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Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Community advisory boards (CABs) are a valuable strategy for engaging and partnering with communities in research. Eighty-nine percent of Clinical and Translational Science Awardees (CTSA) responding to a 2011 survey reported having a CAB. CTSAs’ experiences with CABs are valuable for informing future practice. This study was conducted to describe common CAB implementation practices among CTSAs; document perceived benefits, challenges, and contributions; and examine their progress toward desirable outcomes. A cross-CTSA collaborative team collected survey data from respondents representing academic and/or community members affiliated with CTSAs with CABs. Data representing 44 CTSAs with CABs were analyzed using descriptive statistics. A majority of respondents reported practices reflecting respect for CAB members’ expertise and input such as compensation (75%), advisory purview beyond their CTSA’s Community Engagement program (88%), and influence over CAB operations. Three-quarters provide members with orientation and training on roles and responsibilities and 89% reported evaluating their CAB. Almost all respondents indicated their CTSA incorporates the feedback of their CABs to some degree; over half do so a lot or completely. This study profiles practices that inform CTSAs implementing a CAB and provide an evaluative benchmark for those with existing CABs.
This trial compared weight loss outcomes over 14 weeks in women showing low- or high-satiety responsiveness (low- or high-satiety phenotype (LSP, HSP)) measured by a standardised protocol. Food preferences and energy intake (EI) after low and high energy-density (LED, HED) meals were also assessed. Ninety-six women (n 52 analysed; 41·24 (SD 12·54) years; 34·02 (sd 3·58) kg/m2) engaged in one of two weight loss programmes underwent LED and HED laboratory test days during weeks 3 and 12. Preferences for LED and HED food (Leeds Food Preference Questionnaire) and ad libitum evening meal and snack EI were assessed in response to equienergetic LED and HED breakfasts and lunches. Weekly questionnaires assessed control over eating and ease of adherence to the programme. Satiety quotients based on subjective fullness ratings post LED and HED breakfasts determined LSP (n 26) and HSP (n 26) by tertile splits. Results showed that the LSP lost less weight and had smaller reductions in waist circumference compared with HSP. The LSP showed greater preferences for HED foods, and under HED conditions, consumed more snacks (kJ) compared with HSP. Snack EI did not differ under LED conditions. LSP reported less control over eating and reported more difficulty with programme adherence. In conclusion, low-satiety responsiveness is detrimental for weight loss. LED meals can improve self-regulation of EI in the LSP, which may be beneficial for longer-term weight control.
In the UK, 11.8% of expectant mothers undergo an elective caesarean section (ELCS) representing 92 000 births per annum. It is not known to what extent this procedure has an impact on mental well-being in the longer term.
To determine the prevalence and postpartum progression of anxiety and depression symptoms in women undergoing ELCS in Wales.
Prevalence of depression and anxiety were determined in women at University Hospital Wales (2015–16; n = 308) through completion of the Edinburgh Postnatal Depression Scale (EPDS; ≥13) and State-Trait Anxiety Inventory (STAI; ≥40) questionnaires 1 day prior to ELCS, and three postpartum time points for 1 year. Maternal characteristics were determined from questionnaires and, where possible, confirmed from National Health Service maternity records.
Using these criteria the prevalence of reported depression symptoms was 14.3% (95% CI 10.9–18.3) 1 day prior to ELCS, 8.0% (95% CI 4.2–12.5) within 1 week, 8.7% (95% CI 4.2–13.8) at 10 weeks and 12.4% (95% CI 6.4–18.4) 1 year postpartum. Prevalence of reported anxiety symptoms was 27.3% (95% CI 22.5–32.4), 21.7% (95% CI 15.8–28.0), 25.3% (95% CI 18.5–32.7) and 35.1% (95% CI 26.3–44.2) at these same stages. Prenatal anxiety was not resolved after ELCS more than 1 year after delivery.
Women undergoing ELCS experience prolonged anxiety postpartum that merits focused clinical attention.
Epigenetic DNA modifications in genes related to the hypothalamic–pituitary–adrenal (HPA) axis are discussed as a mechanism underlying the association between prenatal depression and altered child HPA activity. In a longitudinal study, DNA methylation changes related to prenatal depressive symptoms were investigated in 167 children aged 6 to 9 years. At six candidate genes, 126 cytosine–guanine dinucleotides were considered without correcting for multiple testing due to the exploratory nature of the study. Further associations with the basal child HPA activity were examined. Children exposed to prenatal depressive symptoms exhibited lower bedtime cortisol (p = .003, ηp2 = 0.07) and a steeper diurnal slope (p = .023, ηp2 = 0.06). For total cortisol release, prenatal exposure was related to lower cortisol release in boys, and higher release in girls. Furthermore, prenatal depressive symptoms were associated with altered methylation in the glucocorticoid receptor gene (NR3C1), the mineralocorticoid receptor gene (NR3C2), and the serotonin receptor gene (SLC6A4), with some sex-specific effects (p = .012–.040, ηp2 = 0.03–0.04). In boys, prenatal depressive symptoms predicted bedtime cortisol mediated by NR3C2 methylation, indirect effect = –0.07, 95% confidence interval [–0.16, –0.02]. Results indicate relations of prenatal depressive symptoms to both child basal HPA activity and DNA methylation, partially fitting a mediation model, with exposed boys and girls being affected differently.
Effective translational research requires engagement and collaboration between communities, researchers, and practitioners. We describe a community scientist academy (CSA) developed at the suggestion of our Clinical and Translational Science Awards’ (CTSA) community advisory board to engage and capacitate community members by (1) increasing community members’ and patients’ understanding about the research process and (2) increasing their access to opportunities to influence and participate in research. A joint CTSA/community planning committee developed this 8-hour workshop including sessions on: (1) research definitions and processes; (2) study design; (3) study implementation; and (4) ways to get involved in research. The workshop format includes interactive exercises, content slides and videos, and researcher and community presenters.
Community-based information sessions allowed assessment of community interest before piloting. Two pilots of the CSA were conducted with community members and patients. Participant data and a pre/post knowledge and feedback survey provide evaluation data.
The pilot included 24 diverse participants, over half of whom had not previously participated in research. Evaluation data suggest knowledge gains. Post-CSA, one-third have reviewed CTSA pilot grants and over 80% want to attend further training.
The CSA can demystify the research process for those underrepresented in research and facilitate their engagement and influence within CTSAs.
Excavations at the Latin city of Gabii in 2012–15 conducted by the Gabii Project have uncovered a monumental building complex, hitherto known only very partially from previous excavations in the 1990s. Organized on a series of three artificial terraces that regularized the slope of the volcanic terrain, it measures some 60 m by 35 m, occupying an entire city-block. It is prominently situated at one of the most central locations within the city, on the main urban thoroughfare at the important intersection of the roads from Tibur, Praeneste and Rome. Stratigraphic evidence and construction techniques date the original phase of the building to the mid-third century BC. This report focuses on a contextualization and description of this first, mid-Republican phase and offers a preliminary interpretation of this complex as a public building, with spaces designed for a variety of functions: bathing, public feasting, and ritual activity. If this is correct, it now represents one of the very few examples of public buildings other than temples and fortifications known from the mid-Republican period, and sheds important light on the development of Roman architecture and of the Latin cities in a crucial and obscure period.
Recent modelling estimates up to two-thirds of new HIV infections among men who have sex with men occur within partnerships, indicating the importance of dyadic HIV prevention efforts. Although new interventions are available to promote dyadic health-enhancing behaviours, minimal research has examined what factors influence partners’ mutual engagement in these behaviours, a critical component of intervention success. Actor-partner interdependence modelling was used to examine associations between relationship characteristics and several dyadic outcomes theorised as antecedents to health-enhancing behaviours: planning and decision making, communication, and joint effort. Among 270 male-male partnerships, relationship satisfaction was significantly associated with all three outcomes for actors (p = .02, .02, .06 respectively). Latino men reported poorer planning and decision making (actor p = .032) and communication (partner p = .044). Alcohol use was significantly and negatively associated with all outcomes except actors’ planning and decision making (actors: p = .11, .038, .004 respectively; partners: p = .03, .056, .02 respectively). Having a sexual agreement was significantly associated with actors’ planning and decision making (p = .007) and communication (p = .008). Focusing on interactions between partners produces a more comprehensive understanding of male couples’ ability to engage in health-enhancing behaviours. This knowledge further identifies new and important foci for the tailoring of dyadic HIV prevention and care interventions.
