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The files for ultrasound diagnosis of gestating mares belonging to the French equine herd recorded for 3 consecutive years were joined with the files for foal birth of these same mares, allowing the statistical analysis of factors of pregnancy loss. For 28 872 positive diagnoses of gestation, 2898 losses were recorded, that is, a global rate of gestation interruption of 9.12%. The etiology of these interruptions is mainly extrinsic: the year and month of insemination, as well as region for climatic reasons. The intrinsic causes that are implicated are breed of the father (heavy breeds except the hypermetric ones lose fewer pregnancies than warm-blooded breeds), age of the mother (losses are lower in mares of 7 to 10 years of age) and status (mares with foals have fewer pregnancy losses than mares not having foaled the previous year), as well as fetuses with consanguinity (when this increases, the pregnancy losses increase as well). However, the additive genetic effect is extremely low; it corresponds to heritability below 5% and few effects of the environment, common to the offspring of the same mare, were identified. This therefore gives little hope of being able to select against the ‘gestation loss’ trait.

We begin by situating this work and ourselves in graduate writing. Although our experiences as burgeoning researchers are not a focus of this article, we are nonetheless present in the background, not unlike a palimpsest. We trace one aspect of this palimpsest—the use of playful and creative methods to generate ideas for this paper—before then suggesting three key concepts we consider foundational to discussions about play and graduate writing development. These are play, playspace, and mindsets. Building on these concepts, we offer some concluding remarks about the ambivalence some learners may have—which we refer to as play ambivalence—and propose that this ambivalence is partly related to the three concepts underscored in this article. We suggest that future research in play and graduate writing development could better consider this play ambivalence.

A study was conducted near Crowley, Louisiana, to evaluate the efficacy of quizalofop-p-ethyl mixed with different synthetic auxin and ACCase-inhibiting herbicides for barnyardgrass and weedy rice control in rice production systems. Quizalofop was applied at 0 or 120 g ai·ha−1 mixed with 2,4-D at 1336 g ai·ha−1, triclopyr at 282 g ai·ha−1, quinclorac at 420 g ai·ha−1, cyhalofop-butyl at 314 g ai·ha−1, or fenoxaprop-p-ethyl at 122 g ai·ha−1. Cyhalofop, fenoxaprop, 2,4-D, quinclorac, and triclopyr antagonized quizalofop for barnyardgrass control at 14 days after treatment (DAT). At 28 DAT, an antagonistic response persisted for barnyardgrass control, except when cyhalofop was mixed with quizalofop, which indicated a neutral response. Red rice, CLXL-745, and CL-111 control decreased due to antagonism of quizalofop when mixed with 2,4-D. However, quinclorac, triclopyr, cyhalofop, or fenoxaprop mixed with quizalofop resulted in a neutral response for red rice, CLXL-745, and CL-111 control at 28 DAT.

Commercialization of crops tolerant to application of 2, 4-dichlorophenoxyacetic acid (2,4-D) and dicamba is a cause of major concern for sweetpotato (Ipomoea batatas) producers regarding potential negative impacts due to herbicide drift or sprayer contamination events. A field study was initiated in 2016 and repeated in 2017 to assess impacts of reduced rates of combinations of glyphosate with 2,4-D or dicamba on sweetpotato growth and production. Reduced rates of 1/10x, 1/33x, 1/66x, and 1/100x of a 1x rate of glyphosate at 1 lb/acre plus 2,4-D choline at 0.94 lb/acre and glyphosate at 1 lb/acre plus diglycolamine salt of dicamba at 0.5 lb/acre were applied to ‘Beauregard’ sweetpotato at 10 or 30 days after transplanting. With respect to visual injury, in general glyphosate plus dicamba proved to be more injurious than glyphosate plus 2,4-D, especially within the lower rate range. In most cases injury was greater at the later application timing. In either case, typical hormonal herbicide symptomology was quite evident 35 days after application. With respect to U.S. No. 1 and total (U.S. No. 1, canner, and jumbo grade) sweetpotato yield, greatest negative impact was observed with herbicide application at the upper rate range, particularly the 1/10 and 1/33x rates, and at the later application timing regardless of herbicide applied.

In southeastern regions of the US, herbage systems are primarily based on grazing or hay feeding with low nutritive value warm-season perennial grasses. Nutritious herbage such as annual ryegrass (Lolium multiflorum Lam.) may be more suitable for preserving as baleage for winter feeding even with more intensive production inputs. Emerging in-line wrapped baleage storage systems featuring rapid wrapping and low polyethylene film requirements need to be tested for consistency of storing nutritive value of a range of annual ryegrass herbage. A ryegrass storage trial was conducted with 24-h wilted ‘Marshall’ annual ryegrass harvested at booting, heading and anthesis stages using three replicated in-line wrapped tubes containing ten round bales per tube. After a six-month storage period, nutritive value changes and fermentation end products differed significantly by harvest stage but not by bale location. Although wilted annual ryegrass exhibited a restricted fermentation across harvest stages characterized by high pH and low fermentation end product concentrations, butyric acid concentrations were less than 1 g/kg dry matter, and lactic acid was the major organic acid in the bales. Mold coverage and bale aroma did not differ substantially with harvest stage or bale location. Booting and heading stage-harvested ryegrass baleage were superior in nutritive value to anthesis stage-harvested herbage. Based on the investigated nutritive value and fermentation characteristics, individual bale location within in-line tubes did not significantly affect preservation quality of ryegrass round bale silages.

