A Multi-Factorial Risk Prioritization Framework for Food-Borne Pathogens

To lower the incidence of human food-borne disease, experts and stakeholders have urged the development of a science- and risk-based management system in which food-borne hazards are analyzed and prioritized. A literature review shows that most approaches to risk prioritization developed to date are based on measures of health outcomes and do not systematically account for other factors that may be important to decision making. The Multi-Factorial Risk Prioritization Framework developed here considers four factors that may be important to risk managers: public health, consumer risk perceptions and acceptance, market-level impacts, and social sensitivity. The framework is based on the systematic organization and analysis of data on these multiple factors. The basic building block of the information structure is a three-dimensional cube based on pathogen-food-factor relationships. Each cell of the cube has an information card associated with it and data from the cube can be aggregated along different dimensions. The framework is operationalized in three stages, with each stage adding another dimension to decision-making capacity. The first stage is the information cards themselves that provide systematic information that is not pre-processed or aggregated across factors. The second stage maps the information on the various information cards into cobweb diagrams that create a graphical profile of, for example, a food-pathogen combination with respect to each of the four risk prioritization factors. The third stage is formal multi-criteria decision analysis in which decision makers place explicit values on different criteria in order to develop risk priorities. The process outlined above produces a ‘List A’ of priority food-pathogen combinations according to some aggregate of the four risk prioritization factors. This list is further vetted to produce ‘List B’, which brings in feasibility analysis by ranking those combinations where practical actions that have a significant impact are feasible. Food-pathogen combinations where not enough is known to identify any or few feasible interventions are included in ‘List C’. ‘List C’ highlights areas with significant uncertainty where further research may be needed to enhance the precision of the risk prioritization process. The separation of feasibility and uncertainty issues through the use of ‘Lists A, B, and C’ allows risk managers to focus separately on distinct dimensions of the overall prioritization. The Multi-Factorial Risk Prioritization Framework provides a flexible instrument that compares and contrasts risks along four dimensions. Use of the framework is an iterative process. It can be used to establish priorities across pathogens for a particular food, across foods for a particular pathogen and/or across specific food-pathogen combinations. This report provides a comprehensive conceptual paper that forms the basis for a wider process of consultation and for case studies applying the framework.risk analysis, risk prioritization, food-borne pathogens, benefits and costs

Race and sex: teachers' views on who gets ahead in schools?

The research reported here was part of a large study of the impact of age, disability, race and sex on the teaching profession in England. The basic question asked in this research was how do these factors interact with career aspirations and achievements of classteachers, promoted teachers and headteachers? There were three different data sources: a large postal survey drawn from diverse geographic regions across England with over 2000 respondents; face‐to‐face individual interviews with over 100 teachers in 18 case study schools from across all of the main regions of England; discussions with special interest groups of teachers. Not surprisingly, the answer to the above question was complex. Nonetheless, the paper's conclusion highlights some of the noteworthy themes across this broad sample of teachers from primary, secondary and special schools

Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix.

Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exert higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model in which motors and clutches are both increased. Basal-like nonmalignant mammary epithelial cells also display an altered integrin adhesion molecular organization at the nanoscale and recruit a suite of paxillin-associated proteins implicated in invasion and metastasis. Phosphorylation of paxillin by Src family kinases, which regulates adhesion turnover, is similarly enhanced in the metastatic and basal-like tumor cells, fostered by a stiff matrix, and critical for tumor cell invasion in our assays. Bioinformatics reveals an unappreciated relationship between Src kinases, paxillin, and survival of breast cancer patients. Thus adoption of the basal-like adhesion phenotype may favor the recruitment of molecules that facilitate tumor metastasis to integrin-based adhesions. Analysis of the physical properties of tumor cells and integrin adhesion composition in biopsies may be predictive of patient outcome

The Search for Stable, Massive, Elementary Particles

In this paper we review the experimental and observational searches for stable, massive, elementary particles other than the electron and proton. The particles may be neutral, may have unit charge or may have fractional charge. They may interact through the strong, electromagnetic, weak or gravitational forces or through some unknown force. The purpose of this review is to provide a guide for future searches - what is known, what is not known, and what appear to be the most fruitful areas for new searches. A variety of experimental and observational methods such as accelerator experiments, cosmic ray studies, searches for exotic particles in bulk matter and searches using astrophysical observations is included in this review.Comment: 34 pages, 8 eps figure

Trends in, and factors associated with, HIV infection amongst tuberculosis patients in the era of anti-retroviral therapy: a retrospective study in England, Wales and Northern Ireland

Background: HIV increases the progression of latent tuberculosis (TB) infection to active disease and contributed to increased TB in the UK until 2004. We describe temporal trends in HIV infection amongst patients with TB and identify factors associated with HIV infection. / Methods: We used national surveillance data of all TB cases reported in England, Wales and Northern Ireland from 2000 to 2014 and determined HIV status through record linkage to national HIV surveillance. We used logistic regression to identify associations between HIV and demographic, clinical and social factors. / Results: There were 106,829 cases of TB in adults (≥ 15 years) reported from 2000 to 2014. The number and proportion of TB patients infected with HIV decreased from 543/6782 (8.0%) in 2004 to 205/6461 (3.2%) in 2014. The proportion of patients diagnosed with HIV > 91 days prior to their TB diagnosis increased from 33.5% in 2000 to 60.2% in 2013. HIV infection was highest in people of black African ethnicity from countries with high HIV prevalence (32.3%), patients who misused drugs (8.1%) and patients with miliary or meningeal TB (17.2%). / Conclusions: There has been an overall decrease in TB-HIV co-infection and a decline in the proportion of patients diagnosed simultaneously with both infections. However, high rates of HIV remain in some sub-populations of patients with TB, particularly black Africans born in countries with high HIV prevalence and people with a history of drug misuse. Whilst the current policy of testing all patients diagnosed with TB for HIV infection is important in ensuring appropriate management of TB patients, many of these TB cases would be preventable if HIV could be diagnosed before TB develops. Improving screening for both latent TB and HIV and ensuring early treatment of HIV in these populations could help prevent these TB cases. British HIV Association guidelines on latent TB testing for people with HIV from sub-Saharan Africa remain relevant, and latent TB screening for people with HIV with a history of drug misuse, homelessness or imprisonment should also be considered

Lipid Classes and Fatty Acid Patterns are Altered in the Brain of γ-Synuclein Null Mutant Mice

The well-documented link between α-synuclein and the pathology of common human neurodegenerative diseases has increased attention to the synuclein protein family. The involvement of α-synuclein in lipid metabolism in both normal and diseased nervous system has been shown by many research groups. However, the possible involvement of γ-synuclein, a closely-related member of the synuclein family, in these processes has hardly been addressed. In this study, the effect of γ-synuclein deficiency on the lipid composition and fatty acid patterns of individual lipids from two brain regions has been studied using a mouse model. The level of phosphatidylserine (PtdSer) was increased in the midbrain whereas no changes in the relative proportions of membrane polar lipids were observed in the cortex of γ-synuclein-deficient compared to wild-type (WT) mice. In addition, higher levels of docosahexaenoic acid were found in PtdSer and phosphatidylethanolamine (PtdEtn) from the cerebral cortex of γ-synuclein null mutant mice. These findings show that γ-synuclein deficiency leads to alterations in the lipid profile in brain tissues and suggest that this protein, like α-synuclein, might affect neuronal function via modulation of lipid metabolism

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers