people with Type 2 diabetes. Prevalence of diabetes distress was significantly higher in samples with a higher prevalence of comorbid depressive symptoms and a female sample majority. CONCLUSIONS: Diabetes distress is a prominent issue in people with Type 2 diabetes that is associated with female gender and comorbid depressive symptoms. It is important to consider the relationship between diabetes distress and depression, and the significant overlap between conditions. Further work is needed to explore psychological comorbidity in Type 2 diabetes to better understand how best to identify and appropriately treat individuals.

The genetic contribution to sex determination and number of sex chromosomes vary among populations of common frogs (Rana temporaria).

The patterns of sex determination and sex differentiation have been shown to differ among geographic populations of common frogs. Notably, the association between phenotypic sex and linkage group 2 (LG2) has been found to be perfect in a northern Swedish population, but weak and variable among families in a southern one. By analyzing these populations with markers from other linkage groups, we bring two new insights: (1) the variance in phenotypic sex not accounted for by LG2 in the southern population could not be assigned to genetic factors on other linkage groups, suggesting an epigenetic component to sex determination; (2) a second linkage group (LG7) was found to co-segregate with sex and LG2 in the northern population. Given the very short timeframe since post-glacial colonization (in the order of 1000 generations) and its seemingly localized distribution, this neo-sex chromosome system might be the youngest one described so far. It does not result from a fusion, but more likely from a reciprocal translocation between the original Y chromosome (LG2) and an autosome (LG7), causing their co-segregation during male meiosis. By generating a strict linkage between several important genes from the sex-determination cascade (Dmrt1, Amh and Amhr2), this neo-sex chromosome possibly contributes to the 'differentiated sex race' syndrome (strictly genetic sex determination and early gonadal development) that characterizes this northern population.

Comprehensive development and testing of the ASIST-GBV, a screening tool for responding to gender-based violence among women in humanitarian settings.

BACKGROUND: Conflict affected refugees and internally displaced persons (IDPs) are at increased vulnerability to gender-based violence (GBV). Health, psychosocial, and protection services have been implemented in humanitarian settings, but GBV remains under-reported and available services under-utilized. To improve access to existing GBV services and facilitate reporting, the ASIST-GBV screening tool was developed and tested for use in humanitarian settings. This process was completed in four phases: 1) systematic literature review, 2) qualitative research that included individual interviews and focus groups with GBV survivors and service providers, respectively, 3) pilot testing of the developed screening tool, and 4) 3-month implementation testing of the screening tool. Research was conducted among female refugees, aged ≥15 years in Ethiopia, and female IDPs, aged ≥18 years in Colombia. RESULTS: The systematic review and meta-analysis identified a range of GBV experiences and estimated a 21.4 % prevalence of sexual violence (95 % CI:14.9-28.7) among conflict-affected populations. No existing screening tools for GBV in humanitarian settings were identified. Qualitative research with GBV survivors in Ethiopia and Colombia found multiple forms of GBV experienced by refugees and IDPs that occurred during conflict, in transit, and in displaced settings. Identified forms of violence were combined into seven key items on the screening tool: threats of violence, physical violence, forced sex, sexual exploitation, forced pregnancy, forced abortion, and early or forced marriage. Cognitive testing further refined the tool. Pilot testing in both sites demonstrated preliminary feasibility where 64.8 % of participants in Ethiopia and 44.9 % of participants in Colombia were identified with recent (last 12 months) cases of GBV. Implementation testing of the screening tool, conducted as a routine service in camp/district hospitals, allowed for identification of GBV cases and referrals to services. In this phase, 50.6 % of participants in Ethiopia and 63.4 % in Colombia screened positive for recent experiences of GBV. Psychometric testing demonstrated appropriate internal consistency of the tool (Cronbach's α = 0.77) and item response theory demonstrated appropriate discrimination and difficulty of the tool. CONCLUSION: The ASIST-GBV screening tool has demonstrated utility and validity for use in confidential identification and referral of refugees and IDPs who experience GBV.

High-density linkage maps fail to detect any genetic component to sex determination in a Rana temporaria family.

Sex chromosome differentiation in Rana temporaria varies strikingly among populations or families: whereas some males display well-differentiated Y haplotypes at microsatellite markers on linkage group 2 (LG2), others are genetically undistinguishable from females. We analysed with RADseq markers one family from a Swiss lowland population with no differentiated sex chromosomes, and where sibship analyses had failed to detect any association between the phenotypic sex of progeny and parental haplotypes. Offspring were reared in a common tank in outdoor conditions and sexed at the froglet stage. We could map a total of 2177 SNPs (1123 in the mother, 1054 in the father), recovering in both adults 13 linkage groups (= chromosome pairs) that were strongly syntenic to Xenopus tropicalis despite > 200 My divergence. Sexes differed strikingly in the localization of crossovers, which were uniformly distributed in the female but limited to chromosome ends in the male. None of the 2177 markers showed significant association with offspring sex. Considering the very high power of our analysis, we conclude that sex determination was not genetic in this family; which factors determined sex remain to be investigated.

High-density sex-specific linkage maps of a European tree frog (Hyla arborea) identify the sex chromosome without information on offspring sex.

Identifying homology between sex chromosomes of different species is essential to understanding the evolution of sex determination. Here, we show that the identity of a homomorphic sex chromosome pair can be established using a linkage map, without information on offspring sex. By comparing sex-specific maps of the European tree frog Hyla arborea, we find that the sex chromosome (linkage group 1) shows a threefold difference in marker number between the male and female maps. In contrast, the number of markers on each autosome is similar between the two maps. We also find strongly conserved synteny between H. arborea and Xenopus tropicalis across 200 million years of evolution, suggesting that the rate of chromosomal rearrangement in anurans is low. Finally, we show that recombination in males is greatly reduced at the centers of large chromosomes, consistent with previous cytogenetic findings. Our research shows the importance of high-density linkage maps for studies of recombination, chromosomal rearrangement and the genetic architecture of ecologically or economically important traits.

Origin and genome evolution of polyploid green toads in Central Asia: evidence from microsatellite markers.

Polyploidization, which is expected to trigger major genomic reorganizations, occurs much less commonly in animals than in plants, possibly because of constraints imposed by sex-determination systems. We investigated the origins and consequences of allopolyploidization in Palearctic green toads (Bufo viridis subgroup) from Central Asia, with three ploidy levels and different modes of genome transmission (sexual versus clonal), to (i) establish a topology for the reticulate phylogeny in a species-rich radiation involving several closely related lineages and (ii) explore processes of genomic reorganization that may follow polyploidization. Sibship analyses based on 30 cross-amplifying microsatellite markers substantiated the maternal origins and revealed the paternal origins and relationships of subgenomes in allopolyploids. Analyses of the synteny of linkage groups identified three markers affected by translocation events, which occurred only within the paternally inherited subgenomes of allopolyploid toads and exclusively affected the linkage group that determines sex in several diploid species of the green toad radiation. Recombination rates did not differ between diploid and polyploid toad species, and were overall much reduced in males, independent of linkage group and ploidy levels. Clonally transmitted subgenomes in allotriploid toads provided support for strong genetic drift, presumably resulting from recombination arrest. The Palearctic green toad radiation seems to offer unique opportunities to investigate the consequences of polyploidization and clonal transmission on the dynamics of genomes in vertebrates.

Risk factors for fracture among current, persistent users of bisphosphonates.

SUMMARY: Bisphosphonate therapy reduces fracture risk but does not eliminate fracture occurrence. We determined the fracture incidence and risk factors for fractures among 14,674 bisphosphonate users in a community setting. Bisphosphonate users remained at risk of fracture, and additional measures to prevent fractures in these patients would be beneficial. INTRODUCTION: Bisphosphonate therapy reduces but does not eliminate fracture occurrence. The incidence of fracture and risk factors for fractures among persistent, current users of bisphosphonates in a community setting have not been well studied. METHODS: We conducted a retrospective cohort study of 14,674 bisphosphonate users in a health maintenance organization. Patients were followed until a 3-month gap in therapy, creating a pool of highly compliant [mean medication possession ratio (MPR) of 94%] current users. We used Cox proportional hazards models to identify risk factors for fractures among these persistent, current users. RESULTS: There were 867 fractures over the period of observation or 3.7 fractures per 100 users per year. Older patients who take multiple medications, have lower bone mineral density, have a history of prior fracture, and suffer from particular comorbidities (i.e., dementia, chronic kidney disease, and rheumatoid arthritis) are at higher risk of fracture while taking bisphosphonates. CONCLUSION: Persistent, current bisphosphonate users remain at risk of fracture, and additional measures to prevent fractures in these patients would be of benefit.

Inferring the degree of incipient speciation in secondary contact zones of closely related lineages of Palearctic green toads (Bufo viridis subgroup).

Reproductive isolation between lineages is expected to accumulate with divergence time, but the time taken to speciate may strongly vary between different groups of organisms. In anuran amphibians, laboratory crosses can still produce viable hybrid offspring >20 My after separation, but the speed of speciation in closely related anuran lineages under natural conditions is poorly studied. Palearctic green toads (Bufo viridis subgroup) offer an excellent system to address this question, comprising several lineages that arose at different times and form secondary contact zones. Using mitochondrial and nuclear markers, we previously demonstrated that in Sicily, B. siculus and B. balearicus developed advanced reproductive isolation after Plio-Pleistocene divergence (2.6 My, 3.3-1.9), with limited historic mtDNA introgression, scarce nuclear admixture, but low, if any, current gene flow. Here, we study genetic interactions between younger lineages of early Pleistocene divergence (1.9 My, 2.5-1.3) in northeastern Italy (B. balearicus, B. viridis). We find significantly more, asymmetric nuclear and wider, differential mtDNA introgression. The population structure seems to be molded by geographic distance and barriers (rivers), much more than by intrinsic genomic incompatibilities. These differences of hybridization between zones may be partly explained by differences in the duration of previous isolation. Scattered research on other anurans suggests that wide hybrid zones with strong introgression may develop when secondary contacts occur <2 My after divergence, whereas narrower zones with restricted gene flow form when divergence exceeds 3 My. Our study strengthens support for this rule of thumb by comparing lineages with different divergence times within the same radiation.

Eastern Canadian Colorectal Cancer Consensus Conference: standards of care for the treatment of patients with rectal, pancreatic, and gastrointestinal stromal tumours and pancreatic neuroendocrine tumours.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20-22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of folfirinox in pancreatic cancer, and treatment of stage ii colon cancer.

Maintenance of ancestral sex chromosomes in Palearctic tree frogs: direct evidence from Hyla orientalis.

Contrasting with the situation found in birds and mammals, sex chromosomes are generally homomorphic in poikilothermic vertebrates. This homomorphy was recently shown to result from occasional X-Y recombinations (not from turnovers) in several European species of tree frogs (Hyla arborea, H. intermedia and H. molleri). Because of recombination, however, alleles at sex-linked loci were rarely diagnostic at the population level; support for sex linkage had to rely on multilocus associations, combined with occasional sex differences in allelic frequencies. Here, we use direct evidence, obtained from anatomical and histological analyses of offspring with known pedigrees, to show that the Eastern tree frog (H. orientalis) shares the same pair of sex chromosomes, with identical patterns of male heterogamety and complete absence of X-Y recombination in males. Conservation of an ancestral pair of sex chromosomes, regularly rejuvenated via occasional X-Y recombination, seems thus a widespread pattern among Hyla species. Sibship analyses also identified discrepancies between genotypic and phenotypic sex among offspring, associated with abnormal gonadal development, suggesting a role for sexually antagonistic genes on the sex chromosomes.

Within-population polymorphism of sex-determination systems in the common frog (Rana temporaria).

