Moral commitments to community: Mapping social responsibility and its ambiguities among small business owners

This article maps the different moral positions related to social responsibility (SR) as articulated by 25 small business owners and explains how they understand their positions within a range of SR practices. The morality underpinning their social responsibility tended to be embedded in a sense of relationship with and commitment to the well-being of the local geographic community but was threaded with felt ambiguities. Through an ethical analysis, we argue that this moral commitment to community is connected to a relational worldview, distinct from values and assumptions driving the existing economic system, yet they pursue this vision as individual actors rather than working collectively

A framework for a European network for a systematic environmental impact assessment of genetically modified organisms (GMO)

The assessment of the impacts of growing genetically modified (GM) crops remains a major political and scientific challenge in Europe. Concerns have been raised by the evidence of adverse and unexpected environmental effects and differing opinions on the outcomes of environmental risk assessments (ERA). The current regulatory system is hampered by insufficiently developed methods for GM crop safety testing and introduction studies. Improvement to the regulatory system needs to address the lack of well designed GM crop monitoring frameworks, professional and financial conflicts of interest within the ERA research and testing community, weaknesses in consideration of stakeholder interests and specific regional conditions, and the lack of comprehensive assessments that address the environmental and socio economic risk assessment interface. To address these challenges, we propose a European Network for systematic GMO impact assessment (ENSyGMO) with the aim directly to enhance ERA and post-market environmental monitoring (PMEM) of GM crops, to harmonize and ultimately secure the long-term socio-political impact of the ERA process and the PMEM in the EU. These goals would be achieved with a multi-dimensional and multi-sector approach to GM crop impact assessment, targeting the variability and complexity of the EU agro-environment and the relationship with relevant socio-economic factors. Specifically, we propose to develop and apply methodologies for both indicator and field site selection for GM crop ERA and PMEM, embedded in an EU-wide typology of agro-environments. These methodologies should be applied in a pan-European field testing network using GM crops. The design of the field experiments and the sampling methodology at these field sites should follow specific hypotheses on GM crop effects and use state-of-the art sampling, statistics and modelling approaches. To address public concerns and create confidence in the ENSyGMO results, actors with relevant specialist knowledge from various sectors should be involved

Occupational and non-occupational risk factors correlating with the severity of clinical manifestations of carpal tunnel syndrome and related work disability among workers who work with a computer

The contribution of certain occupational and personal factors to the development of carpal tunnel syndrome (CTS) is still uncertain. We investigated which specific occupational and non-occupational factors correlate with the level of clinical manifestations and work disability related to CTS. The study included 190 workers who work with a computer and have diagnosed CTS (100 men, 90 women, aged 20–65 years). Subjective experience of CTS-related impairments was assessed with the Symptom Severity Scale (SSS) and the Functional Status Scale (FSS) of the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ). The objective, neural impairments were tested with electrodiagnostics (EDX), whereas CTS-related work disability data were collected from medical records. We found a high inter-correlation between BCTQ, EDX, and work disability data. These also showed high correlations with certain occupational factors (duration of computer-working in months and hours spent daily in computer-working, certain ergonomic, microclimatic, and other occupational conditions) and non-occupational factors (demographic and lifestyle factors: nutritional status, diet, smoking, alcohol consumption, and physical activity). Despite its limitations, our study has identified occupational and non-occupational risk factors that can aggravate CTS and work disability, but which can also be improved with workplace and lifestyle preventive and corrective measures. More research is needed, though, to establish the possible causal relationships and the independent influence of each of those risk factors

Community effort endorsing multiscale modelling, multiscale data science and multiscale computing for systems medicine

© 2017 The Author 2017. Published by Oxford University Press. Systems medicine holds many promises, but has so far provided only a limited number of proofs of principle. To address this road block, possible barriers and challenges of translating systems medicine into clinical practice need to be identified and addressed. The members of the European Cooperation in Science and Technology COST) Action CA15120 Open Multiscale Systems Medicine OpenMultiMed) wish to engage the scientific community of systems medicine and multiscale modelling, data science and computing, to provide their feedback in a structured manner. This will result in follow-up white papers and open access resources to accelerate the clinical translation of systems medicine.Austrian Science Fund: Special Research Program SFB-F54. The European Cooperation in Science and Technology (COST) Action CA15120 OpenMultiMed (http://openmultimed.net)

Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort

Objective: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts. Design and methods: Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time. Results: In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3–4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes. Conclusion: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways

Predictors of diagnostic yield in bronchoscopy: a retrospective cohort study comparing different combinations of sampling techniques

<p>Abstract</p> <p>Background</p> <p>The reported diagnostic yield from bronchoscopies in patients with lung cancer varies greatly. The optimal combination of sampling techniques has not been finally established.</p> <p>The objectives of this study were to find the predictors of diagnostic yield in bronchoscopy and to evaluate different combinations of sampling techniques.</p> <p>Methods</p> <p>All bronchoscopies performed on suspicion of lung malignancy in 2003 and 2004 were reviewed, and 363 patients with proven malignant lung disease were included in the study. Sampling techniques performed were biopsy, transbronchial needle aspiration (TBNA), brushing, small volume lavage (SVL), and aspiration of fluid from the entire procedure. Logistic regression analyses were adjusted for sex, age, endobronchial visibility, localization (lobe), distance from carina, and tumor size.</p> <p>Results</p> <p>The adjusted odds ratios (OR) with 95% confidence intervals (CI) for a positive diagnostic yield through all procedures were 17.0 (8.5–34.0) for endobronchial lesions, and 2.6 (1.3–5.2) for constriction/compression, compared to non-visible lesions; 3.8 (1.3–10.7) for lesions > 4 cm, 6.7 (2.1–21.8) for lesions 3–4 cm, and 2.5 (0.8–7.9) for lesions 2–3 cm compared with lesions <= 2 cm. The combined diagnostic yield of biopsy and TBNA was 83.7% for endobronchial lesions and 54.2% for the combined group without visible lesions. This was superior to either technique alone, whereas additional brushing, SVL, and aspiration did not significantly increase the diagnostic yield.</p> <p>Conclusion</p> <p>In patients with malignant lung disease, visible lesions and larger tumor size were significant predictors of higher diagnostic yield, after adjustment for sex, age, distance from carina, side and lobe. The combined diagnostic yield of biopsy and TBNA was significant higher than with either technique alone.</p

Genomic characterization of malignant progression in neoplastic pancreatic cysts

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention

Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort

OBJECTIVE: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts. DESIGN AND METHODS: Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time. RESULTS: In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3-4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes. CONCLUSION: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways

The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.

The inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management