Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection

We describe a method for the determination of the two major urinary metabolites of vitamin K as the methyl esters of their agyclone structures, 2-methyl-3-(3-3-carboxymethylpropyl)-1,4-naphthoquinone (5C-side-chain metabolite) and 2-methyl-3-(5-carboxy-3-methyl-2-pentenyl)-1,4-naphthoquinone (7C-side-chain metabolite), by HPLC with electrochemical detection (ECD) in the redox mode. Urinary salts were removed by reversed-phase (C18) solid phase extraction (SPE) and the predominately conjugated vitamin K metabolites hydrolysed with methanolic HCl. The resultant carboxylic acid aglycones were quantitatively methylated with diazomethane and fractionated by normal-phase (silica) SPE. Final analysis was by reversed-phase (C18) HPLC with a methanol-aqueous mobile phase. Metabolites were detected by amperometric, oxidative ECD of their quinol forms, which were generated by post-column coulometric reduction at an upstream electrode. The assay gave excellent linearity (r2 typically = 0.999) and high sensitivity with an on-column detection limit of <3.5 fmol (<1pg). The inter-assay precision was typically 10%. Metabolite recovery was compared to that of an internal standard (2-methyl-3-(7'-carboxy-heptyl)-1,4-naphthoquinone), added to urine samples just before analysis. Using this methodology we confirmed that the 5C- and 7C-metabolite were major catabolites of both phylloquinone (vitamin K1) and menaquinones (vitamin K2) in humans. We propose that the measurement of urinary vitamin K metabolite excretion is a candidate non-invasive marker of total vitamin K status

Experience and perceptions of Social Prescribing interventions; a qualitative study with people with long-term conditions, link workers and health care providers.

BACKGROUND: Long-term conditions (LTC) are a leading cause of reduced quality of life and early mortality. People with LTC are living longer with increasing economic and social needs. Novel patient centred care pathways are required to support traditional medical management of these patients. Social Prescribing (SP) has gained popularity as a non-medical approach to support patients with LTC and their unmet health needs. The current focus group study aims to explore the experiences and perceptions to SP interventions from the perspective of people with long-term conditions, link workers, healthcare providers and community-based services. METHODS: Six-eight participants will be recruited into three specific 60-minute focus groups relative to their role as a patient, link worker and community-based service. Eight-12 participants with a Health care provider and GP background will be interviewed individually online. The participants within these focus groups and semi-structured interviews will be invited to provide opinions on what factors they think are important to the successful implementation of a SP service from their respective stakeholder positions. The data will be recorded and exported to NVivo software for further analysis using Thematic Reflexive analysis methods. Coded categorical data will inform emerging themes from which a narrative summary will be consolidated and presented for dissemination. CONCLUSION: The conclusions made from this study will help inform the next study, which will aim to develop a pilot SP service for patients with long-term musculoskeletal conditions as part of an overall larger project

Integrating attribution with adaptation for unprecedented future heatwaves

Citizens in many countries are now experiencing record-smashing heatwaves that were intensified due to anthropogenic climate change. Whether today’s most impactful heatwaves could have occurred in a pre-industrial climate, traditionally a central focus of attribution research, is fast becoming an obsolete question. The next frontier for attribution science is to inform adaptation decision-making in the face of unprecedented future heat

Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and &gt;18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (&gt;21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption

Loop expansion in Yang-Mills thermodynamics

We argue that a selfconsistent spatial coarse-graining, which involves interacting (anti)calorons of unit topological charge modulus, implies that real-time loop expansions of thermodynamical quantities in the deconfining phase of SU(2) and SU(3) Yang-Mills thermodynamics are, modulo 1PI resummations, determined by a finite number of connected bubble diagrams.Comment: 15 pages, 2 figures, v5: discussion of much more severely constrained nonplanar situation included in Sec.

Changes to population-based emergence of climate change from CMIP5 to CMIP6

Abstract The Coupled Model Intercomparison Project Phase 6 (CMIP6) model ensemble projects climate change emerging soonest and most strongly at low latitudes, regardless of the emissions pathway taken. In terms of signal-to-noise (S/N) ratios of average annual temperatures, these models project earlier and stronger emergence under the Shared Socio-economic Pathways than the previous generation did under corresponding Representative Concentration Pathways. Spatial patterns of emergence also change between generations of models; under a high emissions scenario, mid-century S/N is lower than previous studies indicated in Central Africa, South Asia, and parts of South America, West Africa, East Asia, and Western Europe, but higher in most other populated areas. We show that these global and regional changes are caused by a combination of higher effective climate sensitivity in the CMIP6 ensemble, as well as changes to emissions pathways, component-wise effective radiative forcing, and region-scale climate responses between model generations. We also present the first population-weighted calculation of climate change emergence for the CMIP6 ensemble, quantifying the number of people exposed to increasing degrees of abnormal temperatures now and into the future. Our results confirm the expected inequity of climate change-related impacts in the decades between now and the 2050 target for net-zero emissions held by many countries. These findings underscore the importance of concurrent investments in both mitigation and adaptation.</jats:p

Diel turbidity cycles in a headwater stream: evidence of nocturnal bioturbation?

Purpose: A small number of recent studies have linked daily cycles in stream turbidity to nocturnal bioturbation by aquatic fauna, principally crayfish, and demonstrated this process can significantly impact upon water quality under baseflow conditions. Adding to this limited body of research, we use high-resolution water quality monitoring data to investigate evidence of diel turbidity cycles in a lowland, headwater stream with a known signal crayfish (Pacifastacus leniusculus) population and explore a range of potential causal mechanisms. Materials and methods: Automatic bankside monitoring stations measured turbidity and other water quality parameters at 30-min resolution at three locations on the River Blackwater, Norfolk, UK during 2013. Specifically, we focused on two 20-day periods of baseflow conditions during January and April 2013 which displayed turbidity trends typical of winter and spring seasons, respectively. The turbidity time-series, which were smoothed with 6.5 hour Savitzky-Golay filters to highlight diel trends, were correlated against temperature, stage, dissolved oxygen and pH to assess the importance of abiotic influences on turbidity. Turbidity was also calibrated against suspended particulate matter (SPM) over a wide range of values via linear regression. Results and discussion: Pronounced diel turbidity cycles were found at two of the three sites under baseflow conditions during April. Spring night-time turbidity values consistently peaked between 21:00 and 04:00 with values increasing by ~10 nephelometric turbidity units (NTU) compared with the lowest recorded daytime values which occurred between 10:00 and 14:00. This translated into statistically significant increases in median midnight SPM concentration of up to 76% compared with midday, with night-time (18:00 – 05:30) SPM loads also up to 30% higher than that recorded during the daytime (06:00 – 17:30). Relating turbidity to other water quality parameters exhibiting diel cycles revealed there to be neither any correlation that might indicate a causal link, nor any obvious mechanistic connections to explain the temporal turbidity trends. Diel turbidity cycles were less prominent at all sites during the winter. Conclusions: Considering the seasonality and timing of elevated turbidity, visual observations of crayfish activity, and an absence of mechanistic connections with other water quality parameters, the results presented here are consistent with the hypothesis that nocturnal bioturbation is responsible for generating diel turbidity cycles under baseflow conditions in headwater streams. However, further research in a variety of fluvial environments is required to better assess the spatial extent, importance and causal mechanisms of this phenomenon

Water, sanitation and hygiene systems in Pacific Island schools to promote the health and education of girls and children with disability: a systematic scoping review

Water, sanitation and hygiene (WASH) systems in schools contribute to successful education by promoting good health and supporting school attendance. Girl students and students with disability face significant challenges when there are inadequate WASH systems. Pacific Island Countries and Territories (PICTs) have some of the lowest levels of improved WASH systems on earth. The aim of this review was to document the characteristics and effectiveness of approaches to improve WASH systems that promote the health and education of girl students, and students with disability in PICTs. This systematic scoping review comprehensively searched peer-reviewed and grey literature about WASH, PICTs, schoolgirls and students with disability. At best, there are only fleeting mentions in the grey literature about WASH and disability in schools in PICTs. Inclusion and exclusion criteria resulted in 12 publications being included: 1 review; 7 original research; 4 commentaries/project reports. A holistic approach to WASH in schools in PICTs must consider how the entire school WASH system can be inclusive of girls and children with disability. Incorporating local PICT learning epistemologies (ways of knowing) and local PICT pedagogies (ways of learning) are required to ensure new WASH systems reduce existing inequalities for girls and students with disability

Observational Evidence of For-Profit Delivery and Inferior Nursing Home Care: When Is There Enough Evidence for Policy Change?

This research was financially supported by the Social Sciences and Humanities Research Council