Evaluation of diversity among common beans (Phaseolus vulgaris L.) from two centers of domestication using 'omics' technologies

<p>Abstract</p> <p>Background</p> <p>Genetic diversity among wild accessions and cultivars of common bean (<it>Phaseolus vulgaris </it>L.) has been characterized using plant morphology, seed protein allozymes, random amplified polymorphic DNA, restriction fragment length polymorphisms, DNA sequence analysis, chloroplast DNA, and microsatellite markers. Yet, little is known about whether these traits, which distinguish among genetically distinct types of common bean, can be evaluated using omics technologies.</p> <p>Results</p> <p>Three 'omics' approaches: transcriptomics, proteomics, and metabolomics were used to qualitatively evaluate the diversity of common bean from two Centers of Domestication (COD). All three approaches were able to classify common bean according to their COD using unsupervised analyses; these findings are consistent with the hypothesis that differences exist in gene transcription, protein expression, and synthesis and metabolism of small molecules among common bean cultivars representative of different COD. Metabolomic analyses of multiple cultivars within two common bean gene pools revealed cultivar differences in small molecules that were of sufficient magnitude to allow identification of unique cultivar fingerprints.</p> <p>Conclusions</p> <p>Given the high-throughput and low cost of each of these 'omics' platforms, significant opportunities exist for their use in the rapid identification of traits of agronomic and nutritional importance as well as to characterize genetic diversity.</p

A longitudinal cohort study of malaria exposure and changing serostatus in a malaria endemic area of rural Tanzania.

BACKGROUND: Measurements of anti-malarial antibodies are increasingly used as a proxy of transmission intensity. Most serological surveys are based on the use of cross-sectional data that, when age-stratified, approximates historical patterns of transmission within a population. Comparatively few studies leverage longitudinal data to explicitly relate individual infection events with subsequent antibody responses. METHODS: The occurrence of seroconversion and seroreversion events for two Plasmodium falciparum asexual stage antigens (MSP-1 and AMA-1) was examined using three annual measurements of 691 individuals from a cohort of individuals in a malaria-endemic area of rural east-central Tanzania. Mixed-effect logistic regression models were employed to determine factors associated with changes in serostatus over time. RESULTS: While the expected population-level relationship between seroprevalence and disease incidence was observed, on an individual level the relationship between individual infections and the antibody response was complex. MSP-1 antibody responses were more dynamic in response to the occurrence and resolution of infection events than AMA-1, while the latter was more correlated with consecutive infections. The MSP-1 antibody response to an observed infection seemed to decay faster over time than the corresponding AMA-1 response. Surprisingly, there was no evidence of an age effect on the occurrence of a conversion or reversion event. CONCLUSIONS: While the population-level results concur with previously published sero-epidemiological surveys, the individual-level results highlight the more complex relationship between detected infections and antibody dynamics than can be analysed using cross-sectional data. The longitudinal analysis of serological data may provide a powerful tool for teasing apart the complex relationship between infection events and the corresponding immune response, thereby improving the ability to rapidly assess the success or failure of malaria control programmes

Highly Sensitive and Specific Detection of Rare Variants in Mixed Viral Populations from Massively Parallel Sequence Data

Viruses diversify over time within hosts, often undercutting the effectiveness of host defenses and therapeutic interventions. To design successful vaccines and therapeutics, it is critical to better understand viral diversification, including comprehensively characterizing the genetic variants in viral intra-host populations and modeling changes from transmission through the course of infection. Massively parallel sequencing technologies can overcome the cost constraints of older sequencing methods and obtain the high sequence coverage needed to detect rare genetic variants (<1%) within an infected host, and to assay variants without prior knowledge. Critical to interpreting deep sequence data sets is the ability to distinguish biological variants from process errors with high sensitivity and specificity. To address this challenge, we describe V-Phaser, an algorithm able to recognize rare biological variants in mixed populations. V-Phaser uses covariation (i.e. phasing) between observed variants to increase sensitivity and an expectation maximization algorithm that iteratively recalibrates base quality scores to increase specificity. Overall, V-Phaser achieved >97% sensitivity and >97% specificity on control read sets. On data derived from a patient after four years of HIV-1 infection, V-Phaser detected 2,015 variants across the ∼10 kb genome, including 603 rare variants (<1% frequency) detected only using phase information. V-Phaser identified variants at frequencies down to 0.2%, comparable to the detection threshold of allele-specific PCR, a method that requires prior knowledge of the variants. The high sensitivity and specificity of V-Phaser enables identifying and tracking changes in low frequency variants in mixed populations such as RNA viruses

The Characterization of Twenty Sequenced Human Genomes

We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten “case” genomes from individuals with severe hemophilia A and ten “control” genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways

How do parents manage irritability, challenging behavior, non-compliance and anxiety in children with Autism Spectrum Disorders? A meta-synthesis

Although there is increasing research interest in the parenting of children with ASD, at present, little is known about everyday strategies used to manage problem behaviour. We conducted a meta-synthesis to explore what strategies parents use to manage irritability, non-compliance, challenging behaviour and anxiety in their children with ASD. Approaches included: (1) accommodating the child; (2) modifying the environment; (3) providing structure, routine and occupation; (4) supervision and monitoring; (5) managing non-compliance with everyday tasks; (6) responding to problem behaviour; (7) managing distress; (8) maintaining safety and (9) analysing and planning. Results suggest complex parenting demands in children with ASD and problem behaviour. Findings will inform the development of a new measure to quantify parenting strategies relevant to ASD

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

The effects of integrated care: a systematic review of UK and international evidence

BACKGROUND: Healthcare systems around the world have been responding to the demand for better integrated models of service delivery. However, there is a need for further clarity regarding the effects of these new models of integration, and exploration regarding whether models introduced in other care systems may achieve similar outcomes in a UK national health service context. METHODS: The study aimed to carry out a systematic review of the effects of integration or co-ordination between healthcare services, or between health and social care on service delivery outcomes including effectiveness, efficiency and quality of care. Electronic databases including MEDLINE; Embase; PsycINFO; CINAHL; Science and Social Science Citation Indices; and the Cochrane Library were searched for relevant literature published between 2006 to March 2017. Online sources were searched for UK grey literature, and citation searching, and manual reference list screening were also carried out. Quantitative primary studies and systematic reviews, reporting actual or perceived effects on service delivery following the introduction of models of integration or co-ordination, in healthcare or health and social care settings in developed countries were eligible for inclusion. Strength of evidence for each outcome reported was analysed and synthesised using a four point comparative rating system of stronger, weaker, inconsistent or limited evidence. RESULTS: One hundred sixty seven studies were eligible for inclusion. Analysis indicated evidence of perceived improved quality of care, evidence of increased patient satisfaction, and evidence of improved access to care. Evidence was rated as either inconsistent or limited regarding all other outcomes reported, including system-wide impacts on primary care, secondary care, and health care costs. There were limited differences between outcomes reported by UK and international studies, and overall the literature had a limited consideration of effects on service users. CONCLUSIONS: Models of integrated care may enhance patient satisfaction, increase perceived quality of care, and enable access to services, although the evidence for other outcomes including service costs remains unclear. Indications of improved access may have important implications for services struggling to cope with increasing demand. TRIAL REGISTRATION: Prospero registration number: 42016037725

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference