A community in transition: Analysis of health and well‐being in people living during and following aridification

This paper considers skeletal and dental lesions to assess the effects of aridification on two skeletal samples from the Bronze Age in what is now the United Arab Emirates (UAE), located on the eastern end of the Arabian Peninsula. This paper hypothesized that the sample from Qarn al-Harf (QAH) Tomb 6 would show a greater prevalence of skeletal and dental lesions in comparison with that from QAH Tomb 5, because QAH Tomb 6 dates to a period of aridification when compared with the wetter Wadi Suq period (~2000 B.C.). The skeletal remains from two tombs from QAH cemetery are studied: one dated to the transition period from the Umm an-Nar to Wadi Suq period (~2000 B.C.) (Tomb 6, n = 141) and one Wadi Suq period tomb (Tomb 5, n = 44; 2000–1600 B.C.). Skeletal and dental lesions, including carious lesions, antemortem tooth loss, dental enamel hypoplasia, periosteal new bone formation, cribra orbitalia, and porotic hyperostosis, were recorded and used to assess differential lived experience. Findings from the two tombs are compared with five contemporary sites of the Umm an-Nar and Wadi Suq periods. Fisher's exact tests found more statistically significant differences in the prevalence of cribra orbitalia (p = 0.0050) and non-adult mortality (p = 0.0118) for the QAH Tomb 6 skeletal sample than that from QAH Tomb 5. No other skeletal or dental lesions were significantly different according to Fisher's exact tests. While not significant, periosteal new bone formation rates in QAH 6 in conjunction with cribra orbitalia rates suggest individuals were experiencing stressors that were not impacting QAH Tomb 5 individuals. Skeletal and dental lesion rates are not directly attributable to climate change; however, we argue that intense aridification around 2000 B.C. caused desiccated crops and an increased reliance on marine sources for QAH Tomb 6. This reliance likely promoted nutritionally deficient diets manifesting as observed higher rates of cribra orbitalia and periosteal new bone formation

Smoking and cancer, cardiovascular and total mortality among older adults: The Finrisk Study

Little information is available about the deleterious effect of smoking in older adults The objective of this study was to assess the relationship of smoking habits with cancer, CVD and all-cause mortality in late middle-age (45–64 years) and older (65–74) people. This cohort study of 6516 men and 6514 women studied the relationship of smoking habits with cancer, cardiovascular disease (CVD) and all-cause mortality among middle-aged and older Finnish men and women during 1997–2013. The study cohort was followed up until the end of 2013 (median follow-up time was 11.8 years). Mortality data were obtained from the National Causes of Death Register and data on incident stroke events from the National Hospital Discharge Register. Adjusted Hazard ratios (HR) for total mortality were 2.61 (95% Confidence interval 2.15–3.18) among 45–64 years-old men and 2.59 (2.03–3.29) in 65–74 years-old men. The corresponding HRs for women 45–64 years-of-age were 3.21 (2.47–4.19) and 3.12 (2.09–4.68) for those 65–74 years-old, respectively. Adjusted HRs for CVD mortality in the 45–64 years-old and 65–74 years-old groups were 2.67 (1.92–2.67) and 1.95 (1.33–2.86) in men, and 4.28 (2.29–7.99) and 2.67 (1.28–5.58) in women, respectively. Among men, the risk difference between never and current smokers was 108/100.000 in the age-group 45–64 years, and 324/100.000 in the age group 65–74 years. Among women the differences were 52/100.000 and 196/100.000, respectively. In conclusion, absolute risk difference between never and current smokers are larger among the older age group. Smoking cessation counseling should routinely target also older adults in primary health-care.Peer reviewe

Jadeitite formed during subduction: In situ zircon geochronology constraints from two different tectonic events within the Guatemala Suture Zone

