Exploring atmospheric optical turbulence: observations across zenith angles.

We present measurements of the atmospheric optical turbulence as a function of zenith angle using two identical instruments, Shack-Hartmann Image Motion Monitors (SHIMMs), to measure atmospheric parameters concurrently. One instrument was pointed near zenith, while the other collected data by tracking a single star until it set and thus sampling zenith angles continuously to the horizon. By comparing these measurements, we can attribute changes in the atmospheric parameters to the changing zenith angle rather than variations in local turbulence conditions. The primary purpose of this experiment is to make comparisons between the measurements of the scintillation index, σ I2, and Fried parameter, r 0, with current theories. In this demonstration, we find that there is a strong agreement between the models and the instrument up until zenith angles of 70∘, above which model and measurements begin to deviate. We discuss various ways in which limitations in models and our instrument may cause these deviations.

Land management shapes drought responses of dominant soil microbial taxa across grasslands.

Soil microbial communities are dominated by a relatively small number of taxa that may play outsized roles in ecosystem functioning, yet little is known about their capacities to resist and recover from climate extremes such as drought, or how environmental context mediates those responses. Here, we imposed an in situ experimental drought across 30 diverse UK grassland sites with contrasting management intensities and found that: (1) the majority of dominant bacterial (85%) and fungal (89%) taxa exhibit resistant or opportunistic drought strategies, possibly contributing to their ubiquity and dominance across sites; and (2) intensive grassland management decreases the proportion of drought-sensitive and non-resilient dominant bacteria-likely via alleviation of nutrient limitation and pH-related stress under fertilisation and liming-but has the opposite impact on dominant fungi. Our results suggest a potential mechanism by which intensive management promotes bacteria over fungi under drought with implications for soil functioning.

Real-world treatment sequencing and survival in previously treated advanced renal cell carcinoma patients receiving nivolumab monotherapy: a UK retrospective cohort study.

BACKGROUND: The CheckMate 025 trial established nivolumab monotherapy as one of the standards of care in previously treated advanced or metastatic renal cell carcinoma (aRCC). However, supporting real-world data is lacking. This study investigated characteristics, treatment sequences and clinical outcomes of patients who received nivolumab monotherapy for previously treated aRCC in the UK. METHODS: This was a retrospective cohort study of aRCC patients treated with nivolumab at second line or later (2L +) at 4 UK oncology centres. Eligible patients commenced nivolumab (index date) between 01 March 2016 and 30 June 2018 (index period). Study data were extracted from medical records using an electronic case report form. Data cut-off (end of follow-up) was 31 May 2019. RESULTS: In total, 151 patients were included with median follow-up of 15.2 months. Mean age was 66.9 years, male preponderance (72.2%), and mostly Eastern Cooperative Oncology Group performance status grade 0-1 (71.5%). Amongst 112 patients with a known International Metastatic RCC Database Consortium score, distribution between favourable, intermediate, and poor risk categories was 20.5%, 53.6%, and 25.9% respectively. The majority of patients (n = 109; 72.2%) received nivolumab at 2L, and these patients had a median overall survival (OS) of 23.0 months [95% confidence interval: 17.2, not reached]. All patients who received nivolumab at 2L had received TKIs at 1L. Amongst the 42 patients (27.8%) who received nivolumab in third line or later (3L +) the median OS was 12.4 months [95% CI: 8.8, 23.2]. The most common reasons for nivolumab discontinuation were disease progression (2L: 61.2%; 3L: 68.8%) and adverse events (2L: 34.7%; 3L: 28.1%). CONCLUSION: This study provides real-world evidence on the characteristics, treatment sequences, and outcomes of aRCC patients who received 2L + nivolumab monotherapy in the UK. Nivolumab-specific survival outcomes were similar to those achieved in the CheckMate 025 trial.

Psychedelic-assisted psychotherapy to treat psychiatric and existential distress in life-threatening medical illnesses and palliative care.

Psychiatric and existential distress commonly occur in advanced cancer and other serious, life-threatening or end-of-life medical illnesses and are associated with poor medical and psychiatric outcomes. Currently available treatment modalities in this patient population, including medication and psychotherapy, are limited in effectiveness, especially regarding existential distress. The lack of effective psycho-spiritual interventions is a critical shortcoming in palliative care and represents a high unmet need in medicine. In this commentary, we review the rationale of researching and developing psychedelic-assisted psychotherapy as a novel pharmacologic-psychotherapeutic intervention to treat psychiatric and existential distress in life-threatening medical conditions and palliative care. This paper reviews efficacy data from first and second waves of psychedelic research, and future directions for research and implementation science. More rigorous research, especially funded by governments, is needed to assess effectiveness and mechanisms of action of psychedelic therapies to treat psychiatric and existential distress in life-threatening medical illnesses and palliative care. If psychedelic-assisted treatments were made available as approved and prescribable medications in people with serious medical illnesses, it could be a significant development that opens up a pathway for clinical dissemination and public health impact internationally.

Long-term trends in critical care admissions in Wales*.

As national populations age, demands on critical care services are expected to increase. In many healthcare settings, longitudinal trends indicate rising numbers and proportions of patients admitted to ICU who are older; elsewhere, including some parts of the UK, a decrease has raised concerns with regard to rationing according to age. Our aim was to investigate admission trends in Wales, where critical care capacity has not risen in the last decade. We used the Secure Anonymised Information Linkage Databank to identify and characterise critical care admissions in patients aged ≥ 18 years from 1 January 2008 to 31 December 2017. We categorised 85,629 ICU admissions as youngest (18-64 years), older (65-79 years) and oldest (≥ 80 years). The oldest group accounted for 15% of admissions, the older age group 39% and the youngest group 46%. Relative to the national population, the incidence of admission rates per 10,000 population in the oldest group decreased significantly over the study period from 91.5/10,000 in 2008 to 77.5/10,000 (a relative decrease of 15%), and among the older group from 89.2/10,000 in 2008 to 75.3/10,000 in 2017 (a relative decrease of 16%). We observed significant decreases in admissions with high comorbidity (modified Charlson comorbidity index); increases in the proportion of older patients admitted who were considered 'fit' rather than frail (electronic frailty index); and decreases in admissions with a medical diagnosis. In contrast to other healthcare settings, capacity constraints and surgical imperatives appear to have contributed to a relative exclusion of older patients presenting with acute medical illness.

Guideline for the management of hip fractures 2020: Guideline by the Association of Anaesthetists.

We convened a multidisciplinary Working Party on behalf of the Association of Anaesthetists to update the 2011 guidance on the peri-operative management of people with hip fracture. Importantly, these guidelines describe the core aims and principles of peri-operative management, recommending greater standardisation of anaesthetic practice as a component of multidisciplinary care. Although much of the 2011 guidance remains applicable to contemporary practice, new evidence and consensus inform the additional recommendations made in this document. Specific changes to the 2011 guidance relate to analgesia, medicolegal practice, risk assessment, bone cement implantation syndrome and regional review networks. Areas of controversy remain, and we discuss these in further detail, relating to the mode of anaesthesia, surgical delay, blood management and transfusion thresholds, echocardiography, anticoagulant and antiplatelet management and postoperative discharge destination. Finally, these guidelines provide links to supplemental online material that can be used at readers' institutions, key references and UK national guidance about the peri-operative care of people with hip and periprosthetic fractures during the COVID-19 pandemic.

Identifying children with Cystic Fibrosis in population-scale routinely collected data in Wales: A Retrospective Review.

INTRODUCTION: The challenges in identifying a cohort of people with a rare condition can be addressed by routinely collected, population-scale electronic health record (EHR) data, which provide large volumes of data at a national level. This paper describes the challenges of accurately identifying a cohort of children with Cystic Fibrosis (CF) using EHR and their validation against the UK CF Registry. OBJECTIVES: To establish a proof of principle and provide insight into the merits of linked data in CF research; to identify the benefits of access to multiple data sources, in particular the UK CF Registry data, and to demonstrate the opportunity it represents as a resource for future CF research. METHODS: Three EHR data sources were used to identify children with CF born in Wales between 1st January 1998 and 31st August 2015 within the Secure Anonymised Information Linkage (SAIL) Databank. The UK CF Registry was later acquired by SAIL and linked to the EHR cohort to validate the cases and explore the reasons for misclassifications. RESULTS: We identified 352 children with CF in the three EHR data sources. This was greater than expected based on historical incidence rates in Wales. Subsequent validation using the UK CF Registry found that 257 (73%) of these were true cases. Approximately 98.7% (156/158) of individuals identified as CF cases in all three EHR data sources were confirmed as true cases; but this was only the case for 19.8% (20/101) of all those identified in just a single data source. CONCLUSION: Identifying health conditions in EHR data can be challenging, so data quality assurance and validation is important or the merit of the research is undermined. This retrospective review identifies some of the challenges in identifying CF cases and demonstrates the benefits of linking cases across multiple data sources to improve quality.

The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.

BACKGROUND: Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce. OBJECTIVES: To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival. METHODS: We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome. RESULTS: During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90). CONCLUSIONS: Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.

Does the frequency of routine follow-up after curative treatment for head-and-neck cancer affect survival?

Background: Routine follow-up is a cornerstone of oncology practice, but evidence to support most aspects of follow-up is lacking. Our objective was to investigate the relationship between frequency of routine follow-up and survival. Methods: This population-based study used electronic health care data relating to 5310 patients from Ontario diagnosed with squamous-cell head-and-neck cancer during 2007-2012. Treatments included surgery (24.6%), radiotherapy with or without chemotherapy (52.4%), and combined surgery and radiotherapy (23%). We determined the oncologist who was following each patient after treatment; calculated the average follow-up visits to the oncologist during the subsequent 2.5 years for all patients who were doing well; and used Kaplan-Meier and multiple variable regression analysis to compare, by treatment, overall survival for patients in the high, typical, and low follow-up oncologist groups. Results: Many oncologists saw patients 40%-80% more often than other oncologists did. No relationship of appointment frequency with survival was observed for patients in any treatment group. Conclusions: The practice of routine follow-up varies and is costly both to a health care system and to patients. Without evidence about the effectiveness of current policies, further research is required to investigate new or optimal practices.

Guidelines for the peri-operative care of people with dementia: Guidelines from the Association of Anaesthetists.

Ageing populations have greater incidences of dementia. People with dementia present for emergency and, increasingly, elective surgery, but are poorly served by the lack of available guidance on their peri-operative management, particularly relating to pharmacological, medico-legal, environmental and attitudinal considerations. These guidelines seek to deliver such guidance, by providing information for peri-operative care providers about dementia pathophysiology, specific difficulties anaesthetising patients with dementia, medication interactions, organisational and medico-legal factors, pre-, intra- and postoperative care considerations, training, sources of further information and care quality improvement tools.

Anaesthetic aspects in the treatment of fragility fracture patients.

As longevity increases globally, the number of older, frailer, comorbid patients requiring fragility fracture surgery will increase. Fundamentally, anaesthesia should aim to maintain these patients' pre-fracture cognitive and physiological trajectories and facilitate early (ie day 1) postoperative recovery. This review describes the 10 general principles of anaesthesia for fragility fracture surgery that best achieve these aims: multidisciplinary care, 'getting it right first time', timely surgery, standardisation, sympathetic anaesthesia, avoiding ischaemia, sympathetic analgesia, re-enablement, data collection and training.

Variation in routine follow-up care after curative treatment for head-and-neck cancer: a population-based study in Ontario.

Background: The actual practices of routine follow-up after curative treatment for head-and-neck cancer are unknown, and existing guidelines are not evidence-based. Methods: This retrospective population-based study used administrative data to describe 5 years of routine follow-up care in 3975 head-and-neck cancer patients diagnosed between 2007 and 2012 in Ontario. Results: The mean number of visits per year declined during the follow-up period (from 7.8 to 1.9, p < 0.001). The proportion of patients receiving visits in concordance with guidelines ranged from 80% to 45% depending on the follow-up year. In at least 50% of patients, 1 head, neck, or chest imaging test was performed in the first follow-up year; that proportion subsequently declined (p < 0.001). Factors associated with follow-up practices included comorbidity, tumour site, treatment, geographic region, and physician specialty (p < 0.05). Conclusions: Given current practice variation and the absence of an evidence-based standard, the challenge in identifying a single optimal follow-up strategy might be better addressed with a harmonized approach to providing individualized follow-up care.

Oxidative ß-C-H sulfonylation of cyclic amines.

A transition metal-free strategy for the dehydrogenative ß-sulfonylation of tertiary cyclic amines is described. N-Iodosuccinimide facilitates regioselective oxidative sulfonylation at C-H bonds positioned ß to the nitrogen atom of tertiary amines, installing enaminyl sulfone functionality in cyclic systems. Mild reaction conditions, broad functional group tolerance and a wide substrate scope are demonstrated. The nucleophilic character of the enaminyl sulfone is harnessed, demonstrating potential application for scaffold diversification.

