2,990 research outputs found
Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
No full textGenome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer
Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study
Full text linkPhysical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics. We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (n =5) or sedentary time (n =6), or accelerometer-measured (n =1) or self-reported (n =5) vigorous physical activity. Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women
Discourse on formation of investigators’ competencies
No full textOne of the most important aims of law enforcement agencies is crime investigation and
prevention. Consequently, one of the main activities of the law enforcement agencies, especially in the
pre-trial investigation sphere, is to optimise the organisation of the pre-trial investigation in order to
save the experienced skilled and competent specialists. The author of this research offers a new
approach and analyses the qualification and competence of the pre-trial investigation subjects not only
in terms of personnel management, but all elements of the model of pre-trial investigation to make
pre-trial investigation organisation more effective. It should be noted that the content of an
investigators‘ qualification or levels of competence are still not determined or strictly regulated and
this is the reason for many discussions in this area. These discussions surround what qualification and level of competence the investigators should have in pre-trial investigation, what general and special
competencies they should acquire and how the content of the competencies should be determined. In the present article the author analyses the investigators‘ qualification and competence as a
presumption that it is an essential aspect of an effective pre-trial investigation. Analysing this question
the author compares other subjects such as the regulation of qualifications and levels of competence of
the prosecutors and pre-trial investigation judges. The author also identifies the problem of how to
define an investigators qualification and level of competence making recommendations to create a
Description of Investigators Competencies. Qualification requirements should be determined in this
legal act and general, occupational and special competencies should be identified with the content also
being determined within this framework. Formation of the Description of Investigators‘ Competencies
should determine not only the content of the investigators‘ required level of competence but also this
process should be consistent with the assessment and career development of investigators‘ including
the process of gaining the investigators‘ qualification. The aim of this research is to identify the problems associated with defining an investigators‘
qualification and levels of competence and to propose recommendations on how this could be
achieved. The subject of this research is limited to only looking at investigators‘ qualification and
level of competence. The author is using a qualitative method for this research based upon the contents of documents.
The author will analysis eight legal acts related to the qualification and competence of pre-trial
investigation and fifty different investigators‘ job descriptions.Straipsnyje nagrinėjama ikiteisminio tyrimo pareigūnų (tyrėjų) kvalifikacija ir kompetencija kaip viena iš veiksmingo ikiteisminio tyrimo organizavimo prielaidų. Analizuojant tyrėjų kvalifikacijos ir kompetencijos turinį ir jo reglamentavimą, lyginama kitų ikiteisminio tyrimo subjektų – prokurorų ir ikiteisminio tyrimo teisėjų – kvalifikacijos ir kompetencijos turinio reglamentavimo ypatumai, identifikuojamos tyrėjų kvalifikacijos ir kompetencijos apibrėžties problemos ir pateikiami sprendimo būdai – siūlomas ikiteisminio tyrimo pareigūnų (tyrėjų) kompetencijų aprašas, kuriame būtų tiksliai nustatyti tyrėjų kvalifikaciniai reikalavimai, identifikuotos bendrosios, profesinės ir specialiosios kompetencijos ir apibrėžtas šių kompetencijų turinys. Ikiteisminio tyrimo pareigūnų kompetencijų aprašo suformavimas sudarytų galimybę ne tik aiškiai apibrėžti tyrėjo kompetencijos turinį, bet ir šį procesą nuosekliai susieti su tyrėjo veiklos vertinimu, karjera ir kvalifikacijos tobulinimu. Straipsnį sudaro įvadas ir dvi dalys. Pirmoje dalyje nagrinėjama tyrėjo kvalifikacijos apibrėžties problematika, gretinama ikiteisminio tyrimo pareigūno, prokuroro ir teisėjo kvalifikacijos apibrėžtys. Šioje dalyje siūloma tiksliai nustatyti ir apibrėžti tyrėjo kvalifikacinius reikalavimus. Antrojoje dalyje analizuojama tyrėjo kompetencijos turinys. Nagrinėjant prokurorų, teisėjų kompetencijos turinį ir jo reglamentavimo ypatumus, siūloma sudaryti tyrėjo kompetencijų aprašą, kuriame būtų tiksliai apibrėžtas tyrėjo kompetencijos turinys
Sepsis-driven temporal variability in cytokine secretion and heart rate is potentiated by withdrawing vagal innervation: Evidence of higher order neuroimmunological communication via the cholinergic anti-inflammatory pathway in the ovine fetus near term
No full textFetal brain-gut communication is disrupted during sepsis and associated with a higher degree of intestinal inflammation: Implications for non-evasive monitoring
No full textInternet technologies relevant to private investigators’ working practices
Full text linkMuch has been written and discussed especially in the various US media and in legislative organs, about how the Internet is used illegally (hacking, stalking for instance), but hardly if any research has been done as to how the investigative industry employs the new medium to its benefit. The author described in this thesis how private investigators (PIs) execute their profession these days using the facilities the Internet avail them in contrast to the time before the dawn of the Internet. This contrast is also investigated in an international context, an important part of the thesis, drawn from the author's 32 years of international business experience and that of PIs worldwide. The availability of the various online facilities in different countries are compared. To better understand the new medium, and its facilities a short outline of the Internet’s history, it’s set up in general and for the use of PIs in particular is supplied. PIs also face limitations in their daily work, limitations originating from online, legal, educational, financial and international causes. The new medium not only helps PIs in their investigative, but also in their office work. Finally PIs' wishes for new tools to facilitate their daily investigative work and their outlook as to where the new medium will head are also discussed
A signature of fetal systemic inflammatory response in the temporal pattern of heart rate variability measures
No full textPolygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction
No full textThe 313-variant polygenic risk score (PRS313) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS313 across different European populations which could influence risk estimation has not been performed.Peer reviewe
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