We present a systematic analysis of the effects of synchronizing a large-scale, deeply characterized, multi-omic dataset to the current human reference genome, using updated software, pipelines, and ...annotations. For each of 5 molecular data platforms in The Cancer Genome Atlas (TCGA)—mRNA and miRNA expression, single nucleotide variants, DNA methylation and copy number alterations—comprehensive sample, gene, and probe-level studies were performed, towards quantifying the degree of similarity between the ‘legacy’ GRCh37 (hg19) TCGA data and its GRCh38 (hg38) version as ‘harmonized’ by the Genomic Data Commons. We offer gene lists to elucidate differences that remained after controlling for confounders, and strategies to mitigate their impact on biological interpretation. Our results demonstrate that the hg19 and hg38 TCGA datasets are very highly concordant, promote informed use of either legacy or harmonized omics data, and provide a rubric that encourages similar comparisons as new data emerge and reference data evolve.
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•A systematic analysis on how the reference genome affects various TCGA data types•The GRCh37 (hg19) and GRCh38 (hg38) TCGA data versions are highly concordant•Generate the gene lists showing significant differences between the two versions•Provide detailed information about TCGA software, pipelines, and annotations
Gao et al. performed a systematic analysis of the effects of synchronizing the large-scale, widely used, multi-omic dataset of The Cancer Genome Atlas to the current human reference genome. For each of the five molecular data platforms assessed, they demonstrated a very high concordance between the ‘legacy’ GRCh37 (hg19) TCGA data and its GRCh38 (hg38) version as ‘harmonized’ by the Genomic Data Commons.
The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10 Gy ...single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale.
A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20 Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis.
From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p = .002) but not between the pre-treatment and post-treatment pain scores.
Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background and Aims
The shortage of skilled pruners portends automation as an alternative. To train an Artificial Intelligence (AI) system in cane pruning, the attributes of grapevine dormant shoots ...were characterised.
Methods and Results
Eight attributes of dormant shoots, diameter, length, vertical and horizontal distance, node number, internode length, origin and position relative to bottom fruiting wire, were measured prior to and after pruning. Vine canopies were modified according to a 5 total node numbers on canes: 10, 20, 30, 40, 50 × 3 total node numbers on spurs: 1, 2, 3 factorial design. Compared to non‐retained dormant shoots, retained dormant shoots were thicker (9.2 ± 0.07 mm), longer (104.7 ± 0.93 cm), close to the vine trunk (11.4 ± 0.65 cm) and below the bottom fruiting wire (83.2 ± 0.54 cm). Spurs had the shortest horizontal (9.8 ± 0.93 cm) and vertical (77.8 ± 0.7 cm) distance, originating from the vine head, base nodes and first nodes of old canes and old spurs. Modifying the vine canopy via increased node numbers had a significant effect on all retained dormant shoot attributes (P < 0.05) except on the position relative to the bottom fruiting wire.
Conclusions
Cane pruning in commercial vineyards is consistent and follows rules based on viticulture knowledge. Retained, non‐retained dormant shoots, canes and spurs exhibit distinct attributes useful in quantifying, assessing and modelling cane pruning.
Significance of the Study
Data and knowledge from the research are currently being used in modelling and training AI cane‐pruning algorithms.
Multidisciplinary and multisectoral approaches such as One Health and related concepts (e.g., Planetary Health, EcoHealth) offer opportunities for synergistic expertise to address complex health ...threats. The connections between humans, animals, and the environment necessitate collaboration among sectors to comprehensively understand and reduce risks and consequences on health and wellbeing. One Health approaches are increasingly emphasized for national and international plans and strategies related to zoonotic diseases, food safety, antimicrobial resistance, and climate change, but to date, the possible applications in clinical practice and benefits impacting human health are largely missing.
In 2018 the "Application of the One Health Approach to Global Health Centers" conference held at the Albert Einstein College of Medicine convened experts involved in One Health policy and practice. The conference examined issues relevant to One Health approaches, sharing examples of challenges and successes to guide application to medical school curricula and clinical practice for human health. This paper presents a synthesis of conference proceedings, framed around objectives identified from presentations and audience feedback.
The following objectives provide opportunities for One Health involvement and benefits for medical schools and global health centers by: 1) Improving One Health resource sharing in global health and medical education; 2) Creating pathways for information flow in clinical medicine and global health practice; 3) Developing innovative partnerships for improved health sector outcomes; and 4) Informing and empowering health through public outreach. These objectives can leverage existing resources to deliver value to additional settings and stakeholders through resource efficiency, more holistic and effective service delivery, and greater ability to manage determinants of poor health status. We encourage medical and global health educators, practitioners, and students to explore entry points where One Health can add value to their work from local to global scale.
The importance of accounting for temporal variation in vital rates when modelling population dynamics is well recognized. However, long‐term (usually >5 years) datasets are needed to estimate this ...variation. Consequently, models for newly monitored populations typically assume no temporal variation or use default values provided in software programmes, both of which can give misleading inferences about population dynamics. The goal of this study is to improve estimation of dynamics in the initial years of conservation programmes by incorporating data‐based estimates of temporal variation from other populations with longer‐term data available. We show how data‐derived priors can be generated using estimates of temporal variation in vital rates from other populations, providing information about expected variation until sufficient population‐specific data are available. We specifically evaluated whether data‐derived priors improved our ability to estimate temporal variation for a reintroduced population monitored for 3 years postrelease. We first predicted population growth and probability of extinction assuming no temporal variation in vital rates, then compared projections to those obtained when temporal variation was estimated with uniform priors or with the data‐derived priors. Both types of priors were constrained to plausible ranges, and we also assessed sensitivity of model outputs to widening those ranges. Median projected population size was similar under all three models, but extinction probability was higher with inclusion of temporal variability, reiterating the importance of incorporating this source of uncertainty. Projections with temporal variation were similar irrespective of whether data‐derived priors or uniform priors were used. However, the data‐derived priors generated more precise estimates of annual variation that were less sensitive to relaxation of prior constraints. The approach we present can facilitate management decisions at the outset of conservation programmes when risk assessments that account for all relevant uncertainties can be crucial for determining optimal management strategies.
Conservation biologists are frequently required to make predictions about population persistence from short‐term data. However, analyses of data from short‐term studies typically do not account for temporal variation because longer‐term data are needed to estimate that variation. This paper presents an approach for improving inferences in the initial years of monitoring programmes by incorporating data‐based estimates of temporal variation from other populations with longer‐term data available. We show how data‐derived priors can be generated using estimates of temporal variation in vital rates from other populations, providing information about expected variation until sufficient population‐specific data are available. The approach we present can facilitate management decisions that account for all relevant uncertainties. Photo credit: Ian Douglas
Exposure to Bisphenol A (BPA) has been reported to dysregulate endocrine pathways in a wide array of vertebrate species. The effects of BPA on invertebrate species are less well understood. We tested ...the effects of BPA on growth and development in Drosophila as these processes are governed by well-studied endocrine pathways. In this study, we tested the effects of three concentrations of BPA (0.1mg/L, 1mg/L or 10mg/L) and found a statistically significant increase in larval growth for the low dose treatment group (0.1mg/L), but not statistically significant for the high dose treatment group (10mg/L). BPA exposure resulted in an increased body size in treated animals at 48, 72 and 96h after egg laying (AEL). This finding reflects a non-monotonic dose–response that has been observed for an increasing number of endocrine disrupting compounds. The increase in growth rate found for all treatment groups was associated with a statistically significant increase in food intake observed at 72h AEL. Furthermore, we observed that the increased growth rate was coupled with an earlier onset of pupariation consistent with previously reported phenotypes resulting from increased activity of insulin/insulin growth factor signaling (IIS) in Drosophila. Since the timing of the onset of pupariation in Drosophila is controlled through the complex interaction of the IIS and the ecdysone signaling pathways, our findings suggest that BPA exerts its effects through disruption of endocrine signaling in Drosophila.
•The effects of Bisphenol-A (BPA) on growth and maturation were examined in Drosophila melanogaster.•BPA-treated larvae showed increased size and higher growth rate compared to non-treated control larvae.•BPA treatment was associated with an increased intake of food.•BPA exposure resulted in a non-monotonic dose–response.•BPA treatment was associated with an early onset of metamorphosis.
We report the results of a CCD imaging survey, complemented by astrometric and spectroscopic follow-up studies, that aims to probe the fate of heavy-weight intermediate-mass stars by unearthing new, ...faint, white dwarf members of the rich, nearby, intermediate-age open clusters NGC3532 and NGC2287. We identify a total of four white dwarfs with distances, proper motions and cooling times which can be reconciled with membership of these populations. We find that WDJ0643-203 in NGC2287, with an estimated mass of M= 1.02-1.16Modot, is potentially the most massive white dwarf so far identified within an open cluster. Guided by the predictions of modern theoretical models of the late-stage evolution of heavy-weight intermediate-mass stars, we conclude that there is a distinct possibility that it has a core composed of O and Ne. We also determine that despite the cooling times of the three new white dwarfs in NGC3532 and the previously known degenerate member NGC3532-10 spanning similar to 90Myr, they all have remarkably similar masses (M similar to 0.9-1Modot). This is fully consistent with the results from our previous work on a heterogeneous sample of similar to 50 white dwarfs from 12 stellar populations, on the basis of which we argued that the stellar initial-final mass relation is less steep at Minit > 4Modot than in the adjacent lower initial mass regime. This change in the gradient of the relation could account for the secondary peak observed in the mass distribution of the field white dwarf population and mitigate the need to invoke close binary evolution to explain its existence. Spectroscopic investigation of numerous additional candidate white dwarf members of NGC3532 unearthed by a recent independent study would be useful to confirm (or otherwise) these conclusions.
Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative ...(ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research.
ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H.
Blood samples and clinical information were collected from 13,363 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable.
Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.govNCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.
Summary
Background
Chondromalacia of the cranial medial femoral condyle (CMFC) is a potential cause of stifle lameness in adult horses. However, there is scant published evidence of either its ...occurrence or its clinical significance.
Objectives
To document the occurrence of CMFC seen during diagnostic arthroscopy in adult horses with stifle lameness and to investigate its prognostic significance.
Study design
Retrospective cohort study.
Methods
The records were reviewed of all horses with unilateral or bilateral lameness localised to the stifle that underwent diagnostic arthroscopy of the cranial medial femorotibial joint at a UK equine hospital. The surgical findings were noted from each. Case outcomes were determined by unstructured telephone discussions with owners. A satisfactory outcome was defined as a horse that was in ridden work without ongoing anti‐inflammatory medication. Multivariable logistic regression was used to create a model with an outcome time point at 12‐month post‐operatively.
Results
One hundred and four horses were included in the study. CMFC was found in 79. In 25 CMFC was the only finding, 54 horses had CMFC plus other pathology and 25 had other pathology, but no CMFC. At 12 months, horses with CMFC were 9.9 (95% CI 2.2–45.0, P<0.01) times more likely to have an unsatisfactory outcome than horses without CMFC.
Main limitations
The study relied on retrospective analysis of clinical notes and archived arthroscopy videos. Assessment of outcome was determined by unstructured telephone interview and therefore there is potential for reporting errors to exist.
Conclusions
CMFC is a common arthroscopic finding in horses with stifle lameness and is significantly associated with an increased likelihood of the horse not being in ridden work at long‐term follow‐up.
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