291 research outputs found
The social, cosmopolitanism and beyond
First, this article will outline the metaphysics of ‘the social’ that implicitly and explicitly connects the work of lassical and contemporary cosmopolitan sociologists as different as Durkheim, Weber, Beck and Luhmann. In a second step, I will show that the cosmopolitan outlook of classical sociology is driven by exclusive differences. In understanding human affairs, both classical sociology and contemporary cosmopolitan sociology reflect a very modernist outlook of epistemological, conceptual, methodological and disciplinary rigour that separates the cultural sphere from the natural objects of concern. I will suggest that classical sociology – in order to be cosmopolitan – is forced (1) to exclude non-social and non-human objects as part of its conceptual and methodological rigour, and (2) consequently and methodologically to rule out the non-social and the non-human. Cosmopolitan sociology imagines ‘the social’ as a global, universal explanatory device to conceive and describe the non-social and non-human. In a third and final step the article draws upon the work of the French sociologist Gabriel Tarde and offers a possible alternative to the modernist social and cultural other-logics of social sciences. It argues for a inclusive conception of ‘the social’ that gives the non-social and non-human a cosmopolitan voice as well
Securely Attached, Strongly Committed? On the Influence of Attachment Orientations on Organizational Commitment
Characterization of covalent inhibitors that disrupt the interaction between the tandem SH2 domains of SYK and FCER1G phospho-ITAM
RNA sequencing and genetic data support spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) as putative targets to be modulated for Alzheimer’s disease (AD) therapy. FCER1G is a component of Fc receptor complexes that contain an immunoreceptor tyrosine-based activation motif (ITAM). SYK interacts with the Fc receptor by binding to doubly phosphorylated ITAM (p-ITAM) via its two tandem SH2 domains (SYK-tSH2). Interaction of the FCER1G p-ITAM with SYK-tSH2 enables SYK activation via phosphorylation. Since SYK activation is reported to exacerbate AD pathology, we hypothesized that disruption of this interaction would be beneficial for AD patients. Herein, we developed biochemical and biophysical assays to enable the discovery of small molecules that perturb the interaction between the FCER1G p-ITAM and SYKtSH2. We identified two distinct chemotypes using a high-throughput screen (HTS) and orthogonally assessed their binding. Both chemotypes covalently modify SYK-tSH2 and inhibit its interaction with FCER1G p-ITAM, however, these compounds lack selectivity and this limits their utility as chemical tools
Correlação entre as escalas visual analógica, de Melbourne e filamentos de Von Frey na avaliação da dor pós-operatória em cadelas submetidas à ovariossalpingohisterectomia
Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study
A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study
In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4
Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1
Peer reviewe
No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.
BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant
(agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK
[C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under
grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS
infrastructure came from: the European Community's Seventh Framework Programme under grant agreement
n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710,
C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the
National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19
16
CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1-
0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast
Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer
Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium.
Funding for the project was provided by the Wellcome Trust under award 076113. The results published here
are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer
Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529
Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer.
Background
Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy.
Methods
A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage.
Results
Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed.
Conclusions
Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient.
Trial Registration
ISRCTN 4609929
On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection
A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)
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