Positive-pion production in inelastic π-p interactions between 500 and 1300 MeV

The momentum distributions of the π+ in the reaction π-p→π+π-n were measured at several π+ angles for incident π- beam energies of 516, 550, 599, 667, and 715 MeV; π-n mass spectra were calculated from the π+ momentum distributions. Partial data were also obtained at higher energies. The π- beam was obtained from the Berkeley Bevatron. The momenta of the π+ were measured with a magnetic spectrometer consisting of a C magnet and thin-walled aluminum spark chambers to display the trajectory of the particle entering and leaving the magnet. An array of scintillation counters was used to detect the occurrence of an event. An electronic time-of-flight system was used to distinguish positive pions from protons that passed through the spectrometer. The measured spectra can not be adequately explained by any of the several models with which we tried to fit our spectra, including an isobar model, although production of the (3,3) isobar is prominent

IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen

Health-industry linkages for local health: reframing policies for African health system strengthening

The benefits of local production of pharmaceuticals in Africa for local access to medicines and to effective treatment remain contested. There is scepticism among health systems experts internationally that production of pharmaceuticals in sub-Saharan Africa (SSA) can provide competitive prices, quality and reliability of supply. Meanwhile low-income African populations continue to suffer poor access to a broad range of medicines, despite major international funding efforts. A current wave of pharmaceutical industry investment in SSA is associated with active African government promotion of pharmaceuticals as a key sector in industrialization strategies. We present evidence from interviews in 2013–15 and 2017 in East Africa that health system actors perceive these investments in local production as an opportunity to improve access to medicines and supplies. We then identify key policies that can ensure that local health systems benefit from the investments. We argue for a ‘local health’ policy perspective, framed by concepts of proximity and positionality, which works with local priorities and distinct policy time scales and identifies scope for incentive alignment to generate mutually beneficial health–industry linkages and strengthening of both sectors. We argue that this local health perspective represents a distinctive shift in policy framing: it is not necessarily in conflict with ‘global health’ frameworks but poses a challenge to some of its underlying assumptions

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

The Nlrp3 inflammasome regulates acute graft-versus-host disease

The success of allogeneic hematopoietic cell transplantation is limited by acute graft-versus-host disease (GvHD), a severe complication accompanied by high mortality rates. Yet, the molecular mechanisms initiating this disease remain poorly defined. In this study, we show that, after conditioning therapy, intestinal commensal bacteria and the damage-associated molecular pattern uric acid contribute to Nlrp3 inflammasome-mediated IL-1β production and that gastrointestinal decontamination and uric acid depletion reduced GvHD severity. Early blockade of IL-1β or genetic deficiency of the IL-1 receptor in dendritic cells (DCs) and T cells improved survival. The Nlrp3 inflammasome components Nlrp3 and Asc, which are required for pro-IL-1β cleavage, were critical for the full manifestation of GvHD. In transplanted mice, IL-1β originated from multiple intestinal cell compartments and exerted its effects on DCs and T cells, the latter being preferentially skewed toward Th17. Compatible with these mouse data, increased levels of active caspase-1 and IL-1β were found in circulating leukocytes and intestinal GvHD lesions of patients. Thus, the identification of a crucial role for the Nlrp3 inflammasome sheds new light on the pathogenesis of GvHD and opens a potential new avenue for the targeted therapy of this severe complication

The underlying mechanisms for development of hypertension in the metabolic syndrome

High blood pressure is an important constituent of the metabolic syndrome. However, the underlying mechanisms for development of hypertension in the metabolic syndrome are very complicated and remain still obscure. Visceral/central obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated renin-angiotensin system, increased inflammatory mediators, and obstructive sleep apnea have been suggested to be possible factors to develop hypertension in the metabolic syndrome. Here, we will discuss how these factors influence on development of hypertension in the metabolic syndrome

‘Fourth places’: the Contemporary Public Settings for Informal Social Interaction among Strangers.

This paper introduces ‘fourth places’ as an additional category of informal social settings alongside ‘third places’ (Oldenburg 1989). Through extensive empirical fieldwork on where and how social interaction among strangers occurs in the public and semi-public spaces of a contemporary masterplanned neighbourhood, this paper reveals that ‘fourth places’ are closely related to ‘third places’ in terms of social and behavioural characteristics, involving a radical departure from the routines of home and work, inclusivity, and social comfort. However, the activities, users, locations and spatial conditions that support them are very different. They are characterized by ‘in-betweenness’ in terms of spaces, activities, time and management, as well as a great sense of publicness. This paper will demonstrate that the latter conditions are effective in breaking the ‘placelessness’ and ‘fortress’ designs of newly designed urban public spaces and that, by doing so, they make ‘fourth places’ sociologically more open in order to bring strangers together. The recognition of these findings problematizes well-established urban design theories and redefines several spatial concepts for designing public space. Ultimately, the findings also bring optimism to urban design practice, offering new insights into how to design more lively and inclusive public spaces. Keywords: ‘Fourth places’, Informal Public Social Settings, Social Interaction, Strangers, Public Space Design

Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/μL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence