“Hospital” Treatment Further Refined

R (on the application of CS) v Mental Health Review Tribunal; Managers of Homerton Hospital (East London and the City Mental Health NHS Trust) (Interested Party)Queen’s Bench Division, (Administrative Court), Pitchford J., 6 December 2004EWHC (Admin) 2958The decision of a Mental Health Review Tribunal under section 72(1) Mental Health Act 1983 not to discharge a patient on section 17 leave from hospital was not unlawful. The link between hospital and treatment may be “gossamer thin” but still a “significant component” to justify renewal of detentio

In-situ tryptophan-like fluorescence: a real-time indicator of faecal contamination in drinking water supplies

Enteric pathogens are typically inferred from the presence of surrogate indicator organisms such as thermo-tolerant (faecal) coliforms (TTCs). The analysis of TTCs requires time-consuming incubation in suitable laboratories, which can limit sampling resolution, particularly during critical pollution events. Here, we demonstrate the use of in-situ fluorimeters targeting tryptophan-like compounds as a rapid, reagentless indicator of TTCs in groundwater-derived potable water supplies in Africa. A range of other common indicators of TTCs were also determined including nitrate, turbidity, and sanitary risk survey scores. Sampling was conducted during both the dry and wet seasons to investigate seasonality. Tryptophan-like fluorescence was the most effective predictor of both presence/absence and number of TTCs during both seasons. Seasonal changes in tryptophan-like fluorescence in deeper supplies suggest it is transported more efficiently through the aquifer than TTCs. Moreover, the perennial elevated concentrations in some wells suggest it is more resilient than TTCs in groundwater. Therefore tryptophan-like fluorescence could also be a better indicator of some smaller, more easily transported, and long-lived, pathogenic enteric viruses. These sensors have the potential to be included in real-time pollutionalert systems for drinking water supplies throughout the world, as well as for mapping enteric pathogen risks in developing regions

Unravelling the sources of lead in the urban soils of Greater Glasgow.

Lead (Pb) is toxic to all life and even low blood Pb levels can have neurological effects, especially in children <6. With two thirds of the world's population projected to inhabit urban areas by 2050, elevated Pb levels in urban soils is of especial concern due to the high number of children exposed. This project aims to design a model to predict soil Pb values in urban areas, in order to guide future remediation of Pb polluted soils. Such models require in depth understanding of the sources of Pb in urban soils. Subsequently, the factors influencing soil Pb levels were extracted from the literature and tested in Greater Glasgow using the British Geological Survey (BGS) Geochemical Baseline of the Environment (G-BASE) dataset

Nitrate respiration and diel migration patterns of diatoms are linked in sediments underneath a microbial mat

Diatoms are among the few eukaryotes known to store nitrate (NO3−) and to use it as an electron acceptor for respiration in the absence of light and O2. Using microscopy and 15N stable isotope incubations, we studied the relationship between dissimilatory nitrate/nitrite reduction to ammonium (DNRA) and diel vertical migration of diatoms in phototrophic microbial mats and the underlying sediment of a sinkhole in Lake Huron (USA). We found that the diatoms rapidly accumulated NO3− at the mat-water interface in the afternoon and 40% of the population migrated deep into the sediment, where they were exposed to dark and anoxic conditions for ~75% of the day. The vertical distribution of DNRA rates and diatom abundance maxima coincided, suggesting that DNRA was the main energy generating metabolism of the diatom population. We conclude that the illuminated redox-dynamic ecosystem selects for migratory diatoms that can store nitrate for respiration in the absence of light. A major implication of this study is that the dominance of DNRA over denitrification is not explained by kinetics or thermodynamics. Rather, the dynamic conditions select for migratory diatoms that perform DNRA and can outcompete sessile denitrifiers

Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals:study protocol for a randomised controlled trial

BACKGROUND: Deviation from the physiological glucocorticoid dynamics (circadian and underlying ultradian rhythmicity) is a common characteristic of various neuropsychiatric and endocrine disorders as well as glucocorticoid-based therapeutics. These states may be accompanied by neuropsychiatric symptomatology, suggesting continuous dynamic glucocorticoid equilibrium is essential for brain homeostasis. METHODS/DESIGN: The study consists of two parts. The preliminary stage of the study aims to validate (technically and pharmacologically) and optimise three different patterns of systemic cortisol administration in man. These patterns are based on the combinatory administration of metyrapone, to suppress endogenous cortisol production, and concurrent hydrocortisone replacement. The second, subsequent, core part of the study is a randomised, double-blinded, placebo-controlled, crossover study, where participants (healthy male individuals aged 18–60 years) will undergo all three hydrocortisone replacement schemes. During these infusion regimes, we plan a number of neurobehavioural tests and imaging of the brain to assess neural processing, emotional reactivity and perception, mood and self-perceived well-being. The psychological tests include: ecological momentary assessment, P1vital Oxford Emotional Test Battery and Emotional Potentiated Startle Test, Leeds Sleep Evaluation Questionnaire and the visual working memory task (n-back). The neuroimaging protocol combines magnetic resonance sequences that capture data related to the functional and perfusion status of the brain. DISCUSSION: Results of this clinical trial are designed to evaluate the impact (with possible mechanistic insights) of different patterns of daily glucocorticoid dynamics on neural processing and reactivity related to emotional perception and mood. This evidence should contribute to the optimisation of the clinical application of glucocorticoid-based therapeutics. TRIAL REGISTRATION: UK Clinical Research Network, IRAS Ref: 106181, UKCRN-ID-15236 (23 October 2013

Trends in SARS-CoV-2 infection and vaccination in school staff, students and their household members from 2020 to 2022 in Wales, UK: an electronic cohort study

Objectives We investigated SARS-CoV-2 infection trends, risk of SARS-CoV-2 infection and COVID-19 vaccination uptake among school staff, students and their household members in Wales, UK. Design Seven-day average of SARS-CoV-2 infections and polymerase chain reaction tests per 1000 people daily, cumulative incidence of COVID-19 vaccination uptake and multi-level Poisson models with time-varying covariates. Setting National electronic cohort between September 2020 and May 2022 when several variants were predominant in the UK (Alpha, Delta and Omicron). Participants School students aged 4 to 10/11 years (primary school and younger middle school, n = 238,163), and 11 to 15/16 years (secondary school and older middle school, n = 182,775), school staff in Wales (n = 47,963) and the household members of students and staff (n = 697,659). Main outcome measures SARS-CoV-2 infection and COVID-19 vaccination uptake. Results School students had a sustained period of high infection rates compared with household members after August 2021. Primary schedule vaccination uptake was highest among staff (96.3%) but lower for household members (72.2%), secondary and older middle school students (59.8%), and primary and younger middle school students (3.3%). Multi-level Poisson models showed that vaccination was associated with a lower risk of SARS-CoV-2 infection. The Delta variant posed a greater infection risk for students than the Alpha variant. However, Omicron was a larger risk for staff and household members. Conclusions Public health bodies should be informed of the protection COVID-19 vaccines afford, with more research being required for younger populations. Furthermore, schools require additional support in managing new, highly transmissible variants. Further research should examine the mechanisms between child deprivation and SARS-CoV-2 infection

Kiwi Forego Vision in the Guidance of Their Nocturnal Activities

BACKGROUND: In vision, there is a trade-off between sensitivity and resolution, and any eye which maximises information gain at low light levels needs to be large. This imposes exacting constraints upon vision in nocturnal flying birds. Eyes are essentially heavy, fluid-filled chambers, and in flying birds their increased size is countered by selection for both reduced body mass and the distribution of mass towards the body core. Freed from these mass constraints, it would be predicted that in flightless birds nocturnality should favour the evolution of large eyes and reliance upon visual cues for the guidance of activity. METHODOLOGY/PRINCIPAL FINDINGS: We show that in Kiwi (Apterygidae), flightlessness and nocturnality have, in fact, resulted in the opposite outcome. Kiwi show minimal reliance upon vision indicated by eye structure, visual field topography, and brain structures, and increased reliance upon tactile and olfactory information. CONCLUSIONS/SIGNIFICANCE: This lack of reliance upon vision and increased reliance upon tactile and olfactory information in Kiwi is markedly similar to the situation in nocturnal mammals that exploit the forest floor. That Kiwi and mammals evolved to exploit these habitats quite independently provides evidence for convergent evolution in their sensory capacities that are tuned to a common set of perceptual challenges found in forest floor habitats at night and which cannot be met by the vertebrate visual system. We propose that the Kiwi visual system has undergone adaptive regressive evolution driven by the trade-off between the relatively low rate of gain of visual information that is possible at low light levels, and the metabolic costs of extracting that information

Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells

Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an ‘immature’ neonatal to a ‘mature’ adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation

Countdown to 2030 : tracking progress towards universal coverage for reproductive, maternal, newborn, and child health

Building upon the successes of Countdown to 2015, Countdown to 2030 aims to support the monitoring and measurement of women's, children's, and adolescents' health in the 81 countries that account for 95% of maternal and 90% of all child deaths worldwide. To achieve the Sustainable Development Goals by 2030, the rate of decline in prevalence of maternal and child mortality, stillbirths, and stunting among children younger than 5 years of age needs to accelerate considerably compared with progress since 2000. Such accelerations are only possible with a rapid scale-up of effective interventions to all population groups within countries (particularly in countries with the highest mortality and in those affected by conflict), supported by improvements in underlying socioeconomic conditions, including women's empowerment. Three main conclusions emerge from our analysis of intervention coverage, equity, and drivers of reproductive, maternal, newborn, and child health (RMNCH) in the 81 Countdown countries. First, even though strong progress was made in the coverage of many essential RMNCH interventions during the past decade, many countries are still a long way from universal coverage for most essential interventions. Furthermore, a growing body of evidence suggests that available services in many countries are of poor quality, limiting the potential effect on RMNCH outcomes. Second, within-country inequalities in intervention coverage are reducing in most countries (and are now almost non-existent in a few countries), but the pace is too slow. Third, health-sector (eg, weak country health systems) and non-health-sector drivers (eg, conflict settings) are major impediments to delivering high-quality services to all populations. Although more data for RMNCH interventions are available now, major data gaps still preclude the use of evidence to drive decision making and accountability. Countdown to 2030 is investing in improvements in measurement in several areas, such as quality of care and effective coverage, nutrition programmes, adolescent health, early childhood development, and evidence for conflict settings, and is prioritising its regional networks to enhance local analytic capacity and evidence for RMNCH