ASXL transcriptional regulator 1 (ASXL1) is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside DNA methyltransferase 3 alpha (DNMT3A) and Tet methylcytosine dioxygenase 2 ( TET2) . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin. In contrast, the mechanisms that connect mutant ASXL1 and CH are not yet fully understood. CH/CMML-associated ASXL1 mutations encode C-terminally truncated proteins that enhance the deubiquitinase activity of the ASXL-BAP1 "PR-DUB" deubiquitinase complex, which removes monoubiquitin from H2AK119Ub. Here, we show that ASXL1 mutant proteins interact with the euchromatic histone lysine methyltransferases 1 and 2 (EHMT1-EHMT2) complex, which generates H3K9me1 and me2, the latter a repressive modification in constitutive heterochromatin. Compared to cells from age-matched wild-type mice, we found that expanded myeloid cells from old (≥18-mo-old) Asxl1tm/+ mice, a heterozygous knock-in mouse model of CH, display genome-wide decreases of H3K9me2, H3K9me3, and H2AK119Ub as well as an associated increase in expression of transposable elements (TEs) and satellite repeats. Increased TE expression was also observed in monocytes from ASXL1 -mutant CMML patients compared to monocytes from healthy controls. Our data suggest that mutant ASXL1 proteins compromise the integrity of both constitutive and facultative heterochromatin in an age-dependent manner by reducing the levels of H3K9me2/3 and H2AK119Ub. This increase in TE expression correlated with increased expression of nearby genes, including many interferon-inducible (inflammation-associated) genes (ISGs)., Competing Interests: Competing interests statement:A.R. is a member of the Scientific Advisory Board of biomodal, formerly Cambridge Epigenetix. All other authors declare no competing interests.

Purpose of Review: Occupational asthma (OA) is a complex condition that can be difficult to diagnose. The purpose of this review is to describe some recent findings regarding the epidemiology of OA, the occupational sensitizing agents, the prognosis of OA, and its primary prevention., Recent Findings: The risk of developing OA varies according to the geographic localization of the worker, the type of industry and the type of sensitizing agents. New findings have been reported for several known sensitizing agents, such as isocyanates, seafood & cleaning agents, and their related industries, such as hairdressing salons and schools. Moreover, a few new sensitizing agents, such as cannabis, have been identified in the past few years. The prognosis of OA seems worse than that of nonwork-related asthma. It is mainly determined by the duration and the level of exposure. Primary prevention is crucial to reduce the number of new cases of OA. Complete avoidance of exposure to the causal agent remains the optimal treatment of sensitizer-induced OA., Summary: Improving our knowledge regarding OA and its causative agents is key to enable an early recognition of this condition and improve its prognosis. Further research is still needed to improve primary prevention., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Orthotic devices may be prescribed for the management of foot and ankle deformities caused by Charcot-Marie-Tooth disease (CMT). However, the actual use of these devices is variable. No studies have evaluated the impact of prescription, delivery and follow-up of orthotic devices on their use.We aimed to describe the relationship between the pathways followed by individuals with CMT and orthotic device use., Materials and Methods: Exploratory, cross-sectional, 35-item survey of orthotic device management. Individuals with CMT were recruited from CMT-France Association., Results: Of the 940 respondents, 795 were included, mean age of 52.9 (SD 16.9) years. Rate of orthotic device use was 49.2% (391/795). The most frequent reason for non-use was a poor fit. Non-use was related to the orthotic device type, the health professionals consulted, and the severity of the CMT-related impairments. Follow-up visits (38.7%), re-evaluation of orthotic devices (25.3%) and consultations with the Physical and Rehabilitation Medicine physician were infrequent (28.3%)., Conclusions: Orthotic devices are massively underused. Follow-up and re-evaluation are infrequent. Care pathways, prescription and delivery of orthotic devices must be optimized to meet the expectations of people with CMT. Device fitting, individual needs, and changes in the clinical state must be re-evaluated regularly by specialists to improve orthotic device use.

Purpose: The 6-item Foot Posture Index (FPI-6) is a reliable tool for the evaluation of foot deformities. Our aim was to translate and cross-culturally validate the FPI-6 for use in French-speaking countries and to determine the intra-rater and inter-rater reliability of the French version., Methods: Cross-cultural adaptation was performed according to guidelines. Two clinicians assessed the FPI-6 in 52 asymptomatic individuals. We evaluated intra- and inter-rater reliability with the intraclass correlation coefficients (ICC), correlations (p-value < 0.05) and Bland-Altman plots. Standard error of measurement (SEM) and minimum detectable change (MDC 95 ) were determined., Results: For the cross-cultural adaptation, we modified several items of the FPI-6 user guide and added footnotes to ensure correct interpretation. ICC of the total FPI-6 scores were 0.94 to 0.96 for the intra- and inter-rater reliability for dominant and non-dominant lower limb. Correlations were significant ( p  < 0.001); r 0.88 to 0.92. Total score SEM was 0.68 to 0.78 and MDC 95 was 1.58 to 1.82., Conclusions: Intra- and inter-rater reliability of this French version of the FPI-6 was excellent for the total score and good to excellent for each item. The French FPI-6 can be used in French-speaking countries. The identification of SEM and MDC scores is useful for clinical interpretation.

Background: Satisfaction with hallux valgus repair is often poor, despite good surgical outcomes. Many tools have been developed to assess the outcome of the procedure; however none evaluate the association between the initial motive for repair and the reasons for post-surgical dissatisfaction. The aim of this study was to develop a new tool to analyse the subjective and objective expectations of individuals during a pre-operative consultation for hallux valgus repair in order to improve post-surgical satisfaction., Methods: We first collected the reasons for dissatisfaction with repair from the medical files of dissatisfied individuals. Then, a steering committee of 4 French experts in the management of hallux valgus designed a questionnaire based on the reasons for dissatisfaction. We then used the DELPHI method to validate the questionnaire: we submitted the questionnaire to a panel of 34 francophone experts in hallux valgus repair for rating in 4 rounds., Results: The medical files of 853 individuals were reviewed and a 52-item questionnaire relating to expectations from hallux valgus surgery was drafted. After the 4 rounds, a final 44 item questionnaire reached consensus. Thirteen items related to clinical and psychological profile, 5 to pain, 9 to physical activity, 4 to aesthetics and 13 to footwear., Conclusion: This tool should facilitate gathering of individuals' expectations from hallux valgus repair to ensure realistic goals and reduce post-surgical dissatisfaction., Competing Interests: The authors have declared that no competing interests exist.

Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using 1 H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor.

The COVID-19 health crisis has put to the test Latin America's already precarious social protection systems. This paper comparatively examines what type of social protection has been provided, by whom, and to what extent migrant and refugee populations have been included in these programmes in seven countries of the region during the COVID-19 pandemic, between March and December 2020. We develop a typology of models of social protection highlighting the assemblages of actors, different modes of protection and the emerging migrants' subjectification in Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Uruguay in relation to Non-Contributory Social Transfer (NCST) programmes and other actions undertaken by state and non-state actors. The analysis is based on 85 semi-structured interviews with representatives of national and local governments, International Organisations, Civil Society Organisations, and migrant-led organisations across 16 cities, and a systematic review of regulatory frameworks in the country-case studies. The proposed typology shows broad heterogeneity and complexity regarding different degrees of inclusion of migrant and refugee populations, particularly in pre-existing and new NCST programmes. These actions are furthering notions of migrant protection that are contingent and crisis-driven, imposing temporal limitations that often selectively exclude migrants based on legal status. It also brings to the fore the path-dependent nature of policies and practices of exclusion/inclusion in the region, which impact on migrants' effective access to social and economic rights, while shaping the broader dynamics of migration governance in the region., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2021.)

Tissue homeostasis requires regulation of cell-cell communication, which relies on signaling molecules and cell contacts. In skin epidermis, keratinocytes secrete factors transduced by melanocytes into signaling cues promoting their pigmentation and dendrite outgrowth, while melanocytes transfer melanin pigments to keratinocytes to convey skin photoprotection. How epidermal cells integrate these functions remains poorly characterized. Here, we show that caveolae are asymmetrically distributed in melanocytes and particularly abundant at the melanocyte-keratinocyte interface in epidermis. Caveolae in melanocytes are modulated by ultraviolet radiations and keratinocytes-released factors, like miRNAs. Preventing caveolae formation in melanocytes increases melanin pigment synthesis through upregulation of cAMP signaling and decreases cell protrusions, cell-cell contacts, pigment transfer and epidermis pigmentation. Altogether, we identify that caveolae serve as molecular hubs that couple signaling outputs from keratinocytes to mechanical plasticity of pigment cells. The coordination of intercellular communication and contacts by caveolae is thus crucial to skin pigmentation and tissue homeostasis.

Background: Recent work in international relations theory argues that international regimes do not develop in isolation, as previously assumed, but evolve as open systems that interact with other regimes. The implications of this insight's for sustainable development remains underexplored. Even thought environmental protection and health promotion are clearly interconnected at the impact level, it remains unclear how global environmental governance interacts with global health governance at the institutional level. In order to fill this gap, this article aims to assess how environmental treaties contribute to global health governance., Methods and Results: To assess how environmental treaties contribute to global health governance, we conducted a content analysis of 2280 international environmental treaties. For each of these treaties, we measure the type and number of health-related provisions in these treaties. The result is the Health and Environment Interplay Database (HEIDI), which we make public with the publication of this article. This new database reveals that more than 300 environmental treaties have health-related provisions., Conclusions: We conclude that the global environmental regime contributes significantly to the institutionalization of the global health regime, considering that the health regime includes itself very few treaties focusing primarily on health. When reflecting on how global governance can improve population health, decision makers should not only consider the instruments available to them within the realm of global health institutions. They should broaden their perspectives to integrate the contribution of other global regimes, such as the global environmental regime.

Effective approaches to non-communicable disease (NCD) prevention require intersectoral action targeting health and engaging government, industry, and society. There is an ongoing vigorous exploration of the most effective and appropriate role of government in intersectoral partnerships. This debate is particularly pronounced with regards to the role of government in controlling unhealthy foods and promoting healthy food environments. Given that food environments are a key determinant of health, and the commercial sector is a key player in shaping such environments (eg, restaurants, grocery stores), the relationship between government and the commercial sector is of primary relevance. The principal controversy at the heart of this relationship pertains to the potential influence of commercial enterprises on public institutions. We propose that a clear distinction between the regulatory and catalyst roles of government is necessary when considering the nature of the relationship between government and the commercial food sector. We introduce a typology of three catalyst roles for government to foster healthy food environments with the commercial sector and suggest that a richer understanding of the contrasting roles of government is needed when considering approaches NCD prevention via healthy food environments., (© 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

The Glycoside Hydrolase Family 13 (GH13) is both evolutionarily diverse and relevant to many industrial applications. Its members hydrolyze starch into smaller carbohydrates and members of the family have been bioengineered to improve catalytic function under industrial environments. We introduce a framework to analyze the response to selection of GH13 protein structures given some phylogenetic and simulated dynamic information. We find that the TIM-barrel (a conserved protein fold consisting of eight α-helices and eight parallel β-strands that alternate along the peptide backbone, common to all amylases) is not selectable since it is under purifying selection. We also show a method to rank important residues with higher inferred response to selection. These residues can be altered to effect change in properties. In this work, we define fitness as inferred thermodynamic stability. We show that under the developed framework, residues 112Y, 122K, 124D, 125W, and 126P are good candidates to increase the stability of the truncated α-amylase protein from Geobacillus thermoleovorans (PDB code: 4E2O; α-1,4-glucan-4-glucanohydrolase; EC 3.2.1.1). Overall, this paper demonstrates the feasibility of a framework for the analysis of protein structures for any other fitness landscape.

Over the last years, many actions have been implemented in the Canadian province of Quebec to prevent health issues related to diet, physical activity and obesity. As a new public health programme is being launched, the 'How can we do better?' project aimed to identify priority areas for further action. An exhaustive search led to identify 166 interventions rolled out in Quebec between 2006 and 2014. We compared it with evidence-based recommendations. Findings were challenged during a 2-d deliberative forum gathering 25 key stakeholders. At the crossroads of these analyses, 50 proposals emerged to sustain/bolster current efforts or to implement new initiatives. Specific improvements were recommended, e.g. about food supply quality monitoring, healthy food accessibility and affordability, physical activity promotion through land use policies, schools and childcare facilities retrofit and urban planning. Crosscutting proposals stress the importance to implement a new governmental prevention strategy and to reinforce evaluation at all levels. This call for action takes place at a critical period for political commitment and should be maintained until and after curbing the prevalence of obesity and related diseases. Although Quebec-focused, 'How can we do better?' project outcomes may be informative for other jurisdictions, and the methods may be inspiring for those interested in combining knowledge syntheses and deliberative processes to inform decision makers in a limited time frame., (© 2017 World Obesity Federation.)

Written by a group of political science researchers, this commentary focuses on the contributions of political science to public health and proposes research avenues to increase those contributions. Despite progress, the links between researchers from these two fields develop only slowly. Divergences between the approach of political science to public policy and the expectations that public health can have about the role of political science, are often seen as an obstacle to collaboration between experts in these two areas. Thus, promising and practical research avenues are proposed along with strategies to strengthen and develop them. Considering the interdisciplinary and intersectoral nature of population health, it is important to create a critical mass of researchers interested in the health of populations and in healthy public policy that can thrive working at the junction of political science and public health., (© 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Endurance horses are able to run at more than 20 km/h for 160 km (in bouts of 30-40 km). This level of performance is based on intense aerobic metabolism, effective body heat dissipation and the ability to endure painful exercise. The known heritabilities of endurance performance and exercise-related physiological traits in Arabian horses suggest that adaptation to extreme endurance exercise is influenced by genetic factors. The objective of the present genome-wide association study (GWAS) was to identify single nucleotide polymorphisms (SNPs) related to endurance racing performance in 597 Arabian horses. The performance traits studied were the total race distance, average race speed and finishing status (qualified, eliminated or retired). We used three mixed models that included a fixed allele or genotype effect and a random, polygenic effect. Quantile-quantile plots were acceptable, and the regression coefficients for actual vs. expected log 10 p -values ranged from 0.865 to 1.055. The GWAS revealed five significant quantitative trait loci (QTL) corresponding to 6 SNPs on chromosomes 6, 1, 7, 16, and 29 (two SNPs) with corrected p -values from 1.7 × 10 -6 to 1.8 × 10 -5 . Annotation of these 5 QTL revealed two genes: sortilin-related VPS10-domain-containing receptor 3 ( SORCS3 ) on chromosome 1 is involved in protein trafficking, and solute carrier family 39 member 12 ( SLC39A12 ) on chromosome 29 is active in zinc transport and cell homeostasis. These two coding genes could be involved in neuronal tissues (CNS). The other QTL on chromosomes 6, 7, and 16 may be involved in the regulation of the gene expression through non-coding RNAs, CpG islands and transcription factor binding sites. On chromosome 6, a new candidate equine long non-coding RNA ( KCNQ1OT1 ortholog: opposite antisense transcript 1 of potassium voltage-gated channel subfamily Q member 1 gene) was predicted in silico and validated by RT-qPCR in primary cultures of equine myoblasts and fibroblasts. This lncRNA could be one element of the cardiac rhythm regulation. Our GWAS revealed that equine performance during endurance races is a complex polygenic trait, and is partially governed by at least 5 QTL: two coding genes involved in neuronal tissues and three other loci with many regulatory functions such as slowing down heart rate.

Prospective studies of the potential health consequences of trade and investment treaties, such as the Trans-Pacific Partnership, are critical. These studies can make visible to trade policy-makers the potential negative impacts associated to such treaties and can influence the outcomes of such negotiations. However, few researchers have examined retrospectively the consequences of trade agreements. With more than 400 trade agreements and more than 2000 investment treaties currently in force, researchers have a large corpus of agreements to analyse in order to assess not only their potential impacts on health system and population health, but also their actual impacts. This comment suggests some research questions that would benefit from retrospective inquiry., (© 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objectives: This article presents the first study of the economic consequences of obesity and overweight in the Canadian province of Quebec. The article examines three types of direct costs: hospitalizations, medical visits and drug consumption; and one type of indirect cost: productivity loss due to disability., Methods: The National Population Health Survey, conducted in all Canadian provinces by Statistics Canada between 1994 and 2011, provides self-reported longitudinal data for body mass index and the frequency of health care utilization and disability., Results: When we compared obese adults in Quebec to those with a normal weight at the beginning of the follow-up period, we observed that the former had significantly more frequent visits to the physician, more frequent hospital stays and higher consumption of drugs between 1994 and 2011. We estimated the annual cost of the excess health care utilization and excess disability at more than CAD $2.9 billion in 2011., Conclusion: The results confirm that, similar to what had been found elsewhere in Canada and abroad, there are important economic consequences associated with overweight and obesity in Quebec.

The 5S rDNA gene is a non-coding RNA that can be found in 2 copies (type I and type II) in bony and cartilaginous fish. Previous studies have pointed out that type II gene is a paralog derived from type I. We analyzed the molecular organization of 5S rDNA type II in elasmobranchs. Although the structure of the 5S rDNA is supposed to be highly conserved, our results show that the secondary structure in this group possesses some variability and is different than the consensus secondary structure. One of these differences in Selachii is an internal loop at nucleotides 7 and 112. These mutations observed in the transcribed region suggest an independent origin of the gene among Batoids and Selachii. All promoters were highly conserved with the exception of BoxA, possibly due to its affinity to polymerase III. This latter enzyme recognizes a dT4 sequence as stop signal, however in Rajiformes this signal was doubled in length to dT8. This could be an adaptation toward a higher efficiency in the termination process. Our results suggest that there is no TATA box in elasmobranchs in the NTS region. We also provide some evidence suggesting that the complexity of the microsatellites present in the NTS region play an important role in the 5S rRNA gene since it is significantly correlated with the length of the NTS.

Non-small cell lung cancer (NSCLC) constitutes the most common type of lung cancer and is frequently diagnosed at advanced stages. Clinical studies have shown that molecular targeted therapies increase survival and improve quality of life in patients. Nevertheless, the realization of personalized therapies for NSCLC faces a number of challenges including the integration of clinical and genetic data and a lack of clinical decision support tools to assist physicians with patient selection. To address this problem, we used frequent pattern mining to establish the relationships of patient characteristics and tumor response in advanced NSCLC. Univariate analysis determined that smoking status, histology, epidermal growth factor receptor (EGFR) mutation, and targeted drug were significantly associated with response to targeted therapy. We applied four classifiers to predict treatment outcome from EGFR tyrosine kinase inhibitors. Overall, the highest classification accuracy was 76.56% and the area under the curve was 0.76. The decision tree used a combination of EGFR mutations, histology, and smoking status to predict tumor response and the output was both easily understandable and in keeping with current knowledge. Our findings suggest that support vector machines and decision trees are a promising approach for clinical decision support in the patient selection for targeted therapy in advanced NSCLC.

Protein structures can be conceptualized as context-aware self-organizing systems. One of its emerging properties is a modular architecture. Such modular architecture has been identified as domains and defined as its units of evolution and function. However, this modular architecture is not exclusively defined by domains. Also, the definition of a domain is an ongoing debate. Here we propose differentiating structural, evolutionary and functional domains as distinct concepts. Defining domains or modules is confounded by diverse definitions of the concept, and also by other elements inherent to protein structures. An apparent hierarchy in protein structure architecture is one of these elements, where lower level interactions may create noise for the definition of higher levels. Diverse modularity-molding factors such as folding, function, and selection, can have a misleading effect when trying to define a given type of module. It is thus important to keep in mind this complexity when defining modularity in protein structures and interpreting the outcome modularity inference approaches.

Dysferlinopathies are a family of disabling muscular dystrophies with LGMD2B and Miyoshi myopathy as the main phenotypes. They are associated with molecular defects in DYSF, which encodes dysferlin, a key player in sarcolemmal homeostasis. Previous investigations have suggested that exon skipping may be a promising therapy for a subset of patients with dysferlinopathies. Such an approach aims to rescue functional proteins when targeting modular proteins and specific tissues.We sought to evaluate the dysferlin functional recovery following exon 32 skipping in the cells of affected patients. Exon skipping efficacy was characterized at several levels by use of in vitro myotube formation assays and quantitative membrane repair and recovery tests. Data obtained from these assessments confirmed that dysferlin function is rescued by quasi-dysferlin expression in treated patient cells, supporting the case for a therapeutic antisense-based trial in a subset of dysferlin-deficient patients.

In adopting a whole-of-society (WoS) approach that engages multiple stakeholders in public health policies across contexts, the authors propose that effective governance presents a challenge. The purpose of this paper is to highlight a case for how polycentric governance underlying the WoS approach is already functioning, while outlining an agenda to enable adaptive learning for improving such governance processes. Drawing upon a case study from Quebec, Canada, we employ empirically developed concepts from extensive, decades-long work of the 2009 Nobel laureate Elinor Ostrom in the governance of policy in nonhealth domains to analyze early efforts at polycentric governance in policies around overnutrition, highlighting interactions between international, domestic, state and nonstate actors and processes. Using information from primary and secondary sources, we analyze the emergence of the broader policy context of Quebec's public health system in the 20th century. We present a microsituational analysis of the WoS approach for Quebec's 21st century policies on healthy lifestyles, emphasizing the role of governance at the community level. We argue for rethinking prescriptive policy analysis of the 20th century, proposing an agenda for diagnostic policy analysis, which explicates the multiple sets of actors and interacting variables shaping polycentric governance for operationalizing the WoS approach to policymaking in specific contexts., (© 2014 New York Academy of Sciences.)

The 20th century saw accelerated human and economic development, with increased convergence in income, wealth, and living standards around the world. For a large part, owing to the well-entrenched Western-centric linear and siloed industrialization pattern, this positive transformation has also been associated with complex societal challenges at the nexus of agricultural, industrial, and health sectors. Efforts at cross-sectoral policy coherence have been deployed with limited success. To go beyond what has been possible thus far, the whole-of-society (WoS) paradigm for human and economic development proposes a 21st century convergence where, instead of the rest (of the world) converging with the West, sectoral and cross-sectoral efforts converge in their single and collective policy and action on a common target of human and economic development. In this paper, we first review and discuss contributions and limitations of policy coherence approaches. We then elaborate the institutional foundation of the WoS paradigm, taking as an anchor the well-established model of polycentric governance that views individuals, and state, market, and community, forming society as part of the same complex adaptive system. Actors within such systems self-organize into nested hierarchies that operate at multiple scales and move toward 21st century convergence of human and economic development., (© 2014 New York Academy of Sciences.)

Community structure detection is an important tool in graph analysis. This can be done, among other ways, by solving for the partition set which optimizes the modularity scores [Formula: see text]. Here it is shown that topological constraints in correlation graphs induce over-fragmentation of community structures. A refinement step to this optimization based on Linear Discriminant Analysis (LDA) and a statistical test for significance is proposed. In structured simulation constrained by topology, this novel approach performs better than the optimization of modularity alone. This method was also tested with two empirical datasets: the Roll-Call voting in the 110th US Senate constrained by geographic adjacency, and a biological dataset of 135 protein structures constrained by inter-residue contacts. The former dataset showed sub-structures in the communities that revealed a regional bias in the votes which transcend party affiliations. This is an interesting pattern given that the 110th Legislature was assumed to be a highly polarized government. The [Formula: see text]-amylase catalytic domain dataset (biological dataset) was analyzed with and without topological constraints (inter-residue contacts). The results without topological constraints showed differences with the topology constrained one, but the LDA filtering did not change the outcome of the latter. This suggests that the LDA filtering is a robust way to solve the possible over-fragmentation when present, and that this method will not affect the results where there is no evidence of over-fragmentation.

Background: Projection analyses can provide estimates of the future health burden of increasing BMI and represent a relevant and useful tool for public health planning. Our study presents long-term (2013-2030) projections of the prevalence and numbers of individuals by BMI category for adult men and women in Quebec. Three applications of projections to estimate outcomes more directly pertinent to public health planning, as well as an in-depth discussion of limits, are provided with the aim of encouraging greater use of projection analyses by public health officers., Methods: The weighted compositional regression method is applied to prevalence time series derived from sixteen cross-sectional survey cycles, for scenarios of linear change and deceleration. Estimation of the component of projected change potentially amenable to intervention, future health targets and the projected impact on type 2 diabetes, were done., Results: Obesity prevalence in Quebec is projected to rise steadily from 2013 to 2030 in both men (from 18.0-19.4% to 22.2-30.4%) and women (from 15.5-16.3% to 18.2-22.4%). Corresponding projected numbers of obese individuals are (579,000-625,000 to 790,000-1,084,000) in men and (514,000-543,000 to 661,000-816,000) in women. These projected increases are found to be primarily an 'epidemiologic' rather than 'demographic' phenomenon and thus potentially amenable to public health intervention. Assessment of obesity targets for 2020 illustrates the necessity of using projected rather than current prevalence; for example a targeted 2% drop in obesity prevalence relative to 2013 translates into a 3.6-5.4% drop relative to 2020 projected levels. Type 2 diabetes is projected to increase from 6.9% to 9.2-10.1% in men and from 5.7% to 7.1-7.5% in women, from 2011-2012 to 2030. A substantial proportion of this change (25-44% for men, and 27-43% for women) is attributable to the changing BMI distribution., Conclusions: Obesity in Quebec is projected to increase and should therefore continue to be a public health priority. Application of projections to estimate the proportion of change potentially amenable to intervention, feasible health targets, and future chronic disease prevalence are demonstrated. Projection analyses have limitations, but represent a pertinent tool for public health planning.

Background: Assessing protein modularity is important to understand protein evolution. Still the question of the existence of a sub-domain modular architecture remains. We propose a graph-theory approach with significance and power testing to identify modules in protein structures. In the first step, clusters are determined by optimizing the partition that maximizes the modularity score. Second, each cluster is tested for significance. Significant clusters are referred to as modules. Evolutionary modules are identified by analyzing homologous structures. Dynamic modules are inferred from sets of snapshots of molecular simulations. We present here a methodology to identify sub-domain architecture robustly, biologically meaningful, and statistically supported., Results: The robustness of this new method is tested using simulated data with known modularity. Modules are correctly identified even when there is a low correlation between landmarks within a module. We also analyzed the evolutionary modularity of a data set of α-amylase catalytic domain homologs, and the dynamic modularity of the Niemann-Pick C1 (NPC1) protein N-terminal domain.The α-amylase contains an (α/β)8 barrel (TIM barrel) with the polysaccharides cleavage site and a calcium-binding domain. In this data set we identified four robust evolutionary modules, one of which forms the minimal functional TIM barrel topology.The NPC1 protein is involved in the intracellular lipid metabolism coordinating sterol trafficking. NPC1 N-terminus is the first luminal domain which binds to cholesterol and its oxygenated derivatives. Our inferred dynamic modules in the protein NPC1 are also shown to match functional components of the protein related to the NPC1 disease., Conclusions: A domain compartmentalization can be found and described in correlation space. To our knowledge, there is no other method attempting to identify sub-domain architecture from the correlation among residues. Most attempts made focus on sequence motifs of protein-protein interactions, binding sites, or sequence conservancy. We were able to describe functional/structural sub-domain architecture related to key residues for starch cleavage, calcium, and chloride binding sites in the α-amylase, and sterol opening-defining modules and disease-related residues in the NPC1. We also described the evolutionary sub-domain architecture of the α-amylase catalytic domain, identifying the already reported minimum functional TIM barrel.

The longevity of sport horses is an economic and ethical issue. The aim of this study was to analyze the duration of the competitive life of jumping horses in France to assess the potential for genetic evaluation and to propose rules of management for sport horses. Data included lifetimes spent in jumping competitions for the 209,296 horses born from 1968 onward with performances between 1972 and 2008; the data set contained 22% right-censored records. Longevity was measured in years. Discrete survival analysis included fixed effects of region of birth, month of birth, year of recording, age at first competition, interaction between sex and level of jumping performance as measured by the logarithm of earnings adjusted for sex, age, year, and random sire and maternal grand-sire effects. There were 16,668 sires and maternal grand-sires. All fixed effects were highly significant (P < 0.001). Management of the sports career had an important effect on longevity: against common belief, the younger the horse started competing, the longer it stayed in competition. For horses that started competing at an age of 6 yr, the risk of culling was 1.33-fold that of horses having started at 4 yr of age. The less success in competition, the greater was the chance for leaving competition, especially for horses without earnings. For a gelding without earnings, the risk of culling was 1.40-fold that of an average-performance gelding and 2.57-fold that of a top-rated gelding (performance at least 2 SD above the mean). Mares always had greater relative risk than geldings or stallions because they may be culled from competition to be used for breeding. The risk of culling for females was 1.45-fold that of a gelding with the same performance. The heritability of the length of competitive life was 0.10. Breeding values were predicted for sires, and 3,303 sires showed an accuracy greater than 0.60. Among these sires, 262 were used for breeding in 2008.

Although the α-helical secondary structure of proteins is well-defined, the exact causes and structures of helical kinks are not. This is especially important for transmembrane (TM) helices of integral membrane proteins, many of which contain kinks providing functional diversity despite predominantly helical structure. We have developed a Monte Carlo method based algorithm, MC-HELAN, to determine helical axes alongside positions and angles of helical kinks. Analysis of all nonredundant high-resolution α-helical membrane protein structures (842 TM helices from 205 polypeptide chains) revealed kinks in 64% of TM helices, demonstrating that a significantly greater proportion of TM helices are kinked than those indicated by previous analyses. The residue proline is over-represented by a factor >5 if it is two or three residues C-terminal to a bend. Prolines also cause kinks with larger kink angles than other residues. However, only 33% of TM kinks are in proximity to a proline. Machine learning techniques were used to test for sequence-based predictors of kinks. Although kinks are somewhat predicted by sequence, kink formation appears to be driven predominantly by other factors. This study provides an improved view of the prevalence and architecture of kinks in helical membrane proteins and highlights the fundamental inaccuracy of the typical topological depiction of helical membrane proteins as series of ideal helices.

To date the global health diplomacy agenda has focused primarily on infectious diseases. Policymakers have not dedicated the same level of attention to chronic diseases, despite their rising contribution to the global burden of disease. Negotiation of the Framework convention on tobacco control provides an apt example from global health diplomacy to tackle diet-related chronic diseases. What lessons can be learned from this experience for preventing obesity? This article looks at why a global policy response is necessary, at the actors and interests involved in the negotiations, and at the forum for diplomacy.

Bacterial acyl carrier protein (ACP) is essential for the synthesis of fatty acids and serves as the major acyl donor for the formation of phospholipids and other lipid products. Acyl-ACP encloses attached fatty acyl groups in a hydrophobic pocket within a four-helix bundle, but must at least partially unfold to present the acyl chain to the active sites of its multiple enzyme partners. To further examine the constraints of ACP structure and function, we have constructed a cyclic version of Vibrio harveyi ACP, using split-intein technology to covalently join its closely apposed N and C termini. Cyclization stabilized ACP in a folded helical conformation as indicated by gel electrophoresis, circular dichroism, fluorescence, and mass spectrometry. Molecular dynamics simulations also indicated overall decreased polypeptide chain mobility in cyclic ACP, although no major conformational rearrangements over a 10-ns period were noted. In vivo complementation assays revealed that cyclic ACP can functionally replace the linear wild-type protein and support growth of an Escherichia coli ACP-null mutant strain. Cyclization of a folding-deficient ACP mutant (F50A) both restored its ability to adopt a folded conformation and enhanced complementation of growth. Our results thus suggest that ACP must be able to adopt a folded conformation for biological activity, and that its function does not require complete unfolding of the protein.

Motivation: Aligning protein sequences with the best possible accuracy requires sophisticated algorithms. Since the optimal alignment is not guaranteed to be the correct one, it is expected that even the best alignment will contain sites that do not respect the assumption of positional homology. Because formulating rules to identify these sites is difficult, it is common practice to manually remove them. Although considered necessary in some cases, manual editing is time consuming and not reproducible. We present here an automated editing method based on the classification of 'valid' and 'invalid' sites., Results: A support vector machine (SVM) classifier is trained to reproduce the decisions made during manual editing with an accuracy of 95.0%. This implies that manual editing can be made reproducible and applied to large-scale analyses. We further demonstrate that it is possible to retrain/extend the training of the classifier by providing examples of multiple sequence alignment (MSA) annotation. Near optimal training can be achieved with only 1000 annotated sites, or roughly three samples of protein sequence alignments., Availability: This method is implemented in the software MANUEL, licensed under the GPL. A web-based application for single and batch job is available at http://fester.cs.dal.ca/manuel., Supplementary Information: Supplementary data are available at Bioinformatics online.

The increasing availability of genetic sequence data associated with explicit geographic and ecological information is offering new opportunities to study the processes that shape biodiversity. The generation and testing of hypotheses using these data sets requires effective tools for mathematical and visual analysis that can integrate digital maps, ecological data, and large genetic, genomic, or metagenomic data sets. GenGIS is a free and open-source software package that supports the integration of digital map data with genetic sequences and environmental information from multiple sample sites. Essential bioinformatic and statistical tools are integrated into the software, allowing the user a wide range of analysis options for their sequence data. Data visualizations are combined with the cartographic display to yield a clear view of the relationship between geography and genomic diversity, with a particular focus on the hierarchical clustering of sites based on their similarity or phylogenetic proximity. Here we outline the features of GenGIS and demonstrate its application to georeferenced microbial metagenomic, HIV-1, and human mitochondrial DNA data sets.

The effects of trade and trade liberalisation on the social determinants of health are not well known. Here, we outline a conceptual framework of links between trade liberalisation and health outcomes, and review existing evidence for these by focusing on four key factors: income, inequality, economic insecurity, and unhealthy diets. Even though trade liberalisation seems to have positive effects on economic growth, it is not sufficient to boost growth. In several countries, trade reforms have not translated into enhanced economic expansion because complementary policies are needed. Trade liberalisation and openness are associated with greater wage inequality and raised economic insecurity. Trade liberalisation has facilitated availability of highly processed, calorie-rich, nutrient-poor food in developing countries, but further research is needed to better understand the effects of trade on unhealthy diets. Policymakers and health professionals need to be aware that the global economy affects the health of populations and understand how risks associated with trade liberalisation can be mitigated.

The subtree prune and regraft distance (d(SPR)) between phylogenetic trees is important both as a general means of comparing phylogenetic tree topologies as well as a measure of lateral gene transfer (LGT). Although there has been extensive study on the computation of d(SPR) and similar metrics between rooted trees, much less is known about SPR distances for unrooted trees, which often arise in practice when the root is unresolved. We show that unrooted SPR distance computation is NP-Hard and verify which techniques from related work can and cannot be applied. We then present an efficient heuristic algorithm for this problem and benchmark it on a variety of synthetic datasets. Our algorithm computes the exact SPR distance between unrooted tree, and the heuristic element is only with respect to the algorithm's computation time. Our method is a heuristic version of a fixed parameter tractability (FPT) approach and our experiments indicate that the running time behaves similar to FPT algorithms. For real data sets, our algorithm was able to quickly compute d(SPR) for the majority of trees that were part of a study of LGT in 144 prokaryotic genomes. Our analysis of its performance, especially with respect to searching and reduction rules, is applicable to computing many related distance measures.