This work decribes the enhancement of the electrical figures of merit of an Electrolyte Gated Thin-Film Transistor (EG-TFT) comprising a nanocomposite of n-type tungsten disulfide (WS2) nanotubes (NTs) dispersed in a regio-regular p-type poly(3-hexylthiophene-2,5-diyl) (P3HT) polymeric matrix. P3HT/WS2 nanocomposites loaded with different concentrations of NTs, serving as EG-TFTs electronic channel materials have been studied and the formulation has been optimized. The resulting EG-TFTs figures of merit (field-effect mobility, threshold voltage and on-off ratio) are compared with those of the device comprising a bare P3HT semiconducting layer. The optimized P3HT/WS2 nanocomposite, comprising a 60% by weight of NTs, results in an improvement of all the elicited figures of merit with a striking ten-fold increase in the field-effect mobility and the on/off ratio along with a sizable enhancement of the in-water operational stability of the device.
West Antarctic climate and surface mass balance (SMB) records are sparse. To fill this gap, regional atmospheric climate modelling is useful, providing that such models are employed at sufficiently high horizontal resolution and coupled with a snow model. Here we present the results of a high-resolution (5.5 km) regional atmospheric climate model (RACMO2) simulation of coastal West Antarctica for the period 1979–2015. We evaluate the results with available in situ weather observations, remote-sensing estimates of surface melt, and SMB estimates derived from radar and firn cores. Moreover, results are compared with those from a lower-resolution version, to assess the added value of the resolution. The high-resolution model resolves small-scale climate variability invoked by topography, such as the relatively warm conditions over ice-shelf grounding zones, and local wind speed accelerations. Surface melt and SMB are well reproduced by RACMO2. This dataset will prove useful for picking ice core locations, converting elevation changes to mass changes, for driving ocean, ice-sheet and coupled models, and for attributing changes in the West Antarctic Ice Sheet and shelves to changes in atmospheric forcing.
Work on thermal pools at Poggetti Vecchi in Grosseto, Italy, exposed an up to 3-meter-thick succession of seven sedimentary units. Unit 2 in the lower portion of the succession contained vertebrate bones, mostly of the straight-tusked elephant, Palaeoloxodon antiquus, commingled with stone, bone, and wooden tools. Thermal carbonates overlying Unit 2 are radiometrically dated to the latter part of the middle Pleistocene. This time span indicates that early Neanderthals produced the human artifacts from Poggetti Vecchi. The elephant bones belong to seven individuals of different ages. Sedimentary facies analysis and paleoecological evidence suggest a narrow lacustrine-palustrine embayment affected by water-level fluctuations and, at times, by hydrothermal water. Cyclic lake-level variations were predominantly forced by the rapid climatic fluctuations that occurred at Marine Isotope Stage (MIS) 6–7 transition and throughout the MIS 6. Possibly an abrupt, intense, and protracted cold episode during the onset of MIS 6 led to the sudden death of the elephants, which formed an unexpected food resource for the humans of the area. The Poggetti Vecchi site adds new information on the behavioral plasticity and food procurement strategies that early Neanderthals were able to develop in Italy during the middle to the late Pleistocene transition.
Low heart rate variability (HRV) predicts sudden cardiac death. Long-chain (LC) n-3 PUFA (C20–C22) status is positively associated with HRV. This cross-sectional study investigated whether vegans aged 40–70 years (n 23), whose diets are naturally free from EPA (20 : 5n-3) and DHA (22 : 6n-3), have lower HRV compared with omnivores (n 24). Proportions of LC n-3 PUFA in erythrocyte membranes, plasma fatty acids and concentrations of plasma LC n-3 PUFA-derived lipid mediators were significantly lower in vegans. Day-time interbeat intervals (IBI), adjusted for physical activity, age, BMI and sex, were significantly shorter in vegans compared with omnivores (mean difference −67 ms; 95 % CI −130, −3·4, P<0·05), but there were no significant differences over 24 h or during sleep. Vegans had higher overall HRV, measured as 24 h standard deviation of normal-to-normal intervals (SDNN) (mean adjusted difference 27 ms; 95 % CI 1, 52, P=0·039). Conversely, vegans presented with decreased 8 h day-time HRV: mean adjusted difference in SDNN −20 ms; 95 % CI −37, −3, P=0·021, with no differences during nocturnal sleep. Day-time parameters of beat-to-beat HRV (root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals, percentage of adjacent normal-to-normal intervals that differ by >50 % and high-frequency power) were similarly lower in vegans, with no differences during sleep. In conclusion, vegans have higher 24 h SDNN, but lower day-time HRV and shorter day-time IBI relative to comparable omnivores. Vegans may have reduced availability of precursor markers for pro-resolving lipid mediators; it remains to be determined whether there is a direct link with impaired cardiac function in populations with low-n-3 status.
