58 research outputs found

    An Empirical Study of a Software Maintenance Process

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    This paper describes how a process support tool is used to collect metrics about a major upgrade to our own electronic retail system. An incremental prototyping lifecycle is adopted in which each increment is categorised by an effort type and a project component. Effort types are Acquire, Build, Comprehend and Design and span all phases of development. Project components include data models and process models expressed in an OO modelling language and process algebra respectively as well as C++ classes and function templates and build components including source files and data files. This categorisation is independent of incremental prototyping and equally applicable to other software lifecycles. The process support tool (PWI) is responsible for ensuring the consistency between the models and the C++ source. It also supports the interaction between multiple developers and multiple metric-collectors. The first two releases of the retailing software are available for ftp from oracle.ecs.soton.ac.uk in directory pub/peter. Readers are invited to use the software and apply their own metrics as appropriate. We would be interested to correspond with anyone who does so

    Prediction of individual probabilities of livebirth and multiple birth events following in vitro fertilization (IVF): a new outcomes counselling tool for IVF providers and patients using HFEA metrics

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    In vitro fertilization (IVF) has become a standard treatment for subfertility after it was demonstrated to be of value to humans in 1978. However, the introduction of IVF into mainstream clinical practice has been accompanied by concerns regarding the number of multiple gestations that it can produce, as multiple births present significant medical consequences to mothers and offspring. When considering IVF as a treatment modality, a balance must be set between the chance of having a live birth and the risk of having a multiple birth. As IVF is often a costly decision for patients—financially, medically, and emotionally—there is benefit from estimating a patient’s specific chance that IVF could result in a birth as fertility treatment options are contemplated. Historically, a patient’s “chance of success” with IVF has been approximated from institution-based statistics, rather than on the basis of any particular clinical parameter (except age). Furthermore, the likelihood of IVF resulting in a twin or triplet outcome must be acknowledged for each patient, given the known increased complications of multiple gestation and consequent increased risk of poor birth outcomes. In this research, we describe a multivariate risk assessment model that incorporates metrics adapted from a national 7.5-year sampling of the Human Fertilisation & Embryology Authority (HFEA) dataset (1991–1998) to predict reproductive outcome (including estimation of multiple birth) after IVF. To our knowledge, http://www.formyodds.com is the first Software-as-a-Service (SaaS) application to predict IVF outcome. The approach also includes a confirmation functionality, where clinicians can agree or disagree with the computer-generated outcome predictions. It is anticipated that the emergence of predictive tools will augment the reproductive endocrinology consultation, improve the medical informed consent process by tailoring the outcome assessment to each patient, and reduce the potential for adverse outcomes with IVF

    Weak breeding seasonality of a songbird in a seasonally arid tropical environment arises from individual flexibility and strongly seasonal moult

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    Funding: C.J.N. was supported by a studentship funded by the Leventis Conservation Foundation through the University of St. Andrews UK and an Ubbo Emmius grant of the University of Groningen.In some tropical birds, breeding seasonality is weak at the population level, even where there are predictable seasonal peaks in environmental conditions. It therefore remains unclear whether individuals are adapted to breeding at specific times of the year or flexible to variable environmental conditions. We tested whether the relative year-round breeding activity of the Common Bulbul Pycnonotus barbatus arises due to within-individual variability in breeding dates. We collected data from 827 birds via mist-netting over two years with corresponding local weather data. We used a combination of climate envelope and generalised linear mixed models to explore how the timing of breeding is influenced by time of year, individual variation, rainfall and temperature in a West African savannah where seasonal precipitation determines annual variation in environmental conditions. We also pooled 65 breeding records from 19 individuals recorded between 2006 and 2017 based on brood patch occurrence and behavioural observation to compare within individual and population variability in breeding dates. We show that the breeding dates of individuals may be as variable as the population as a whole. However, we observed a seasonal peak in juvenile occurrence that varies significantly between years. Models suggest no relationship between nesting and moult, and within-year variation in rainfall and temperature, and birds were unlikely to breed during moult but may do afterwards. Moult was very seasonal, correlating strongly with day length. We suggest that because environmental conditions permit year-round breeding, and because reproductive output is subject to high predation risk, there is probably a weak selection for individuals to match breeding with variable peak conditions in the environment. Instead moult, which always occurs annually and successfully, is probably under strong selection to match variable peak conditions in the environment so that long term survival ensures future reproduction.Peer reviewe

    Enhancing chemical sensitivity of a tilted planar Bragg grating using a thin gold layer

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    The use of weakly tilted Bragg gratings to couple light from core waveguide modes to plasmon resonances within thin gold layers has gained increased interest over recent years. Chemical sensing using such techniques has a multitude of advantages, including access to developed gold based chemistry for surface functionalisation and an enhancement of chemical sensitivity, particularly for the biochemically ubiquitous solvent, water (1.33). Despite the obvious benefits of such devices, fabrication has principally been limited to optical fibre platforms, with little fabrication development being made in the planar regime. This work reports the use of a thin (50 nm) sputtered gold layer to enhance the chemical sensitivity of a weakly tilted planar Bragg grating (TPBG), illustrated in Figure 1 (a). Therefore, allowing access to the benefits of planar integration for this newly emerging technology

    Molecular Characterization of the Viroporin Function of Foot-and-Mouth Disease Virus Nonstructural Protein 2B

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    Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function analyses demonstrated that FMDV 2B is an ion channel-forming protein. Infrared spectroscopy measurements using partially overlapping peptides that spanned regions between amino acids 28 and 147 demonstrated the adoption of helical conformations in two putative transmembrane regions between residues 60 and 78 and between residues 119 and 147 and a third transmembrane region between residues 79 and 106, adopting a mainly extended structure. Using synthetic peptides, ion channel activity measurements in planar lipid bilayers and imaging of single giant unilamellar vesicles (GUVs) revealed the existence of two sequences endowed with membrane-porating activity: one spanning FMDV 2B residues 55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to 147. Mapping the latter sequence identified residues 119 to 147 as being responsible for the activity. Experiments to assess the degree of insertion of the synthetic peptides in bilayers and the inclination angle adopted by each peptide regarding the membrane plane normal confirm that residues 55 to 82 and 119 to 147 of 2B actively insert as transmembrane helices. Using reverse genetics, a panel of 13 FMD recombinant mutant viruses was designed, which harbored nonconservative as well as alanine substitutions in critical amino acid residues in the area between amino acid residues 28 and 147. Alterations to any of these structures interfered with pore channel activity and the capacity of the protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin family containing two distinct pore domains

    Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

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    BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Twins in genetic research.

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