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Therapies for osteoporosis have been traditionally based on our understanding of bone cell activities. Bone tissue is constantly being removed and replaced (bone turnover) by osteoclasts which resorb bone and osteoblasts which lay down new bone. Bone turnover is essential for the maintenance of a healthy skeleton by removing or repairing the microscopic damage that results from everyday physical activity.
Another large outbreak of mumps occurred in Lothian from October 2017, which coincided with the commencement of the higher education term. During this period 324 cases were notified, most of whom were aged 18–22 years old. Although previous outbreaks had a focus in student populations, 43% of current cases reported that they were not a student. There has been increases in private student housing where students from all universities live, which may have contributed to the wide spread of the outbreak and complicated outbreak control. Information on vaccination status was available for 244 cases (75%), of whom the majority (75.8%) reported having two MMR doses. To investigate potential waning vaccine immunity the mean length of time since last mumps containing vaccine was calculated as 14.3 years. The outbreak was declared over in May 2018 after case numbers returned to background levels. This outbreak highlighted that mumps outbreaks occur cyclically coinciding with new cohorts of susceptible students entering the Lothian population. The lessons from this outbreak are to encourage students to have two MMR doses and also be prepared for mumps outbreaks in the near future. In future outbreaks the utility of a third MMR for outbreak control could be examined.
Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes.
Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements.
Urine collection methodologies were developed within home settings.
Different cohorts of free-living volunteers.
Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals.
This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies.
This article uses the Church of Jesus Christ of Latter-day Saints in post-independence Nigeria to examine the transition from individuated agents of religious exchange to integration into global corporate religiosity. Early Latter-day Saint adherents saw Mormonism as a mechanism by which they could acquire access to monetary resources from a financially stable Western patronage, despite political animosity due to Mormonism's racist policies and sectional tumult during the Nigeria-Biafra war. Drawing on oral and archival records, this article highlights how Mormonism as an American-based faith was able to be "translated" to meet the exigencies of indigenous adherents.
OBJECTIVES/GOALS: HIV-specific CD8+ T-cells play a critical role in partially controlling viral replication in infected-individuals, but ultimately fail to eliminate infection. Enhancing these T-cell responses through lymphocyte engineering approaches has the potential as a novel therapy capable of achieving durable control or eradication of infection. METHODS/STUDY POPULATION: IL-15 Superagonist (IL-15SA) potently supports the in vivo persistence and antiviral activity of adoptively transferred CD8+ T-cells. The Deep-PrimingTM technology platform, developed by Torque, allows for loading of immunomodulators onto the surface of T-cells via electrostatic ‘nanogels’, which slowly release to deliver sustained autocrine immune stimulation without the harmful effects of systemic exposure. Here, we investigate the impact of IL-15SA Deep-Priming on HIV-specific CD8+ T-cells in a humanized mouse model of HIV infection. Humanized mice were generated by engrafting NOD-scid-IL2Rgnull mice with memory CD4+ T-cells isolated from an ARV-suppressed HIV+ donor. An autologous HIV-specific Cytotoxic T-Lymphocyte (CTL) clone was isolated, and killing potential confirmed. Four weeks post humanization, mice were infected with HIV and received an infusion of unmodified HIV-Specific CTLs, or IL-15SA Deep-Primed HIV-specific CTLs (CTL-DP). T-cell numbers and plasma viral loads were quantified weekly by flow cytometry and qRT-PCR. RESULTS/ANTICIPATED RESULTS: Mice receiving unmodified CTLs trended toward reduced viral loads compared to the No Treatment condition, while mice receiving CTL-DP saw significant, 2-Log10 reductions in VL (p < 0.01). At 41 days post-infection 100% (5/5) of the No Treatment, 66.7% (4/6) of the CTL treatment, and 16.7% (1/6) of CTL-DP treatment mice had detectable viremia. IL-15SA Deep-Priming increased CTL expansion and persistence in peripheral blood which correlated with improved CD4+T-cell preservation. DISCUSSION/SIGNIFICANCE OF IMPACT: Here we demonstrate the first in vivo analysis of IL-15SA Deep-Priming of HIV-Specific CTLs. These data suggest that Deep-Priming of patient T-cells can enhance in vivo function and persistence, leading to improved viral suppression; a significant advancement in the field of HIV cure research. CONFLICT OF INTEREST DESCRIPTION: Austin Boesch, Thomas Andresen, and Douglas Jones are employees of Torque. Darrell Irvine is a co-founder of Torque and Chairman of Torque’s Scientific Advisory Board.
We report two cases of respiratory toxigenic Corynebacterium diphtheriae infection in fully vaccinated UK born adults following travel to Tunisia in October 2019. Both patients were successfully treated with antibiotics and neither received diphtheria antitoxin. Contact tracing was performed following a risk assessment but no additional cases were identified. This report highlights the importance of maintaining a high index of suspicion for re-emerging infections in patients with a history of travel to high-risk areas outside Europe.
Social scientists use the concept of interactions to study effect dependency. In the causal inference literature, interaction terms may be used in two distinct type of analysis. The first type of analysis focuses on causal interactions, where the analyst is interested in whether two treatments have differing effects when both are administered. The second type of analysis focuses on effect modification, where the analyst investigates whether the effect of a single treatment varies across levels of a baseline covariate. While both forms of interaction analysis are typically conducted using the same type of statistical model, the identification assumptions for these two types of analysis are very different. In this paper, we clarify the difference between these two types of interaction analysis. We demonstrate that this distinction is mostly ignored in the political science literature. We conclude with a review of several applications where we show that the form of the interaction is critical to proper interpretation of empirical results.
The aim of the study was to assess the experiences of discrimination as reported by people with mental health problems and to explore the impact of hospitalisation.
306 people with mental health problems provided sociodemographic data and data on discrimination using the discrimination and stigma scale version 12 (DISC-12) with the domains negative experienced discrimination, anticipated discrimination, overcoming stigma and discrimination, and positive experienced discrimination. Logistic regression analysis was used to test the impact of hospitalisation on discrimination, controlled for age, gender, education, employment, diagnosis and having been prescribed medication.
Hospitalisation had a major impact on negative discrimination: People were more likely to be treated unfairly in making or keeping friends, in marriage or divorce, by people in their neighbourhood, in social life, by mental health staff and in terms of privacy, if they had been hospitalised. They were also more likely to be avoided or shunned by people who knew about the mental health problem. People with a history of hospitalisation also reported more anticipated discrimination: They had stopped themselves more often from having a close personal relationship and concealed their mental health problem from others more often than those without a history of hospitalisation. However, people who had been hospitalised also experienced more positive discrimination in terms of being treated more positively in getting welfare benefits or disability pensions and in housing.
Findings suggest that treatment in hospital contributed to a higher extent to experienced discrimination than treatment in the community.
The '2005 National Framework for Service Change in the National Health Service (NHS) in Scotland' promoted the need for NHS service delivery in local communities rather than in hospitals, and to develop a systematic approach for the most vulnerable (especially older people) with long term conditions with a view to managing their conditions at home or in the community and reducing the chance of hospitalization. This combined with the recognition of an aging population encouraged service redesign in a Scottish health region with the focus on community assessment of older people with mental health needs.
To establish and assess the functioning of a joint Health and Social Services enhanced assessment and support team (EAST) for community-dwelling elders with significant mental health needs living in a Scottish health region, and to determine the impact of this team on mental health hospital services.
Prospective three-year data collection of local service activity involving EAST, and both inpatient and day hospital facilities for older adults with mental health problems.
EAST assessed 111 patients during the study, 83% with a diagnosis of dementia. The mean duration of assessment was 6 weeks with 9% of patients receiving an overnight home assessment and 6% requiring hospital admission. Overall there was a substantial reduction in utilization of both acute admission beds and day hospital placements.
Multi-agency community assessment of older adults with mental health problems can be addressed effectively without recourse to hospital admission, which may allow resource release for further service developments.
Psychiatric morbidity in young adults can lead to a host of poor sequelae including later psychiatric disorder, welfare dependence and psychosocial disability, all worse if the disorder becomes chronic.Early intervention strategies could be enhanced by targeting those likely to have a more chronic or repetitive course.
Material and Methods:
Twenty thousand young Australians, aged 17-24, were recruited into a prospective cohort study at the time of obtaining their driving license. A random sample of 5000 were recontacted a year later and 2994 completed re-survey questionnaires. Psychiatric morbidity was assessed using the Kessler 10 (cut point 21/22) and DSH was assessed by slef report. Two trained research assistants and a psychiatrist then coded the open responses.
Psychiatric morbidity was present in 954 of the sample at baseline. 45& of these were still cases one year later. Older age, female gender, previous deliberate self harm and symptom scores, but not substance or alcohol misuse were the baseline independent association with chronicity vs. remission. Short sleep duration was the only other independent factor, with a 10% decrease in the likelihood of having morbidity at follow up for every extra hour slept on average per night.
Discussion and Conclusions:
This study suggests yet another poor outcome of short sleep duration in young adults which may aid targeting of early intervention for psychiatric morbidity.
Although antidepressants are the most commonly used treatment for depressive illness, there is uncertainty if their use is associated with a reduction in suicide rate. Antidepressant prescribing in Northern Ireland has increased over fivefold in the decade 1989–1999. The authors sought to explore whether this increase was associated with a reduction in suicide rate taking into account social and political factors thought also to have an influence on suicide.
Materials and methods
Factors that have been suggested to influence suicide were entered into a linear regression with frequency of suicide and undetermined deaths (referred to as suicide rate) as the dependent variable. The above factors were antidepressant prescribing, unemployment rate, household alcohol expenditure and persons charged with terrorist offences. The rise in younger suicides, in recent decades, suggests this analysis should be carried out separately for younger (less than 30 years) and older (30 years and above) suicides separately. The predictors in the two models are based on aggregate data for the total group.
In the younger group there was no association between antidepressant prescribing and suicide. For the older group increased antidepressant prescribing was associated with a reduction in suicide rate over the 10 years of the study.
Increasing antidepressant prescribing appears to be an effective strategy for reducing suicide. This has been demonstrated in older individuals.
A number of definitions for 'psychiatric intensive care' exist but generally they detail care in a multidisciplinary, highly staffed, and often secure, unit for persons with mental disorder and associated behavioural disturbance. The role of psychiatric intensive care units (PICU) is well established for the general adult psychiatric population, but these units are often less suitable for older adults. A dedicated PICU for older adults in a Scottish Health Region serving a population of 350,000 was established in 2001 to deal primarily with an increase of behaviourally challenging demented male patients in the psychogeriatric admission wards of that region.
To detail patient characteristics and outcomes of admission to the PICU for older adults in a Scottish Health Region.
Prospective survey of admissions to the PICU from January 2006 until August 2007, using routinely collected data.
25 male patients, mean age 74 years, were admitted during the survey, with 52% detained under Mental Health legislation. The main transfer reasons were resistive behaviours and persistent physical aggression. The majority (32%) of patients had a primary diagnosis of Alzheimer's dementia, 20% with vascular dementia. The average mini-mental state score was 15/30, and the mean duration of patient stay in the PICU was 54 days, with 84% of admissions discharged from the unit during the evaluation period.
A regional psychogeriatric intensive care unit can serve a useful function in the management of disturbed elders who are otherwise difficult to manage within existing psychogeriatric acute admission wards.
The Scottish Office Department of Health issued guidance in 1996 on ‘National Health Service (NHS) Responsibility for Continuing Health Care’ which is provided free of charge to patients whose complexity, nature or intensity of care needs (medical, nursing) are sufficient to fulfil certain criteria. Due in part to differing NHS guidance in England, there has been increased complaints to Health Boards and the Scottish Public Service Ombudsman (SPSO) about patients deemed not to fulfil the Scottish criteria.
To establish the level of knowledge amongst experienced psychiatrists about current Scottish regulations on NHS Continuing Care.
Following a pilot survey, a modified postal questionnaire comprising 19 structured questions was sent to 134 psychiatric consultants and specialist trainees in south-east Scotland in mid-2007, with a reminder to non-responders.
A 54% response rate increased to 66% following reminders. Of these, 82% were consultants and 88% had clinical responsibility for inpatient care within the past decade. Only 24% of responders were aware of the current Scottish guidance for NHS Continuing Care, with only 14% aware of the actual 1996 document. There was uncertainty regarding responsibility for both discharge and appeal processes although 8% had been involved with a formal complaint relating to NHS Continuing Care and 10% involved with the SPSO.
Clinical uncertainty abounds regarding the criteria in Scotland for NHS Continuing Care, despite guidance being issued over a decade earlier. There is urgent need for review of the criteria by the Scottish Government, with raised awareness among practising clinicians.
Hip hop, reggae/raggamuffin, and fusions between these genres, emerged in the Italian island of Sardinia in the 1980s and 1990s. In this article, we examine the ways in which these transnational music forms have found fertile terrain in post-colonial Sardinia across generations and cultures through the music of the historic hip hop crew, Sa Razza, the next generation ‘rappamuffin’ artist, Randagiu Sardu, and the Senegalese-Sardinian Afro-reggae musician, Momar Gaye. Through the analysis of selected tracks and video clips we explore how overlapping cultural, social, and political discourses of decolonisation are framed and narrated through language, music, and images as a means of expressing cultural and political agency, critiquing the impacts of exploitation and colonisation, and consciously and self-reflexively reinterpreting and celebrating marginality.
This paper explores dependencies between operational risks and between operational risks and other risks such as market, credit and insurance risk. The paper starts by setting the regulatory context and then goes into practical aspects of operational risk dependencies. Next, methods of modelling operational risk dependencies are considered with a simulation study exploring the sensitivity of diversification benefits arising from dependency models. The following two sections consider how correlation assumptions may be set, highlighting some generic dependencies between operational risks and with non-operational risks to assist in the assessment of dependencies and correlation assumptions. Supplementary appendices provide further detail on generic dependencies as well as a case study of how business models can lead to operational risks interacting with other risks. Finally, the paper finishes with a literature review of operational risk dependency papers including correlation studies and benchmark reports.
With ageing there is a reduction in muscle mass and strength, termed sarcopenia. A further consequence of ageing is a reduction in appetite and this can result in a reduced energy intake and malnutrition. Increased dietary protein intake may reduce the risk of sarcopenia, however, protein is particularly satiating. Increasing protein intake in the older adult population, without a reduction of overall energy intake and appetite is desirable. The primary aim of this study was to investigate the effect of protein supplementation on dietary intake and appetite. A further aim was to explore whether the time of consumption (morning vs evening) modified the impact of protein on energy intake and appetite.
Materials and methods
Twenty-four middle-older aged (50–75 years) participants were recruited to a randomised cross-over trial. In phase 1 (pre-supplementation) participants completed a 3d food diary and were asked to report hunger and appetite using visual analogue scale questionnaires. In the second and third phases, participants consumed a whey protein gel (containing 20 g protein and 376kJ of energy) for 4 days at either the evening (before bed) or in the morning (after breakfast) and completed the same tasks as phase 1. There was a 1-week wash-out period before crossing over to the alternative time point. Repeated measures ANOVA was used to analyse the data.
There was no significant difference in average daily energy and macronutrient intake provided by the habitual diet in the pre-supplementation phase compared to the whey protein supplementation phases, irrespective of timing (p > 0.05). Similarly, no significant differences were observed in reported feelings of hunger and appetite (p > 0.05).
Contrary to expectations, the addition of a 20g/day whey protein supplement did not alter subsequent energy and macronutrient intake when consumed over a 4-day period in this middle-older adult population. This may be due to the low-calorie composition of the supplement, or the timing of the intake. This research helps to inform protein delivery strategies, however different product formulations need to be explored, and studies of longer duration are required to understand the impact of prolonged supplementation on eating behaviour.
Vitamins and minerals play an essential role within many cellular processes including energy production and metabolism. Biochemical changes and heightened metabolic demands lead to increases in the requirement for certain micronutrients alongside higher excretion of micronutrients through waste products, such as sweat and urine. Previously, supplementation with a multivitamin/mineral (MVM) for ≥ 28 days resulted in improvements to cognition and subjective state. Shifts in metabolism have also been demonstrated during cognitively demanding tasks following MVM in females, both acutely and following 8-week supplementation, suggesting that enhanced recovery is possible following MVM supplementation. The current study aimed to assess these effects further in males and females using metabolically challenging exercise and cognitive tasks.
Materials and Methods
This randomised, placebo-controlled, parallel groups study investigated the effects of a MVM complex in 82 healthy young (18–35y) exercisers. Subjective ratings and substrate metabolism were assessed during 30 minutes each of increasingly effortful incremental exercise and demanding cognitive tasks. Assessments took place on acute study days following a single dose (Day 1) of MVM, containing 3 times recommended daily allowance of water-soluble vitamins plus CoQ10, and following 4-week supplementation (Day 28).
Energy expenditure (EE) was increased during cognitive tasks following MVM across Day 1 and Day 28, with greater effects in males. In males, MVM also increased carbohydrate oxidation and EE during exercise across Day 1 and Day 28. In females, mental tiredness was lower during exercise; increases in physical tiredness following 30 minutes of exercise were attenuated; and stress ratings following cognitive tasks were reduced following MVM. In males, MVM only lowered mental tiredness following 10 minutes of exercise. Those receiving MVM also reported lower ratings of perceived exertion following 10 minutes of exercise. These effects were apparent irrespective of day, but effects on mental tiredness were greater on Day 28. Ferritin levels were also higher on Day 28 in those receiving MVM.
These findings extend on existing knowledge, demonstrating increased carbohydrate oxidation and EE in males following MVM supplementation for the first time. Importantly, they show modulation of EE and subjective tiredness following a single dose, providing further evidence for acute effects of MVM. Differential effects in men and women suggest that whilst males expend more energy, females may conserve their energy but report lower tiredness instead, demonstrating that sex may play an important role in the effects of MVM on energy metabolism and should be considered in future research.