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Roe deer (Capreolus capreolus) is the most abundant cervid in Europe and, as such, has a considerable impact over several human activities. Accurate roe deer population size estimates are useful to ensure their proper management. We tested 3 methods for estimating roe deer abundance (drive counts, pellet-group counts, and camera trapping) during two consecutive years (2012 and 2013) in the Apennines (Italy) in order to assess their precision and applicability. During the study period, population density estimates were: drive counts 21.89±12.74 roe deer/km2 and pellet-group counts 18.74±2.31 roe deer/km2 in 2012; drive counts 19.32±11.12 roe deer/km2 and camera trapping 29.05±7.48 roe deer/km2 in 2013. Precision of the density estimates differed widely among the 3 methods, with coefficients of variation ranging from 12% (pellet-group counts) to 58% (drive counts). Drive counts represented the most demanding method on account of the higher number of operators involved. Pellet-group counts yielded the most precise results and required a smaller number of operators, though the sampling effort was considerable. When compared to the other two methods, camera trapping resulted in an intermediate level of precision and required the lowest sampling effort. We also discussed field protocols of each method, considering that volunteers, rather than technicians, will more likely be appointed for these tasks in the near future. For this reason, we strongly suggest that for each method managers of population density monitoring projects take into account ease of use as well as the quality of the results obtained and the resources required. [ABSTRACT FROM AUTHOR]

Background: Previous studies of radiological damage in rheumatoid arthritis (RA) have used candidate-gene approaches, or evaluated single genome-wide association studies (GWAS). We undertook the first meta-analysis of GWAS of RA radiological damage to: (1) identify novel genetic loci for this trait; and (2) test previously validated variants. Methods: Seven GWAS (2,775 RA cases, of a range of ancestries) were combined in a meta-analysis. Radiological damage was assessed using modified Larsen scores, Sharp van Der Heijde scores, and erosive status. Single nucleotide polymophsim (SNP) associations with radiological damage were tested at a single time-point using regression models. Primary analyses included age and disease duration as covariates. Secondary analyses also included rheumatoid factor (RF). Meta-analyses were undertaken in trans-ethnic and European-only cases. Results: In the trans-ethnic primary meta-analysis, one SNP (rs112112734) in close proximity to HLA-DRB1, and strong linkage disequilibrium with the shared-epitope, attained genome-wide significance (P = 4.2x10-8). In the secondary analysis (adjusting for RF) the association was less significant (P = 1.7x10-6). In both trans-ethnic primary and secondary meta-analyses 14 regions contained SNPs with associations reaching P<5x10-6; in the European primary and secondary analyses 13 and 10 regions contained SNPs reaching P<5x10-6, respectively. Of the previously validated SNPs for radiological progression, only rs660895 (tagging HLA-DRB1*04:01) attained significance (P = 1.6x10-5) and had a consistent direction of effect across GWAS. Conclusions: Our meta-analysis confirms the known association between the HLA-DRB1 shared epitope and RA radiological damage. The lack of replication of previously validated non-HLA markers highlights a requirement for further research to deliver clinically-useful prognostic genetic markers. [ABSTRACT FROM AUTHOR]

Expression quantitative trait loci (eQTL) provide insight on transcription regulation and illuminate the molecular basis of phenotypic outcomes. High-throughput RNA sequencing (RNA-seq) is becoming a popular technique to measure gene expression abundance. Traditional eQTL mapping methods for microarray expression data often assume the expression data follow a normal distribution. As a result, for RNA-seq data, total read count measurements can be normalized by normal quantile transformation in order to fit the data using a linear regression. Other approaches model the total read counts using a negative binomial regression. While these methods work well for common variants (minor allele frequencies > 5% or 1%), an extension of existing methodology is needed to accommodate a collection of rare variants in RNA-seq data. Here, we examine 2 approaches that are direct applications of existing methodology and apply these approaches to RNAseq studies: 1) collapsing the rare variants in the region and using either negative binomial regression or Poisson regression and 2) using the normalized read counts with the Sequence Kernel Association Test (SKAT), the burden test for SKAT (SKAT-Burden), or an optimal combination of these two tests (SKAT-O). We evaluated these approaches via simulation studies under numerous scenarios and applied these approaches to the 1,000 Genomes Project. [ABSTRACT FROM AUTHOR]

Introduction: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines, using existing electronic healthcare record (eHR) databases in Europe. Part of the data in such sources is missing due to incomplete follow-up hampering the accurate estimation of vaccination coverage. We compared different methods for coverage estimation from eHR databases; naïve period prevalence, complete case period prevalence, period prevalence adjusted for follow-up time, Kaplan-Meier (KM) analysis and (adjusted) inverse probability weighing (IPW). Methods: We created simulation scenarios with different proportions of completeness of follow-up. Both completeness independent and dependent from vaccination date and status were considered. The root mean squared error (RMSE) and relative difference between the estimated and true coverage were used to assess the performance of the different methods for each of the scenarios. We included data examples on the vaccination coverage of human papilloma virus and pertussis component containing vaccines from the Spanish BIFAP database. Results: Under completeness independent from vaccination date or status, several methods provided estimates with bias close to zero. However, when dependence between completeness of follow-up and vaccination date or status was present, all methods generated biased estimates. The IPW/CDF methods were generally the least biased. Preference for a specific method should be based on the type of censoring and type of dependence between completeness of follow-up and vaccination. Additional insights into these aspects, might be gained by applying several methods. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma (PC) is a lethal malignancy that is familial or associated with genetic syndromes in 10% of cases. Gene-based surveillance strategies for at-risk individuals may improve clinical outcomes. However, familial PC (FPC) is plagued by genetic heterogeneity and the genetic basis for the majority of FPC remains elusive, hampering the development of gene-based surveillance programs. The study was powered to identify genes with a cumulative pathogenic variant prevalence of at least 3%, which includes the most prevalent PC susceptibility gene, BRCA2. Since the majority of known PC susceptibility genes are involved in DNA repair, we focused on genes implicated in these pathways. We performed a region-based association study using the Mixed-Effects Score Test, followed by leave-one-out characterization of PC-associated gene regions and variants to identify the genes and variants driving risk associations. We evaluated 398 cases from two case series and 987 controls without a personal history of cancer. The first case series consisted of 109 patients with either FPC (n = 101) or PC at ≤50 years of age (n = 8). The second case series was composed of 289 unselected PC cases. We validated this discovery strategy by identifying known pathogenic BRCA2 variants, and also identified SMG1, encoding a serine/threonine protein kinase, to be significantly associated with PC following correction for multiple testing (p = 3.22x10-7). The SMG1 association was validated in a second independent series of 532 FPC cases and 753 controls (p<0.0062, OR = 1.88, 95%CI 1.17–3.03). We showed segregation of the c.4249A>G SMG1 variant in 3 affected relatives in a FPC kindred, and we found c.103G>A to be a recurrent SMG1 variant associating with PC in both the discovery and validation series. These results suggest that SMG1 is a novel PC susceptibility gene, and we identified specific SMG1 gene variants associated with PC risk. [ABSTRACT FROM AUTHOR]

Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted in genetic variation underlying lipid levels, they mainly comprise individuals of European ancestry and thus their transferability to non-European populations is unclear. We performed genome-wide (GWAS) and imputed transcriptome-wide association studies of four lipid traits in the Hispanic Community Health Study/Study of Latinos cohort (HCHS/SoL, n = 11,103), replicated top hits in the Multi-Ethnic Study of Atherosclerosis (MESA, n = 3,855), and compared the results to the larger, predominantly European ancestry meta-analysis by the Global Lipids Genetics Consortium (GLGC, n = 196,475). In our GWAS, we found significant SNP associations in regions within or near known lipid genes, but in our admixture mapping analysis, we did not find significant associations between local ancestry and lipid phenotypes. In the imputed transcriptome-wide association study in multiple tissues and in different ethnicities, we found 59 significant gene-tissue-phenotype associations (P < 3.61×10−8) with 14 unique significant genes, many of which occurred across multiple phenotypes, tissues, and ethnicities and replicated in MESA (45/59) and in GLGC (44/59). These include well-studied lipid genes such as SORT1, CETP, and PSRC1, as well as genes that have been implicated in cardiovascular phenotypes, such as CCL22 and ICAM1. The majority (40/59) of significant associations colocalized with expression quantitative trait loci (eQTLs), indicating a possible mechanism of gene regulation in lipid level variation. To fully characterize the genetic architecture of lipid traits in diverse populations, larger studies in non-European ancestry populations are needed. [ABSTRACT FROM AUTHOR]

Background: Nabiximols (THC/CBD Oromucosal Spray, Sativex) is used as an add-on therapy to treat moderate to severe spasticity of Multiple Sclerosis (MS). Objectives: To examine the impact of physiotherapy (PT) programs on effectiveness and persistence of nabiximols treatment in people with MS-related spasticity. Methods: This is an observational multicenter study with a follow-up period of 12 weeks, conducted in routine care settings in Italy. Patients with moderate to severe MS-related spasticity who started nabiximols were included. Spasticity was evaluated by the patient-rated 0–10 numerical rating scale (NRS). Clinical data were collected at baseline (T0), 4 weeks (T1) and 12 weeks (T2) months after enrollment. Results: A total of 297 MS patients were selected, 290 completed the 3 months follow-up period. Mean NRS scores were 7.6 ± 1.1 at T0, 5.8 ± 1.4 at T1 and 5.5 ± 1.5 at T2. At T1, 77% of patients reached ≥20% improvement (initial response, IR); 22% reached ≥30% improvement (clinically relevant response, CRR). At T1, patients undergoing PT had a higher probability to reach CRR (Odds Ratio = 2.6 95% CI 1.3–5.6, p = 0.01). Nabiximols was discontinued in 30/290 (10.3%) patients at T1 (early discontinuers) and in 71/290 (24.5%) patients at T2 (late discontinuers). The probability of being late discontinuers was reduced in patients undergoing PT (Hazard Ratio = 0.41; 95% CI 0.23–0.69, p = 0.001). Conclusions: Our real-life study confirms nabiximols’ effectiveness in MS-related spasticity and suggests that the association of a PT program may improve overall response and persistence to nabiximols treatment. [ABSTRACT FROM AUTHOR]

Recent years have seen tremendous advances in the scientific study of networks, as more and larger data sets of relationships among nodes have become available in many different fields. This has led to pathbreaking discoveries of near-universal network behavior over time, including the principle of preferential attachment and the emergence of scaling in complex networks. Missing from the set of network analysis methods to date is a measure that describes for each node how its relationship (or links) with other nodes changes from one period to the next. Conventional measures of network change for the most part show how the degrees of a node change; these are scalar comparisons. Our contribution is to use, for the first time, the cosine similarity to capture not just the change in degrees of a node but its relationship to other nodes. These are vector (or matrix)-based comparisons, rather than scalar, and we refer to them as “rewiring” coefficients. We apply this measure to three different networks over time to show the differences in the two types of measures. In general, bigger increases in our rewiring measure are associated with larger increases in network density, but this is not always the case. [ABSTRACT FROM AUTHOR]

The outcomes of bargaining over losses, the subject of this paper, have rarely been studied. But experimental studies of related situations, such as those involving bankruptcies or bequests in which the sum of the legal claims that can be made against a bank or firm or estate are greater than their values, have produced strong support for the proportionality principle. To test whether this principle would find support in other situations involving losses we designed an experimental game in which four players start out with differing initial endowments of real money. They are then informed that a certain amount of this resource has to be given back to the experimenter. How should the loss be shared among the agents? This game was run at different locations and under different treatments over a period of almost three years. We found that the proportionality principle was rarely proposed and even less frequently accepted as a solution to this problem. One of the main reasons for this result was that the two players with the smallest endowments opposed most of the proposals which asked them to contribute at least some positive amount of their own initial resource. [ABSTRACT FROM AUTHOR]

Background: Maternal iodine deficiency is related to high neonatal thyroid-stimulating hormone (TSH) values, with the threshold of 5 mIU/L recommended as an indicator of iodine nutrition status. The objective of this study was to analyse possible risk factors for increased TSH that could distort its validity as a marker of iodine status. The clinical relevance of this research question is that if the factors associated with iodine deficiency are known, iodine supplementation can be introduced in risk groups, both during pregnancy and in newborns. Methods: A case-control study was carried out in a sample of 46,622 newborns in 2002–2015 in Spain. Of these, 45,326 had a neonatal TSH value ≥5 mIU/L. The main variable was having TSH ≥5 mIU/L and the secondary variables were: sex, gestational age, day of sample extraction and maternal origin. Associated factors were analysed through a logistic regression model, calculating the odds ratio (OR). Results: The factors associated with this outcome were: male sex (OR = 1.34, 95% CI: 1.20–1.50, p<0.001), originating from an Asian/Oceanic country (OR = 0.80, 95% CI: 0.54–1.20, p = 0.536) or Europe (OR = 0.80, 95% CI: 0.66–0.96, p = 0.285) (including Spain, OR = 1) [p<0.001 for America (OR = 0.54, 95% CI: 0.44–0.68) and p = 0.025 for Africa (OR = 0.78, 95% CI: 0.62–0.97)] and fewer days from birth to sampling (OR = 0.80, 95% CI: 0.77–0.82, p<0.001). Conclusions: The risk of high neonatal TSH without congenital hypothyroidism is higher in males, decreases with a greater number of days from birth to extraction, and is dependent on maternal ethnicity but not on gestational age. [ABSTRACT FROM AUTHOR]

Linden (Tilia spp.), a profusely flowering temperate tree that provides bees with vital pollen and nectar, has been associated with bumble bee (Bombus spp.) mortality in Europe and North America. Bee deaths have been attributed, with inadequate evidence, to toxicity from mannose in nectar or starvation due to low nectar in late blooming linden. Here, we investigated both factors via untargeted metabolomic analyses of nectar from five T. cordata trees beneath which crawling/dead bumble bees (B. vosnesenskii) were observed, and of thoracic muscle of 28 healthy foraging and 29 crawling bees collected from linden trees on cool mornings (< 30°C). Nectar contained the pyridine alkaloid trigonelline, a weak acetylcholinesterase inhibitor, but no mannose. Principal component analysis of muscle metabolites produced distinct clustering of healthy and crawling bees, with significant differences (P<0.05) in 34 of 123 identified metabolites. Of these, TCA (Krebs) cycle intermediates were strongly represented (pathway analysis; P<0.01), suggesting that the central metabolism is affected in crawling bees. Hence, we propose the following explanation: when ambient temperature is low, bees with energy deficit are unable to maintain the thoracic temperature required for flight, and consequently fall, crawl, and ultimately, die. Energy deficit could occur when bees continue to forage on linden despite limited nectar availability either due to loyalty to a previously energy-rich source or trigonelline-triggered memory/learning impairment, documented earlier with other alkaloids. Thus, the combination of low temperature and nectar volume, resource fidelity, and alkaloids in nectar could explain the unique phenomenon of bumble bee mortality associated with linden. [ABSTRACT FROM AUTHOR]

In fish, the circadian clock represents a key regulator of many aspects of biology and is controlled by combinations of abiotic and biotic factors. These environmental factors are frequently manipulated in fish farms as part of strategies designed to maximize productivity. The flatfish turbot, Scophthalmus maximus, represents one of the most important species within the aquaculture sector in Asia and Europe. Despite the strategic importance of this species, the function and regulation of the turbot circadian system remains poorly understood. Here, we have characterized the core circadian clock genes, clock1, per1, per2 and cry1 in turbot and have studied their daily expression in various tissues under a range of lighting conditions and feeding regimes. We have also explored the influence of light and feeding time on locomotor activity. Rhythmic expression of the four core clock genes was observed in all tissues studied under light dark (LD) cycle conditions. Rhythmicity of clock gene expression persisted upon transfer to artificial free running, constant conditions confirming their endogenous circadian clock control. Furthermore, turbot showed daily cycles of locomotor activity and food anticipatory activity (FAA) under LD and scheduled-feeding, with the activity phase as well as FAA coinciding with and being dependent upon exposure to light. Thus, while FAA was absent under constant dark (DD) conditions, it was still detected in constant light (LL). In contrast, general locomotor activity was arrhythmic in both constant darkness and constant light, pointing to a major contribution of light, in concert with the circadian clock, in timing locomotor activity in this species. Our data represents an important contribution to our understanding of the circadian timing system in the turbot and thereby the optimization of rearing protocols and the improvement of the well-being of turbot within fish farming environments. [ABSTRACT FROM AUTHOR]

Ecoregionalization is the process by which a territory is classified in similar areas according to specific environmental and climatic factors. The climate and the environment strongly influence the presence and distribution of vectors responsible for significant human and animal diseases worldwide. In this paper, we developed a map of the eco-climatic regions of Italy adopting a data-driven spatial clustering approach using recent and detailed spatial data on climatic and environmental factors. We selected seven variables, relevant for a broad set of human and animal vector-borne diseases (VBDs): standard deviation of altitude, mean daytime land surface temperature, mean amplitude and peak timing of the annual cycle of land surface temperature, mean and amplitude of the annual cycle of greenness value, and daily mean amount of rainfall. Principal Component Analysis followed by multivariate geographic clustering using the k-medoids technique were used to group the pixels with similar characteristics into different ecoregions, and at different spatial resolutions (250 m, 1 km and 2 km). We showed that the spatial structure of ecoregions is generally maintained at different spatial resolutions and we compared the resulting ecoregion maps with two datasets related to Bluetongue vectors and West Nile Disease (WND) outbreaks in Italy. The known characteristics of Culicoides imicola habitat were well captured by 2/22 specific ecoregions (at 250 m resolution). Culicoides obsoletus/scoticus occupy all sampled ecoregions, according to its known widespread distribution across the peninsula. WND outbreak locations strongly cluster in 4/22 ecoregions, dominated by human influenced landscape, with intense cultivations and complex irrigation network. This approach could be a supportive tool in case of VBDs, defining pixel-based areas that are conducive environment for VBD spread, indicating where surveillance and prevention measures could be prioritized in Italy. Also, ecoregions suitable to specific VBDs vectors could inform entomological surveillance strategies. [ABSTRACT FROM AUTHOR]

Background: The electrocardiographically quantified QRS duration measures ventricular depolarization and conduction. QRS prolongation has been associated with poor heart failure prognosis and cardiovascular mortality, including sudden death. While previous genome-wide association studies (GWAS) have identified 32 QRS SNPs across 26 loci among European, African, and Asian-descent populations, the genetics of QRS among Hispanics/Latinos has not been previously explored. Methods: We performed a GWAS of QRS duration among Hispanic/Latino ancestry populations (n = 15,124) from four studies using 1000 Genomes imputed genotype data (adjusted for age, sex, global ancestry, clinical and study-specific covariates). Study-specific results were combined using fixed-effects, inverse variance-weighted meta-analysis. Results: We identified six loci associated with QRS (P<5x10-8), including two novel loci: MYOCD, a nuclear protein expressed in the heart, and SYT1, an integral membrane protein. The top SNP in the MYOCD locus, intronic SNP rs16946539, was found in Hispanics/Latinos with a minor allele frequency (MAF) of 0.04, but is monomorphic in European and African descent populations. The most significant QRS duration association was with intronic SNP rs3922344 (P = 1.19x10-24) in SCN5A/SCN10A. Three other previously identified loci, CDKN1A, VTI1A, and HAND1, also exceeded the GWAS significance threshold among Hispanics/Latinos. A total of 27 of 32 previously identified QRS duration SNPs were shown to generalize in Hispanics/Latinos. Conclusions: Our QRS duration GWAS, the first in Hispanic/Latino populations, identified two new loci, underscoring the utility of extending large scale genomic studies to currently under-examined populations. [ABSTRACT FROM AUTHOR]

Aluminum is increasingly globally bioavailable with acidification from industrial emissions and poor mining practices. This bioavailability increases uptake by flora, contaminating products such as fruit, pollen, and nectar. Concentrations of aluminum in fruit and pollen have been reported between 0.05 and 670mg/L in North America. This is particularly concerning for pollinators that ingest pollen and nectar. Honey bees represent a globally present species experiencing decline in Europe and North America. Region specific decline may be a result of differential toxicity of exposure between subspecies. We find that European honey bees (Apis mellifera mellifera) may have differential toxicity as compared to two allopatric Mediterranean subspecies (Apis mellifera carnica and Apis mellifera caucasica) which showed no within subspecies exposure differences. European honey bees were then used in a laboratory experiment and exposed to aluminum in their daily water supply to mimic nectar contamination at several concentrations. After approximately 3 weeks of aluminum ingestion these bees showed significantly shorter captive longevity than controls at concentrations as low as 10.4mg/L and showed a possible hormetic response in motility. We also compared European honey bees to Africanized/European hybrid bees (Apis mellifera mellifera/scutellata hybrid) in short-term free-flight experiments. Neither the European honey bee nor the hybrid showed immediate foraging deficits in flight time, color choice, or floral manipulation after aluminum exposure. We conclude that European honey bees are at the greatest risk of aluminum related decline from chronic ingestion as compared to other subspecies and offer new methods for future use in honey bee toxicology. [ABSTRACT FROM AUTHOR]

Aims: Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM. Methods and results: SRM 3–5 cases (N = 505) and statin treatment-tolerant controls (N = 2047) were recruited from multiple sites in North America and Europe. SRM 3–5 was defined as symptoms consistent with muscle injury and an elevated creatine phosphokinase level >4 times upper limit of normal without another likely cause of muscle injury. Whole-exome sequencing and variant calling was coordinated from two analysis centres, and results of single-variant and gene-based burden tests were meta-analysed. No genome-wide significant associations were identified. Given the large number of cases, we had 80% power to identify a variant with minor allele frequency of 0.01 that increases the risk of SRM 6-fold at genome-wide significance. Conclusions: In this large whole-exome sequencing study of severe statin-related muscle injury conducted to date, we did not find evidence that rare coding variants are responsible for this adverse drug reaction. Larger sample sizes would be required to identify rare variants with small effects, but it is unclear whether such findings would be clinically actionable. [ABSTRACT FROM AUTHOR]

Ceterach officinarum Willd is a plant widespread throughout Europe and used in southern Italy as a diuretic. Beliefs in the benefits of C. officinarum aqueous extract in the treatment of calcium oxalate kidney stones are widely held. Little is known, however, about the actual mechanism of its antilithiatic action. Our results in this in vitro study corroborate C. officinarum aqueous extract as a good source of antioxidants with a high antioxidant effects. Our results also demonstrate a major impact of C. officinarum aqueous extract on in vitro induced calcium oxalate crystallization kinetics and crystal morphology, showing its critical role in kidney stone formation and/or elimination. We show that progressively increasing doses of C. officinarum aqueous extract cause a sequence of effects. A powerful inhibitory action on calcium oxalate monohydrate (COM) growth and aggregation is first observed. C. officinarum aqueous extract also appears highly effective in stimulating nucleation increasing the number and reducing the size of COM crystals, which become progressively thinner, rounded and concave in a dose-dependent manner. These shape-modified COM crystals are known to be less adherent to renal tubular cells and more easily excreted through the urinary tract preventing kidney stone formation. Further, C. officinarum aqueous extract promotes the formation of calcium oxalate dihydrate (COD) rather than the monohydrate so that, at the highest concentrations used, only COD crystals are observed, in significant greater numbers with a clear reduction in their size, in a dose-dependent manner. Furthermore, AFM analyses allowed us to reveal the presence of C. officinarum component(s) on the surfaces of COD and modified COM crystals. The crystal surface adsorbed component(s) are shown to be similarly active as the total aqueous extract, suggesting a trigger factor which may direct crystal modification towards COD forms. In urolithiasis pathogenesis COD crystals are less dangerous than the COM forms due to their lower affinity for renal tubular cells. Our results are important in understanding the mechanisms which guide the modification induced by C. officinarum on the crystallization process. Based on these data, together with no adverse toxic effect being observed on the in vitro model of human intestinal enterocytes, C. officinarum aqueous extract could represent an attractive natural therapy for the treatment of urolithiasis. [ABSTRACT FROM AUTHOR]

Sustainable development goals are used as a guidance for strategies development on local, regional and national levels. The importance of including young people in this complex process is recognized in all relevant documents (i.e. Agenda 21), however it is not an easy task to elicit opinions and preferences from the youth. Furthermore, the assessment of the sustainable development goals itself presents a challenge for the noisy data and nonlinear relationships in data. Popular approach is fuzzy set models where expert knowledge is presented with comprehensible rules; however expert knowledge elicitation takes a long time too. Several studies proposed an adaptive neuro-fuzzy inference system approach that combines the fuzzy set theory to model expert knowledge with neural networks for inferring rules and membership functions from data to assess the sustainable development performance. We base our assumptions that ANFIS can be used to predict the importance of sustainable development pillars from the demographic data of young people. For this purpose, we have conducted an online survey on sustainable development goals opinions and importance of young people in Serbia. The sample of 386 respondents has been split into a training sample of 300 instances (to generate membership functions and fuzzy rules) and a testing sample of 86 instances to predict the importance of the three pillars. We have conducted a trace-driven simulation test to validate the results of the proposed ANFIS model. Results of the study provided insights into how the young people in Serbia assess the importance of sustainable development goals. Secondly, the results suggest that ANFIS can be applied to predict values of importance of the three sustainable development pillars with the relative error of Rel Err < 5%. It must be noted that the considered model could be further improved by using training samples with more data. [ABSTRACT FROM AUTHOR]

Objectives: Value of information (VOI) analysis provides information on opportunity cost of a decision in healthcare by estimating the cost of reducing parametric uncertainty and quantifying the value of generating additional evidence. This study is an application of the VOI methodology to the problem of choosing between home telemonitoring and nurse telephone support over usual care in chronic heart failure management in the Netherlands. Methods: The expected value of perfect information (EVPI) and the expected value of partially perfect information (EVPPI) analyses were based on an informal threshold of €20K per quality-adjusted life-year. These VOI-analyses were applied to a probabilistic Markov model comparing the 20-year costs and effects in three interventions. The EVPPI explored the value of decision uncertainty caused by the following group of parameters: treatment-specific transition probabilities between New York Heart Association (NYHA) defined disease states, utilities associated with the disease states, number of hospitalizations and ER visits, health state specific costs, and the distribution of patients per NYHA group. We performed the analysis for two population sizes in the Netherlands—patients in all NYHA classes of severity, and patients in NYHA IV class only. Results: The population EVPI for an effective population of 2,841,567 CHF patients in All NYHA classes of severity over the next 20 years is more than €4.5B, implying that further research is highly cost-effective. In the NYHA IV only analysis, for the effective population of 208,003 patients over next 20 years, the population EVPI at the same informal threshold is approx. €590M. The EVPPI analysis showed that the only relevant group of parameters that contribute to the overall decision uncertainty are transition probabilities, in both All NYHA and NYHA IV analyses. Conclusions: Results of our VOI exercise show that the cost of uncertainty regarding the decision on reimbursement of telehealth interventions for chronic heart failure patients is high in the Netherlands, and that future research is needed, mainly on the transition probabilities. [ABSTRACT FROM AUTHOR]

The rich Mediterranean imports found in Early Celtic princely sites (7th-5th cent. BC) in Southwestern Germany, Switzerland and Eastern France have long been the focus of archaeological and public interest. Consumption practices, particularly in the context of feasting, played a major role in Early Celtic life and imported ceramic vessels have consequently been interpreted as an attempt by the elite to imitate Mediterranean wine feasting. Here we present the first scientific study carried out to elucidate the use of Mediterranean imports in Early Celtic Central Europe and their local ceramic counterparts through organic residue analyses of 99 vessels from Vix-Mont Lassois, a key Early Celtic site. In the Mediterranean imports we identified imported plant oils and grape wine, and evidence points towards appropriation of these foreign vessels. Both Greek and local wares served for drinking grape wine and other plant-based fermented beverage(s). A wide variety of animal and plant by-products (e.g. fats, oils, waxes, resin) were also identified. Using an integrative approach, we show the importance of beehive products, millet and bacteriohopanoid beverage(s) in Early Celtic drinking practices. We highlight activities related to biomaterial transformation and show intra-site and status-related differences in consumption practices and/or beverage processing. [ABSTRACT FROM AUTHOR]

Both basic and translational research are continuously evolving, but the principles that underpin research integrity remain constant. These include rational, hypothesis-driven, and adequately planned and controlled science, which is carried out openly, honestly, and ethically. An important component of this should be minimising experimental irreproducibility. Biological systems, in particular, are inherently variable due to the nature of cells and tissues, as well as the complex molecules within them. As a result, it is important to understand and identify sources of variability and to strive to minimise their influence. In many instances, the application of metrology (the science of measurement) can play an important role in ensuring good quality research, even within biological systems that aren’t always amenable to many of the metrological concepts applied in other fields. Here, we introduce the basic concepts of metrology in relation to biological systems and promote the application of these principles to help avoid potentially costly mistakes in both basic and translational research. We also call on funders to encourage the uptake of metrological principles, as well as provide funding and support for later engagement with regulatory bodies. [ABSTRACT FROM AUTHOR]

Freshwater ecosystems rank among the most endangered ecosystems in the world and are under increasing threat from aquatic invasive species (AIS). Understanding the range expansion of AIS is key for mitigating their impacts. Most approaches rely on Species Distribution Models (SDMs) to predict the expansion of AIS, using mainly environmental variables, yet ignore the role of human activities in favouring the introduction and range expansion of AIS. In this study, we use five SDM algorithms (independently and in ensemble) and two accuracy measures (TSS, AUC), combined with a null modelling approach, to assess the predictive performance of the models and to quantify which predictors (environmental and anthropogenic from the native and introduced regions) best explain the distribution of nine freshwater invasive species (including fish, arthropods, molluscs, amphibians and reptiles) in a large island (Great Britain), and which species characteristics affect model performance. Our results show that the distribution of invasive species is difficult to predict by SDMs, even in cases when TSS and AUC model accuracy values are high. Our study strongly advocates the use of null models for testing SDMs performance and the inclusion of information from the native area and a variety of both human-related and environmental predictors for a more accurate modelling of the range expansion of AIS. Otherwise, models that only include climatic variables, or rely only on standard accuracy measures or a single algorithm, might result in mismanagement of AIS. [ABSTRACT FROM AUTHOR]

This study assessed the prevalence and patterns of drug use among people living with HIV (PLHIV) in Spain. We conducted an observational cross-sectional study including 1401 PLHIV. Data were collected through 33 sites across Spain using an online computer-assisted self-administered interview. The survey measured use of illicit drugs and other substances, treatment adherence and health-related variables. To analyse patterns of drug use we performed cluster analysis in two stages. The most frequently consumed substances were: alcohol (86.7%), tobacco (55.0%), illicit drugs (49.5%), other substances (27.1%). The most prevalent illicit drugs used were cannabis (73.8%), cocaine powder (53.9%), and poppers (45.4%). Results found four clusters of PLHIV who used drugs. Two of them were composed mainly of heterosexuals (HTX): Cluster 1 (n = 172) presented the lowest polydrug use and they were mainly users of cannabis, and Cluster 2 (n = 84) grouped mostly men who used mainly heroin and cocaine; which had the highest percentage of people who inject drugs and presented the lowest level of treatment adherence (79.8±14.2; p < .0001). The other two clusters were composed mainly of men who have sex with men (MSM), who were mostly users of recreational drugs. Cluster 3 (n = 285) reported moderate consumption, both regarding frequency and diversity of drugs used, while Cluster 4 (n = 153) was characterized by the highest drug polyconsumption (7.4±2.2; p < .0001), and 4 grouped MSM who injected recreational drugs, and who reported the highest frequency of use of drugs in a sexual context (2.6±0.8; p < .0001) and rates of sexually transmitted infections (1.8±1.1; p < .01). This is the largest multi-centre cross-sectional study assessing the current prevalence and patterns of drug use among PLHIV in Spain. The highest prevalence of drug use was found among MSM, although HTX who used heroin and cocaine (Cluster 2) had the most problems with adherence to HIV treatment and the worst health status. [ABSTRACT FROM AUTHOR]

The fast pace of urbanisation may benefit or be detrimental to the socio-economic status of urban areas. Understanding how the configuration of urban areas influences the socio-economic status of their inhabitants is of crucial importance for urban planning. In theory, urban scaling laws and polycentric development are two well-known concepts developed to increase our understanding of urbanisation and its socio-economic effects. In practice, however, they fall short to explain the socio-economic status of urban regions. The urban scaling concept is constructed from a theoretical perspective, but functional relationships between urban centres are not taken into account in scaling models. In contrast, the concept of polycentricity is developed from a practical perspective and incorporates the socio-economic effect of relationships between urban centres in the process of urban development. However, polycentricity lacks a theoretical foundation, which would explain the socio-economic status of urban regions. In this study, we assess whether combining both concepts improves the ability to explain personal incomes in metropolitan areas in Switzerland. We first delineated metropolitan areas by implementing a modularity maximisation algorithm on the settlement network. Nodes in this network are Swiss municipalities and links are inter-municipal commuter flows. We found a strong relationship between the hierarchical organisation of functional connections within metropolitan areas and the socio-economic status of these areas. Both concepts were complementary and combining them proved to enhance the ability to explain socio-economic status. The combined model is a theoretical progress, which complements the traditional approaches and increases our understanding of cities and urbanisation processes. [ABSTRACT FROM AUTHOR]

Because sexual orientation concealment can exact deep mental and physical health costs and dampen the public visibility necessary for advancing equal rights, estimating the proportion of the global sexual minority population that conceals its sexual orientation represents a matter of public health and policy concern. Yet a historic lack of cross-national datasets of sexual minorities has precluded accurate estimates of the size of the global closet. We extrapolated the size of the global closet (i.e., the proportion of the global sexual minority population who conceals its sexual orientation) using a large sample of sexual minorities collected across 28 countries and an objective index of structural stigma (i.e., discriminatory national laws and policies affecting sexual minorities) across 197 countries. We estimate that the majority (83.0%) of sexual minorities around the world conceal their sexual orientation from all or most people and that country-level structural stigma can serve as a useful predictor of the size of each country’s closeted sexual minority population. Our analysis also predicts that eliminating structural stigma would drastically reduce the size of the global closet. Given its costs to individual health and social equality, the closet represents a considerable burden on the global sexual minority population. The present projection suggests that the surest route to improving the wellbeing of sexual minorities worldwide is through reducing structural forms of inequality. Yet, another route to alleviating the personal and societal toll of the closet is to develop public health interventions that sensitively reach the closeted sexual minority population in high-stigma contexts worldwide. An important goal of this projection, which relies on data from Europe, is to spur future research from non-Western countries capable of refining the estimate of the association between structural stigma and sexual orientation concealment using local experiences of both. [ABSTRACT FROM AUTHOR]

Biophysical and biochemical data on hyaluronan (HA)-based dermal fillers strongly support their optimal use and design to meet specific requisites. Here, four commercially available (in Europe) HA “volumetric” fillers, among the most used in the clinical practice, have been characterized in vitro. Analyses revealed the highest amounts of water-soluble HA reported so far and provided hydrodynamic data for these soluble polymeric fractions. Volumetric gels exhibit a wide range of rigidity with most of them showing G’ values around 200-300Pa. They greatly differ in cohesivity. 1mL of gel hydrates up to 2.4–3.2mL. The products completely solubilize due to Bovine Testicular Hyaluronidase (BTH)’s action, thus predicting in vivo complete resorption. For the first time, filler degradation due to reactive oxygen species (ROS) was studied by rheological measurements and a rank in stability was established. Studies using Human Dermal Fibroblasts (HDF) indicated a positive biological response to the HA networks. Further, gel capacity to prompt collagen I, elastin and aquaporin3 synthesis was demonstrated, thus suggesting a positive effect on skin elasticity and hydration, besides the physical volumetric action. The findings are the first wide assessment of features for the volumetric class of HA-fillers and include first data on their resistance to degradation by ROS and biological effects on HDF. The study represents a valuable contribution to the understanding of HA-fillers, useful to optimize their use and manufacture. [ABSTRACT FROM AUTHOR]

Objectives: This paper focuses on the issue of intimate partner violence and, specifically, on the distribution of femicides over time and the existence of copycat effects. This is the subject of an ongoing debate often triggered by the social alarm following multiple intimate partner homicides (IPHs) occurring in a short span of time. The aim of this research is to study the evolution of IPHs and provide a far-reaching answer by rigorously analyzing and searching for patterns in data on femicides. Methods: The study analyzes an official dataset, provided by the system VioGén of the Secretaría de Estado de Seguridad (Spanish State Secretariat for Security), including all the femicides occurred in Spain in 2007-2017. A statistical methodology to identify temporal interdependencies in count time series is proposed and applied to the dataset. The same methodology can be applied to other contexts. Results: There has been a decreasing trend in the number of femicides per year. No interdependencies among the temporal distribution of femicides are observed. Therefore, according to data, the existence of copycat effect in femicides cannot be claimed. Conclusions: Around 2011 there was a clear change in the average number of femicides which has not picked up. Results allow for an informed answer to the debate on copycat effect in Spanish femicides. The planning of femicides prevention activities should not be a reaction to a perceived increase in their occurrence. As a copycat effect is not detected in the studied time period, there is no evidence supporting the need to censor media reports on femicides. [ABSTRACT FROM AUTHOR]

Background: Extensive studies have been carried out over the years to determine the maximum acceptable weight that a worker is capable of lifting in a given situation among Occidental populations across Europe and US. Nonetheless, studies that place emphasis on using lifting frequency as the quantifying task parameter, especially in developing countries such as Malaysia, appear to be in scarcity. Hence, this study determined the maximum acceptable frequency of lift (MAFL) for combined manual material handling (MMH) tasks amongst Malaysian males. Method: Two lifting loads were considered in this study: 1 kg and 5 kg. Each subject adjusted his frequency of lifting using a psychophysical approach. The subjects were instructed to perform combined MMH task as fast as they could over a period of 45 minutes without exhausting themselves or becoming overheated. The physiological response energy expenditure was recorded during the experimental sessions. The ratings of perceived exertion (RPE) for four body parts (forearms, upper arm, lower back and entire body) were recorded after the subjects had completed the instructed task. Results: The mean frequencies of the MMH task had been 6.8 and 5.5 cycles/minute for lifting load of 1 and 5 kg, respectively, while the mean energy expenditure values were 4.16 and 5.62 kcal/min for 1 and 5 kg load, respectively. These displayed a significant difference in the Maximum Acceptable Frequency of Lift (MAFL) between the two loads, energy expenditure and RPE (p < 0.05) whereby the subjects appeared to work harder physiologically for heavier load. Conclusion: It can be concluded that it is significant to assess physiological response and RPE in determining the maximum acceptable lifting frequency at varied levels of load weight. The findings retrieved in this study can aid in designing tasks that do not exceed the capacity of workers in order to minimise the risk of WRMSDs. [ABSTRACT FROM AUTHOR]

Purpose: We aim to assess if air pollution levels and climatological factors are associated with hospital admissions for exacerbation of chronic obstructive pulmonary disease (COPD) in Spain from 2004 to 2013. Methods: We conducted a retrospective study. Information on pollution level and climatological factors were obtained from the Spanish Meteorological Agency and hospitalizations from the Spanish hospital discharge database. A case-crossover design was used to identify factors associated with hospitalizations and in hospital mortality. Postal codes were used to assign climatic and pollutant factors to each patient. Results: We detected 162,338 hospital admissions for COPD exacerbation. When seasonal effects were evaluated we observed that hospital admissions and mortality were more frequent in autumn and winter. In addition, we found significant associations of temperature, humidity, ozone (O3), carbon monoxide (CO), particulate matter up to 10 μm in size (PM10) and nitrogen dioxide (NO2) with hospital admissions. Lower temperatures at admission with COPD exacerbation versus 1, 1.5, 2 and 3 weeks prior to hospital admission for COPD exacerbation, were associated with a higher probability of dying in the hospital. Other environmental factors that were related to in-hospital mortality were NO2, O3, PM10 and CO. Conclusions: Epidemiology of hospital admissions by COPD exacerbation was negatively affected by colder climatological factors (seasonality and absolute temperature) and short-term exposure to major air pollution (NO2, O3, CO and PM10). [ABSTRACT FROM AUTHOR]

The development of industrial agriculture has enabled a sharp increase in food trade at the global scale. Worldwide trade underpins food security by distributing food surpluses to food deficient countries. The study of agricultural product flows can provide insights on the complex interactions between exporting and importing countries and the resulting network structures. Commercial partnerships between countries can be modelled using a complex network approach. Based on the detailed trade matrices from FAO covering the period from 1986 to 2013, we present an analysis of the world cereal trade in terms of weighted and directed networks. The network nodes are the countries and the links are the trades of agricultural products in mass. We reveal the changing topology and degree distribution of the world network during the studied period. We distinguish three entangled subnetwork structures when considering the temporal stability of the trades. The three subnetworks display distinct properties and a differential contribution in total trade. Trades of uninterrupted activity over the 28-year study period compose the backbone network which accounts for two thirds of all traded mass and is scale-free. Inversely, two thirds of the trades only have one or two consecutive years of activity and define the transient subnetwork which displays random growth and accounts for very little traded mass. The trades of intermediate duration display an exponential growth both in numbers and in traded mass and define the intermediate subnetwork. The topology of each subnetwork is a time invariant. The identification of invariant structures is a useful basis for developing prospective agri-food network modelling to assess their resilience to perturbations and shocks. [ABSTRACT FROM AUTHOR]

Extended-spectrum β-lactamase (ESBL)- and plasmid mediated AmpC-type cephalosporinase (pAmpC)-producing Escherichia coli (ESBL/pAmpC E. coli) in food-producing animals is a major public health concern. This study aimed at quantifying ESBL/pAmpC-E. coli occurrence and transfer in Italy’s broiler production pyramid. Three production chains of an integrated broiler company were investigated. Cloacal swabs were taken from parent stock chickens and offspring broiler flocks in four fattening farms per chain. Carcasses from sampled broiler flocks were collected at slaughterhouse. Samples were processed on selective media, and E. coli colonies were screened for ESBL/pAmpC production. ESBL/pAmpC genes and E. coli phylogroups were determined by PCR and sequencing. Average pairwise overlap of ESBL/pAmpC E. coli gene and phylogroup occurrences between subsequent production stages was estimated using the proportional similarity index, modelling uncertainty in a Monte Carlo simulation setting. In total, 820 samples were processed, from which 513 ESBL/pAmpC E. coli isolates were obtained. We found a high prevalence (92.5%, 95%CI 72.1–98.3%) in day-old parent stock chicks, in which blaCMY-2 predominated; prevalence then dropped to 20% (12.9–29.6%) at laying phase. In fattening broilers, prevalence was 69.2% (53.6–81.3%) at the start of production, 54.2% (38.9–68.6%) at slaughter time, and 61.3% (48.1–72.9%) in carcasses. Significantly decreasing and increasing trends for respectively blaCMY-2 and blaCTX-M-1 gene occurrences were found across subsequent production stages. ESBL/pAmpC E. coli genetic background appeared complex and bla-gene/phylogroup associations indicated clonal and horizontal transmission. Modelling revealed that the average transfer of ESBL/pAmpC E. coli genes between subsequent production stages was 47.7% (42.3–53.4%). We concluded that ESBL/pAmpC E. coli in the broiler production pyramid is prevalent, with substantial transfer between subsequent production levels. [ABSTRACT FROM AUTHOR]

Background: Image-based blood flow simulations have been increasingly applied to investigate intracranial aneurysm (IA) hemodynamics. However, the acceptance among physicians remains limited due to the high variability in the underlying assumptions and quality of results. Methods: To evaluate the vessel segmentation as one of the most important sources of error, the international Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH) was announced. 26 research groups from 13 different countries segmented three datasets, which contained five IAs in total. Based on these segmentations, 73 time-dependent blood flow simulations under consistent conditions were carried out. Afterwards, relevant flow and shear parameters (e.g., neck inflow rate, parent vessel flow rate, spatial mean velocity, and wall shear stress) were analyzed both qualitatively and quantitatively. Results: Regarding the entire vasculature, the variability of the segmented vessel radius is 0.13 mm, consistent and independent of the local vessel radius. However, the centerline velocity shows increased variability in more distal vessels. Focusing on the aneurysms, clear differences in morphological and hemodynamic parameters were observed. The quantification of the segmentation-induced variability showed approximately a 14% difference among the groups for the parent vessel flow rate. Regarding the mean aneurysmal velocity and the neck inflow rate, a variation of 30% and 46% was observed, respectively. Finally, time-averaged wall shear stresses varied between 28% and 51%, depending on the aneurysm in question. Conclusions: MATCH reveals the effect of state-of-the-art segmentation algorithms on subsequent hemodynamic simulations for IA research. The observed variations may lead to an inappropriate interpretation of the simulation results and thus, can lead to inappropriate conclusions by physicians. Therefore, accurate segmentation of the region of interest is necessary to obtain reliable and clinically helpful flow information. [ABSTRACT FROM AUTHOR]

Despite considerable air pollution prevention and control measures that have been put into practice in recent years, outdoor air pollution remains one of the most important risk factors for health outcomes. To identify the potential research gaps, we conducted a scoping review focused on health outcomes affected by outdoor air pollution across the broad research area. Of the 5759 potentially relevant studies, 799 were included in the final analysis. The included studies showed an increasing publication trend from 1992 to 2008, and most of the studies were conducted in Asia, Europe, and North America. Among the eight categorized health outcomes, asthma (category: respiratory diseases) and mortality (category: health records) were the most common ones. Adverse health outcomes involving respiratory diseases among children accounted for the largest group. Out of the total included studies, 95.2% reported at least one statistically positive result, and only 0.4% showed ambiguous results. Based on our study, we suggest that the time frame of the included studies, their disease definitions, and the measurement of personal exposure to outdoor air pollution should be taken into consideration in any future research. The main limitation of this study is its potential language bias, since only English publications were included. In conclusion, this scoping review provides researchers and policy decision makers with evidence taken from multiple disciplines to show the increasing prevalence of outdoor air pollution and its adverse effects on health outcomes. [ABSTRACT FROM AUTHOR]

Background: An outbreak of HIV infections among people who inject drugs (PWID) started in 2014 in Luxembourg. Objectives: We conducted phylogenetic and epidemiological analyses among the PWID infected with HIV in Luxembourg or attending the supervised drug consumption facility (SDCF) to understand the main causes of the outbreak. Methods: Between January 2013 and December 2017, analysis of medical files were performed from all PWID infected with HIV at the National Service of Infectious Diseases (NSID) providing clinical care nationwide. PWID were interviewed at NSID and SDCF using a standardized questionnaire focused on drug consumption and risk behaviours. The national drug monitoring system RELIS was consulted to determine the frequency of cocaine/heroin use. Transmission clusters were analysed by phylogenetic analyses using approximate maximum-likelihood. Univariate and multivariate logistic regression analyses were performed on epidemiological data collected at NSID and SDCF to determine risk factors associated with cocaine use. Results: From January 2013 to December 2017, 68 new diagnosis of HIV infection reported injecting drug use as the main risk of transmission at NSID. The proportion of female cases enrolled between 2013–2017 was higher than the proportion among cases enrolled prior to 2013. (33% vs 21%, p < 0.05). Fifty six viral sequences were obtained from the 68 PWID newly diagnosed for HIV. Two main transmission clusters were revealed: one HIV-1 subtype B cluster and one CRF14_BG cluster including 37 and 9 patients diagnosed since 2013, respectively. Interviews from 32/68 (47%) newly diagnosed PWID revealed that 12/32 (37.5%) were homeless and 27/32 (84.4%) injected cocaine. Increased cocaine injection was indeed reported by the RELIS participants from 53 to 63% in drug users with services contacts between 2012 and 2015, and from 5 to 22% in SDCF users between 2012 and 2016. Compared with PWID who injected only heroin (n = 63), PWID injecting cocaine and heroin (n = 107) were younger (mean of 38 vs 44 years, p≤0.001), reported more frequent piercing (≤0.001), shared and injected drugs more often (p≤0.01), and were more frequently HIV positive (p<0.05) at SDCF using univariate logistic regression analysis. Finally, in the multivariate analysis, use of heroin and cocaine was independently associated with younger age, piercing, sharing of drugs, and regular consumption (p<0.05). Conclusions: Injecting cocaine is a new trend of drug use in Luxembourg associated with HIV infection in this recent outbreak among PWID. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to develop a risk stratification model to predict the presence of a potentially more sinister injury in patients exposed to a whiplash trauma. Methods: The study base comprised of 3,115 residents who first sought healthcare contact within one week after being exposed to a whiplash trauma between 1999–2008, from within a defined geographical area, Skaraborg County in south-western Sweden. Information about gender, age, time elapsed prior to seeking care, type of health care contact, and hospitalisation was retrieved. Seventeen potential risk factors were identified and evaluated using multivariable logistic regression. Results: Of 3,115 patients, 215 (6.9%) required hospital admission so theoretically 93% could have been initially assessed by primary health care. However, only 46% had their first contact in primary health care. All patients had symptoms resulting in a diagnosis of whiplash injury. Four risk factors were found to be associated with hospital admission: commotio cerebri (OR 31, 19–51), fracture / luxation (OR 11, 5.1–22), serious injury (OR 41, 8.0–210), and the patient sought care during the same day as the trauma (OR 5.9, 3.7–9.5). These four risk factors explained 27% of the variation for hospital admission and the area under curve (AUC) was 0.77 (0.74–0.80). Ninety-six percent of patients (2,985) had only a whiplash injury with no other injury. These could be split into those attending health care the same day as the trauma, 1,737 (56%) with a 7.1% risk for hospital admission, and those attending health care later, 1,248 (40%) with a 1.3% risk for hospital admission. Conclusion: Patients with no signs of commotio cerebri, no fracture/luxation injury, no serious injury, comprising 96% of all patients exposed to a whiplash trauma can initially be referred to primary health care for initial assessment. However, those contacting the health care the same day as the trauma should be referred to a hospital for evaluation if they can’t get an appointment with a general practitioner the same day. [ABSTRACT FROM AUTHOR]

Background: The intentional use of drugs to have sex–chemsex–among men who have sex with men (MSM) might contribute to the high sexually transmitted infections (STI) prevalence in this group. Limited data is available on chemsex outside major cities. The current study investigated the use of a wide variety of drugs during sex among MSM living outside major cities in the Netherlands and their associations with STI. Methods: In 2018, 350 MSM were recruited at STI clinics and 250 MSM completed an online questionnaire. Questionnaire data were linked to clients’ most recent STI laboratory test results. Chemsex was defined as using cocaine, crystal meth, designer drugs, GHB/GBL, ketamine, speed, or XTC/MDMA during sex in the preceding six months. The use of other drugs was also assessed. Determinants (chemsex, specific drugs, number of drugs, combining, and frequency) potentially associated with STI were assessed using multivariable logistic regression analyses adjusting for sociodemographic characteristics and sexual history. Results: Chemsex was reported by 35% (95%CI: 29–41) of the 250 participants. XTC/MDMA (27%; 68/250) and GHB/GBL (26%; 64/250) were the most used drugs. STI positivity was 33% (29/87) in MSM engaging in chemsex and 12% (12/163) in MSM not engaging in chemsex (p<0.001). Half of MSM engaging in chemsex (45/87) used three of more different chemsex drugs; STI positivity in this group was 44% (20/45). The only factor independently associated with STI was the use of three or more chemsex drugs (aOR: 4.13, 95%CI: 1.77–9.62). Conclusion: This study shows that chemsex is prevalent among MSM visiting the STI clinic outside major cities in the Netherlands, suggesting that health services in both urban and non-urban areas should be aware of and informed on chemsex. MSM who used multiple drugs are at particular risk for STI, indicating a special need for STI prevention and care in this group. [ABSTRACT FROM AUTHOR]

Vaginal lubricants are commonly used by couples trying-to-conceive. However, most vaginal lubricants are sperm toxic and therefore should not be used by couples trying-to-conceive. Despite this, lubricant sperm toxicity is insufficiently reported and guidance for healthcare professionals (HCPs) is absent. In this study, lubricant-related practices of fertility-based HCPs in Scotland were sampled via an online survey. Lubricants identified as being utilised in the fertility setting were subsequently incubated with prepared sperm samples to establish effects on sperm motility. HCP recommendations (n = 32) on lubricant use were varied although knowledge related to sperm toxicity was generally poor. HCPs infrequently asked about lubricant use and were unaware of guidance in this area. Aquagel, the only prescribed lubricant identified in this study, reduced sperm progressive motility to 49% of control after 10 minutes, even at concentrations as low as 5%. Vitality testing suggested the deterioration in progressive motility with Aquagel was not as a result of cell death. Conversely, Pré Vaginal Lubricant, a ‘sperm-safe’ lubricant, did not significantly affect any markers of sperm function assessed. Development of clinical guidance in this area is recommended to ensure HCPs deliver informed advice as lubricant use in couples trying-to-conceive may inadvertently contribute to delay in conception. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance and related metabolic disturbances are major risk factors for the higher T2D risk and associated morbidity and mortality amongst South Asians. The contribution of physical activity to the increased prevalence of insulin resistance and related disturbances amongst South Asians is unknown. Methods: We recruited 902 South Asian and European men and women, aged 35–85 years from the ongoing LOLIPOP study. Clinical characterisation comprised standardised questionnaire and measurement of height, weight, waist and hip circumference and blood pressure. Fasting bloods were taken for assessment of glucose, insulin, lipids and HbA1c. Physical activity was quantified using a validated accelerometer, Actigraph GT3X+, worn for 7 days. Univariate and multivariate approaches were used to investigate the relationship between ethnicity, physical activity, insulin resistance and related metabolic disturbances. Results: Total physical activity was ~31% (P = 0.01) lower amongst South Asians compared to Europeans (Mean MET.minutes [SD]: 1505.2 [52] vs. 2050.9 [86.6], P<0.001). After adjusting for age and sex, total physical activity had a negative association with HOMA-IR (B [SE]: -0.18 [0.08], P = 0.04) and fasting glucose levels (B[SE]: -0.11 [0.04], P = 0.02). There was no association between physical activity and other glycemic and lipid parameters. Total physical activity per week contributed towards the differences in insulin resistance and associated metabolic disturbances between South Asians and Europeans. Conclusion: Lower levels of physical activity may contribute to the increased insulin resistance in South Asians compared to Europeans. Our results suggest that lifestyle modification through increased physical activity may help to improve glucose metabolism and reduce the burden of excess T2D and related complications amongst South Asians. [ABSTRACT FROM AUTHOR]

Background: Previous ischemic stroke is a predictor of recurrent ischemic stroke after an acute myocardial infarction (AMI). Dual antiplatelet therapy, including a P2Y12-inhibitor, is important in secondary prevention after AMI. Ticagrelor, a P2Y12-inhibitor, is more potent than the commonly used clopidogrel. Here, we evaluated the impact of ticagrelor on the risk of ischemic stroke following AMI in patients with previous ischemic stroke. Methods: Data for patients with AMI that had a previous ischemic stroke were obtained from the Swedish Registry of Information and Knowledge about Swedish Heart Intensive Care Admissions. Patients were assigned to early and late cohorts, each covering a two-year time period before and after, respectively, the introduction of ticagrelor prescriptions (20 Dec 2011). Patients in the early cohort (n = 1633) were treated with clopidogrel (100%); those in the late cohort (n = 1642) were treated with either clopidogrel (66.3%) or ticagrelor (33.7%). We assessed the risk of ischemic stroke and intracranial bleeding over time with Kaplan-Meier analyses. We identified predictors of ischemic stroke with multivariable Cox regression analyses. Results: Of 3275 patients, 311 experienced ischemic stroke after AMI. Cumulative Kaplan-Meier incidence estimates of ischemic stroke within one year after AMI were 12.1% versus 8.6% for the early and late cohorts, respectively (p<0.01). Intracranial bleeding incidences (1.2% versus 1.5%) were similar between the two cohorts. Conclusions: Ticagrelor introduction was associated with a lower rate of ischemic stroke, with no increase in intracranial bleeding, in an AMI population with a history of ischemic stroke. [ABSTRACT FROM AUTHOR]

Most of the Paleolithic art and ornaments discovered in Romania come from the site of Poiana Cireșului. Four Paleolithic layers have been studied at this site—the oldest one belongs to the Early Gravettian period between 30 ka and 31 ka BP. The ornaments discovered in this layer include perforated shells from three species of mollusks: freshwater Lithoglyphus naticoide and Lithoglyphus apertus as well as Homalopoma sanguineum (an exclusively Mediterranean species). Poiana Cireșului is one of the very few Gravettian sites where perforated Homalopoma sanguineum shells were found, and the importance of this discovery is stressed even more by the very long distance between the site and the nearest source located over 900 km away. This find suggests the connection of communities here with the Mediterranean area as well as a possible movement of populations from the south of the continent to the east of the Carpathians with significant implications in understanding human group mobility and the origin of the Early Gravettian in this area. Furthermore, Poiana Cireșului is the only Gravettian settlement where Lithoglyphus naticoides shells were used. The unique association of perforated shells—not found in any other Gravettian settlement—contributes to the identity of the Paleolithic community of Poiana Cireșului through their ornaments. [ABSTRACT FROM AUTHOR]

Little is known about the types of social organization characterizing the pre-Roman Celtic populations of Italy. Here, we explore the funerary variability characterizing the late Iron Age site of Seminario Vescovile (SV: Verona, Italy, 3rd-1st c. BC), and test its possible correlation to diet and relative exposure to developmental stressors. Patterns on funerary treatment (N = 125), δ13C and δ15N (N = 90), and linear enamel hypoplasia (N = 47) from SV are compared, and their possible association with sex and age-at-death further discussed. Results point to the presence at SV of variable funerary customs while at the same time demonstrating a rather homogenous diet and exposure to developmental stressors: funerary treatment is mainly correlated to age-at-death but do not appear to be associated to either isotopic patterns or hypoplasia frequencies. Accordingly, even if some weak social differentiation may have characterized the individuals buried at SV, this was not reflected in markedly differing living conditions. Our study is the first to attempt an exploration of the links between age, sex, funerary variability, and diet in a pre-Roman Celtic community from Italy. While highlighting the potential of a multifaceted approach in bioarcheology, it also points to a series of analytical and theoretical issues relevant when trying to disentangle the cultural and biological dimensions of social differentiation in the past. [ABSTRACT FROM AUTHOR]

Eleven biconical vessels from the Copper Age sites Pietrele and Blejeşti (Romania) have been investigated using p-XRF. In most cases, traces of lead could be measured on their surfaces. Samples of slag-like material from two vessels and the clay of one vessel were investigated using laboratory methods, namely SEM, XRD, LIA and optical microscopy. The vessels were obviously used as a kind of crucible in which slag-like remains and galena ore were detected. It still remains unclear as to what final product was gained by smelting galena in this way. The amount of these such vessels in the Pietrele settlement, their appearance as grave goods in Pietrele and Vărăști (Romania), and their supposed occurrence in a number of other Copper Age settlements in Romania and Bulgaria show the significance of this phenomenon. It must have been a widespread and more or less well known practice, an important part of cultural habit during a particular period in the Lower Danube region and likely even farther afield. For the first time, extensive experimentation with lead ore can be shown in a clear chronological horizon, ca. 4400–4300 BCE in southeastern Europe. [ABSTRACT FROM AUTHOR]

The tetraploid wheat species Triticum turgidum and Triticum timopheevii are morphologically similar, and misidentification of material collected from the wild is possible. We compared published sequences for the Ppd-A1, Ppd-B1 and Ppd-G1 genes from multiple accessions of T. turgidum and T. timopheevii and devised a set of four polymerase chain reactions (PCRs), two specific for Ppd-B1 and two for Ppd-G1. We used these PCRs with 51 accessions of T. timopheevii and 20 of T. turgidum. Sixty of these accessions gave PCR products consistent with their taxon identifications, but the other eleven accessions gave anomalous results: ten accessions that were classified as T. turgidum were identified as T. timopheevii by the PCRs, and one T. timopheevii accession was typed as T. turgidum. We believe that these anomalies are not due to errors in the PCR tests because the results agree with a more comprehensive analysis of genome-wide single nucleotide polymorphisms, which similarly suggest that these eleven accessions have been misclassified. Our results therefore show that the accepted morphological tests for discrimination between T. turgidum and T. timopheevii might not be entirely robust, but that species identification can be made cheaply and quickly by PCRs directed at the Ppd-1 gene. [ABSTRACT FROM AUTHOR]

England’s national Improving Access to Psychological Therapies (IAPT) programme advocates stepped care as its organizational delivery of psychological therapies to common mental health problems. There is limited evidence regarding the efficacy of stepped care as a service delivery model, heterogeneity of definition and differences in model implementation in both research and routine practice, hence outcome comparison in terms of effectiveness of model is difficult. Despite sound evidence of the efficacy of low intensity interventions there appears to be a perpetuation of the notion that severity and complexity should only be treated by a high intensity intervention through the continuation of a stratified care model. Yet no psychotherapy treatment is found to be more superior to another, and not enough is known about what works for whom to aid the matching of treatment decision. In the absence of understanding precise treatment factors optimal for recovery, it may be useful to better understand the impact of a service delivery model, and whether different models achieve different outcomes. This study aims to contribute to the discussion regarding the stepped care definition and delivery, and explores the impact on clinical outcomes where different types of stepped care have been implemented within the same service. An observational cohort study analysed retrospective data (n = 16,723) over a 4 year period, in a single IAPT service, where delivery changed from one type of stepped care model to another. We compared the outcomes of treatment completers with a stratified care model and a progression care model. We also explored the assumption that patients who score severe on psychological measures, and therefore are potentially complex, would achieve better outcomes in a stratified model. Outcomes in each model type were compared, alongside baseline factor variables. A significant association was observed between a recovery outcome and model type, with patients 1.5 times more likely to recover in the progression delivery model. The potential implications are that with a progression stepped care model of service delivery, more patients can be treated with a lower intensity intervention, even with initial severe presentations, ensuring that only those that need high intensity CBT or equivalent are stepped up. This could provide services with an effective clinical model that is efficient and potentially more cost effective. [ABSTRACT FROM AUTHOR]

The radiological consequences of a nuclear power plant (NPP) accident, resulting in the release of radionuclides to the environment, will depend largely on the mitigating actions instigated shortly after the accident. It is therefore important to make predictions of the radiation dose to the affected population, from external as well as internal exposure, soon after an accident, despite the fact that data are scarce. The aim of this study was to develop a model for the prediction of the cumulative effective dose up to 84 years of age based on the ground deposition of 137Cs that is determined soon after fallout. The model accounts for different assumptions regarding external and internal dose contributions, and the model parameters in this study were chosen to reflect various mitigating actions. Furthermore, the relative importance of these parameters was determined by sensitivity analysis. To the best of our knowledge, this model is unique as it allows quantification of both the external and the internal effective dose using only a fallout map of 137Cs after a nuclear power plant accident. The cumulative effective dose over a period of 50 years following the accident per unit 137Cs deposited was found to range from 0.14 mSv/kBq m-2 to 1.5 mSv/kBq m-2, depending on the mitigating actions undertaken. According to the sensitivity analysis, the most important parameters governing the cumulative effective dose to various adult populations during 50 years after the fallout appear to be: the correlation factor between the local areal deposition of 137Cs and the maximum initial ambient dose rate; the maximum transfer from regional average fallout on the ground to body burden; the local areal deposition of 137Cs; and the regional average 137Cs deposition. Therefore, it is important that mapping of local 137Cs deposition is carried out immediately after fallout from a nuclear power plant accident, followed by calculations of radiation doses for different scenarios using well-known parameters, in order to identify the most efficient mitigation strategies. Given this 137Cs mapping, we believe our model is a valuable tool for long-term radiological assessment in the early phase after NPP accidents. [ABSTRACT FROM AUTHOR]

Background: The Hopkins Symptom Checklist in 25 items (HSCL-25) helps to assess anxiety and depression in Primary Care. Anxiety and depression show considerable overlap in primary care. This self-administrated questionnaire is valid, reliable and ergonomic in the original US version. We have translated it into French. The aim of this study was to estimate the test characteristics of the HSCL-25, in its French version (F-HSCL-25), by comparing it to the Present State Examination-9 French version (F-PSE-9) and by determining its internal validity and dimensions. Method: Outpatients from three French General Practice settings (rural, semi-rural and urban) were recruited: approximately 20,000 outpatients among 17 GPs. Two groups were formed: F-HSCL-25 ≥1.75 and F-HSCL-25 <1.75. A validated cut-off score of > 1.75 was considered to indicate a clinically relevant level of symptoms of depression and anxiety. In order to obtain two balanced groups, a different method of randomization was chosen for each group. The F-PSE-9 was randomly administered to 1 in 2 patients in the F-HSCL-25 ≥1.75 group, and to 1 in 16 in the (much larger) F-HSCL-25 <1.75 group. The diagnostic performance was assessed and the test results obtained from both groups were compared with their F-PSE-9 results. Results: Of the 1126 patients who completed the F-HCL-25, 886 joined the F-HSCL-25 <1.75 group and 240 the F-HSCL-25 ≥1.75 group. The overall prevalence of depression, using the F-HSCL-25, was 21% in these medical practices. The diagnostic performance of the F-HSCL-25 versus the F-PSE-9, the external criteria were as follows: Positive Predictive Value (PPV) 69.8%, Negative Predictive Value (NPV) 87%; Sensitivity 59.1%, and Specificity 91.4%. The Principal Component Analysis showed that F-HSCL-25 is a one-dimensional tool (anxiety and depression dimensions combined) with a Cronbach Alpha of 0.93. Conclusion: The F-HSCL-25 is an appropriate diagnostic tool for anxiety and depression in primary care in France due to its high specificity and high NPV. The HSCL-25 scale has a high eigenvalue. This pilot study will be extended throughout Europe; however, preliminary evidence suggests that the HSCL-25 is a reliable and suitable diagnostic tool for primary care. [ABSTRACT FROM AUTHOR]

Background: International comparisons of trajectories of depressive symptoms in older adults are scarce and longitudinal associations with co-morbid conditions not fully understood. Objective: To compare trajectories of depressive symptoms from participants living in 10 European Countries and identify ages at which the associations of co-morbid conditions with these trajectories become more relevant. Methods: Latent growth curve models were fitted to depressive symptoms scores from participants of the Survey of Health and Retirement in Europe (SHARE) initiative (combined n = 21,253) and co-morbid conditions modelled as time varying covariates. To identify the ages at which the association between co-morbid conditions and depressive symptoms was significant the Johnson-Neyman (JN) technique was used. Results: The shape of depressive symptoms trajectories varied between countries, and was highly dependent on modelling decisions. The association between the average number of co-morbidities reported over time and depressive symptoms was consistent and positive across countries and ages. Conclusion: International differences in ageing-related trajectories of depressive symptoms emerged. The longitudinal association of co-morbid conditions with trajectories of depressive symptoms was found, but the results overall suggest that modelling decisions could greatly influence the outcomes, and should thus be interpreted with caution. [ABSTRACT FROM AUTHOR]

Many disciplines of scholarship are interested in the Relative Age Effect (RAE), whereby age-banding confers advantages on older members of the cohort over younger ones. Most research does not test this relationship in a manner consistent with theory (which requires a decline in frequency across the cohort year), instead resorting to non-parametric, non-directional approaches. In this article, the authors address this disconnect, provide an overview of the benefits associated with Poisson regression modelling, and two managerially useful measures for quantifying RAE bias, namely the Indices of Discrimination and Wastage. In a tutorial-like exposition, applications and extensions of this approach are illustrated using data on professional soccer players competing in the top two tiers of the “Big Five” European football leagues in the search to identify paragon clubs, leagues, and countries from which others may learn to mitigate this form of age-discrimination in the talent identification process. As with OLS regression, Poisson regression may include more than one independent variable. In this way we test competing explanations of RAE; control for unwanted sources of covariation; model interaction effects (that different clubs and countries may not all be subject to RAE to the same degree); and test for non-monotonic versions of RAE suggested in the literature. [ABSTRACT FROM AUTHOR]

Based on the entire population of Nobel laureates in science from 1901 to 2017, we show that North America’s rise as global power in science started in the 1920s. Following a transition period (1940s to 1960s), its scientific hegemony was consolidated in the 1970s. Yet since the 2000s, North America’s global leadership in science has come under pressure. In that time, its share of laureates across disciplines dropped, although it has retained its attractiveness as a destination for future laureates from Europe and the Asia-Pacific region. In addition, we find that North America has become apparently less effective since 2010 in transferring capacities for conducting ground-breaking research from one generation of scientists to another. Furthermore, both Europe and the Asia-Pacific region have similarly high shares of newcomer organizations with regard to where prize-winning work is conducted, indicating that these two regions are very active in the inter-organizational competition for scientific talent. Despite this competition, however, we find no support for the rise of a new global center of science. [ABSTRACT FROM AUTHOR]

Background: Folate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis. Objectives: The aim of this study was to assess the relationship between folate/homocysteine concentrations, the functional polymorphisms of folate/homocysteine genes and lung cancer risk among cigarette smokers. Study design: The study included 132 lung cancer patients and 396 controls from northern Poland, matched by sex, age and smoking status. The median cigarette pack-years of smoking among both cases and controls was 30.0. Serum, red blood cell (RBC) folates and serum homocysteine concentrations were measured. The genotypes in selected polymorphic sites of the MTHFR, CBS, SHMT1, MTHFD1, MTRR, MTR, TYMS DHFR, TCN2, and SLC19A1 genes were determined. All study participants underwent scanning with low-dose computed tomography. Results: Serum folate concentrations above the median (> 17.5 nmol/l among the healthy controls) were associated with an increased lung cancer risk (odds ratio [OR], 1.54, 95% confidence intervals [CI], 1.04–2.29, P = 0.031). An analogous trend was observed when the population was analysed after subdivision according to RBC folate concentrations, that is, above a value of 506.5 nmol/l (OR, 1.53; 95% CI, 0.95–2.47; P = 0.084). Additionally, in a subset of women, an increased risk of lung cancer development was associated with the SLC19A1 c.80AA genotype (c.80AA versus GG OR, 3.14; 95% CI, 1.32–7.46; P = P = 0.010). Conclusion: These results suggest that, in the population consisting of heavy smokers, high folate levels add to the cancerogenic effect of smoking. [ABSTRACT FROM AUTHOR]