The Effect of Blue-Light-Blocking Amber Glasses on Sleep & Affect

Sleep disturbance and mood dysregulation are widely-experienced and costly concerns, even at the sub-clinical level. Sleep disturbance and mood dysregulation are mechanistically and diagnostically linked through circadian rhythms. Blue light has strong influence on entraining circadian rhythms, and controlling blue light has become a target of many interventions aiming to improve sleep and mood. The use of amber lenses, which selectively block blue wavelengths of light, are one such intervention. Past studies have found that amber glasses can be a helpful adjunct treatment for some severe mental illness (e.g., bipolar disorder), but research has been inconclusive about how amber glasses affect people with sub-clinical sleep and mood concerns. Using a randomized crossover design with a wide variety of objective and self-report measures, the present study examined the effect of blue-blocking amber glasses on sleep quality, latency, efficiency, and duration, as well as positive and negative affect in 15 participants over a 14-day period. Overall, our results did not support our hypothesis that amber glasses would increase sleep quality, duration, and efficiency, and decrease sleep latency, although minor but non- significant positive changes were observed on some sleep outcome variables. Our results did, however, provide strong preliminary evidence that amber glasses enhance positive mood at night, and some evidence that amber glasses decrease negative mood in the morning. This study was limited by a small sample size, large interpersonal variation, and some participant noncompliance. Future studies should work to address these limitations, as well as solve extant methodological and analytical problems surrounding objective measures of sleep.Bachelor of Scienc

“I Always Worry about What Might Happen Ahead”: Implementing Safer Conception Services in the Current Environment of Reproductive Counseling for HIV-Affected Men and Women in Uganda

We explored healthcare provider perspectives and practices regarding safer conception counseling for HIV-affected clients. Methods. We conducted semistructured interviews with 38 providers (medical and clinical officers, nurses, peer counselors, and village health workers) delivering care to HIV-infected clients across 5 healthcare centres in Mbarara District, Uganda. Interview transcripts were analyzed using content analysis. Results. Of 38 providers, 76% were women with median age 34 years (range 24–57). First, we discuss providers\u27 reproductive counseling practices. Emergent themes include that providers (1) assess reproductive goals of HIV-infected female clients frequently, but infrequently for male clients; (2) offer counseling focused on "family planning" and maternal and child health; (3) empathize with the importance of having children for HIV-affected clients; and (4) describe opportunities to counsel HIV-serodiscordant couples. Second, we discuss provider-level challenges that impede safer conception counseling. Emergent themes included the following: (1) providers struggle to translate reproductive rights language into individualized risk reduction given concerns about maternal health and HIV transmission and (2) providers lack safer conception training and support needed to provide counseling. Discussion. Tailored guidelines and training are required for providers to implement safer conception counseling. Such support must respond to provider experiences with adverse HIV-related maternal and child outcomes and a national emphasis on pregnancy prevention

The TIGGE project and its achievements

TIGGE was a major component of the THORPEX (The Observing System Research and Predictability Experiment) research program, whose aim is to accelerate improvements in forecasting high-impact weather. By providing ensemble prediction data from leading operational forecast centers, TIGGE has enhanced collaboration between the research and operational meteorological communities and enabled research studies on a wide range of topics. The paper covers the objective evaluation of the TIGGE data. For a range of forecast parameters, it is shown to be beneficial to combine ensembles from several data providers in a Multi-model Grand Ensemble. Alternative methods to correct systematic errors, including the use of reforecast data, are also discussed. TIGGE data have been used for a range of research studies on predictability and dynamical processes. Tropical cyclones are the most destructive weather systems in the world, and are a focus of multi-model ensemble research. Their extra-tropical transition also has a major impact on skill of mid-latitude forecasts. We also review how TIGGE has added to our understanding of the dynamics of extra-tropical cyclones and storm tracks. Although TIGGE is a research project, it has proved invaluable for the development of products for future operational forecasting. Examples include the forecasting of tropical cyclone tracks, heavy rainfall, strong winds, and flood prediction through coupling hydrological models to ensembles. Finally the paper considers the legacy of TIGGE. We discuss the priorities and key issues in predictability and ensemble forecasting, including the new opportunities of convective-scale ensembles, links with ensemble data assimilation methods, and extension of the range of useful forecast skill

Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

BACKGROUND: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. METHODS: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. FINDINGS: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. CONCLUSIONS: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Point-of-care testing in paediatric settings in the UK and Ireland: A cross-sectional study

Background: Point-of-care testing (POCT) is diagnostic testing performed at or near to the site of the patient. Understanding the current capacity, and scope, of POCT in this setting is essential in order to respond to new research evidence which may lead to wide implementation. Methods: A cross-sectional online survey study of POCT use was conducted between 6th January and 2nd February 2020 on behalf of two United Kingdom (UK) and Ireland-based paediatric research networks (Paediatric Emergency Research UK and Ireland, and General and Adolescent Paediatric Research UK and Ireland). Results: In total 91/109 (83.5%) sites responded, with some respondents providing details for multiple units on their site based on network membership (139 units in total). The most commonly performed POCT were blood sugar (137/139; 98.6%), urinalysis (134/139; 96.4%) and blood gas analysis (132/139; 95%). The use of POCT for Influenza/Respiratory Syncytial Virus (RSV) (45/139; 32.4%, 41/139; 29.5%), C-Reactive Protein (CRP) (13/139; 9.4%), Procalcitonin (PCT) (2/139; 1.4%) and Group A Streptococcus (5/139; 3.6%) and was relatively low. Obstacles to the introduction of new POCT included resources and infrastructure to support test performance and quality assurance. Conclusion: This survey demonstrates significant consensus in POCT practice in the UK and Ireland but highlights specific inequity in newer biomarkers, some which do not have support from national guidance. A clear strategy to overcome the key obstacles of funding, evidence base, and standardising variation will be essential if there is a drive toward increasing implementation of POCT

Carbapenem resistance expressed by Gram-negative bacilli isolated from a cohort of Libyan patients

Background and objectives: Carbapenem-resistant Enterobacteriaceae (CRE) and other Gram-negative bacteria are among the most common pathogens responsible for both community and hospital acquired infection. The global spread of cephalosporinases in Enterobacteriaceae has led to the increased use of carbapenems resulting in the emergence and rapid spread of CRE. This has become an alarming public health concern, yet the condition in Libya remains unclear. The aim of this study was to obtain a better understanding of CRE strains prevalent in Libyan patients by investigating their phenotypic characteristics and antibiograms. Methods: Gram-negative bacterial species were collected from Misrata Central Hospital, Misrata Cancer Centre and Privet Pathology Laboratories. Clinical samples and swabs were obtained from hospitalised and non-hospitalised patients and from mechanical ventilation and suction machines. Patients who had received antibiotic therapy for at least three days prior to the study were excluded. The identification and characterization of the isolated species were achieved using the growth characteristics on MacConkey and blood agar, spot tests and API 20E or API 20NE biochemical testing systems. Screening for carbapenem resistance was performed using the disk diffusion method with carbapenem 10 μg and cephalosporin 30 μg disks and minimum inhibitory concentrations (MIC) determined using the Sensititre Gram-negative Xtra plate format (GNX2F). All strains demonstrating resistance or reduced susceptibility to one of the four carbapenems were subjected to carbapenememase activity detection using the RAPIDEC CARBA NP test, Modified Hodge test and carbapenem inactivation methods. Results: A total of one hundred and forty isolates representing fourteen bacterial species were isolated from 140 non-duplicated specimens. Clinical specimens included urine samples (96/140, 68.57%), sputum (15/140, 10.71%), surgical wound swabs (18/140, 12.85%), foot swabs from diabetes mellitus (DM) patients (6/140, 4.29%), ear swabs (3/140, 2.14%) and wound swabs (2/140, 1.43%). Thirty-four (24.29%) isolates demonstrated resistance to at least one of the four carbapenems with Klebsiella pneumoniae representing 73.53% (25 isolates) of all carbapenem resistant species, followed by 8.82% for Pseudomonas aeruginosa (3 isolates), 5.88% for both Proteus mirabilis (2 isolates) and Escherichia coli (2 isolates) and 2.94% for both Citrobacter koseri (1 isolate) and Rahnella aquatilis (1 isolate). The other isolates were either susceptible or cephalosporinase producers. Conclusion: This study has revealed the high rate of carbapenem resistance amongst Libyan patients and emphasizes the crucial need for accurate screening, identification and susceptibility testing to prevent further spread of nosocomial and community acquired resistance. This may be achieved through the establishment of antibiotic stewardship programmes along with firm infection control practices.National Research Foundation of South Africa; Libyan GovernmentWeb of Scienc

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research