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The objective of the present work was to evaluate the behavior of osteogenesis of mesenchymal stem cells (MSCs) on a double-layer, protective, and bioactive hybrid coating sterilized by 3 different processes: steam autoclave, hydrogen peroxide plasma, and ethylene oxide. The hybrid coating was obtained from a sol consisting of the silane precursors tetraethoxysilane (TEOS) and methyltriethoxysilane (MTES), applied on a Ti6Al4V substrate. To promote bioactivity, hydroxyapatite (HA) particles were dispersed in a second coating (bioactive layer: TEOS/MTES + HA) applied on the first (TEOS/MTES). The sterilized coatings were evaluated by scanning electron microscopy, wettability, and micrometer roughness. The behavior of hydrolytic degradation was evaluated by the mass variation of the samples and the release of silicon by the technique of high-resolution atomic absorption spectrometry. All coatings presented morphological and superficial alterations after sterilization. Sterilization by ethylene oxide and hydrogen peroxide plasma intensified the hydrolytic degradation of the bioactive coating causing a greater release of silicon. The sterilized hybrid coatings did not show cytotoxicity to MSCs. Adhesion, viability, and osteogenic differentiation were favored on the sterilized coating of hydrogen peroxide plasma, which is opposite to what was observed for the ethylene oxide-sterilized coating.
Neuropsychological tests are important instruments to determine a cognitive profile, giving insight into the etiology of dementia; however, these tests cannot readily be used in culturally diverse, low-educated populations, due to their dependence upon (Western) culture, education, and literacy. In this review we aim to give an overview of studies investigating domain-specific cognitive tests used to assess dementia in non-Western, low-educated populations. The second aim was to examine the quality of these studies and of the adaptations for culturally, linguistically, and educationally diverse populations.
A systematic review was performed using six databases, without restrictions on the year or language of publication.
Forty-four studies were included, stemming mainly from Brazil, Hong Kong, Korea, and considering Hispanics/Latinos residing in the USA. Most studies focused on Alzheimer’s disease (n = 17) or unspecified dementia (n = 16). Memory (n = 18) was studied most often, using 14 different tests. The traditional Western tests in the domains of attention (n = 8) and construction (n = 15), were unsuitable for low-educated patients. There was little variety in instruments measuring executive functioning (two tests, n = 13), and language (n = 12, of which 10 were naming tests). Many studies did not report a thorough adaptation procedure (n = 39) or blinding procedures (n = 29).
Various formats of memory tests seem suitable for low-educated, non-Western populations. Promising tasks in other cognitive domains are the Stick Design Test, Five Digit Test, and verbal fluency test. Further research is needed regarding cross-cultural instruments measuring executive functioning and language in low-educated people.
Cybermentoring refers to virtual peer support in which young people themselves are trained as cybermentors and interact with those needing help and advice (cybermentees) online. This article describes the training in, and implementation of, a cross-national cybermentoring scheme, Beatbullying Europe, developed in the United Kingdom. It involved train-the-trainer workshops for partners and life mentors in six European countries (Italy, Spain, Portugal, Romania, Poland and the Czech Republic) in 2013–2014, followed by training sessions for pupil cybermentors aged 11–16 years. Although BeatBullying went into liquidation in November 2014, the project was largely completed. We (1) report an evaluation of the training of the life mentors and mentors, via questionnaire survey; and (2) discuss findings about the implementation of the scheme and its potential at a cross-national level, via partner interviews during and at the end of the project. The training was found to be highly rated in all respects, and in all six countries involved. The overall consensus from the data available is that there was a positive impact for the schools and professionals involved; some challenges encountered are discussed. The BeatBullying Europe project, despite being unfinished, was promising, and a similar approach deserves further support and evaluation in the future.
The current study aimed to examine the psychometric properties of two geriatric anxiety measures: the Geriatric Anxiety Inventory (GAI) and the Geriatric Anxiety Scale (GAS). This study also aimed to determine the relationships of these measures with two measures of functional ability and impairment: the Barkley Functional Impairment Scale (BFIS) and the Everyday Cognition Scale (E-Cog).
Confirmatory factor analyses (CFA) were used to analyze the factor structures of the GAI and GAS in older adults. Tests for dependent correlations were used to examine the relationship between anxiety scales and functioning.
Amazon’s Mechanical Turk
348 participants (aged 55–85, M= 62.75 (4.8), 66.5% female) with no history of psychosis or traumatic brain injury.
CFAs supported the previously demonstrated bifactor solution for the GAI. For the GAS, the previously demonstrated three-factor model demonstrated a good-to-excellent fit. Given the high correlation between the cognitive and affective factors (r =.89), a bifactor solution was also tested. The bifactor model of the GAS was found to be primarily unidimensional. Tests for dependent correlations revealed that the GAS demonstrated stronger relationships with measures of self-reported functional impairment than the GAI.
The current study provides further psychometric validation of the factor structure of two geriatric anxiety measures in an older adult sample. The results support previous work completed on the GAI and the GAS. The GAS was more strongly correlated with self-reported functional impairment than the GAI, which may reflect differences in content in the two measures.
We provide an update on diagnostic methods for the detection of urogenital schistosomiasis (UGS) in men and highlight that satisfactory urine-antigen diagnostics for UGS lag much behind that for intestinal schistosomiasis, where application of a urine-based point-of-care strip assay, the circulating cathodic antigen (CCA) test, is now advocated. Making specific reference to male genital schistosomiasis (MGS), we place greater emphasis on parasitological detection methods and clinical assessment of internal genitalia with ultrasonography. Unlike the advances made in defining a clinical standard protocol for female genital schistosomiasis, MGS remains inadequately defined. Whilst urine filtration with microscopic examination for ova of Schistosoma haematobium is a convenient but error-prone proxy of MGS, we describe a novel low-cost sampling and direct visualization method for the enumeration of ova in semen. Using exemplar clinical cases of MGS from our longitudinal cohort study among fishermen along the shoreline of Lake Malawi, the portfolio of diagnostic needs is appraised including: the use of symptomatology questionnaires, urine analysis (egg count and CCA measurement), semen analysis (egg count, circulating anodic antigen measurement and real-time polymerase chain reaction analysis) alongside clinical assessment with portable ultrasonography.
Our target article modeled conflict within and between groups as an asymmetric game of strategy and developed a framework to explain the evolved neurobiological, psychological, and sociocultural mechanisms underlying attack and defense. Twenty-seven commentaries add insights from diverse disciplines, such as animal biology, evolutionary game theory, human neuroscience, psychology, anthropology, and political science, that collectively extend and supplement this model in three ways. Here we draw attention to the superordinate structure of attack and defense, and its subordinate means to meet the end of status quo maintenance versus change, and we discuss (1) how variations in conflict structure and power disparities between antagonists can impact strategy selection and behavior during attack and defense; (2) how the positions of attack and defense emerge endogenously and are subject to rhetoric and propaganda; and (3) how psychological and economic interventions can transform attacker-defender conflicts into coordination games that allow mutual gains and dispute resolution.
In this study we determined the probability of predator attacks on livestock around Bardia National Park, Nepal. We conducted semi-structured interviews to explore the patterns and factors affecting livestock losses in four administrative sectors of the Park's buffer zone. We developed models to investigate the overall probability of livestock loss, economic damage caused, and the respondents’ attitudes towards wildlife. The probability of leopard attacks on livestock was much higher (85% of all livestock lost to depredation) than that of tiger attacks (8%), and the northern sector experienced the highest loss of livestock (50% modelled probability of livestock loss) in the buffer zone. Livestock loss was significantly related to the number of livestock owned by respondents, their ethnic group, and village distance to the Park boundary. Economic damage was influenced by buffer zone sector, number of livestock owned, and distance to the Park boundary. Conservation attitudes depended on respondents’ knowledge of wildlife, levels of education and self-sufficiency, and the probability of livestock being killed by leopards. Respondents who were male, highly educated and self-sufficient were most likely to support conservation. Tigers are tolerated based on religious beliefs, and these cultural values, together with the sharing of conservation benefits, facilitate conservation. Leopards, however, are not tolerated in the same way and are the most damaging predators.
A skew brace, as introduced by L. Guarnieri and L. Vendramin, is a set with two group structures interacting in a particular way. When one of the group structures is abelian, one gets back the notion of brace as introduced by W. Rump. Skew braces can be used to construct solutions of the quantum Yang–Baxter equation. In this article, we introduce a notion of action of a skew brace, and show how it leads to solutions of the closely associated reflection equation.
Reduced plasma vitamin D (VD) levels may contribute to excessive white adipose tissue, insulin resistance (IR) and dyslipidaemia. We evaluated the effect of chronic oral VD supplementation on adiposity and insulin secretion in monosodium glutamate (MSG)-treated rats. During their first 5 d of life, male neonate rats received subcutaneous injections of MSG (4 g/kg), while the control (CON) group received saline solution. After weaning, groups were randomly distributed into VD supplemented (12 µg/kg; three times/week) and non-supplemented (NS) rats, forming four experimental groups (n 15 rats/group): CON-NS, CON-VD, MSG-NS and MSG-VD. At 76 d of life, rats were submitted to an oral glucose tolerance test (OGTT; 2 g/kg), and at 86 d, obesity, IR and plasma metabolic parameters were evaluated. Pancreatic islets were isolated for glucose-induced insulin secretion (GIIS), cholinergic insulinotropic response and muscarinic 3 receptor (M3R), protein kinase C (PKC) and protein kinase A (PKA) expressions. Pancreas was submitted to histological analyses. VD supplementation decreased hyperinsulinaemia (86 %), hypertriacylglycerolaemia (50 %) and restored insulin sensibility (89 %) in MSG-VD rats, without modifying adiposity, OGTT or GIIS, compared with the MSG-NS group. The cholinergic action was reduced (57 %) in islets from MSG-VD rats, without any change in M3R, PKA or PKC expression. In conclusion, chronic oral VD supplementation of MSG-obese rats was able to prevent hyperinsulinaemia and IR, improving triacylglycerolaemia without modifying adiposity. A reduced cholinergic pancreatic effect, in response to VD, could be involved in the normalisation of plasma insulin levels, an event that appears to be independent of M3R and its downstream pathways.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron (SMN1) gene. In the phase 1 trial (NCT02122952), SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of 15 symptomatic SMA1 patients (3 at a lower dose [cohort 1] and 12 at the proposed therapeutic dose [cohort 2]). This report describes long-term follow-up study design and data from the phase 1 study. Methods: Patients in the phase 1 study could rollover into a long-term follow-up study (NCT03421977). The primary objective is to collect long-term safety data (serious adverse events, hospitalizations, and adverse events of special interest). Annual follow-up will occur for 15 years. Additionally, patient record transfers from local clinician(s) will be requested. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include physical examination to assess developmental milestones. Results: As of September 27, 2018, the oldest patients are 59.2 (cohort 1) and 52.1 (cohort 2) months old and free of permanent ventilation. Preliminary data, including survival and developmental milestones, will be presented. Conclusions: Patients treated with a one-time dose of AVXS-101 continue to gain strength, develop, and achieve new milestones, demonstrating a long-term, durable response.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of SMN1. Copies of a similar gene (SMN2) modify disease severity. In a phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA patients with two SMN2 copies (2xSMN2) dosed ≤6 months. Because motor neuron loss can be insidious and disease progression is rapid, early intervention is critical. This study evaluates AVXS-101 in presymptomatic SMA newborns. Methods: SPR1NT is a multicenter, open-label, phase 3 study enrolling ≥27 SMA patients with 2–3xSMN2. Asymptomatic infants ≤6 weeks receive a one-time intravenous AVXS-101 infusion (1.1x1014 vg/kg). Safety and efficacy are assessed through study end (18 [2xSMN2] or 24 months [3xSMN2]). Primary outcomes: independent sitting for ≥30 seconds (18 months [2xSMN2]) or assisted standing (24 months [3xSMN2]). Results: From April–September 2018, 7 infants received AVXS-101 (4 female; 6 with 2xSMN2) at ages 8–37 days. Mean baseline CHOP-INTEND score was 41.7 (n=6), which increased by 6.8, 11.0, 18.0, and 22.5 points at day 14 (n=4), month 1 (n=3), 2 (n=3), and 3 (n=2). Updated data available at the time of the congress will be presented. Conclusions: Preliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients.
A mother's nutritional choices while pregnant may have a great influence on her baby's development in the womb and during infancy. There is evidence that what a mother eats during pregnancy interacts with her genes to affect her child's susceptibility to poor health outcomes including childhood obesity, pre-diabetes, allergy and asthma. Furthermore, after what an infant eats can change his or her intestinal bacteria, which can further influence the development of these poor outcomes. In the present paper, we review the importance of birth cohorts, the formation and early findings from a multi-ethnic birth cohort alliance in Canada and summarise our future research directions for this birth cohort alliance. We summarise a method for harmonising collection and analysis of self-reported dietary data across multiple cohorts and provide examples of how this birth cohort alliance has contributed to our understanding of gestational diabetes risk; ethnic and diet-influences differences in the healthy infant microbiome; and the interplay between diet, ethnicity and birth weight. Ongoing work in this birth cohort alliance will focus on the use of metabolomic profiling to measure dietary intake, discovery of unique diet–gene and diet–epigenome interactions, and qualitative interviews with families of children at risk of metabolic syndrome. Our findings to-date and future areas of research will advance the evidence base that informs dietary guidelines in pregnancy, infancy and childhood, and will be relevant to diverse and high-risk populations of Canada and other high-income countries.
The mechanisms underlying both depressive and anxiety disorders remain poorly understood. One of the reasons for this is the lack of a valid, evidence-based system to classify persons into specific subtypes based on their depressive and/or anxiety symptomatology. In order to do this without a priori assumptions, non-parametric statistical methods seem the optimal choice. Moreover, to define subtypes according to their symptom profiles and inter-relations between symptoms, network models may be very useful. This study aimed to evaluate the potential usefulness of this approach.
A large community sample from the Canadian general population (N = 254 443) was divided into data-driven clusters using non-parametric k-means clustering. Participants were clustered according to their (co)variation around the grand mean on each item of the Kessler Psychological Distress Scale (K10). Next, to evaluate cluster differences, semi-parametric network models were fitted in each cluster and node centrality indices and network density measures were compared.
A five-cluster model was obtained from the cluster analyses. Network density varied across clusters, and was highest for the cluster of people with the lowest K10 severity ratings. In three cluster networks, depressive symptoms (e.g. feeling depressed, restless, hopeless) had the highest centrality. In the remaining two clusters, symptom networks were characterised by a higher prominence of somatic symptoms (e.g. restlessness, nervousness).
Finding data-driven subtypes based on psychological distress using non-parametric methods can be a fruitful approach, yielding clusters of persons that differ in illness severity as well as in the structure and strengths of inter-symptom relationships.
The investigation of the glycan repertoire of several organisms has revealed a wide variation in terms of structures and abundance of glycan moieties. Among the parasites, it is possible to observe different sets of glycoconjugates across taxa and developmental stages within a species. The presence of distinct glycoconjugates throughout the life cycle of a parasite could relate to the ability of that organism to adapt and survive in different hosts and environments. Carbohydrates on the surface, and in excretory-secretory products of parasites, play essential roles in host–parasite interactions. Carbohydrate portions of complex molecules of parasites stimulate and modulate host immune responses, mainly through interactions with specific receptors on the surface of dendritic cells, leading to the generation of a pattern of response that may benefit parasite survival. Available data reviewed here also show the frequent aspect of parasite immunomodulation of mammalian responses through specific glycan interactions, which ultimately makes these molecules promising in the fields of diagnostics and vaccinology.
The Strengths and Difficulties Questionnaire (SDQ) has been used in many epidemiological studies to assess adolescent mental health problems, but cross-country comparisons of the self-report SDQ are scarce and so far failed to find a good-fitting, common, invariant measurement model across countries. The present study aims to evaluate and establish a version of the self-report SDQ that allows for a valid cross-country comparison of adolescent self-reported mental health problems.
Using the Health Behaviour in School-aged Children study, the measurement model and measurement invariance of the 20 items of the self-report SDQ measuring adolescent mental health problems were evaluated. Nationally representative samples of 11-, 13- and 15-year old adolescents (n = 33 233) from seven countries of different regions in Europe (Bulgaria, Germany, Greece, the Netherlands, Poland, Romania, Slovenia) were used.
In order to establish a good-fitting and common measurement model, the five reverse worded items of the self-report SDQ had to be removed. Using this revised version of the self-report SDQ, the SDQ-R, partial measurement invariance was established, indicating that latent factor means assessing conduct problems, emotional symptoms, peer relationships problems and hyperactivity-inattention problems could be validly compared across the countries in this study. Results showed that adolescents in Greece scored relatively low on almost all problem subscales, whereas adolescents in Poland scored relatively high on almost all problem subscales. Adolescents in the Netherlands reported the most divergent profile of mental health problems with the lowest levels of conduct problems, low levels of emotional symptoms and peer relationship problems, but the highest levels of hyperactivity-inattention problems.
With six factor loadings being non-invariant, partial measurement invariance was established, indicating that the 15-item SDQ-R could be used in our cross-country comparison of adolescent mental health problems. To move the field of internationally comparative research on adolescent mental health forward, studies should test the applicability of the SDQ-R in other countries in- and outside Europe, continue to develop the SDQ-R as a cross-country invariant measure of adolescent mental health, and examine explanations for the found country differences in adolescent mental health problems.
Introduction: The number of seniors presenting to emergency departments after a fall is increasing. Head injury concerns in this population often leads to a head CT scan. The CT rate among physicians is variable and the reasons for this are unknown. This study examined the role of patient characteristics and country of practice in the decision to order a CT. Methods: This study used a case-based survey of physicians across multiple countries. Each survey included 9 cases pertaining to an 82-year old man who falls. Each case varied in one aspect compared to a base case (aspirin, warfarin, or rivaroxaban use, occipital hematoma, amnesia, dementia, and fall with no head trauma). For each case, participants indicated how “likely” they were to order a head CT scan, measured on a 100-point scale. A response of 80 or more was defined a priori as ‘likely to order a CT scan’. The survey was piloted among emergency residents for feedback on design and comprehension, and was published in French and English. Recruitment was through the Canadian Association of Emergency Physicians, Twitter and CanadiEM. For each case we compared the proportion of physicians who were ‘likely to scan’ with relative to the base case. We also compared the proportion of participants who were ‘likely to scan’ each case in the USA, UK and Australia, relative to Canada. Results: Data was collected from 484 respondents (Canada-308, USA-64, UK-67, Australia-27, and 18 from other countries). Social media distribution limited our ability to estimate of the response rate. Physicians were most likely to scan in the anticoagulation cases (90% likely to order a scan compared to 36% for the base case (p = <0.001)). Other features associated with increased scans were occipital hematoma (48%), multiple falls (68%), and amnesia (68%) (all p < 0.005). Compared to Canada, US physicians were more likely to order CT scans for all cases (p = <0.05). Compared to Canada, UK physicians were significantly less likely to order CT for patients in every case except in the patient with amnesia. Finally, Australian physicians differed from Canada only for the occipital hematoma case where they were significantly more likely to order CT scan. Conclusion: Anticoagulation, amnesia and a history of multiple falls appear to drive the ordering a head CT scan in elderly patients who had fallen. We observed variations in practice between countries. Future clinical decision rules will likely have variable impact on head CT scan rates depending on baseline practice variation.