In sharp contrast with birds and mammals, the sex chromosomes of ectothermic vertebrates are often undifferentiated, for reasons that remain debated. A linkage map was recently published for Rana temporaria (Linnaeus, 1758) from Fennoscandia (Eastern European lineage), with a proposed sex-determining role for linkage group 2 (LG2). We analysed linkage patterns in lowland and highland populations from Switzerland (Western European lineage), with special focus on LG2. Sibship analyses showed large differences from the Fennoscandian map in terms of recombination rates and loci order, pointing to large-scale inversions or translocations. All linkage groups displayed extreme heterochiasmy (total map length was 12.2 cM in males, versus 869.8 cM in females). Sex determination was polymorphic within populations: a majority of families (with equal sex ratios) showed a strong correlation between offspring phenotypic sex and LG2 paternal haplotypes, whereas other families (some of which with female-biased sex ratios) did not show any correlation. The factors determining sex in the latter could not be identified. This coexistence of several sex-determination systems should induce frequent recombination of X and Y haplotypes, even in the absence of male recombination. Accordingly, we found no sex differences in allelic frequencies on LG2 markers among wild-caught male and female adults, except in one high-altitude population, where nonrecombinant Y haplotypes suggest sex to be entirely determined by LG2. Multifactorial sex determination certainly contributes to the lack of sex-chromosome differentiation in amphibians.

Low rates of X-Y recombination, not turnovers, account for homomorphic sex chromosomes in several diploid species of Palearctic green toads (Bufo viridis subgroup).

Contrasting with birds and mammals, most ectothermic vertebrates present homomorphic sex chromosomes, which might be due either to a high turnover rate or to occasional X-Y recombination. We tested these two hypotheses in a group of Palearctic green toads that diverged some 3.3 million years ago. Using sibship analyses of sex-linked markers, we show that all four species investigated share the same pair of sex chromosomes and a pattern of male heterogamety with drastically reduced X-Y recombination in males. Phylogenetic analyses of sex-linked sequences show that X and Y alleles cluster by species, not by gametolog. We conclude that X-Y homomorphy and fine-scale sequence similarity in these species do not stem from recent sex-chromosome turnovers, but from occasional X-Y recombination.

Within- and among-population impact of genetic erosion on adult fitness-related traits in the European tree frog Hyla arborea.

Assessing in wild populations how fitness is impacted by inbreeding and genetic drift is a major goal for conservation biology. An approach to measure the detrimental effects of inbreeding on fitness is to estimate correlations between molecular variation and phenotypic performances within and among populations. Our study investigated the effect of individual multilocus heterozygosity on body size, body condition and reproductive investment of males (that is, chorus attendance) and females (that is, clutch mass and egg size) in both small fragmented and large non-fragmented populations of European tree frog (Hyla arborea). Because adult size and/or condition and reproductive investment are usually related, genetic erosion may have detrimental effects directly on reproductive investment, and also on individual body size and condition that in turn may affect reproductive investment. We confirmed that the reproductive investment was highly size-dependent for both sexes. Larger females invested more in offspring production, and larger males attended the chorus in the pond more often. Our results did not provide evidence for a decline in body size, condition and reproductive effort with decreased multilocus heterozygosity both within and among populations. We showed that the lack of heterozygosity-fitness correlations within populations probably resulted from low inbreeding levels (inferior to ca. 20% full-sib mating rate), even in the small fragmented populations. The detrimental effects of fixation load were either low in adults or hidden by environmental variation among populations. These findings will be useful to design specific management actions to improve population persistence.

Cryptic recombination in the ever-young sex chromosomes of Hylid frogs.

Sex chromosomes are expected to evolve suppressed recombination, which leads to degeneration of the Y and heteromorphism between the X and Y. Some sex chromosomes remain homomorphic, however, and the factors that prevent degeneration of the Y in these cases are not well understood. The homomorphic sex chromosomes of the European tree frogs (Hyla spp.) present an interesting paradox. Recombination in males has never been observed in crossing experiments, but molecular data are suggestive of occasional recombination between the X and Y. The hypothesis that these sex chromosomes recombine has not been tested statistically, however, nor has the X-Y recombination rate been estimated. Here, we use approximate Bayesian computation coupled with coalescent simulations of sex chromosomes to quantify X-Y recombination rate from existent data. We find that microsatellite data from H. arborea, H. intermedia and H. molleri support a recombination rate between X and Y that is significantly different from zero. We estimate that rate to be approximately 10(5) times smaller than that between X chromosomes. Our findings support the notion that very low recombination rate may be sufficient to maintain homomorphism in sex chromosomes.