The effects of age at menarche and first sexual intercourse on reproductive and behavioural outcomes:A Mendelian randomization study

There is substantial variation in the timing of significant reproductive life events such as menarche and first sexual intercourse. Life history theory explains this variation as an adaptive response to an individual's environment and it is important to examine how traits within life history strategies affect each other. Here we applied Mendelian randomization (MR) methods to investigate whether there is a causal effect of variation in age at menarche and age at first sexual intercourse (markers or results of exposure to early life adversity) on outcomes related to reproduction, education and risky behaviour in UK Biobank (N = 114 883-181 255). Our results suggest that earlier age at menarche affects some traits that characterize life history strategies including earlier age at first and last birth, decreased educational attainment, and decreased age at leaving education (for example, we found evidence for a 0.26 year decrease in age at first birth per year decrease in age at menarche, 95% confidence interval: -0.34 to -0.17; p < 0.001). We find no clear evidence of effects of age at menarche on other outcomes, such as risk taking behaviour. Age at first sexual intercourse was also related to many life history outcomes, although there was evidence of horizontal pleiotropy which violates an assumption of MR and we therefore cannot infer causality from this analysis. Taken together, these results highlight how MR can be applied to test predictions of life history theory and to better understand determinants of health and social behaviour

Time to Treat: A System Redesign Focusing on Decreasing the Time from Suspicion of Lung Cancer to Diagnosis

IntroductionMultiple investigations often result in a lengthy process from the onset of lung cancer–related symptoms until diagnosis. An unpublished chart audit indicated suboptimal delays in patients' courses from onset of symptoms until diagnosis of cancer.MethodsThe Time to Treat Program was designed for patients with clinical or radiographic suspicion of lung cancer. Pre- and postimplementation data on median wait times were compared.ResultsFrom April 2005 to January 2007, 430 patients were referred. After Time to Treat Program implementation, the median time from suspicion of lung cancer to referral for specialist consultation decreased from 20 days to 6 days, and the median time from such referral to the actual consultation date decreased from 17 days to 4 days. The median time from specialist consultation to computed tomography scan decreased from 52 days to 3 days, and the median time from computed tomography scan to diagnosis decreased from 39 days to 6 days. Overall, the median time from suspicion of lung cancer to diagnosis decreased from 128 days to 20 days. Of all patients in the Time to Treat Program, 33% were eventually diagnosed with lung cancer.ConclusionsTime to Treat Program was effective in shortening the time from suspicion of lung cancer to diagnosis and reduced time intervals at each step in the process. Earlier diagnosis of lung cancer may allow increased treatment options for patients and may improve outcomes

'Ava’: a Beaker-associated woman from a cist at Achavanich, Highland, and the story of her (re-) discovery and subsequent study

This contribution describes the discovery and subsequent investigation of a cist in a rock-cut pit at Achavanich, Highland. Discovered and excavated in 1987, the cist was found to contain the tightly contracted skeletal remains of a young woman, accompanied by a Beaker, three flint artefacts and a cattle scapula. Initial post excavation work established a date for the skeleton together with details of her age and sex, and preliminary pollen analysis of sediments attaching to the Beaker was undertaken. The findings were never fully published and, upon the death of the excavator, Robert Gourlay, the documentary archive was left in the Highland Council Archaeology Unit. Fresh research in 2014–17, initiated and co-ordinated by the first-named author and funded by the Society of Antiquaries of Scotland with assistance from National Museums Scotland, the Natural History Museum and Harvard Medical School, has produced a significant amount of new information on the individual and on some of the items with which she was buried. This new information includes two further radiocarbon dates, a more detailed osteological report, isotopic information pertaining to the place where she had been raised and to her diet, histological information on the decomposition of her body, and genetic information that sheds light on her ancestry, her hair, eye and skin colour and her intolerance of lactose. (This is the first time that an ancient DNA report has been published in the Proceedings.) Moreover, a facial reconstruction adds virtual flesh to her bones. The significance of this discovery within the Chalcolithic to Early Bronze Age of this part of Scotland is discussed, along with the many and innovative ways in which information on this individual, dubbed ‘Ava’, has been disseminated around the world.Copyright © 2018 rests with the Society and the individual authors. Except where otherwise noted, this work is licensed under CreativeCommons Attribution-NonCommercial-No Derivatives licence.https://creativecommons.org/licenses/by-nc-nd/4.0/ The permission to reproduce the Society's copyright-protected ma-terial does not extend to any material which is identified as being the copyright of a third party. Authorisation to reproduce such material must be obtained from the copyright holders concerned. The attached file is the published pdf

Nudging art lovers to donate.

Many nonprofit organizations face revenue uncertainty due to funding cuts. It is crucial for them to supplement existing revenue streams by private donations, and apply thoughtful market segmentation in their pursuit of donors. We introduce the behavioral concept of ‘nudge’ based on the possibility of loss aversion affecting willingness-to-donate, and investigate its implications for fundraising strategies. Potential donors are nudged to donate by the hypothetical scenario of ‘losing’ an existing exhibition, and also by that of ‘gaining’ an additional exhibition. We observe significant loss aversion effects as frequent gallery-goers donate more in order to avoid losing an exhibition. While both prospective gain and loss scenarios are effective in nudging non-frequent gallery-goers, the prospect of enjoying ‘one more’ event is observed to be stronger. We argue that there may be scope to increase support for nonprofit organizations, particularly in the cultural sector, by exploiting the psychological characteristics of prospective donors

Heteroepitaxial growth of ferromagnetic MnSb(0001) films on Ge/Si(111) virtual substrates

Molecular beam epitaxial growth of ferromagnetic MnSb(0001) has been achieved on high quality, fully relaxed Ge(111)/Si(111) virtual substrates grown by reduced pressure chemical vapor deposition. The epilayers were characterized using reflection high energy electron diffraction, synchrotron hard X-ray diffraction, X-ray photoemission spectroscopy, and magnetometry. The surface reconstructions, magnetic properties, crystalline quality, and strain relaxation behavior of the MnSb films are similar to those of MnSb grown on GaAs(111). In contrast to GaAs substrates, segregation of substrate atoms through the MnSb film does not occur, and alternative polymorphs of MnSb are absent

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Thermochronology of the modern Indus River bedload: New insight into the controls on the marine stratigraphic record

The Indus River is the only major drainage in the western Himalaya and delivers a long geological record of continental erosion to the Arabian Sea, which may be deciphered and used to reconstruct orogenic growth if the modern bedload can be related to the mountains. In this study we collected thermochronologic data from river sediment collected near the modern delta. U-Pb ages of zircons spanning 3 Gyr show that only ∼5% of the eroding crust has been generated since India-Asia collision. The Greater Himalaya are the major source of zircons, with additional contributions from the Karakoram and Lesser Himalaya. The 39Ar/40Ar dating of muscovites gives ages that cluster between 10 and 25 Ma, differing from those recorded in the Bengal Fan. Biotite ages are generally younger, ranging 0–15 Ma. Modern average exhumation rates are estimated at ∼0.6 km/m.y. or less, and have slowed progressively since the early Miocene (∼20 Ma), although fission track (FT) dating of apatites may indicate a recent moderate acceleration in rates since the Pliocene (∼1.0 km/m.y.) driven by climate change. The 39Ar/40Ar and FT techniques emphasize the dominance of high topography in controlling the erosional flux to the ocean. Localized regions of tectonically driven, very rapid exhumation (e.g., Nanga Parbat, S. Karakoram metamorphic domes) do not dominate the erosional record

Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury

Context: Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. Objective: To evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. Methods: In 210 Israeli Defence Forces (IDF) military conscripts, stress fracture injury was diagnosed (n=43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n=125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson Chi-square (χ2) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. Results: The variant allele of P2X7R SNP rs3751143 (Glu496Ala- loss of function) was associated with stress fracture injury, while the variant allele of rs1718119 (Ala348Thr- gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P<0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P<0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P<0.05). Conclusions: The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury

Dynamics of cardiac re-entry in micro-CT and serial histological sections based models of mammalian hearts

Cardiac re-entry regime of self-organised abnormal synchronisation underlie dangerous arrhythmias and fatal fibrillation. Recent advances in the theory of dissipative vortices, experimental studies, and anatomically realistic computer simulations, elucidated the role of cardiac re-entry interaction with fine anatomical features in the heart, and anatomy induced drift. The fact that anatomy and structural anisotropy of the heart is consistent within a species suggested its possible functional effect on spontaneous drift of cardiac re-entry. A comparative study of the anatomy induced drift could be used in order to predict evolution of atrial arrhythmia, and improve low-voltage defibrillation protocols and ablation strategies. Here, in micro-CT based model of rat pulmonary vein wall, and in sheep atria models based on high resolution serial histological sections, we demonstrate effects of heart geometry and anisotropy on cardiac re-entry anatomy induced drift, its pinning to fluctuations of thickness in the layer. The data sets of sheep atria and rat pulmonary vein wall are incorporated into the BeatBox High Performance Computing simulation environment. Re-entry is initiated at prescribed locations in the spatially homogeneous mono-domain models of cardiac tissue. Excitation is described by FitzHugh-Nagumo kinetics. In the in-silico models, isotropic and anisotropic conduction show specific anatomy effects and the interplay between anatomy and anisotropy of the heart. The main objectives are to demonstrate the functional role of the species hearts geometry and anisotropy on cardiac re-entry anatomy induced drift. In case of the rat pulmonary vein wall with ~90 degree transmural fibre rotation, it is shown that the joint effect of the PV wall geometry and anisotropy turns a plane excitation wave into a re-entry pinned to a small fluctuation of thickness in the wall