Contextual factors among indiscriminate or larger attacks on food or water supplies, 1946-2015

This research updates previous inventories of malicious attacks on food and water to include data from 1946 through mid-2015. A systematic search of news reports, databases and previous inventories of poisoning events was undertaken. Incidents that threatened or were intended to achieve direct harm to humans, and that were either relatively large (number of victims > 4 or indiscriminate in intent or realisation were included. Agents could be chemical, biological or radio-nuclear. Reports of candidate incidents were subjected to systematic inclusion and exclusion criteria as well as validity analysis (not always clearly undertaken in previous inventories of such attacks). We summarise contextual aspects of the attacks that may be important for scenario prioritisation, modelling and defensive preparedness. Opportunity is key to most realised attacks, particularly access to dangerous agents. The most common motives and relative success rate in causing harm were very different between food and water attacks. The likelihood that people were made ill or died also varied by food/water mode, and according to motive and opportunity for delivery of the hazardous agent. Deaths and illness associated with attacks during food manufacture and prior to sale have been fewer than those in some other contexts. Valuable opportunities for food defence improvements are identified in other contexts, especially food prepared in private or community settings

A cross-sectional study of physical activity and sedentary behaviours in a Caribbean population: combining objective and questionnaire data to guide future interventions

BACKGROUND: Current understanding of population physical activity (PA) levels and sedentary behaviour in developing countries is limited, and based primarily on self-report. We described PA levels using objective and self-report methods in a developing country population. METHODS: PA was assessed in a cross-sectional, representative sample of the population of Barbados (25-54 years), using a validated questionnaire (RPAQ) and individually calibrated combined heart rate and movement sensing monitors. The RPAQ collects information on recalled activity in 4 domains: home, work, transport, and leisure. Physical inactivity was defined according to World Health Organization (WHO) guidelines; sedentary lifestyle was defined as being sedentary for 8 h or more daily; PA overestimation was defined as perceiving activity to be sufficient, when classified as 'inactive' by objective measurement. RESULTS: According to objective estimates, 90.5 % (95 % CI: 83.3,94.7) of women and 58.9 % (48.4,68.7) of men did not accumulate sufficient activity to meet WHO minimum recommendations. Overall, 50.7 % (43.3,58.1) of the population was sedentary for 8 h or more each day, and 60.1 % (52.8,66.9) overestimated their activity levels. The prevalence of inactivity was underestimated by self-report in both genders by 28 percentage points (95 % CI: 18,38), but the accuracy of reporting differed by age group, education level, occupational grade, and overweight/obesity status. Low PA was greater in more socially privileged groups: higher educational level and higher occupational grade were both associated with less objectively measured PA and more sedentary time. Variation in domain-specific self-reported physical activity energy expenditure (PAEE) by educational attainment was observed: higher education level was associated with more leisure activity and less occupational activity. Occupational PA was the main driver of PAEE for women and men according to self-report, contributing 57 % (95 % CI: 52,61). The most popular leisure activities for both genders were walking and gardening. CONCLUSIONS: The use of both objective and self-report methods to assess PA and sedentary behaviour provides important complementary information to guide public health programmes. Our results emphasize the urgent need to increase PA and reduce sedentary time in this developing country population. Women and those with higher social economic position are particularly at risk from low levels of physical activity

Educational intervention improves anticoagulation control in atrial fibrillation patients:the TREAT randomised trial

Background: Stroke prevention in atrial fibrillation (AF), most commonly with warfarin, requires maintenance of a narrow therapeutic target (INR 2.0 to 3.0) and is often poorly controlled in practice. Poor patient-understanding surrounding AF and its’ treatment may contribute to patient’s willingness to adhere to recommendations. Method: A theory-driven intervention, developed using patient interviews and focus groups, consisting of a one-off group session (1-6 patients) utilising an ‘expert-patient’ focussed DVD, educational booklet, self-monitoring diary and worksheet, was compared in a randomised controlled trial (ISRCTN93952605) against usual care, with patient postal follow-ups at 1, 2, 6, and 12-months. Ninety-seven warfarin-naïve AF patients were randomised to intervention (n=46, mean age (SD) 72.0 (8.2), 67.4% men), or usual care (n=51, mean age (SD) 73.7 (8.1), 62.7% men), stratified by age, sex, and recruitment centre. Primary endpoint was time within therapeutic range (TTR); secondary endpoints included knowledge, quality of life, anxiety/depression, beliefs about medication, and illness perceptions. Main findings: Intervention patients had significantly higher TTR than usual care at 6-months (76.2% vs. 71.3%; p=0.035); at 12-months these differences were not significant (76.0% vs. 70.0%; p=0.44). Knowledge increased significantly across time (F (3, 47) = 6.4; p<0.01), but there were no differences between groups (F (1, 47) = 3.3; p = 0.07). At 6-months, knowledge scores predicted TTR (r=0.245; p=0.04). Patients’ scores on subscales representing their perception of the general harm and overuse of medication, as well as the perceived necessity of their AF specific medications predicted TTR at 6- and 12-months. Conclusions: A theory-driven educational intervention significantly improves TTR in AF patients initiating warfarin during the first 6-months. Adverse clinical outcomes may potentially be reduced by improving patients’ understanding of the necessity of warfarin and reducing their perception of treatment harm. Improving education provision for AF patients is essential to ensure efficacious and safe treatment

Submicroscopic Gametocytes and the Transmission of Antifolate-Resistant Plasmodium falciparum in Western Kenya

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up. CONCLUSIONS/SIGNIFICANCE: In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites

Dynamic Activation and Repression of the Plasmodium falciparum rif Gene Family and Their Relation to Chromatin Modification

The regulation of variant gene expression in Plasmodium falciparum is still only partially understood. Regulation of var genes, the most studied gene family involved in antigenic variation, is orchestrated by a dynamic pattern of inherited chromatin states. Although recent evidence pointed to epigenetic regulation of transcribed and repressed rif loci, little is known about specific on/off associated histone modifications of individual rif genes. To investigate the chromatin marks for transcribed and repressed rif loci, we cultivated parasites and evaluated the transcriptional status of chosen rif targets by qRT-PCR and performed ChIP assays using H3K9ac and H3K9me3 antibodies. We then monitored changes in the epigenetic patterns in parasites after several reinvasions and also evaluated the “poised” mark in trophozoites and schizonts of the same erythrocytic cycle by ChIP using H3K4me2 specific antibodies. Our results show that H3K9 is acetylated in transcribed rif loci and trimethylated or even unmodified in repressed rif loci. These transcriptional and epigenetic states are inherited after several reinvasions. The poised modification H3K4me2 showed a tendency to be more present in loci in trophozoites that upon progression to schizonts strongly transcribe the respective locus. However, this effect was not consistently observed for all monitored loci. While our data show important similarities to var transcription-associated chromatin modifications, the observed swiftly occurring modifications at rif loci and the absence of H3K9 modification point to a different dynamic of recruitment of chromatin modifying enzymes

Allelic Variation, Alternative Splicing and Expression Analysis of Psy1 Gene in Hordeum chilense Roem. et Schult

Background: The wild barley Hordeum chilense Roem. et Schult. is a valuable source of genes for increasing carotenoid content in wheat. Tritordeums, the amphiploids derived from durum or common wheat and H. chilense, systematically show higher values of yellow pigment colour and carotenoid content than durum wheat. Phytoene synthase 1 gene (Psy1) is considered a key step limiting the carotenoid biosynthesis, and the correlation of Psy1 transcripts accumulation and endosperm carotenoid content has been demonstrated in the main grass species. Methodology/Principal findings: We analyze the variability of Psy1 alleles in three lines of H. chilense (H1, H7 and H16) representing the three ecotypes described in this species. Moreover, we analyze Psy1 expression in leaves and in two seed developing stages of H1 and H7, showing mRNA accumulation patterns similar to those of wheat. Finally, we identify thirtysix different transcripts forms originated by alternative splicing of the 59 UTR and/or exons 1 to 5 of Psy1 gene. Transcripts function is tested in a heterologous complementation assay, revealing that from the sixteen different predicted proteins only four types (those of 432, 370, 364 and 271 amino acids), are functional in the bacterial system. Conclusions/Significance: The large number of transcripts originated by alternative splicing of Psy1, and the coexistence of functional and non functional forms, suggest a fine regulation of PSY activity in H. chilense. This work is the first analysis of H. chilense Psy1 gene and the results reported here are the bases for its potential use in carotenoid enhancement in duru

On the interpretation of removable interactions: A survey of the field 33 years after Loftus

In a classic 1978 Memory &Cognition article, Geoff Loftus explained why noncrossover interactions are removable. These removable interactions are tied to the scale of measurement for the dependent variable and therefore do not allow unambiguous conclusions about latent psychological processes. In the present article, we present concrete examples of how this insight helps prevent experimental psychologists from drawing incorrect conclusions about the effects of forgetting and aging. In addition, we extend the Loftus classification scheme for interactions to include those on the cusp between removable and nonremovable. Finally, we use various methods (i.e., a study of citation histories, a questionnaire for psychology students and faculty members, an analysis of statistical textbooks, and a review of articles published in the 2008 issue of Psychology andAging) to show that experimental psychologists have remained generally unaware of the concept of removable interactions. We conclude that there is more to interactions in a 2 × 2 design than meets the eye

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Systematic evaluation of immune regulation and modulation

Cancer immunotherapies are showing promising clinical results in a variety of malignancies. Monitoring the immune as well as the tumor response following these therapies has led to significant advancements in the field. Moreover, the identification and assessment of both predictive and prognostic biomarkers has become a key component to advancing these therapies. Thus, it is critical to develop systematic approaches to monitor the immune response and to interpret the data obtained from these assays. In order to address these issues and make recommendations to the field, the Society for Immunotherapy of Cancer reconvened the Immune Biomarkers Task Force. As a part of this Task Force, Working Group 3 (WG3) consisting of multidisciplinary experts from industry, academia, and government focused on the systematic assessment of immune regulation and modulation. In this review, the tumor microenvironment, microbiome, bone marrow, and adoptively transferred T cells will be used as examples to discuss the type and timing of sample collection. In addition, potential types of measurements, assays, and analyses will be discussed for each sample. Specifically, these recommendations will focus on the unique collection and assay requirements for the analysis of various samples as well as the high-throughput assays to evaluate potential biomarkers