The phase identification of a polycrystalline mixture by X-ray powder diffraction data is often requested for studying materials interesting to different scientific and technological fields: chemistry, pharmaceutics, mineralogy, archeometry, forensic science, etc. The availability of user friendly computer programs, able to carry out qualitative phase analysis in efficient and possibly automatic way, is extremely useful to the scientific community involved in powder diffraction. QUALX2.0, the evolution of QUALX, is a freely distributed software for qualitative phase analysis. Based on the traditional search–match method, it is able to manage both a commercial database (PDF-2 maintained by ICDD), and a freely available database (POW_COD generated by the structure information contained in the Crystallography Open Database). QUALX2.0 is continuously improved in terms of computing and graphic tools. Correspondingly, the database POW_COD is suitably modified to make efficient the operations of search. The search–match approach can be facilitated by the use of restraints, when available, involving the chemical composition, the kind of compound(s) (e.g., organic, inorganic, etc.), the symmetry (space group, crystal system), the unit-cell parameters and/or volume, the crystal properties (measured and/or calculated crystal density, crystal color). An outline of the main features of QUALX2.0 and an example of application is described.
Illegal killing/taking of birds is a growing concern across the Mediterranean. However, there are few quantitative data on the species and countries involved. We assessed numbers of individual birds of each species killed/taken illegally in each Mediterranean country per year, using a diverse range of data sources and incorporating expert knowledge. We estimated that 11–36 million individuals per year may be killed/taken illegally in the region, many of them on migration. In each of Cyprus, Egypt, Italy, Lebanon and Syria, more than two million birds may be killed/taken on average each year. For species such as Blackcap Sylvia atricapilla, Common Quail Coturnix coturnix, Eurasian Chaffinch Fringilla coelebs, House Sparrow Passer domesticus and Song Thrush Turdus philomelos, more than one million individuals of each species are estimated to be killed/taken illegally on average every year. Several species of global conservation concern are also reported to be killed/taken illegally in substantial numbers: Eurasian Curlew Numenius arquata, Ferruginous Duck Aythya nyroca and Rock Partridge Alectoris graeca. Birds in the Mediterranean are illegally killed/taken primarily for food, sport and for use as cage-birds or decoys. At the 20 worst locations with the highest reported numbers, 7.9 million individuals may be illegally killed/taken per year, representing 34% of the mean estimated annual regional total number of birds illegally killed/taken for all species combined. Our study highlighted the paucity of data on illegal killing/taking of birds. Monitoring schemes which use systematic sampling protocols are needed to generate increasingly robust data on trends in illegal killing/taking over time and help stakeholders prioritise conservation actions to address this international conservation problem. Large numbers of birds are also hunted legally in the region, but specific totals are generally unavailable. Such data, in combination with improved estimates for illegal killing/taking, are needed for robustly assessing the sustainability of exploitation of birds.
This work is focused on the laser ablation synthesis of Cu/Ag nanocolloids in chitosan-based aqueous solution using a flow cell. A two-step process using femtosecond laser pulses was applied to consecutively ablate each metal. As-prepared nanomaterials were morphologically and spectroscopically characterized by Transmission Electron Microscopy, UV-Vis and X-ray Photoelectron spectroscopies. Application of Cu/Ag nanomaterials is envisaged as antibacterial materials for food packaging.
Ultrasensitive biosensors based on bottom gate organic field-effect transistors can be developed by depositing a functional biological (protein) interlayer directly on the silicon oxide gate dielectric and underneath the organic semiconductor film. However, the deposition methods for assembling the protein biological recognition layer can affect the biosensor analytical performances for the target analyte detection. Here, spin-coating and layer-by-layer techniques were considered as different approaches for streptavidin protein deposition. X-ray photoelectron spectroscopy (XPS) was systematically used in the non-destructive parallel angle resolved mode to characterize the multilayer device at each step of its assembly to gain information on elemental depth profiles. Scanning electron and scanning Helium ion microscopies gave information about stacked layer structure and morphology corroborating XPS results.