Health outcomes for youth with type 1 diabetes at 18 months and 30 months post transition from pediatric to adult care.

AIMS: To identify (a) determinants of glycated haemoglobin (HbA1c) at 18 and 30 months following transition in young people with Type 1 diabetes mellitus (T1DM) to a youth-specific diabetes service; and to (b) evaluate the impact of the service on acute admissions with diabetic ketoacidosis (DKA) over a 14-year period. METHODS: An audit of records of youth with T1DM referred from paediatric services to the multidisciplinary transition service at Westmead Hospital, from 2001 to 2012, and followed-up to 2014. RESULTS: Data from 439 adolescents and young adults (Median age: 18) were analysed. The recommended standard of glycaemic control, HbA1c < 7.5% (58 mmol/mol), was achieved by 23% at baseline, 22% at 18-months, and 20% at 30-month. After adjusting for lag time (>3 months) and diabetes duration (>7 years), glycaemic control at first visit predicted subsequent glycaemic control at 18-month and 30-month follow-up. From 2001 to 2014, only 8.6% were lost to follow-up; admissions and readmissions for DKA reduced from 72% (32/47) to 4% (14/340) (p < 0.001). Furthermore, mean length of stay (LOS) significantly decreased from 6.56 to 2.36 days (p < 0.001). CONCLUSIONS: Continuing engagement with the multidisciplinary transition service prevented deterioration in HbA1c following transition. Age-appropriate education and regular follow-up prevents DKA admissions and significantly reduced admission LOS.

An observational feasibility study of a new anaesthesia drug storage tray.

Drug errors in the anaesthetic domain remain a serious cause of iatrogenic harm. To help reduce this issue, we explored the potential safety impact of using a simple colour-coded tray for anaesthetic drug preparation and storage. Over a six-month period, three different trained researchers observed 30 cases at three NHS Trusts. Ten observations involved standard drug trays in 'normal' practice, and 20 observations, involved 'Rainbow trays' before and after their introduction. We conducted 20 semi-structured interviews immediately after completing the Rainbow tray observation with the anaesthetists involved. All discussions and detailed notes taken were transcribed, qualitatively analysed using line-by-line coding and then synthesised into narrative themes. We found that using standard, single compartment trays enabled quick, cheap, and portable drug preparation and storage, but was linked to potential or actual harmful errors, such as syringe swaps. Rainbow trays were perceived to be easy to use and effective at all three sites, aiding drug identification and separation, and hence likely to reduce drug error and increase patient safety. We have demonstrated that it is feasible to introduce a new colour-coded compartmentalised Rainbow drugs tray into clinical practice at three NHS hospitals in England. Further research is needed into their effect on the prevalence of drug error.

Assessment of neuronal autoantibodies in patients with small cell lung cancer treated with chemotherapy with or without ipilimumab.

Small-cell lung cancer (SCLC) is often associated with paraneoplastic syndromes. To assess the role of anti-neuronal autoantibodies (NAAs) as biomarkers of treatment outcome, we assessed NAAs in serial samples from SCLC patients treated with chemoimmunotherapy compared to chemotherapy alone. We evaluated 2 cohorts: in cohort 1 (C1), 47 patients received standard platinum/etoposide, and in cohort 2 (C2), 38 patients received ipilimumab, carboplatin and etoposide. Serum samples at baseline and subsequent time points were analyzed for the presence of NAAs. NAAs were detected at baseline in 25 patients (53.2%) in C1 and in 20 patients (52.6%) in C2 (most frequently anti-Sox1). NAA at baseline was associated with limited disease (75% vs 50%; p: 0.096) and better overall survival (15.1 m vs 11.7 m; p: 0.032) in C1. Thirteen patients (28.9%) showed 2 or more reactivities before treatment; this was associated with worse PFS (5.5 m vs 7.3 m; p: 0.005) in patients treated with chemoimmunotherapy. NAA titers decreased after therapy in 68.9% patients, with no differential patterns of change between cohorts. Patients whose NAA titer decreased after treatment, showed longer OS [18.5 m (95% CI: 15.8 - 21.2)] compared with those whose NAA increased [12.3 m (95% CI: 8.1 - 16.5; p 0.049)], suggesting that antibody levels correlate to tumor load. Our findings reinforce the role of NAAs as prognostic markers and tumor activity/burden in SCLC, warrant further investigation in their predictive role for immunotherapy and raise concern over the use of immunotherapy in patients with more than one anti-NAA reactivity.