Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD

A case study involving continuous system methods of inverse simulation for an unmanned aerial vehicle application

Inverse simulation allows input time histories to be found that generate specified outputs for non-linear dynamic models in cases where analytical methods of inversion present difficulties. The two approaches considered involve continuous system simulation principles. One is an approximate differentiation method while the second involves feedback principles. These approaches are compared for a non-linear six-degrees-of-freedom flight-mechanics model of a fixed-wing unmanned aerial vehicle incorporating actuator sub-models with saturation and rate limits. Additional insight is provided through analysis of a linearised version of the vehicle model. It is concluded that both the continuous system simulation methods for finding inverse solutions, for the type of application described in this paper, provide a useful alternative to more conventional iterative methods of inverse simulation based on discrete models. In many cases, including those involving hard non-linearities in control surface actuator sub-systems, they allow issues of vehicle handling and manoeuvrability to be addressed in a more direct fashion than is possible using conventional simulation methods alone

Glucocorticoid maturation of mitochondrial respiratory capacity in skeletal muscle before birth

In adults, glucocorticoids act to match the supply and demand for energy during physiological challenges, partly through actions on tissue mitochondrial oxidative phosphorylation (OXPHOS) capacity. However, little is known about the role of the natural prepartum rise in fetal glucocorticoid concentrations in preparing tissues for the increased postnatal energy demands. This study examined the effect of manipulating cortisol concentrations in fetal sheep during late gestation on mitochondrial OXPHOS capacity of two skeletal muscles with different postnatal locomotive functions. Mitochondrial content, biogenesis markers, respiratory rates and expression of proteins and genes involved in the electron transfer system (ETS) and OXPHOS efficiency were measured in the biceps femoris (BF) and superficial digital flexor (SDF) of fetuses either infused with cortisol before the prepartum rise or adrenalectomised to prevent this increment. Cortisol infusion increased mitochondrial content, biogenesis markers, substrate-specific respiration rates and abundance of ETS Complex I and adenine nucleotide translocator (ANT1) in a muscle-specific manner that was more pronounced in the SDF than BF. Adrenalectomy reduced mitochondrial content and expression of PGC1α and ANT1 in both muscles, and ETS Complex IV abundance in the SDF near term. Uncoupling protein gene expression was unaffected by cortisol manipulations in both muscles. Gene expression of the myosin heavy chain isoform, MHCIIx, was increased by cortisol infusion and reduced by adrenalectomy in the BF alone. These findings show that cortisol has a muscle-specific role in prepartum maturation of mitochondrial OXPHOS capacity with important implications for the health of neonates born pre-term or after intrauterine glucocorticoid overexposure

Analysis of symmetries in models of multi-strain infections

In mathematical studies of the dynamics of multi-strain diseases caused by antigenically diverse pathogens, there is a substantial interest in analytical insights. Using the example of a generic model of multi-strain diseases with cross-immunity between strains, we show that a significant understanding of the stability of steady states and possible dynamical behaviours can be achieved when the symmetry of interactions between strains is taken into account. Techniques of equivariant bifurcation theory allow one to identify the type of possible symmetry-breaking Hopf bifurcation, as well as to classify different periodic solutions in terms of their spatial and temporal symmetries. The approach is also illustrated on other models of multi-strain diseases, where the same methodology provides a systematic understanding of bifurcation scenarios and periodic behaviours. The results of the analysis are quite generic, and have wider implications for understanding the dynamics of a large class of models of multi-strain diseases

Adverse reactions to metal debris occur with all types of hip replacement not just metal-on-metal hips: a retrospective observational study of 3340 revisions for adverse reactions to metal debris from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Adverse reactions to metal debris (ARMD) have resulted in the high short-term failure rates observed with metal-on-metal hip replacements. ARMD has recently been reported in non-metal-on-metal total hip replacements (non-MoM THRs) in a number of small cohort studies. However the true magnitude of this complication in non-MoM THRs remains unknown. We used a nationwide database to determine the risk of ARMD revision in all non-MoM THRs, and compared patient and surgical factors associated with ARMD revision between non-MoM and MoM hips. METHODS: We performed a retrospective observational study using data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. All primary hip replacements undergoing revision surgery for ARMD were included (n = 3,340). ARMD revision risk in non-MoM THRs was compared between different commonly implanted bearing surfaces and femoral head sizes (Chi-squared test). Differences in patient and surgical factors between non-MoM hips and MoM hips revised for ARMD were also analysed (Chi-squared test and unpaired t-test). RESULTS: Of all ARMD revisions, 7.5% (n = 249) had non-MoM bearing surfaces. The relative risk of ARMD revision was 2.35 times (95% CI 1.76-3.11) higher in ceramic-on-ceramic bearings compared with hard-on-soft bearings (0.055 vs. 0.024%; p < 0.001), and 2.80 times (95% CI 1.74-4.36) higher in 36 mm metal-on-polyethylene bearings compared to 28 mm and 32 mm metal-on-polyethylene bearings (0.058 vs. 0.021%; p < 0.001). ARMD revisions were performed earlier in non-MoM hips compared to MoM hips (mean 3.6-years vs. 5.6-years; p < 0.0001). Non-MoM hips had more abnormal findings at revision (63.1 vs. 35.7%; p < 0.001), and more intra-operative adverse events (6.4 vs. 1.6%; p < 0.001) compared to MoM hips. CONCLUSIONS: Although the overall risk of ARMD revision surgery in non-MoM THRs appears low, this risk is increasing, and is significantly higher in ceramic-on-ceramic THRs and 36 mm metal-on-polyethylene THRs. ARMD may therefore represent a significant clinical problem in non-MoM THRs

The helicobacter eradication aspirin trial (HEAT): demographic data for randomised (H.pylori positive) patients

Introduction The Helicobacter Eradication Aspirin Trial (HEAT) is a multicentre, double blind, randomised controlled trial investigating whether Helicobacter pylori eradication reduces the incidence of hospitalisation for peptic ulcer bleeding [1]. Participants are subjects aged over 60, taking low dose aspirin for at least four months at the time of recruitment; all participants were recruited from primary care. H. pylori positive participants were randomised to receive one week active trial treatment (lansoprazole 30mg, clarithromycin 500mg and metronidazole 400mg twice daily) or placebo. Recruitment to the trial started in 2012 and completed in 2017; follow-up is endpoint driven and is ongoing. Methods Participants are followed up using a bespoke web-based trial management system that communicates directly with HEAT Toolkit software downloaded at participating GP practices, which issues MIQUEST [2] queries searching follow-up criteria. The primary endpoint of the study is the rate of hospitalisation due to definite or probable peptic ulcer bleeding. The study will end when 87 adjudicated events have occurred. Events are tracked by accumulating information from MIQUEST searches of GP databases via the HEAT toolkit, patient contact, review of national secondary care admission and mortality data. Results HEAT is being conducted in practices across the whole of the UK with 188,428 invitation letters sent from 1,208 GP practices. A total of 37,247 positive responses were received, representing a 20% response rate. Of those, 30,025 patients were consented to the study of whom 5,356 H. pylori positive patients were randomised. The percent of H. pylori positive patients varied from 13% to 39% throughout the country. Multiple deprivation scores applied to the data indicated an increase in response with less deprivation, but a decrease in the number of randomised patients. The mean age at randomisation for all participants was 73.6 ± 7.0 (SD) years, and 73.8% of participants are male. Only 7.2% of participants are smokers although 52.9% are ex-smokers. A total of 15% of the randomised patients have withdrawn from the trial, and 100 patients have died so far. Discussion The trial methodology has shown that recruitment of large numbers of patients from primary care is attainable, with the assistance of the NIHR Clinical Research Network, and could be applied to other outcomes studies at relatively low cost. Last year, there were almost 17,000 hospital admissions for gastric ulcers [3] and more than 1,850 recorded deaths [4] for gastric and duodenal ulcers. If successful, the study will help to reduce NHS costs and improve health outcomes by reducing hospital admissions, increasing patient safety and preventing premature deaths

Prediction of preterm birth with and without preeclampsia using mid-pregnancy immune and growth-related molecular factors and maternal characteristics.

OBJECTIVE:To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia. STUDY DESIGN:Included were 400 women with singleton deliveries in California in 2009-2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS:Twenty-five serum biomarkers along with maternal age &lt;34 years and poverty status identified &gt;80% of women with PTB ± preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822-0.959) training; 0.883 (0.804-0.963) testing). CONCLUSION:Together with maternal age and poverty status, mid-pregnancy immune and growth factors reliably identified most women who went on to have a PTB ± preeclampsia

The effects of symmetry on the dynamics of antigenic variation

In the studies of dynamics of pathogens and their interactions with a host immune system, an important role is played by the structure of antigenic variants associated with a pathogen. Using the example of a model of antigenic variation in malaria, we show how many of the observed dynamical regimes can be explained in terms of the symmetry of interactions between different antigenic variants. The results of this analysis are quite generic, and have wider implications for understanding the dynamics of immune escape of other parasites, as well as for the dynamics of multi-strain diseases.Comment: 21 pages, 4 figures; J. Math. Biol. (2012), Online Firs

Resettlement experiences and resilience in refugee youth in Perth, Western Australia

Background: In Australia, the two major pathways of refugee entry are the United Nations High Commissioner for Refugees resettlement programme and irregular maritime arrivals (IMAs) seeking asylum. The Australian Government’s policies towards IMAs since July 2013 are controversial, uncompromising and consistently harsh, with asylum seekers held in detention centres for prolonged periods. Refugees and asylum seekers have distinct and unique stressors that make resettlement difficult. Methods: This exploratory study examines resettlement experiences for refugee youth in Western Australia using the psychosocial conceptual framework and qualitative methods. Focus group discussions and key informant interviews were undertaken with verbatim transcripts analysed using thematic analysis to identify themes. Results: Themes documented that language and its impact, and experience with education, health, and social activities, support structures provided to youth and supporting future aspirations as critical to successful resettlement. This exploratory study contributes to developing a broader understanding of the resettlement experiences of refugee youth, drawing on their current and past experiences, cultural differences and mechanisms for coping. Conclusion: Fluency in English language, especially spoken, was a facilitator of successful resettlement. Our results align with previous studies documenting that support programs are vital for successful resettlement. Although faced with immense difficulties refugee youth are resilient, want to succeed and have aspirations for the future. Strategies and recommendations suggested by refugee youth themselves could be used for developing interventions to assist successful resettlement

Malaysian primary care doctors' views on men's health: an unresolved jigsaw puzzle

<p>Abstract</p> <p>Background</p> <p>Men have been noted to utilise health care services less readily then women. Primary care settings provide an opportunity to engage men in health care activities because of close proximity to the target group (men in the community). Understanding attitudes towards men's health among Malaysian primary care doctors is important for the effective delivery of health services to men. We aimed to explore the opinions and attitudes of primary care doctors (PCDs) relating to men's health and help-seeking behaviour.</p> <p>Methods</p> <p>A qualitative approach to explore the opinions of 52 PCDs was employed, using fourteen in-depth interviews and eight focus group discussions in public and private settings. Purposive sampling of PCDs was done to ensure maximum variation in the PCD sample. Interviews were recorded and transcribed verbatim for analysis. Open coding with thematic analysis was used to identify key issues raised in the interview.</p> <p>Results</p> <p>The understanding of the concept of men's health among PCDs was fragmented. Although many PCDs were already managing health conditions relevant and common to men, they were not viewed by PCDs as "men's health". Less attention was paid to men's help-seeking behaviour and their gender roles as a potential determinant of the poor health status of men. There were opposing views about whether men's health should focus on men's <it>overall </it>health or a more focused approach to sexual health. There was also disagreement about whether special attention was warranted for men's health services. Some doctors would prioritise more common conditions such as hypertension, diabetes and hypercholesterolaemia.</p> <p>Conclusions</p> <p>The concept of men's health was new to PCDs in Malaysia. There was wide variation in understanding and opposing attitudes towards men's health among primary care doctors. Creating awareness and having a systematic approach would facilitate PCDs in delivering health service to men.</p