Species-specific responses to landscape features shaped genomic structure within Alaska galliformes

Aim: Connectivity is vital to the resiliency of populations to environmental change and stochastic events, especially for cold-adapted species as Arctic and alpine tundra habitats retract as the climate warms. We examined the influence of past and current landscapes on genomic connectivity in cold-adapted galliformes as a critical first step to assess the vulnerability of Alaska ptarmigan and grouse to environmental change. We hypothesize that the mosaic of physical features and habitat within Alaska promoted the formation of genetic structure across species. Location: Alaska, United States of America. Taxa: Ptarmigan and Grouse (Galliformes: Tetraoninae). Methods: We collected double digest restriction-site- associated DNA sequence data from six ptarmigan and grouse species (N = 13–145/ species) sampled across multiple ecosystems up to ~10 degrees of latitude. Spatial genomic structure was analysed using methods that reflect different temporal scales: (1) principal components analysis to identify major trends in the distribution of genomic variation; (2) maximum likelihood clustering analyses to test for the presence of multiple genomic groupings; (3) shared co-ancestry analyses to assess contemporary relationships and (4) effective migration surfaces to identify regions that deviate from a null model of isolation by distance. Results: Levels of genomic structure varied across species (ΦST =0.009–0.042). Three general patterns of structure emerged: (1) east-west partition located near the Yukon-Tanana uplands; (2) north-south split coinciding with the Alaska Range and (3) northern group near the Brooks Range. Species-specific patterns were observed; not all landscape features were barriers to gene flow for all ptarmigan and grouse and temporal contrasts were detected at the Brooks Range. Main conclusions: Within Alaska galliformes, patterns of genomic structure coincide with physiographic features and highlight the importance of physical and ecological barriers in shaping how genomic diversity is arrayed across the landscape. Lack of concordance in spatial patterns indicates that species behaviour and habitat affinities play key roles in driving the contrasting patterns of genomic structure

Phylogenomics reveals ancient and contemporary gene flow contributing to the evolutionary history of sea ducks (Tribe Mergini)

Insight into complex evolutionary histories continues to build through broad comparative phylogenomic and population genomic studies. In particular, there is a need to understand the extent and scale that gene flow contributes to standing genomic diversity and the role introgression has played in evolutionary processes such as hybrid speciation. Here, we investigate the evolutionary history of the Mergini tribe (sea ducks) by coupling multi-species comparisons with phylogenomic analyses of thousands of nuclear ddRAD-seq loci, including Z-sex chromosome and autosomal linked loci, and the mitogenome assayed across all extant sea duck species in North America. All sea duck species are strongly structured across all sampled marker types (pair-wise species ΦST \u3e 0.2), with clear genetic assignments of individuals to their respective species, and phylogenetic relationships recapitulate known relationships. Despite strong species integrity, we identify at least 18 putative hybrids; with all but one being late generational backcrosses. Most interesting, we provide the first evidence that an ancestral gene flow event between long-tailed ducks (Clangula hyemalis) and true Eiders (Somateria spp.) not only moved genetic material into the former species, but likely generated a novel species — the Steller’s eider (Polysticta stelleri) — via hybrid speciation. Despite generally low contemporary levels of gene flow, we conclude that hybridization has and continues to be an important process that shifts novel genetic variation between species within the tribe Mergini. Finally, we outline methods that permit researchers to contrast genomic patterns of contemporary versus ancestral gene flow when attempting to reconstruct potentially complex evolutionary histories

Patients' perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with a survival of only three to five years from the time of diagnosis. Due to a paucity of studies, large gaps remain in our understanding of how IPF affects the quality of patients' lives. In only one other study did investigators ask patients directly for their perspectives on this topic. Further, currently there is no disease-specific instrument to measure health-related quality of life (HRQL) in patients with IPF. A carefully constructed measurement instrument, sensitive to underlying change, is needed for use in clinical trials and longitudinal studies of patients with IPF. Before developing such an instrument, researchers must improve their understanding of the relevant effects of IPF on patients' lives. On a broader scale, to provide the best care for people with IPF, clinicians must appreciate – from patients' perspectives – how this disease affects various aspects of their lives. METHODS: We used focus groups and individual in-depth interviews with 20 IPF patients to collect their perspectives on how IPF affects their lives (with a focus on the quality of their lives). We then analyzed these perspectives and organized them into a conceptual framework for describing HRQL in patients with IPF. Next, we examined how well certain existing measurement instruments – which have been administered to IPF patients in prior studies – covered the domains and topics our patients identified. RESULTS: In our framework, we identified 12 primary domains: symptoms, IPF therapy, sleep, exhaustion, forethought, employment and finances, dependence, family, sexual relations, social participation, mental and spiritual well-being, mortality. Each domain is composed of several topics, which describe how IPF affects patients' lives. When we compared the content of our conceptual framework with the existing instruments, we found the coverage of the existing instruments to be inadequate for several reasons, including they may tap general areas of QOL or HRQL but not some areas that appear to be most directly affected by IPF, and they include items that are relevant to symptoms and effects of other respiratory diseases but not IPF. CONCLUSION: Collecting patients' perspectives and developing an organized inventory of the relevant effects of IPF on patients' lives provides valuable information for improving our understanding of the impact of this disease on patients and their loved ones. We believe our findings will help alert clinicians and researchers to IPF patients' experiences and concerns. Based on the comparison or our conceptual framework with the content of four existing instruments, it would appear that developing an IPF-specific measurement instrument is justified. Our conceptual framework for describing health-related quality of life in patients with IPF lays a solid foundation for constructing such an instrument

Iron deficiency in the elderly

Anemia é comum em idosos e é associada a significante morbidade e mortalidade. Mais de 10% dos indivíduos acima de 65 anos tem anemia. Com uma proporção crescente da população mundial atingindo idade igual ou superior a 65 anos, a prevalência de anemia certamente aumentará no futuro. O diagnóstico precoce é importante para prevenir piora do quadro, diminuir progressão da doença e melhorar a evolução dos pacientes. Os critérios mais utilizados em estudos epidemiológicos para definir anemia em idosos são os da OMS (hemoglobina<12 g/dL para mulheres e hemoglobina <13 g/dL para homens). Aproximadamente um terço dos idosos com anemia tem deficiência de ferro, folato e/ou vitamina B12, um terço tem insuficiência renal e/ou inflamação crônica e o terço remanescente tem anemia inexplicada. A anemia ferropênica é microcítica e hipocrômica e caracteriza-se por baixos níveis de ferritina sérica, capacidade total de ligação de ferro do plasma aumentada, saturação da transferrina diminuída, concentração do receptor solúvel da transferrina elevada e ausência de ferro na medula óssea. É causada geralmente por perda de sangue pelo trato gastrointestinal devido a gastrite, úlceras, câncer de colo ou angiodisplasia. Anormalidades do trato gastrointestinal podem ser identificadas na maioria dos pacientes. Em alguns casos, ingestão ou absorção inadequada de ferro pode contribuir para a anemia. Entretanto, em todos os casos deveria ser exaustivamente investigada e excluída perda de sangue antes de assumir que a deficiência de ferro é devida a outras causas. O tratamento inclui parar o sangramento e repor o ferro.Anemia is a common problem in the elderly and is associated with significant morbidity and mortality. More than 10% of all individuals above the age of 65 have anemia. Because an increasing proportion of the world's population is aged 65 and older, it is inevitable that the prevalence of anemia will increase in the future. Thus, early diagnosis of anemia is important to prevent the condition from worsening, to slow disease progression, and improve outcomes in patients. The WHO definition of anemia (hemoglobin concentration <12 g/dL, in women and <13 g/dL, in men) is most often used in epidemiologic studies of older adults. Among older adults with anemia approximately one-third have evidence of iron, folate, and/or vitamin B12 deficiency, another third have renal insufficiency and/or chronic inflammation, and the remaining third have anemia that is unexplained. Anemia due to iron deficiency (IDA) is microcytic and hypochromic. Low serum ferritin levels, high total iron-binding capacity, low transferrin saturation, high concentrations of soluble transferrin receptor, and absent bone marrow iron stores accompany IDA. Iron deficiency in the elderly usually occurs as a result of chronic gastrointestinal blood loss caused by gastritis, ulcers, colon cancer, or angiodysplasia. Gastrointestinal tract abnormalities can be identified in the majority of patients with IDA. In some cases, inadequate intake or inadequate absorption of iron may contribute to the anemia. However, in all cases blood loss should be investigated and excluded before assuming that iron deficiency is due to other causes. Treatment includes stopping blood loss and replacing iron

Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency.

Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17 beta-hydroxysteroid dehydrogenase isoenzymes

Patient and Provider Perspectives on How Trust Influences Maternal Vaccine Acceptance Among Pregnant Women in Kenya

Background Pregnant women and newborns are at high risk for infectious diseases. Altered immunity status during pregnancy and challenges fully vaccinating newborns contribute to this medical reality. Maternal immunization is a strategy to protect pregnant women and their newborns. This study aimed to find out how patient-provider relationships affect maternal vaccine uptake, particularly in the context of a lower middle- income country where limited research in this area exists. Methods We conducted semi-structured, in-depth narrative interviews of both providers and pregnant women from four sites in Kenya: Siaya, Nairobi, Mombasa, and Marsabit. Interviews were conducted in either English or one of the local regional languages. Results We found that patient trust in health care providers (HCPs) is integral to vaccine acceptance among pregnant women in Kenya. The HCP-patient relationship is a fiduciary one, whereby the patients’ trusts is primarily rooted in the provider’s social position as a person who is highly educated in matters of health. Furthermore, patient health education and provider attitudes are crucial for reinstating and fostering that trust, especially in cases where trust was impeded by rumors, community myths and misperceptions, and religious and cultural factors. Conclusion Patient trust in providers is a strong facilitator contributing to vaccine acceptance among pregnant women in Kenya. To maintain and increase immunization trust, providers have a critical role in cultivating a positive environment that allows for favorable interactions and patient health education. This includes educating providers on maternal immunizations and enhancing knowledge of effective risk communication tactics in clinical encounters

Livestock ownership is associated with higher odds of anaemia among preschool‐aged children, but not women of reproductive age in Ghana

Livestock ownership may influence anaemia through complex and possibly contradictory mechanisms. In this study, we aimed to determine the association of household livestock ownership with anaemia among women aged 15–49 years and children aged 6–59 months in Ghana and to examine the contribution of animal source foods (ASFs) to consumption patterns as a potential mechanism mediating this association. We analysed data on 4,441 women and 2,735 children from the 2014 Ghana Demographic and Health Survey and 16,772 households from the Ghana Living Standards Survey Round 6. Haemoglobin measurements were used to define anaemia (non‐pregnant women: <120 g/L; children: <110 g/L). Child‐ and household‐level ASF consumption data were collected from 24‐hour food group intake and food consumption and expenditure surveys, respectively. In multiple logistic regression models, household livestock ownership was associated with anaemia among children (OR, 95% CI: 1.5 [1.1, 2.0]), but not women (1.0 [0.83, 1.2]). Household ownership of chickens was associated with higher odds of anaemia among children (1.6 [1.2, 2.2]), but ownership of other animal species was not associated with anaemia among women or children. In path analyses, we observed no evidence of mediation of the association of household livestock ownership with child anaemia by ASF consumption. Ownership of livestock likely has limited importance for consumption of ASFs among young children in Ghana and may in fact place children at an increased risk of anaemia. Further research is needed to elucidate if and how pathogen exposure associated with livestock rearing may underlie this increased risk of anaemia.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144629/1/mcn12604_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144629/2/mcn12604.pd

Enhancing faba bean (Vicia faba L.) genome resources

Grain legume improvement is currently impeded by a lack of genomic resources. The paucity of genome information for faba bean can be attributed to the intrinsic difficulties of assembling/annotating its giant (~13Gb) genome. In order to address this challenge, RNA-seq analysis was performed on faba bean (cv Wizard) leaves. Read alignment to the faba bean reference transcriptome identified 16,300 high quality unigenes. In addition, Illumina paired-end sequencing was used to establish a baseline for genomic information assembly. Genomic reads were assembled de novo into contigs with a size range of 50-5000 bp. Over 85% of sequences did not align to known genes, of which ~10 % could be aligned to known repetitive genetic elements. Over 26,000 of the reference transcriptome unigenes could be aligned to DNA-seq reads with high confidence. Moreover, this comparison identified 56,668 potential splice points in all identified unigenes. Sequence length data was extended at 461 putative loci through alignment of DNA-seq contigs to full length, publically available linkage marker sequences. Reads also yielded coverages of 3466x and 650x for the chloroplast and mitochondrial genomes respectively. Inter- and intra-species organelle genome comparisons established core legume organelle gene sets, and revealed polymorphic regions of faba bean organelle genomes

The Breathe Easier through Weight Loss Lifestyle (BE WELL) Intervention: A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Obesity and asthma have reached epidemic proportions in the US. Their concurrent rise over the last 30 years suggests that they may be connected. Numerous observational studies support a temporally-correct, dose-response relationship between body mass index (BMI) and incident asthma. Weight loss, either induced by surgery or caloric restriction, has been reported to improve asthma symptoms and lung function. Due to methodological shortcomings of previous studies, however, well-controlled trials are needed to investigate the efficacy of weight loss strategies to improve asthma control in obese individuals.</p> <p>Methods/Design</p> <p>BE WELL is a 2-arm parallel randomized clinical trial (RCT) of the efficacy of an evidence-based, comprehensive, behavioral weight loss intervention, focusing on diet, physical activity, and behavioral therapy, as adjunct therapy to usual care in the management of asthma in obese adults. Trial participants (n = 324) are patients aged 18 to 70 years who have suboptimally controlled, persistent asthma, BMI between 30.0 and 44.9 kg/m², and who do not have serious comorbidities (e.g., diabetes, heart disease, stroke). The 12-month weight loss intervention to be studied is based on the principles of the highly successful Diabetes Prevention Program lifestyle intervention. Intervention participants will attend 13 weekly group sessions over a four-month period, followed by two monthly individual sessions, and will then receive individualized counseling primarily by phone, at least bi-monthly, for the remainder of the intervention. Follow-up assessment will occur at six and 12 months. The primary outcome variable is the overall score on the Juniper Asthma Control Questionnaire measured at 12 months. Secondary outcomes include lung function, asthma-specific and general quality of life, asthma medication use, asthma-related and total health care utilization. Potential mediators (e.g., weight loss and change in physical activity level and nutrient intake) and moderators (e.g., socio-demographic characteristics and comorbidities) of the intervention effects also will be examined.</p> <p>Discussion</p> <p>This RCT holds considerable potential for illuminating the nature of the obesity-asthma relationship and advancing current guidelines for treating obese adults with asthma, which may lead to reduced morbidity and mortality related to the comorbidity of the two disorders.</p> <p>Trial registration</p> <p>NCT00901095</p

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al