611 research outputs found

    Sustainability performance measurement : a preliminary classification framework of models and indicators

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    In this position paper we focus on the diversity of sustainability measurements. Based on existing research on performance measurement, we propose a preliminary classification framework summarizing sustainability models and indicators. By describing illustrative examples, we claim that several models and indicators can be distinguished with their own peculiarities. Having such a framework is interesting for both academia and business to structure the range of models and indicators and to ultimately select the appropriate sustainability measurement approach. The proposed framework should be validated by further research

    Direct entropy determination and application to artificial spin ice

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    From thermodynamic origins, the concept of entropy has expanded to a range of statistical measures of uncertainty, which may still be thermodynamically significant. However, laboratory measurements of entropy continue to rely on direct measurements of heat. New technologies that can map out myriads of microscopic degrees of freedom suggest direct determination of configurational entropy by counting in systems where it is thermodynamically inaccessible, such as granular and colloidal materials, proteins and lithographically fabricated nanometre-scale arrays. Here, we demonstrate a conditional-probability technique to calculate entropy densities of translation-invariant states on lattices using limited configuration data on small clusters, and apply it to arrays of interacting nanometre-scale magnetic islands (artificial spin ice). Models for statistically disordered systems can be assessed by applying the method to relative entropy densities. For artificial spin ice, this analysis shows that nearest-neighbour correlations drive longer-range ones.Comment: 10 page

    Socioeconomic predictors and consequences of depression among primary care attenders with non-communicable diseases in the Western Cape, South Africa:Cohort study within a randomised trial

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    Background: Socioeconomic predictors and consequences of depression and its treatment were investigated in 4393 adults with specified non-communicable diseases attending 38 public sector primary care clinics in the Eden and Overberg districts of the Western Cape, South Africa.   Methods: Participants were interviewed at baseline in 2011 and 14 months later, as part of a randomised controlled trial of a guideline-based intervention to improve diagnosis and management of chronic diseases. The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) was used to assess depression symptoms, with higher scores representing more depressed mood. Results: Higher CESD-10 scores at baseline were independently associated with being less educated (p=0.004) and having lower income (p=0.003). CESD-10 scores at follow-up were higher in participants with less education (p=0.010) or receiving welfare grants (p=0.007) independent of their baseline scores. Participants with CESD-10 scores of 10 or more at baseline (56% of all participants) had 25% higher odds of being unemployed at follow-up (p=0.016), independently of baseline CESD-10 score and treatment status. Among participants with baseline CESD-10 scores of 10 or more, antidepressant medication at baseline was independently more likely in participants who had more education (p=0.002), higher income (p<0.001), or were unemployed (p=0.001). Antidepressant medication at follow up was independently more likely in participants with higher income (p=0.023), and in clinics with better access to pharmacists (p=0.053) and off-site drug delivery (p=0.013).  Conclusions: Socioeconomic disadvantage appears to be both a cause and consequence of depression, and may also be a barrier to treatment. There are opportunities for improving the prevention, diagnosis and treatment of depression in primary care in inequitable middle income countries like South Africa.  Trial registration: The trial is registered with Current Controlled Trials (ISRCTN20283604) and the Office for Human Research Protections Database (IRB00001938, FWA00001637)

    EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen.

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    Chordoma is a rare malignant bone tumour with a poor prognosis and limited therapeutic options. We undertook a focused compound screen (FCS) against 1097 compounds on three well-characterized chordoma cell lines; 154 compounds were selected from the single concentration screen (1 µm), based on their growth-inhibitory effect. Their half-maximal effective concentration (EC50 ) values were determined in chordoma cells and normal fibroblasts. Twenty-seven of these compounds displayed chordoma selective cell kill and 21/27 (78%) were found to be EGFR/ERBB family inhibitors. EGFR inhibitors in clinical development were then studied on an extended cell line panel of seven chordoma cell lines, four of which were sensitive to EGFR inhibition. Sapitinib (AstraZeneca) emerged as the lead compound, followed by gefitinib (AstraZeneca) and erlotinib (Roche/Genentech). The compounds were shown to induce apoptosis in the sensitive cell lines and suppressed phospho-EGFR and its downstream pathways in a dose-dependent manner. Analysis of substituent patterns suggested that EGFR-inhibitors with small aniline substituents in the 4-position of the quinazoline ring were more effective than inhibitors with large substituents in that position. Sapitinib showed significantly reduced tumour growth in two xenograft mouse models (U-CH1 xenograft and a patient-derived xenograft, SF8894). One of the resistant cell lines (U-CH2) was shown to express high levels of phospho-MET, a known bypass signalling pathway to EGFR. Neither amplifications (EGFR, ERBB2, MET) nor mutations in EGFR, ERBB2, ERBB4, PIK3CA, BRAF, NRAS, KRAS, PTEN, MET or other cancer gene hotspots were detected in the cell lines. Our findings are consistent with the reported (p-)EGFR expression in the majority of clinical samples, and provide evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

    A case report on a patient suffering from recurrent vomiting episodes, whose condition improved markedly during pregnancy and breast feeding

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    BACKGROUND: The normal physiology of the gastrointestinal tract has been only cursorily examined. Consequently, the pathophysiology of disturbances of the gastrointestinal functions is poorly known. Recurrent vomiting is one of many functional conditions for which it is difficult to find an explanation and to treat. In the following a case is described of a patient presenting with recurrent vomiting episodes, whose condition improved spontaneously during pregnancy and breast feeding. CASE PRESENTATION: A woman with recurrent vomiting episodes over several years was examined by esophagogastroduodenoscopy. This showed a non-peristaltic ventricle. Treatment with the procinetic drug cisapride (Prepulsid(®)) improved the peristalsis and reduced the symptoms. During pregnancy and breast feeding, she was free of symptoms, in spite of having discontinued her medication with cisapride (Prepulsid(®)). CONCLUSION: The fact that the patient improved during pregnancy and breast feeding, would seem to indicate the involvement of factors in the physiology of pregnancy and breast feeding that are of importance for gastric motility. This deserves further investigation

    Association of IFNGR2 gene polymorphisms with pulmonary tuberculosis among the Vietnamese

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    Interferon-γ (IFN-γ) is a key molecule of T helper 1 (Th1)-immune response against tuberculosis (TB), and rare genetic defects of IFN-γ receptors cause disseminated mycobacterial infection. The aim of the present study was to investigate whether genetic polymorphisms found in the Th1-immune response genes play a role in TB. In our study, DNA samples were collected from two series of cases including 832 patients with new smear-positive TB and 506 unrelated individuals with no history of TB in the general population of Hanoi, Vietnam. Alleles of eight microsatellite markers located around Th1-immune response-related genes and single nucleotide polymorphisms near the promising microsatellites were genotyped. A set of polymorphisms within the interferon gamma receptor 2 gene (IFNGR2) showed a significant association with protection against TB (P = 0.00054). Resistant alleles tend to be less frequently found in younger age at diagnosis (P = 0.011). Luciferase assays revealed high transcriptional activity of the promoter segment in linkage disequilibrium with resistant alleles. We conclude that the polymorphisms of IFNGR2 may confer resistance to the TB development of newly infected individuals. Contribution of the genetic factors to TB appeared to be different depending on age at diagnosis

    Effects of dopamine D2/D3 receptor antagonism on human planning and spatial working memory

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    Psychopharmacological studies in humans suggest important roles for dopamine (DA) D2 receptors in human executive functions, such as cognitive planning and spatial working memory (SWM). However, studies that investigate an impairment of such functions using the selective DA D2/3 receptor antagonist sulpiride have yielded inconsistent results, perhaps because relatively low doses were used. We believe we report for the first time, the effects of a higher (800 mg p.o.) single dose of sulpiride as well as of genetic variation in the DA receptor D2 gene (DA receptor D2 Taq1A polymorphism), on planning and working memory. With 78 healthy male volunteers, we apply a between-groups, placebo-controlled design. We measure outcomes in the difficult versions of the Cambridge Neuropsychological Test Automated Battery One-Touch Stockings of Cambridge and the self-ordered SWM task. Volunteers in the sulpiride group showed significant impairments in planning accuracy and, for the more difficult problems, in SWM. Sulpiride administration speeded response latencies in the planning task on the most difficult problems. Volunteers with at least one copy of the minor allele (A1+) of the DA receptor D2 Taq1A polymorphism showed better SWM capacity, regardless of whether they received sulpiride or placebo. There were no effects on blood pressure, heart rate or subjective sedation. In sum, a higher single dose of sulpiride impairs SWM and executive planning functions, in a manner independent of the DA receptor D2 Taq1A polymorphism.This research work was funded by a Core Award from the Medical Research Council and the Wellcome Trust to the Behavioural and Clinical Neuroscience Institute (MRC Ref G1000183; WT Ref 093875/Z/10/Z). Also supported by a Wellcome Trust Senior Investigator Award (104631/Z/14/Z) awarded to TWR. CE was supported by the Swiss National Science Foundation (PA00P1_134135) and the Vienna Science and Technology Fund (WWTF VRG13-007)

    Men and COVID-19: the aftermath

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    The global pandemic as a result of the SARS-CoV2 virus has seen over 16m people infected and over 650,000 deaths, with men at double the risk of both developing the severe form of the disease and mortality. There are both biological (sex) and socio-cultural (gender) factors, compounded by socio-economic factors and ethnicity, that impact on the aftermath of what has occurred over the short time that this novel coronavirus has been circulating the world. The potential life-long morbidity as a result of the infection and as a consequence of highly invasive critical care treatment needs to be factored into the rehabilitation of survivors. There are also many men whose lives will have been severely affected both physically and emotionally by the pandemic without ever contracting the disease, with the widespread disruption to normal existence and its impact on their social world and the economy. The implications of the closure of many healthcare services over the initial lockdown will also have both a shorter- and longer-term impact on other diseases due to missed early diagnosis and disrupted treatment regimes. Getting effective public health messages out to the population is critical and this current pandemic is demonstrating that there needs to be a more focused view on men's health behaviour. Without effective public support for preventative action the more likely the disease will continue its path unabated. This review explores the wider ramifications of the disease both for those men who have survived the disease and those that have been affected by the wider social effects of the pandemic. The pandemic should be a wake-up call for all involved in the planning and delivery of health and social care for the greater attention to the central role of sex and gender
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