Jadeitite is a rare rock type associated with high-pressure–low-temperature blocks within serpentinite matrix mélanges. Models of formation involve precipitation from subduction-zone aqueous fluids veining the overlying mantle wedge (P-type), or metasomatism of igneous and/or sedimentary protoliths previously emplaced into the mélange (R-type). Age determinations of mélange lithologies provide constraints on the timing of “peak metamorphism” and subsequent exhumation. The timing of jadeitite formation, particularly in the rich source of the Guatemala Suture Zone (GSZ), is a controversial subject needing further attention. Over 80 in situ zircon crystals from three jadeitites and two mica–albite rocks from the North Motagua Mélange and one phengite jadeitite from the South Motagua Mélange of the GSZ were studied for age and trace-element determination. Most of these zircons are characterized by low Th/U ratios, depleted chondrite-normalized REE patterns relative to zircons from oceanic gabbros, and contain fluid and mineral inclusions that reflect the primary mineralogy (i.e., jadeite) and context (i.e., crystallization from an aqueous fluid) of the host rock, and thus formed during jadeitite crystallization. The SHRIMP-RG and LAM-ICP-MS U–Pb dates from zircon indicate that jadeitites and mica–albite rocks from the GSZ were formed through vein precipitation at ~98−80 and ~154–158 Ma, respectively. These data show (a) older ages that indicate jadeitite crystallization occurred ~10–30 Ma before the preserved subduction-zone peak metamorphism (e.g., exhumed eclogite), and (b) a second group of ages slightly younger than, or similar to, exhumation ages given by Ar–Ar dates from micas. Similar relationships occur at other jadeitite occurrences, such as the Syum-Keu ultramafic complex in the Polar Urals (Russia) and the serpentinite mélanges of the Río San Juan complex (Dominican Republic). The data argue for formation of jadeitite within the mantle wedge during active subduction. Thus, jadeitite provides a record of fluid introduction into the mantle wedge during subduction rather than during exhumation

Effective recruitment of participants to a phase I study using the internet and publicity releases through charities and patient organisations: analysis of the adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D).

A barrier to the successful development of new disease treatments is the timely recruitment of participants to experimental medicine studies that are primarily designed to investigate biological mechanisms rather than evaluate clinical efficacy. The aim of this study was to analyse the performance of three recruitment sources and the effect of publicity events during the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D).This work is funded by the JDRF (9-2011-253), the Wellcome Trust (091157) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140).This is the final version of the article. It first appeared from BMC via http://dx.doi.org/10.1186/s13063-015-0583-

CP violating neutrino oscillation and uncertainties in Earth matter density

We propose a statistical formulation to estimate possible errors in long baseline neutrino oscillation experiments caused by uncertainties in the Earth matter density. A quantitative investigation of the effect is made on the CP asymmetry in future neutrino factory experiments.Comment: Latex, 10 pages, 5 figure

The Effect of Chromosome 9p21 Variants on Cardiovascular Disease May Be Modified by Dietary Intake: Evidence from a Case/Control and a Prospective Study

Peer reviewe

SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike N-terminal domain (NTD) remains poorly characterized despite enrichment of mutations in this region across variants of concern (VOCs). Here, we examine the contribution of the NTD to infection and cell-cell fusion by constructing chimeric spikes bearing B.1.617 lineage (Delta and Kappa variants) NTDs and generating spike pseudotyped lentivirus. We find that the Delta NTD on a Kappa or wild-type (WT) background increases S1/S2 cleavage efficiency and virus entry, specifically in lung cells and airway organoids, through use of TMPRSS2. Delta exhibits increased cell-cell fusogenicity that could be conferred to WT and Kappa spikes by Delta NTD transfer. However, chimeras of Omicron BA.1 and BA.2 spikes with a Delta NTD do not show more efficient TMPRSS2 use or fusogenicity. We conclude that the NTD allosterically modulates S1/S2 cleavage and spike-mediated functions in a spike context-dependent manner, and allosteric interactions may be lost when combining regions from more distantly related VOCs

Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications