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Integrated Modular Avionics enables applications of different criticality levels to share the same hardware platform with an established temporal and spatial isolation. On-chip communication systems for such platforms must support different bandwidth and latency requirements of applications while preserving time predictability. In this paper, our concern is a time-predictable on-chip network architecture for targeting applications in mixed-criticality aerospace systems. The proposed architecture introduces a mixed, priority-based and time-division-multiplexed arbitration scheme to accommodate different bandwidth and latency in the same network while preserving worst-case time predictability for end-to-end communication without packet loss. Furthermore, as isolation of erroneous transmission by a faulty application is a key aspect of contingency management, the communication system should support isolation mechanisms to prevent interference. For this reason, a sampling port and isolated sampling buffer-based approach is proposed with a transmission authorisation control mechanism, guaranteeing spatial and temporal isolation between communicating systems.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
South Asian migrants have a higher burden of life-threatening diseases and chronic diseases compared to other ethnic groups. Yet, knowledge gaps remain around their palliative care needs in the host countries. The aim of the review was to present results from a systematic literature review of available international evidence on experiences with and perspectives on palliative care among older South Asian migrants, relatives, and healthcare providers.
A systematic review in accordance with PRISMA guidelines was conducted in February 2018, searching PubMed, CINAHL, PsychINFO, and EMBASE databases. PROSPERO #CRD42018093464. Studies included empirical research, providing international evidence on experiences and perspectives on palliative care of South Asian migrants and were published between 2000 and 2018. Thematic synthesis was used to analyze data.
A total of 30 articles were included: qualitative (24), quantitative (5), and mixed methods (1). Three main themes were discovered: 1) palliative care practice within the family, 2) trust as a precondition of palliative care, and 3) the importance of knowledge and cultural competency. All the themes, to a greater or lesser extent, are related to access to and use of palliative care services by South Asian migrant families.
Significance of results
Involvement of family members in palliative care decision making could improve the satisfaction of South Asian migrant families toward the service. For example, Advanced Care Planning involving family members could be a possible way to engage family members in palliative care decision making. Supportive interventions, e.g. providing knowledge, aimed at patients and their family members might improve knowledge and increase awareness among South Asian migrant families of palliative care. Knowledge gained from this review could be implemented with other ethnic minority groups.
OBJECTIVES/SPECIFIC AIMS: The primary objective of this study was to evaluate the performance of a bone fracture targeted systemically administrable bone anabolic as a potential therapeutic for bone fracture repair. Currently all bone fracture repair therapeutic require local administration during surgery. However, the population that need the most assistance in repair bone fractures are not eligible for surgery. So, it was our goal to design an inject-able therapeutic to assist in bone fracture repair to reduce the invasiveness. The injectable nature of it allows for repair administration of the bone anabolic and for therapeutic effect throughout the entire bone fracture healing process. Targeting it to the bone fracture site reduces the toxicity and increases the efficacy. METHODS/STUDY POPULATION: METHODS To achieve the above objective, a bone mineral-(hydroxyapatite-) targeting oligopeptide was conjugated to the non-signaling end of an engineered parathyroid hormone related protein fragment 1-46 with substitutions at Glu22,25, Leu23,28,31, Aib29, Lys26,30 (ePTHrP). The negatively charged oligopeptide has been shown to target raw hydroxyapatite with remarkable specificity, while the attached PTHrP has been demonstrated to induce sustained and accelerated bone growth under control of endogenous morphogenic regulatory factors. The conjugate’s specificity arises from the fact that raw hydroxyapatite is only exposed whenever a bone is fractured, surgically cut, grafted, or induced to undergo accelerated remodeling. The hydroxyapatite-targeted conjugate can therefore be administered systemically (i.e. without invasive surgery or localized injection) and still accumulate on the exposed hydroxyapatite at the fracture site where it accelerates the healing process Murine in vivo experiments were conducted on female Swiss Webster mice (10 per group). Femoral fractures were induced with a 3-point bending device and stabilized. Mice were dosed with 3 nmol/kg/d of targeted-ePTHrP, non-conjugated (free) ePTHrP, or saline. Following a 4-week study, fracture callus densities were measured using microCT. Canine in vivo experiments were conducted on 1-year-old male beagles. Beagles underwent a 10 mm bilateral ulnar ostectomy. Two dogs in the treatment group and Three dogs in the control group were dosed daily with either targeted-ePTHrP 0.5nmol/kg/d or saline respectively. Dogs were x-rayed weekly for the first 6 weeks and then every other week thereafter. One tailed ANOVA followed by Dunnett’s post-hoc test was used to establish significance. All animal experiments were conducted as described in approved IACUC protocols. P<0.05 was considered significant. RESULTS/ANTICIPATED RESULTS: RESULTS SECTION: In the murine studies we observed a marked increase in fracture callus size and a 2-fold increase in bone deposition was observed in the targeted-ePTHrP group over the saline group (P<0.01). A significant doubling in bone density was also observed. Targeted-ePTHrP group fractured femurs were able to achieve their pre-fracture strength as early as 3 weeks compared to 9 weeks in the saline mice representing a 66% reduction in healing time. In the canine studies, we observe a significantly higher closure of the ostectomy gap than saline controls (P<0.05). In addition, no significant differences in weight are observed in the treatment vs. saline controls. No significant difference between the control group and treatment groups was found in a histological investigation of the organs. DISCUSSION/SIGNIFICANCE OF IMPACT: DISCUSSION: Although attempts have been made in developing a systemically administered fracture therapeutic for fracture repair, i.e. teriparatide, to date, no such anabolics have been approved for this use. In these studies there is evidence that anabolic activity was occurring at the fracture site, but at a level that did not meet FDA required end-points.2 It is plausible that if sufficient drug were to be delivered to a fracture site then improved fracture repair would be possible. In previous studies, we demonstrated fracture specific accumulation bone anabolics can be achieved by modifying the drug with acidic oligopeptides.3 Here, by modifying a safe, clinically proven, parathyroid hormone receptor agonist with an acidic oligopeptide we observe improved bone deposition and strength in mice. Furthermore, when administered to canine critical sized defect ostectomies, a more relevant and difficult model, we observe improved ostectomy closure. CLINICAL RELEVANCE:: The ability to accelerate bone fracture repair is a fundamental need that has not been addressed by conventional methods. By targeting bone anabolic agents to bone fractures, we can deliver sufficient concentrations of anabolic agent to the fracture site to accelerate healing, thus avoiding surgery and any ectopic bone growth associated with locally-applied bone anabolic agents.
Using hermeneutic phenomenology to aid the reader ‘experience’ the data collected, this study reports on 18 college students, 4 staff members and the author's trip to a remote island on the Great Barrier Reef. It is a story of the (re)discovery of the social and natural ecologies that bind us together, and of how explicit teaching and learning about these ecologies can make a difference to young people's abilities to consciously be part of, contribute to, and sustain these ecologies. A grounded theory of five dimensions of giving (to self, others, communities, environment, and the whole) is offered as a beginning framework from which to imbue teaching and learning with meaning and social concern.
The Association of Polar Early Career Scientists (APECS) is an important legacy of the International Polar Year (IPY). APECS continues to foster engagement in education, outreach and communication (EOC) activities relating to the polar regions and provide training for early career researchers (ECRs). We highlight opportunities for training, leadership and skills development, such as the annual Polar Weeks and Antarctica Day celebrations. Participation and engagement in EOC activities actively contributes to career development by enabling ECRs to develop valuable soft skills such as networking, communication and interdisciplinary knowledge. A pilot survey on EOC engagement highlighted that those who organise events also gain leadership skills such as team management. We discuss several factors contributing to the success of APECS in training the next generation of polar leaders. These include the geographical rather than discipline-specific focus of the organisation, utilisation of online resources, including social media, and the strong links with partner organisations. These examples demonstrate how the EOC legacy of IPY has continued due to APECS’ targeted efforts to create EOC opportunities and provide skills and leadership training for ECRs.
The chemical enrichment of the Universe is considerably affected by the contribution of cool evolved stars. We studied the O-rich star R Peg and the C-rich star V Oph, using respectively the VLTI/GRAVITY and VLTI/MIDI instruments. We interpret the data using grids of 1-D and 3-D dynamic model atmospheres.
The Holocene climatic optimum was a period 8–5 kyr ago when annual mean surface temperatures in Greenland were 2–3°C warmer than present-day values. However, this warming left little imprint on commonly used temperature proxies often used to derive the climate forcing for simulations of the past evolution of the Greenland ice sheet. In this study, we investigate the evolution of the Greenland ice sheet through the Holocene when forced by different proxy-derived temperature histories from ice core records, focusing on the effect of sustained higher surface temperatures during the early Holocene. We find that the ice sheet retreats to a minimum volume of ~0.15–1.2 m sea-level equivalent smaller than present in the early or mid-Holocene when forcing an ice-sheet model with temperature reconstructions that contain a climatic optimum, and that the ice sheet has continued to recover from this minimum up to present day. Reconstructions without a warm climatic optimum in the early Holocene result in smaller ice losses continuing throughout the last 10 kyr. For all the simulated ice-sheet histories, the ice sheet is approaching a steady state at the end of the 20th century.
Significant increases in excess all-cause mortality, particularly in the elderly, were observed during the winter of 2014/15 in England. With influenza A(H3N2) the dominant circulating influenza A subtype, this paper determines the contribution of influenza to this excess controlling for weather. A standardised multivariable Poisson regression model was employed with weekly all-cause deaths the dependent variable for the period 2008–2015. Adjusting for extreme temperature, a total of 26 542 (95% CI 25 301–27 804) deaths in 65+ and 1942 (95% CI 1834–2052) in 15–64-year-olds were associated with influenza from week 40, 2014 to week 20, 2015. This is compatible with the circulation of influenza A(H3N2). It is the largest estimated number of influenza-related deaths in England since prior to 2008/09. The findings highlight the potential health impact of influenza and the important role of the annual influenza vaccination programme that is required to protect the population including the elderly, who are vulnerable to a severe outcome.
Textual data are plagued by underreporting bias. For example, news sources often fail to report human rights violations. Cook et al. propose a multi-source estimator to gauge, and to account for, the underreporting of state repression events within human codings of news texts produced by the Agence France-Presse and Associated Press. We evaluate this estimator with Monte Carlo experiments, and then use it to compare the prevalence and seriousness of underreporting when comparable texts are machine coded and recorded in the World-Integrated Crisis Early Warning System dataset. We replicate Cook et al.’s investigation of human-coded state repression events with our machine-coded events, and validate both models against an external measure of human rights protections in Africa. We then use the Cook et al. estimator to gauge the seriousness and prevalence of underreporting in machine and human-coded event data on human rights violations in Colombia. We find in both applications that machine-coded data are as valid as human-coded data.
Studies of the association between pre-deployment cognitive ability and post-deployment post-traumatic stress disorder (PTSD) have shown mixed results.
To study the inflence of pre-deployment cognitive ability on PTSD symptoms 6–8 months post-deployment in a large population while controlling for pre-deployment education and deployment-related variables.
Study linking prospective pre-deployment conscription board data with post-deployment self-reported data in 9695 Danish Army personnel deployed to different war zones in 1997–2013. The association between pre-deployment cognitive ability and post-deployment PTSD was investigated using repeated-measure logistic regression models. Two models with cognitive ability score as the main exposure variable were created (model 1 and model 2). Model 1 was only adjusted for pre-deployment variables, while model 2 was adjusted for both pre-deployment and deployment-related variables.
When including only variables recorded pre-deployment (cognitive ability score and educational level) and gender (model 1), all variables predicted post-deployment PTSD. When deployment-related variables were added (model 2), this was no longer the case for cognitive ability score. However, when educational level was removed from the model adjusted for deployment-related variables, the association between cognitive ability and post-deployment PTSD became significant.
Pre-deployment lower cognitive ability did not predict post-deployment PTSD independently of educational level after adjustment for deployment-related variables.
Fluid–structure interactions are ubiquitous in nature and technology. However, the systems are often so complex that numerical simulations or ad hoc assumptions must be used to gain insight into the details of the complex interactions between the fluid and solid mechanics. In this paper, we present experiments and theory on viscous flow in a simple bioinspired soft valve which illustrate essential features of interactions between hydrodynamic and elastic forces at low Reynolds numbers. The set-up comprises a sphere connected to a spring located inside a tapering cylindrical channel. The spring is aligned with the central axis of the channel and a pressure drop is applied across the sphere, thus forcing the liquid through the narrow gap between the sphere and the channel walls. The sphere’s equilibrium position is determined by a balance between spring and hydrodynamic forces. Since the gap thickness changes with the sphere’s position, the system has a pressure-dependent hydraulic resistance. This leads to a nonlinear relation between applied pressure and flow rate: flow initially increases with pressure, but decreases when the pressure exceeds a certain critical value as the gap closes. To rationalize these observations, we propose a mathematical model that reduced the complexity of the flow to a two-dimensional lubrication approximation. A closed-form expression for the pressure drop/flow rate is obtained which reveals that the flow rate
depends on the pressure drop
, sphere radius
, gap thickness
, and viscosity
, where the critical pressure
scales with the spring constant
. These predictions compared favourably to the results of our experiments with no free parameters.
Berseem clover (Trifolium alexandrinum L.) is an important forage legume and is the primary winter forage crop in Pakistan. There are significant gaps in yield potential among varieties of berseem clover, as well as yields obtained at research stations and on-farm. To address this problem a survey of farmers was undertaken in the districts of Kasur and Okara, Punjab, Pakistan to determine the level of knowledge and understanding of berseem forage cultivation and seed production. The study comprised 44% smallholder (<3 ha), 26% medium (3–5 ha) and 30% large farmers (>5 ha) with average age of 42 years. Most farmers had little or no knowledge of the role of seed quality, inoculation with rhizobium, pollination, fertiliser use, irrigation management and the importance of forage nutritional value in improving livestock productivity. Most farmers (56%) had received no input from the government or private sector to improve forage production, relying instead on traditional knowledge. Knowledge of the importance of land preparation (95%), sowing rate (98%) and insect and pest management (75%) was higher than seed selection and fertilisation. Adoption of improved varieties (3%) and production technologies (14%) was low due to various constraints including ignorance, high cost of inputs, lack of availability of inputs in the market and a perceived high level of financial risk. Almost 100% of the respondents agreed that seed of improved varieties was a pre-requisite for higher forage and seed production as well as essential to start village-based forage seed enterprises.
The spread of African swine fever virus (ASFV) threatens to reach further parts of Europe. In countries with a large swine production, an outbreak of ASF may result in devastating economic consequences for the swine industry. Simulation models can assist decision makers setting up contingency plans. This creates a need for estimation of parameters. This study presents a new analysis of a previously published study. A full likelihood framework is presented including the impact of model assumptions on the estimated transmission parameters. As animals were only tested every other day, an interpretation was introduced to cover the weighted infectiousness on unobserved days for the individual animals (WIU). Based on our model and the set of assumptions, the within- and between-pen transmission parameters were estimated to βw = 1·05 (95% CI 0·62–1·72), βb = 0·46 (95% CI 0·17–1·00), respectively, and the WIU = 1·00 (95% CI 0–1). Furthermore, we simulated the spread of ASFV within a pig house using a modified SEIR-model to establish the time from infection of one animal until ASFV is detected in the herd. Based on a chosen detection limit of 2·55% equivalent to 10 dead pigs out of 360, the disease would be detected 13–19 days after introduction.
The surveillance of Clostridium difficile (CD) in Denmark consists of laboratory based data from Departments of Clinical Microbiology (DCMs) sent to the National Registry of Enteric Pathogens (NREP). We validated a new surveillance system for CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects microbiological test results from all Danish DCMs. We built an algorithm to identify positive test results for CD recorded in MiBa. A CD case was defined as a person with a positive culture for CD or PCR detection of toxin A and/or B and/or binary toxin. We compared CD cases identified through the MiBa-based surveillance with those reported to NREP and locally in five DCMs representing different Danish regions. During 2010–2014, NREP reported 13 896 CD cases, and the MiBa-based surveillance 21 252 CD cases. There was a 99·9% concordance between the local datasets and the MiBa-based surveillance. Surveillance based on MiBa was superior to the current surveillance system, and the findings show that the number of CD cases in Denmark hitherto has been under-reported. There were only minor differences between local data and the MiBa-based surveillance, showing the completeness and validity of CD data in MiBa. This nationwide electronic system can greatly strengthen surveillance and research in various applications.
Several studies have examined whether use of substances can cause schizophrenia. However, due to methodological limitations in the existing literature (e.g. selection bias and lack of adjustment of co-abuse) uncertainties still remain. We aimed to investigate whether substance abuse increases the risk of developing schizophrenia, addressing some of these limitations.
The longitudinal, nationwide Danish registers were linked to establish a cohort of 3 133 968 individuals (105 178 673 person-years at risk), identifying 204 505 individuals diagnosed with substance abuse and 21 305 diagnosed with schizophrenia. Information regarding substance abuse was extracted from several registers and did not include psychotic symptoms caused by substance abuse in the definition. This resulted in a large, generalizable sample of exposed individuals. The data was analysed using Cox regression analyses, and adjusted for calendar year, gender, urbanicity, co-abuse, other psychiatric diagnosis, parental substance abuse, psychiatric history, immigration and socioeconomic status.
A diagnosis of substance abuse increased the overall risk of developing schizophrenia [hazard ratio (HR) 6.04, 95% confidence interval (CI) 5.84–6.26]. Cannabis (HR 5.20, 95% CI 4.86–5.57) and alcohol (HR 3.38, 95% CI 3.24–3.53) presented the strongest associations. Abuse of hallucinogens (HR 1.86, 95% CI 1.43–2.41), sedatives (HR 1.68, 95% CI 1.49–1.90), and other substances (HR 2.85, 95% CI 2.58–3.15) also increased the risk significantly. The risk was found to be significant even 10–15 years subsequent to a diagnosis of substance abuse.
Our results illustrate robust associations between almost any type of substance abuse and an increased risk of developing schizophrenia later in life.
Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression.
We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol.
We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47–2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04–1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94–1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81–1.32).
Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
Dietary long-chain n-3 PUFA (n-3 LCPUFA) in infancy may have long-term effects on lifestyle disease risk. The present follow-up study investigated whether maternal fish oil (FO) supplementation during lactation affected growth and blood pressure in adolescents and whether the effects differed between boys and girls. Mother–infant pairs (n 103) completed a randomised controlled trial with FO (1·5 g/d n-3 LCPUFA) or olive oil (OO) supplements during the first 4 months of lactation; forty-seven mother–infant pairs with high fish intake were followed-up for 4 months as the reference group. We also followed-up 100 children with assessment of growth, blood pressure, diet by FFQ and physical activity by 7-d accelerometry at 13·5 (sd 0·4) years of age. Dried whole-blood fatty acid composition was analysed in a subgroup (n 49). At 13 years of age, whole-blood n-3 LCPUFA, diet, physical activity and body composition did not differ between the three groups. The children from the FO group were 3·4 (95 % CI 0·2, 6·6) cm shorter (P=0·035) than those from the OO group, and tended to have less advanced puberty (P=0·068), which explained the difference in height. There was a sex-specific effect on diastolic blood pressure (Psex×group=0·020), which was driven by a 3·9 (95 % CI 0·2, 7·5) mmHg higher diastolic blood pressure in the FO compared with the OO group among boys only (P=0·041). Our results indicate that early n-3 LCPUFA intake may reduce height in early adolescence due to a delay in pubertal maturation and increase blood pressure specifically in boys, thereby tending to counteract existing sex differences.
Technological advancements in remote sensing and telemetry provide opportunities for assessing the effects of expanding extractive industries on animal populations. Here, we illustrate the applicability of resource selection functions (RSFs) for modelling wildlife habitat selection on industrially-disturbed landscapes. We used grizzly bears (Ursus arctos) from a threatened population in Canada and surface mining as a case study. RSF predictions based on GPS radiocollared bears (nduring mining = 7; npost mining = 9) showed that males and solitary females selected areas primarily outside mineral surface leases (MSLs) during active mining, and conversely inside MSLs after mine closure. However, females with cubs selected areas within compared to outside MSLs irrespective of mining activity. Individual variability was pronounced, although some environmental- and human-related variables were consistent across reproductive classes. For males and solitary females, regional-scale RSFs yielded comparable results to site-specific models, whereas for females with cubs, modelling the two scales produced divergent results. While mine reclamation may afford opportunities for bear persistence, managing public access will likely decrease the risk of human-caused bear mortality. RSFs are powerful tools that merit widespread use in quantitative and visual investigations of wildlife habitat selection on industrially-modified landscapes, using Geographic Information System layers that precisely characterize site-specific conditions.