The Keck+Magellan Survey for Lyman Limit Absorption II: A Case Study on Metallicity Variations

We present an absorption line analysis of the Lyman limit system (LLS) at z=3.55 in our Magellan/MIKE spectrum of PKS2000-330. Our analysis of the Lyman limit and full HI Lyman series constrains the total HI column density of the LLS (N_HI = 10^[18.0 +/- 0.25] cm^{-2} for b_HI >= 20 km/s) and also the N_HI values of the velocity subsystems comprising the absorber. We measure ionic column densities for metal-line transitions associated with the subsystems and use these values to constrain the ionization state (>90% ionized) and relative abundances of the gas. We find an order of magnitude dispersion in the metallicities of the subsystems, marking the first detailed analysis of metallicity variations in an optically thick absorber. The results indicate that metals are not well mixed within the gas surrounding high $z$ galaxies. Assuming a single-phase photoionization model, we also derive an N_H-weighted metallicity, = -1.66 +/- 0.25, which matches the mean metallicity in the neutral ISM in high z damped Lya systems (DLAs). Because the line density of LLSs is ~10 times higher than the DLAs, we propose that the former dominate the metal mass-density at z~3 and that these metals reside in the galaxy/IGM interface. Considerations of a multi-phase model do not qualitatively change these conclusions. Finally, we comment on an anomalously large O^0/Si^+ ratio in the LLS that suggests an ionizing radiation field dominated by soft UV sources (e.g. a starburst galaxy). Additional abundance analysis is performed on the super-LLS systems at z=3.19.Comment: 20 pages, 7 figures (most in color). Accepted to Ap

A co-production approach guided by the behaviour change wheel to develop an intervention for reducing sedentary behaviour after stroke

Background Stroke survivors are highly sedentary; thus, breaking up long uninterrupted bouts of sedentary behaviour could have substantial health benefit. However, there are no intervention strategies specifically aimed at reducing sedentary behaviour tailored for stroke survivors. The purpose of this study was to use co-production approaches to develop an intervention to reduce sedentary behaviour after stroke. Methods A series of five co-production workshops with stroke survivors, their caregivers, stroke service staff, exercise professionals, and researchers were conducted in parallel in two-stroke services (England and Scotland). Workshop format was informed by the behaviour change wheel (BCW) framework for developing interventions and incorporated systematic review and empirical evidence. Taking an iterative approach, data from activities and audio recordings were analysed following each workshop and findings used to inform subsequent workshops, to inform both the activities of the next workshop and ongoing intervention development. Findings Co-production workshop participants (n = 43) included 17 staff, 14 stroke survivors, six caregivers and six researchers. The target behaviour for stroke survivors is to increase standing and moving, and the target behaviour for caregivers and staff is to support and encourage stroke survivors to increase standing and moving. The developed intervention is primarily based on co-produced solutions to barriers to achieving the target behaviour. The developed intervention includes 34 behaviour change techniques. The intervention is to be delivered through stroke services, commencing in the inpatient setting and following through discharge into the community. Participants reported that taking part in intervention development was a positive experience. Conclusions To our knowledge, this is the first study that has combined the use of co-production and the BCW to develop an intervention for use in stroke care. In-depth reporting of how a co-production approach was combined with the BCW framework, including the design of bespoke materials for workshop activities, should prove useful to other researchers and practitioners involved in intervention development in stroke

Symptom recognition and perceived urgency of help-seeking for rheumatoid arthritis and other diseases in the general public: A mixed method approach.

OBJECTIVE: Clinical outcomes in rheumatoid arthritis (RA) are improved if the disease is treated early. However, treatment is often significantly delayed as a result of delayed help-seeking by patients who fail to recognise its symptoms or the need for rapid medical attention. Two studies were conducted to investigate the role of symptom recognition in help-seeking for the symptoms of RA and compared this with angina and bowel cancer. METHODS: A qualitative interview study with 31 individuals and a survey of 1088 members of the general public (all without RA) were conducted. Both studies used vignettes describing the symptoms of RA, bowel cancer and angina. Participants made causal attributions and rated the perceived seriousness of the symptoms and the urgency with which they would seek medical help if confronted with these symptoms. RESULTS: Only a small proportion of participants in both studies recognised the symptoms of RA, whereas the symptoms of bowel cancer and angina were readily recognised by many participants and considered to be more serious and to require more rapid medical attention (Z values of 14.7 to 34.2, p<.001). CONCLUSION: Accurate symptom attribution and the perception that symptoms are indicative of a serious underlying condition are both important drivers for rapid help-seeking. In the case of angina and bowel cancer, recent campaigns have promoted not only recognition of symptoms and their seriousness, but also emphasised the consequences of not seeking timely help. Our results suggest that these consequences should also be addressed in any public health campaign for RA. This article is protected by copyright. All rights reserved

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

The dynamics of measles in sub-Saharan Africa.

Although vaccination has almost eliminated measles in parts of the world, the disease remains a major killer in some high birth rate countries of the Sahel. On the basis of measles dynamics for industrialized countries, high birth rate regions should experience regular annual epidemics. Here, however, we show that measles epidemics in Niger are highly episodic, particularly in the capital Niamey. Models demonstrate that this variability arises from powerful seasonality in transmission-generating high amplitude epidemics-within the chaotic domain of deterministic dynamics. In practice, this leads to frequent stochastic fadeouts, interspersed with irregular, large epidemics. A metapopulation model illustrates how increased vaccine coverage, but still below the local elimination threshold, could lead to increasingly variable major outbreaks in highly seasonally forced contexts. Such erratic dynamics emphasize the importance both of control strategies that address build-up of susceptible individuals and efforts to mitigate the impact of large outbreaks when they occur

Qualitative process study to explore the perceived burdens and benefits of a digital intervention for self-managing high blood pressure in Primary Care in the UK.

OBJECTIVES: Digital interventions can change patients' experiences of managing their health, either creating additional burden or improving their experience of healthcare. This qualitative study aimed to explore perceived burdens and benefits for patients using a digital self-management intervention for reducing high blood pressure. A secondary aim was to further our understanding of how best to capture burdens and benefits when evaluating health interventions. DESIGN: Inductive qualitative process study nested in a randomised controlled trial. SETTING: Primary Care in the UK. PARTICIPANTS: 35 participants taking antihypertensive medication and with uncontrolled blood pressure at baseline participated in semistructured telephone interviews. INTERVENTION: Digital self-management intervention to support blood pressure self-monitoring and medication change when recommended by the healthcare professional. ANALYSIS: Data were analysed using inductive thematic analysis with techniques from grounded theory. RESULTS: Seven themes were developed which reflected perceived burdens and benefits of using the intervention, including worry about health, uncertainty about self-monitoring and reassurance. The analysis showed how beliefs about their condition and treatment appeared to influence participants' appraisal of the value of the intervention. This suggested that considering illness and treatment perceptions in Burden of Treatment theory could further our understanding of how individuals appraise the personal costs and benefits of self-managing their health. CONCLUSIONS: Patients' appraisal of the burden or benefit of using a complex self-management intervention seemed to be influenced by experiences within the intervention (such as perceived availability of support) and beliefs about their condition and treatment (such as perceived control and risk of side effects). Developing our ability to adequately capture these salient burdens and benefits for patients could help enhance evaluation of self-management interventions in the future. Many participants perceived important benefits from using the intervention, highlighting the need for theory to recognise that engaging in self-management can include positive as well as negative aspects. TRIAL REGISTRATION NUMBER: ISRCTN13790648; Pre-results

The Symptom Monitoring with Feedback Trial (SWIFT):protocol for a registry‑based cluster randomised controlled trial in haemodialysis

BACKGROUND: Kidney failure prevalence is increasing worldwide. Haemodialysis, peritoneal dialysis or kidney transplantation are undertaken to extend life with kidney failure. People receiving haemodialysis commonly experience fatigue, pain, nausea, cramping, itching, sleeping difficulties, anxiety and depression. This symptom burden contributes to poor health-related quality of life (QOL) and is a major reason for treatment withdrawal and death. The Symptom monitoring WIth Feedback Trial (SWIFT) will test the hypothesis that regular symptom monitoring with feedback to people receiving haemodialysis and their treating clinical team can improve QOL. METHODS: We are conducting an Australia and New Zealand Dialysis and Transplant (ANZDATA) registry-based cluster randomised controlled trial to determine the clinical- and cost-effectiveness at 12 months, of 3-monthly symptom monitoring using the Integrated Palliative Outcome Scale-Renal (IPOS-Renal) survey with clinician feedback, compared with usual care among adults treated with haemodialysis. Participants complete symptom scoring using a tablet, which are provided to participants and to clinicians. The trial aims to recruit 143 satellite haemodialysis centres, (up to 2400 participants). The primary outcome is change in health-related QOL, as measured by EuroQol 5-Dimension, 5-Level (EQ-5D-5L) instrument. Secondary outcomes include overall survival, symptom severity (including haemodialysis-associated fatigue), healthcare utilisation and cost-effectiveness. DISCUSSION: SWIFT is the first registry-based trial in the Australian haemodialysis population to investigate whether regular symptom monitoring with feedback to participants and clinicians improves QOL. SWIFT is embedded in the ANZDATA Registry facilitating pragmatic recruitment from public and private dialysis clinics, throughout Australia. SWIFT will inform future collection, storage and reporting of patient-reported outcome measures (PROMs) within a clinical quality registry. As the first trial to rigorously estimate the efficacy and cost-effectiveness of routine PROMs collection and reporting in haemodialysis units, SWIFT will provide invaluable information to health services, clinicians and researchers working to improve the lives of those with kidney failure. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620001061921. Registered on 16 October 2020 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06355-0

Leptin Receptor Signaling and Action in the Central Nervous System

The increasing incidence of obesity in developed nations represents an ever‐growing challenge to health care by promoting diabetes and other diseases. The discovery of the hormone, leptin, a decade ago has facilitated the acquisition of new knowledge regarding the regulation of energy balance. A great deal remains to be discovered regarding the molecular and anatomic actions of leptin, however. Here, we discuss the mechanisms by which leptin activates intracellular signals, the roles that these signals play in leptin action in vivo, and sites of leptin action in vivo. Using “reporter” mice, in which LRb‐expressing (long form of the leptin receptor) neurons express the histological marker, β‐galactosidase, coupled with the detection of LRb‐mediated signal transducer and activator of transcription 3 signaling events, we identified LRb expression in neuronal populations both within and outside the hypothalamus. Understanding the regulation and physiological function of these myriad sites of central leptin action will be a crucial next step in the quest to understand mechanisms of leptin action and energy balance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93692/1/oby.2006.310.pd