Synthesis and reactivity of N,N’-1,4-diazabutadiene derived borocations

A series of borocations have been synthesised from the addition of haloboranes to synthetically accessible N,N′-1,4-diazabutadiene precursors, which are derived from commercially available anilines. The synthesis and structural studies of the borocations are described

Investigating the formation and diagnostic value of ω-(o-alkylphenyl)alkanoic acids in ancient pottery

Long chain ω‐(o‐alkylphenyl)alkanoic acids (APAAs) derived from the heating of unsaturated fatty acids have been widely used for the identification of aquatic products in archaeological ceramic vessels. To date, little attention has been paid to the diagnostic potential of shorter chain (<C20) APAAs, despite their frequent occurrence. Here, a range of laboratory and field experiments and analyses of archaeological samples were undertaken to investigate whether APAAs could be used to further differentiate different commodities. The results of this study provide new insights regarding conditions for the formation of APAAs and enable us to propose novel criteria to distinguish different natural products

An international study of the quality of life of adult patients treated with home parenteral nutrition

Background & aims: Home parenteral nutrition-quality of life (HPN-QOL©) is a self-assessment tool for the measurement of QOL in patients on HPN. The aims of this study were: to re-assess the basic psychometric properties of the HPN-QOL© in a multinational sample of adult patients; to provide a description of QOL dimensions by short and long HPN treatment duration; to explore clinical factors potentially associated to QOL scores. Methods: Patients (n = 699) from 14 countries completed the HPN-QOL©. The questionnaires were analysed to evaluate data completeness, convergent/discriminant validity and internal-consistency reliability. The association of overall QOL and HPN treatment duration as well as other clinical factors were investigated using multivariable linear regression models. Results: The analysis of the multitrait-scaling and internal consistency indicates a good fit with the questionnaire structure for most items. Item discriminant validity correlation was satisfactory and psychometric evaluation of the HPN-QOL© in the different English, French and Italian language patient sub-groups confirmed psychometric equivalence of the three questionnaire versions. The results of the multivariable linear regression showed that QOL scores were significantly associated with HPN duration (better in long-term), underlying disease (better in Crohn's disease and mesenteric ischaemia) and living status (worse in living alone) and, after adjusting for the other factors, with the number of days of HPN infusion per week. Conclusions: The HPN-QOL©, is a valid tool for measurement of QOL in patients on HPN, to be used in the clinical practice as well as in research

Neolithic farmers or Neolithic foragers? Organic residue analysis of early pottery from Rakushechny Yar on the Lower Don (Russia)

The emergence of pottery in Europe is associated with two distinct traditions: hunter-gatherers in the east of the continent during the early 6th millennium BC and early agricultural communities in the south-west in the late 7th millennium BC. Here we investigate the function of pottery from the site of Rakushechny Yar, located at the Southern fringe of Eastern Europe, in this putative contact zone between these two economic ‘worlds’. To investigate, organic residue analysis was conducted on 120 samples from the Early Neolithic phase (ca. mid-6th millennium BC) along with microscopic and SEM analysis of associated foodcrusts. The results showed that the earliest phase of pottery use was predominantly used to process riverine resources. Many of the vessels have molecular and isotopic characteristics consistent with migratory fsh, such as sturgeon, confrmed by the identifcation of sturgeon bony structures embedded in the charred surface deposits. There was no evidence of dairy products in any of the vessels, despite the fact these have been routinely identifed in coeval sites to the south. Further analysis of some of the mammalian bones using ZooMS failed to demonstrate that domesticated animals were present in the Early Neolithic. Nevertheless, we argue that intensive exploitation of seasonally migratory fsh, accompanied by large-scale pottery production, created storable surpluses that led to similar socio-economic outcomes as documented in early agricultural societies

Is Higher Docetaxel Clearance in Prostate Cancer Patients Explained by Higher CYP3A? An In Vivo Phenotyping Study with Midazolam

Patients with prostate cancer (PCa) have a lower docetaxel exposure for both intravenous (1.8-fold) and oral administration (2.4-fold) than patients with other solid cancers, which could influence efficacy and toxicity. An altered metabolism by cytochrome P450 3A (CYP3A) due to castration status might explain the observed difference in docetaxel pharmacokinetics. In this in vivo phenotyping, pharmacokinetic study, CYP3A activity defined by midazolam clearance (CL) was compared between patients with PCa and male patients with other solid tumors. All patients with solid tumors who did not use CYP3A-modulating drugs were eligible for participation. Patients received 2 mg midazolam orally and 1 mg midazolam intravenously on 2 consecutive days. Plasma concentrations were measured with a validated liquid chromatography–tandem mass spectrometry method. Genotyping was performed for CYP3A4 and CYP3A5. Nine patients were included in each group. Oral midazolam CL was 1.26-fold higher in patients with PCa compared to patients with other solid tumors (geometric mean [coefficient of variation], 94.1 [33.5%] L/h vs 74.4 [39.1%] L/h, respectively; P =.08). Intravenous midazolam CL did not significantly differ between the 2 groups (P =.93). Moreover, the metabolic ratio of midazolam to 1′-hydroxy midazolam did not differ between the 2 groups for both oral administration (P =.67) and intravenous administration (P =.26). CYP3A4 and CYP3A5 genotypes did not influence midazolam pharmacokinetics. The observed difference in docetaxel pharmacokinetics between both patient groups therefore appears to be explained neither by a difference in midazolam CL nor by a difference in metabolic conversion rate of midazolam

Examination of psychological risk factors for chronic pain following cardiac surgery: protocol for a prospective observational study

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Approximately 400 000 Americans and 36 000 Canadians undergo cardiac surgery annually, and up to 56% will develop chronic postsurgical pain (CPSP). The primary aim of this study is to explore the association of pain-related beliefs and gender-based pain expectations on the development of CPSP. Secondary goals are to: (A) explore risk factors for poor functional status and patient-level cost of illness from a societal perspective up to 12 months following cardiac surgery; and (B) determine the impact of CPSP on quality-adjusted life years (QALYs) borne by cardiac surgery, in addition to the incremental cost for one additional QALY gained, among those who develop CPSP compared with those who do not. METHODS AND ANALYSES: In this prospective cohort study, 1250 adults undergoing cardiac surgery, including coronary artery bypass grafting and open-heart procedures, will be recruited over a 3-year period. Putative risk factors for CPSP will be captured prior to surgery, at postoperative day 3 (in hospital) and day 30 (at home). Outcome data will be collected via telephone interview at 6-month and 12-month follow-up. We will employ generalised estimating equations to model the primary (CPSP) and secondary outcomes (function and cost) while adjusting for prespecified model covariates. QALYs will be estimated by converting data from the Short Form-12 (version 2) to a utility score. ETHICS AND DISSEMINATION: This protocol has been approved by the responsible bodies at each of the hospital sites, and study enrolment began May 2015. We will disseminate our results through CardiacPain.Net, a web-based knowledge dissemination platform, presentation at international conferences and publications in scientific journals. TRIAL REGISTRATION NUMBER: NCT01842568

Chemical analysis of pottery reveals the transition from a maritime to a plant-based economy in pre-colonial coastal Brazil

Understanding long-term dynamics of past socio-ecological systems is essential for their future management. The southern Atlantic Forest coast of Brazil with its biodiverse littoral zone and artisanal fishing communities, is a priority for conservation. Traditional maritime knowledge is thought to have a deep-history and indeed, marine exploitation can be traced back to the middle Holocene. As part of one of South America’s largest diasporas, Guarani groups reached the southern Brazilian coast at around 1000 years ago. Their impact on the long-standing coastal economy is unknown, due to poor preservation of organic remains. Through the first organic residue study on Guarani pottery, we show that maize rather than aquatic foods was the most dominant product in pottery at this time. By developing a mixing model based on carbon isotope values of saturated and mono-unsaturated fatty acids we propose new criteria for the identification of maize, opening up avenues for future research. Our data confirms the importance of maize to the pre-colonial Guarani, even in a highly productive coastal environment. The Guarani occupation of this region marks a significant departure from previous socio-economic systems, potentially leading to loss of traditional knowledge and alleviating anthropogenic pressure, albeit temporarily, on the marine environment

The role of networks to overcome large-scale challenges in tomography: The non-clinical tomography users research network

Our ability to visualize and quantify the internal structures of objects via computed tomography (CT) has fundamentally transformed science. As tomographic tools have become more broadly accessible, researchers across diverse disciplines have embraced the ability to investigate the 3D structure-function relationships of an enormous array of items. Whether studying organismal biology, animal models for human health, iterative manufacturing techniques, experimental medical devices, engineering structures, geological and planetary samples, prehistoric artifacts, or fossilized organisms, computed tomography has led to extensive methodological and basic sciences advances and is now a core element in science, technology, engineering, and mathematics (STEM) research and outreach toolkits. Tomorrow's scientific progress is built upon today's innovations. In our data-rich world, this requires access not only to publications but also to supporting data. Reliance on proprietary technologies, combined with the varied objectives of diverse research groups, has resulted in a fragmented tomography-imaging landscape, one that is functional at the individual lab level yet lacks the standardization needed to support efficient and equitable exchange and reuse of data. Developing standards and pipelines for the creation of new and future data, which can also be applied to existing datasets is a challenge that becomes increasingly difficult as the amount and diversity of legacy data grows. Global networks of CT users have proved an effective approach to addressing this kind of multifaceted challenge across a range of fields. Here we describe ongoing efforts to address barriers to recently proposed FAIR (Findability, Accessibility, Interoperability, Reuse) and open science principles by assembling interested parties from research and education communities, industry, publishers, and data repositories to approach these issues jointly in a focused, efficient, and practical way. By outlining the benefits of networks, generally, and drawing on examples from efforts by the Non-Clinical Tomography Users Research Network (NoCTURN), specifically, we illustrate how standardization of data and metadata for reuse can foster interdisciplinary collaborations and create new opportunities for future-looking, large-scale data initiatives

Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = -0.59, p-value = 3.14 × 10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology