Next Generation Mapping of Enological Traits in an F2 Interspecific Grapevine Hybrid Family

In winegrapes (Vitis spp.), fruit quality traits such as berry color, total soluble solids content (SS), malic acid content (MA), and yeast assimilable nitrogen (YAN) affect fermentation or wine quality, and are important traits in selecting new hybrid winegrape cultivars. Given the high genetic diversity and heterozygosity of Vitis species and their tendency to exhibit inbreeding depression, linkage map construction and quantitative trait locus (QTL) mapping has relied on F1 families with the use of simple sequence repeat (SSR) and other markers. This study presents the construction of a genetic map by single nucleotide polymorphisms identified through genotyping-by-sequencing (GBS) technology in an F2 mapping family of 424 progeny derived from a cross between the wild species V. riparia Michx. and the interspecific hybrid winegrape cultivar, ‘Seyval’. The resulting map has 1449 markers spanning 2424 cM in genetic length across 19 linkage groups, covering 95% of the genome with an average distance between markers of 1.67 cM. Compared to an SSR map previously developed for this F2 family, these results represent an improved map covering a greater portion of the genome with higher marker density. The accuracy of the map was validated using the well-studied trait berry color. QTL affecting YAN, MA and SS related traits were detected. A joint MA and SS QTL spans a region with candidate genes involved in the malate metabolism pathway. We present an analytical pipeline for calling intercross GBS markers and a high-density linkage map for a large F2 family of the highly heterozygous Vitis genus. This study serves as a model for further genetic investigations of the molecular basis of additional unique characters of North American hybrid wine cultivars and to enhance the breeding process by marker-assisted selection. The GBS protocols for identifying intercross markers developed in this study can be adapted for other heterozygous species

Search Based Clustering for Protecting Software with Diversified Updates

Reverse engineering is usually the stepping stone of a variety of at-tacks aiming at identifying sensitive information (keys, credentials, data, algo-rithms) or vulnerabilities and flaws for broader exploitation. Software applica-tions are usually deployed as identical binary code installed on millions of com-puters, enabling an adversary to develop a generic reverse-engineering strategy that, if working on one code instance, could be applied to crack all the other in-stances. A solution to mitigate this problem is represented by Software Diversity, which aims at creating several structurally different (but functionally equivalent) binary code versions out of the same source code, so that even if a successful attack can be elaborated for one version, it should not work on a diversified ver-sion. In this paper, we address the problem of maximizing software diversity from a search-based optimization point of view. The program to protect is subject to a catalogue of transformations to generate many candidate versions. The problem of selecting the subset of most diversified versions to be deployed is formulated as an optimisation problem, that we tackle with different search heuristics. We show the applicability of this approach on some popular Android apps

Pharmacotherapy and the risk for community-acquired pneumonia

<p>Abstract</p> <p>Background</p> <p>Some forms of pharmacotherapy are shown to increase the risk of community-acquired pneumonia (CAP). The purpose of this study is to investigate whether pharmacotherapy with proton pump inhibitors (PPI), inhaled corticosteroids, and atypical antipsychotics was associated with the increased risk for CAP in hospitalized older adults with the adjustment of known risk factors (such as smoking status and serum albumin levels).</p> <p>Methods</p> <p>A retrospective case-control study of adults aged 65 years or older at a rural community hospital during 2004 and 2006 was conducted. Cases (N = 194) were those with radiographic evidence of pneumonia on admission. The controls were patients without the discharge diagnosis of pneumonia or acute exacerbation of chronic obstructive pulmonary disease (COPD) (N = 952). Patients with gastric tube feeding, ventilator support, requiring hemodialysis, metastatic diseases or active lung cancers were excluded.</p> <p>Results</p> <p>Multiple logistic regression analysis revealed that the current use of inhaled corticosteroids (adjusted odds ratio [AOR] = 2.89, 95% confidence interval [CI] = 1.56-5.35) and atypical antipsychotics (AOR = 2.26, 95% CI = 1.23-4.15) was an independent risk factor for CAP after adjusting for confounders, including age, serum albumin levels, sex, smoking status, a history of congestive heart failure, coronary artery disease, and COPD, the current use of PPI, β2 agonist and anticholinergic bronchodilators, antibiotic(s), iron supplement, narcotics, and non-steroidal anti-inflammatory drugs. The crude OR and the AOR of PPI use for CAP was 1.41 [95% CI = 1.03 - 1.93] and 1.18 [95% CI = 0.80 - 1.74] after adjusting for the above confounders, respectively. Lower serum albumin levels independently increased the risk of CAP 1.89- fold by decreasing a gram per deciliter (AOR = 2.89, 95% CI = 2.01 - 4.16).</p> <p>Conclusion</p> <p>Our study reaffirmed that the use of inhaled corticosteroids and atypical antipsychotics was both associated with an increased risk for CAP in hospitalized older adults of a rural community. No association was found between current PPI use and the risk for CAP in this patient population of our study.</p

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications

BackgroundThere is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Genius and the Stages of Life in Eighteenth-Century Britain and Germany

In this paper I wish to argue for a socio-cultural history of genius. During the eighteenth century in Great Britain and Germany, the term genius had powerful political and moral dimensions which many historians have tended to ignore. As I hope to illustrate in this paper, the notion of genius was a potent rhetorical device used to legitimate one’s artisitic and natural beliefs on the one hand and political and social values on the other. I wish to argue that the main characters in the discus..