Mitogenomics and the genetic differentiation of contemporary <i>Balaena mysticetus</i> (Cetacea) from Svalbard

Full mitochondrial genomes were assembled for 12 recently sampled animals from the Svalbard bowhead whale (Balaena mysticetus) stock via high-throughput sequencing data, facilitating analysis of the demographic history of the population for the first time. The Svalbard population has retained noticeable amounts of mitochondrial genome diversity despite extreme historical harvest levels. Haplotype and nucleotide diversities were similar to those estimated earlier for other bowhead whale populations. The reconstructed demographic history was in accordance with a boom–bust scenario, combining a slight Pleistocene population growth 25 000–35 000 years ago and a Holocene decline. Employing a mutation rate of 3.418 × 10–8 substitutions per site per year, the time to the most recent common ancestor for the mitochondrial genomes of the contemporary Svalbard bowhead whales was estimated to be 68 782 (54 353–83 216) years before the present. Based on 370 bp fragments of the D-loop region, significant genetic differentiation was detected between all extant bowhead whale populations across the circumpolar Arctic. Thus, the Svalbard bowhead whales can be regarded as a population with its own genetic legacy

Milk products in the treatment of hypophosphatemic rickets: A pilot study

Background: Standard treatment of hypophosphatemic rickets (HR) is oral phosphate tablets plus vitamin D. Due to the rapid absorption of phosphate tablets, frequent daily doses are necessary, which is cumbersome and may cause fluctuations in plasma phosphate and risk of secondary hyperparathyroidism. It was hypothesized that phosphate from milk or cheese is less rapidly absorbed, and reduces fluctuations in plasma phosphate. Objectives: The current randomized, multiple crossover study aimed at investigating if an equivalent phosphate dose given as milk or cheese is comparable to phosphate tablets in patients with HR. Methods: Seven females with HR were included. They went through three different four-day treatment sessions of either oral phosphate tablets consisting of 800 mg elemental phosphorus divided into five doses over the day or an equivalent phosphorus dose ingested as skimmed milk or cheese divided over five daily doses. Blood and urine samples were taken from patients after each treatment session. Except the usual doses of vitamin D, no phosphate or calcium-modifying treatments were allowed. Statistical analyses were performed using mixed models. Results: Treatment feasibility was independent of the phosphorus source. The study demonstrated reduced plasma levels of parathyroid hormone (PTH), reduced fluctuations in plasma phosphate and plasma PTH, and reduced renal phosphate excretion when ingesting phosphorus supplementation as milk compared to phosphate tablets. The same trend was observed when administering phosphorus as cheese, though not statistically significant. Conclusions: Phosphorus supplements can be administered as phosphate tablets, milk or cheese when given in equimolar doses. The current study findings indicated that milk may be superior to phosphate tablets as the phosphate source in patients with HR

Iterative qualitative approach to establishing content validation of a patient-reported outcome measure for arm lymphedema:the LYMPH-Q Upper Extremity Module

Background: Breast cancer-related lymphedema (BRCL) is one of the most common causes of upper extremity (UE) lymphedema in developed nations and substantially impacts health-related quality of life. To advance our understanding of the epidemiology and treatment of BRCL, rigorously developed and validated patient-reported outcome measures (PROMs) are needed. This study aimed to demonstrate the iterative content validity of a modular UE lymphedema-specific PROM called the LYMPH-Q UE module. Methods:A multi-step iterative qualitative approach was used. Semi-structured interview data from in-depth qualitative interviews with adult women (18 years and older) with BCRL were used to develop the first set of the LYMPH-Q UE scales. The content validity of these scales was demonstrated with patient and clinician feedback. Over the course of cognitive debriefing interviews, additional concepts of lymphedema worry and impact on work were identified as missing from the LYMPH-Q UE module. Subsequently, two new qualitative studies (a focus group and in-depth concept elicitation interviews with patients) were conducted, and two new scales were developed to measure lymphedema worry and impact on work life and their content validity was dResults: emonstrated. Qualitative data from in-depth and cognitive interviews with 15 (age 40–74 years) and 16 (age 38–74 years) women with BRCL, respectively, and feedback from 12 clinical experts, were used to develop and demonstrate the content validity of six LYMPH-Q UE scales measuring symptoms, function, appearance, psychological, information, and arm sleeve. Additionally, data from in-depth interviews with 12 (age 35–72 years) women with UE lymphedema and four focus groups (n = 16 women; age 35–74 years) was used to develop and assess the content validity of two new LYMPH-Q UE scales measuring lymphedema worry and impact on work life. The content validity of the previously established six scales was also demonstrated in these subsequent qualitative studies. Conclusion: The LYMPH-Q UE is a modular PROM developed using international guidelines for PROM development and can be used in clinical practice, research, and quality improvement to enhance patient-centered shared decision-making. This study’s innovative and iterative approach to content validation demonstrates that the LYMPH-Q UE is a comprehensive measure that includes important concepts relevant to patients with UE lymphedema.</p

Best practice guidelines for cetacean tagging

Animal-borne electronic instruments (tags) are valuable tools for collecting information on cetacean physiology, behaviour and ecology, and for enhancing conservation and management policies for cetacean populations. Tags allow researchers to track the movement patterns, habitat use andother aspects of the behaviour of animals that are otherwise difficult to observe. They can even be used to monitor the physiology of a tagged animal within its changing environment. Such tags are ideal for identifying and predicting responses to anthropogenic threats, thus facilitating the development of robust mitigation measures. With the increasing need for data best provided by tagging and the increasing availability of tags, such research is becoming more common. Tagging can, however, pose risks to the health and welfare of cetaceans and to personnel involved in tagging operations. Here we provide ‘best practice’ recommendations for cetacean tag design, deployment and follow-up assessment of tagged individuals, compiled by biologists and veterinarians with significant experience in cetacean tagging. This paper is intended to serve as a resource to assist tag users, veterinarians, ethics committees and regulatory agency staff in the implementation of high standards of practice, and to promote the training of specialists in this area. Standardised terminology for describing tag design and illustrations of tag types and attachment sites are provided, along with protocols for tag testing and deployment (both remote and through capture-release), including training of operators. The recommendations emphasise the importance of ensuring that tagging is ethically and scientifically justified for a particular project and that tagging only be used to address bona fide research or conservation questions that are best addressed with tagging, as supported by an exploration of alternative methods. Recommendations are provided for minimising effects on individual animals (e.g. through careful selection of the individual, tag design and implant sterilisation) and for improving knowledge of tagging effects on cetaceans through increased post-tagging monitoring.Publisher PDFPeer reviewe

Atlas of the clinical genetics of human dilated cardiomyopathy

[Abstract] Aim. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results. In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion. This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.Hôpitaux de Paris; PHRC AOM0414

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe