Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals

Background Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We sought to utilise our short-term CD154 detection method to further analyse the relationship between these T cell subsets and investigate differences between seasonal and perennial allergens. Using peripheral blood samples from grass-allergic, cat-allergic and healthy non-atopic subjects, we compared the frequencies and phenotype of CD154-positive T helper cells following stimulation with seasonal (grass) and perennial (cat dander) allergens. Results We identified a higher frequency of CD154+ T cells in grass-allergic individuals compared to healthy controls; this difference was not evident following stimulation with cat allergen. Activated Th1, Th2 and Tr1-like cells, that co-express IFNγ, IL4 and IL10, respectively, were identified in varying proportions in grass-allergic, cat-allergic and non-allergic individuals. We confirmed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. This relationship was dysregulated in grass-allergic individuals with no correlation between the T cell subsets and a higher Th2: Th1 ratio. We confirmed previous reports of a late-differentiated T cell phenotype in response to seasonal allergens compared to early-differentiated T cell responses to perennial allergens. Conclusions The findings confirm our existing work illustrating an important balance between Th1, Th2 and Tr1-like responses to allergens in health, where Th2 responses are frequently observed, but balanced by Th1 and regulatory responses. We confirm previous tetramer-based reports of phenotypic differences in T cells responding to seasonal and perennial allergens

Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition

Inositol phosphates (InsPs) are signaling molecules with multiple roles in cells. In particular Graphic (InsP6) is involved in mRNA export and editing or chromatin remodeling among other events. InsP6 accumulates as mixed salts (phytate) in storage tissues of plants and plays a key role in their physiology. Human diets that are exclusively grain-based provide an excess of InsP6 that, through chelation of metal ions, may have a detrimental effect on human health. Ins(1,3,4,5,6)P5 2-kinase (InsP5 2-kinase or Ipk1) catalyses the synthesis of InsP6 from InsP5 and ATP, and is the only enzyme that transfers a phosphate group to the axial 2-OH of the myo-inositide. We present the first structure for an InsP5 2-kinase in complex with both substrates and products. This enzyme presents a singular structural region for inositide binding that encompasses almost half of the protein. The key residues in substrate binding are identified, with Asp368 being responsible for recognition of the axial 2-OH. This study sheds light on the unique molecular mechanism for the synthesis of the precursor of inositol pyrophosphates

White savior projects: An examination of the Antitrafficking Social Movement

For this dissertation, I conduct an ethnography of three antitrafficking programs; interview 38 activists and survivors of trafficking; and analyze organizational texts, websites, and social media. I examine the history of the antitrafficking movement. Among the three organizations, activists provide housing; food, clothing, and hygiene items; medical services; mental health services and counseling; mentorship; education for survivors; a 24-hour hotline; outreach; case management and referrals; training for law enforcement; a drop-in center; and education and awareness events. I examine activists’ diagnostic, prognostic, and motivational framing of sex trafficking, and other framing tactics, such as frame alignment, frame diffusion, frame resonance, and cycles of protest. Activists within the three organizations connect sex trafficking to the Atlantic Slave Trade, referring to human trafficking as “modern-day slavery.” Activists also frame trafficking as happening in “our own backyards;” happening primarily to girls and women; and conflate sex work and sex trafficking. Activists believe that sex trafficking is caused by childhood sexual abuse, pornography and pornography addiction, and systems of oppression. I find that evangelical Christianity influences the organizations through services for survivors, training for staff and the public, the recruitment of staff and volunteers at church, and the practice of Christianity in front of and with survivors. I also find that evangelical activists employ language and strategies that cast them as white saviors seeking to ‘rescue’ survivors. There are several factors that have contributed to the success of the antitrafficking movement, such as increased political opportunities, resource mobilization, effective leadership, strategic use of grievances, and cultural context. Activists face several challenges in their work, namely lack of funding and resources, like housing. For the future, activists would like to see increased punishment of clients and traffickers; reductions in pornography and pornography addiction; increased education and awareness about trafficking; installation of survivors in leadership; and increased funding. I conclude by recommending that sex work and sex trafficking be distinguished in research, legislation, policies, and practice; rehabilitation of traffickers and clients; and make systematic changes to lessen the factors which contribute to trafficking

Antihypertensive treatment decreases arterial stiffness at night but not during the day. Results from the Hypertension in the Very Elderly Trial

The main Hypertension in the Very Elderly Trial (HYVET) demonstrated a very marked reduction in cardiovascular events by treating hypertensive participants 80 years or older with a low dose, sustained release prescription of indapamide (indapamide SR, 1.5 mg) to which was added a low dose of an angiotensin converting enzyme inhibitor in two-thirds of cases (perindopril 2–4 mg). This report from the ambulatory blood pressure sub-study investigates whether changes in arterial stiffness and ambulatory blood pressure (BP) could both explain the benefits observed in the main trial. A total of 139 participants were randomized to placebo [67] and to active treatment [72] and had both day and night observations of BP and arterial stiffness as determined from the Q wave Korotkoff diastolic (QKD) interval. The QKD interval was 5.6 ms longer (p = 0.017) in the actively treated group at night than in the placebo group. This was not true for the more numerous daytime readings so that 24-h results were similar in the two groups. The QKD interval remained longer at night in the actively treated group even when adjusted for systolic pressure, heart rate and height. The reduced arterial stiffness at night may partly explain the marked benefits observed in the main trial

Playing the game: service users' management of risk status in a UK medium secure forensic mental health service

In this article we examine how forensic mental health service users actively attempt to manage their risk status through playing the game of containing frustration and demonstrating compliance. The article draws on an observational study (2006 to 2009) which explored the practices of risk assessment and management within one inner city forensic mental health medium secure service in the UK. We used a grounded theory approach to explore service users and providers experiences of risk assessment and management. We interviewed forensic mental health service users and providers. We also collected data using participant and non-participant observation. Since access to forensic mental health services is tightly controlled, there are participant observation studies undertaken in these settings. We found that service users attempted to understand the system of assessment and sought to affect and reduce their risk status by engaging in overt, compliant behaviours. We argue that in doing so service users are active agents in the process of risk management. However, we indicate that there are adverse effects of this approach to risk management as the risk assessment process is subverted by the restriction of the flow of information, and service users are left with frustrations that they must contain and manage

SORTING OUT CONCERN: EUROPEAN ATTITUDES TOWARD HUMAN TRAFFICKING

Human trafficking is a global phenomenon, which is sometimes conflated with other cross-national social problems. While trafficking certainly occurs within countries, much of it occurs across borders. In this paper we examine one of the only available datasets that addresses individual concern about human trafficking: the Eurobarometer 2003. Individual concern about human trafficking matters, especially in democracies, because government policy is in part shaped by citizen preferences. When democratic governments are not responsive to citizens, they risk being voted out in the next election cycle. What we find is that concern for human trafficking varies by gender, age, marital status, income, political preference, distance from Africa and Asia, and percent immigrant. More interesting, we find that concern for human trafficking looks a lot like concern for illegal immigration. We discuss the multiple meanings of “concern”, the implications for public policy based on attitudinal research, the importance of asking the right questions, and the need for education on what human trafficking

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Surrogate models for direct dark matter detection

In this work we introduce RAPIDD, a surrogate model that speeds up the computation of the expected spectrum of dark matter particles in direct detection experiments. RAPIDD replaces the exact calculation of the dark matter differential rate (which in general involves up to three nested integrals) with a much faster parametrization in terms of ordinary polynomials of the dark matter mass and couplings, obtained in an initial training phase. In this article, we validate our surrogate model on the multi-dimensional parameter space resulting from the effective field theory description of dark matter interactions with nuclei, including also astrophysical uncertainties in the description of the dark matter halo. As a concrete example, we use this tool to study the complementarity of different targets to discriminate simplified dark matter models. We demonstrate that RAPIDD is fast and accurate, and particularly well-suited to explore a multi-dimensional parameter space, such as the one in effective field theory approach, and scans with a large number of evaluations