Middle Phanerozoic mass extinctions and a tribute to the work of Professor Tony Hallam

Tony Hallam's contributions to mass extinction studies span more than 50 years and this thematic issue provides an opportunity to pay tribute to the many pioneering contributions he has made to this field. Early work (1961) on the Jurassic in Europe revealed a link, during the Toarcian Stage, between extinction and the spread of anoxic waters during transgression – the first time such a common leitmotif had been identified. He also identified substantial sea-level changes during other mass extinction intervals with either regression (end-Triassic) or early transgression (end-Permian) coinciding with the extinction phases. Hallam's (1981) study on bivalves was also the first to elevate the status of the end-Triassic crisis and place it amongst true mass extinctions, changing previous perceptions that it was a part of a protracted period of turnover, although debates on the duration of this crisis continue (Hallam, 2002). Conflicting views on the nature of recovery from mass extinctions have also developed, especially for the aftermath of the end-Permian mass extinction. These discussions can be traced to Hallam's seminal 1991 paper that noted the considerable delay in benthic recovery during Early Triassic time and attributed it to the persistence of the harmful, high-stress conditions responsible for the extinction itself. This idea now forms the cornerstone of one of the more favoured explanations for this ultra-low diversity interval

Girls’ preferences for HPV vaccination

A discrete choice experiment was developed to investigate if girls aged 12–16 years make trade-offs between various aspects of human papillomavirus (HPV) vaccination, and to elicit the relative weight that girls’ place on these characteristics. Degree of protection against cervical cancer, protection duration, risk of side-effects, and age of vaccination, all proved to influence girls’ preferences for HPV vaccination. We found that girls were willing to trade-off 38% protection against cervical cancer to obtain a lifetime protection instead of a protection duration of 6 years, or 17% to obtain an HPV vaccination with a 1 per 750,000 instead of 1 per 150,000 risk of serious side-effects. We conclude that girls indeed made a trade-off between degree of protection and other vaccine characteristics, and that uptake of HPV vaccination may chang

Columbus’ footprint in Hispaniola:A paleoenvironmental record of indigenous and colonial impacts on the landscape of the central Cibao Valley, northern Dominican Republic

The 1100-year sedimentary record of Laguna Biajaca reveals human-driven landscape changes in the central Cibao Valley, Dominican Republic, Hispaniola. This sediment-filled cutoff meander is located in close proximity to pre-Colonial archaeological sites and a Colonial urban hub. It provided a nutrient-rich floodable locus for agricultural activities for indigenous communities and for the first introduction of Old World crops and cattle in the Americas. Integration of paleoecological proxies revealed the formation of a clear-water body surrounded by a palm-rich forested landscape around 1100 cal yr BP. Changes in the drainage system were linked to human-driven deforestation, which also changed the composition of the vegetation and fungal communities around the site between AD 1150 and 1500 (800 and 700 cal yr BP). Pre-Colonial modifications of the landscape were primarily the result of fire-use and small-scale clearings. Crop cultivation developed between AD 1250 and 1450 (700–500 cal yr BP). Within decades after Columbus’ arrival in Hispaniola in AD 1492, the first impacts of European colonization included the abandonment of indigenous sites and the introduction of Old World domesticated animals. During the 15th and 16th centuries the area underwent intensive land-clearing that allowed for larger scale crop cultivation. An increase of aquatic vegetation points to sediment-filling around AD 1700 (250 cal yr BP). At that time, cattle breeding expanded and rapidly provoked eutrophication while, concurrently, monocultures became regionally established. This paper provides a framework of past environmental dynamics and offers an opportunity to place archaeological findings in a context of natural and anthropogenic change

Totally thoracoscopic ablation for atrial fibrillation:a systematic safety analysis

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Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation

Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia

Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10−5 and c.2702T > G [p.V901G], MAF 2.51 × 10−3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05–13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10−8), viability (P = 8.9 × 10−7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10−4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10−5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia