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Abstract. Preeclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. This disorder has profound short-term and long-term impacts on both the affected woman's and her child's health. Early-onset PE requiring preterm delivery (preterm PE) is of particular importance because it is associated with a higher risk of adverse pregnancy outcomes than term PE. First trimester screening model developed by the Fetal Medicine Foundation (FMF), which uses Bayes-theorem to combine maternal characteristics and medical history together with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, has been proven to be effective and have superior screening performance to that of traditional risk factor-based approach for the prediction of PE. Identification of high risk pregnant women for preterm PE and giving aspirin prophylaxis before 16th week of gestation would reduce the incidence of preterm PE. In Asia, although the prevalence of PE is slightly lower than the global estimation, early screening and prevention of this life-threatening condition is still crucial. The FMF Bayes-theorem based screening method has been validated in a large-scale prospective Asia-wide study and revealed that the first trimester triple test achieves the highest detection rate, compared with the traditional risk factor-based approaches, and that the screening performance is comparable to the published data from the FMF in East Asian women. However, in order to achieve optimal screening performance, the key is to establish standardized methods for biomarker measurements and regular biomarker quality assessment, as each biomarker is susceptible to inaccurate measurement, thus affecting performance of screening. Furthermore, it is of great importance to emphasize that the optimal preventive effect of aspirin on preterm PE is clearly associated with good compliance to treatment. In conclusion, global implementation of an effective first trimester “screen and prevent” program for preterm PE would provide the opportunity to reduce the risk of both short-term maternal and perinatal morbidity and mortality, with the possibility of intergenerational prevention of future chronic diseases for both the mother and her offspring.

Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutritional supplement α-lipoic acid inhibits cystine stone formation in the Slc3a1-/- mouse model of cystinuria by increasing the solubility of urinary cystine. These findings identify a novel therapeutic strategy for the clinical treatment of cystinuria.

Black pearl Grapes are highly nutritious and one of the richest sources of polyphenols, but due to being delicate with very high loss at harvest and during distribution, is not consumed adequately. This study intended to develop functional lactic acid starter culture based fermented grapes beverage, in order to improve the quality and stability of this low pH fruit and to develop a fermented non-dairy beverage. Results showed that grapes blend was an excellent matrix for LAB growth with more than 9.38 log10 CFUml-1 of viability at the end of fermentation. LAB fermentation affectedly enhanced the total polyphenols and flavonoids content. Likewise, antioxidants capacities based on DPPH and FRAP activity were considerably increased correlating with each other, impacting the color and sensory properties of the grapes beverage. This way, the lactic acid fermentation can be considered as an appropriate tool for developing black pearl grapes based novel bio-intervention with enhanced antioxidants, polyphenols and flavonoids with anti-proliferative activity and antagonistic efficacy against recurring food borne pathogen in this post-antibiotic era.

ABSTRACT Bisphosphonates have been found to be effective in preventing fragility fractures. However, their comparative effectiveness in populations at risk has yet to be defined. In light of recent clinical trials, we aimed to compare four bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and to identify which are the most effective for the prevention of fragility fractures. This is an update of a systematic review previously published as part of a NICE HTA report. We conducted a systematic review and network meta‐analysis, updating the estimates regarding the comparative effectiveness of the aforementioned bisphosphonates. Studies identified from published and unpublished sources between 2014 and 2021 were added to the studies identified in the previous review. Screening, data extraction and risk of bias assessment were independently undertaken by two reviewers. Outcomes were fractures, femoral neck bone mineral density (BMD), mortality, and adverse events. We identified 25 additional trials, resulting in a total population of 47,007 participants. All treatments had beneficial effects on fractures versus placebo with zoledronate being the most effective treatment in preventing vertebral fractures (hazard ratio [HR] 0.38; 95% credibility interval [CrI], 0.28–0.49). Zoledronate (HR 0.71; 95% CrI, 0.61–0.81) and risedronate (HR 0.70; 95% CrI, 0.53–0.84) were found to be the most effective treatments in preventing nonvertebral fractures. All treatments were associated with increases in femoral neck BMD versus placebo with zoledronate being the most effective treatment mean difference (MD 4.02; 95% CrI, 3.2–4.84). There was a paucity of data regarding hip and wrist fractures. Depending on its cost‐effectiveness, zoledronate could be considered a first‐line option for people at increased risk of fragility fractures. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Previous studies have pointed to a role for regional cerebral hemodynamic stress in neurological complications in patients with sickle cell anemia (SCA), with watershed regions identified as particularly at risk of ischemic tissue injury. Using single- and multi-inflow time (TI) arterial spin labeling sequences (ASL) in 94 patients with SCA and 42 controls, the present study sought to investigate cerebral blood flow (CBF) and bolus arrival times (BAT) across gray matter, white matter with early arrival times, and in individual watershed areas (iWSAs). In iWSAs, associations between hemodynamic parameters, lesion burden, white matter integrity, and general cognitive performance were also explored. In patients, increases in CBF and reductions in BAT were observed in association with reduced arterial oxygen content across gray matter and white matter with early arrival times using both sequences (all p < 0.001, d = −1.55–−2.21). Across iWSAs, there was a discrepancy between sequences, with estimates based on the single-TI sequence indicating higher CBF in association with reduced arterial oxygen content in SCA patients, and estimates based on the multi-TI sequence indicating no significant between-group differences or associations with arterial oxygen content. Lesion burden was similar between white matter with early arrival times and iWSAs in both patients and controls, and using both sequences, only trend-level associations between iWSA CBF and iWSA lesion burden were observed in patients. Further, using the multi-TI sequence in patients, increased iWSA CBF was associated with reduced iWSA microstructural tissue integrity and slower processing speed. Taken together, the results highlight the need for researchers to consider BAT when estimating CBF using single-TI sequences. Moreover, the findings demonstrate the feasibility of multi-TI ASL for objective delineation of iWSAs and for detection of regional hemodynamic stress that is associated with reduced microstructural tissue integrity and slower processing speed. This technique may hold promise for future studies and treatment trials.

Background: Neurocognitive impairment is common in people with Sickle Cell Disease (SCD) and evidence is accumulating that sleep disturbances play a role. The interaction between cortisol and sleep in the general population is associated with cognition as well as general wellbeing but there are few data in SCD. We aimed to understand the relationship between cortisol and sleep in individuals with SCD and explored associations with cognition. Methods: Forty-five participants of black heritage (SCD: N = 27, 9–29 years, 16 females; Controls: N = 18, 11–25 years, 13 females) were recruited from the community between 2018 - 2020. Participants completed standardized questionnaires about their sleep behaviour and wore actigraphy MotionWatch8 for 7 nights to assess nocturnal sleep patterns. Salivary cortisol samples were taken on wakening and 3 times after 14:00. Cognition was assessed using the Wechsler Intelligence Scales for children and adults. Results: People with SCD took longer to fall asleep and experienced greater wake bouts, mobile minutes and fragmented sleep compared to controls. Although non-significant, people with SCD experienced lower morning cortisol, with a flattened diurnal cortisol ratio compared to controls. Interestingly, SCD participants, but not controls, with low diurnal variation scored lowest on processing speed (PSI) and perceptual reasoning index (PRI). A moderator analysis revealed that the effect of morning cortisol and diurnal cortisol ratio on PRI by group health (i.e., SCD and healthy controls) depended on sleep quality. Discussion: Sleep and cortisol may play a crucial role in the expression of cognitive difficulties seen in SCD. This should be considered for the development of interventions to optimise cognitive functioning and sleep. This, in turn, could positively impact on secretion of cortisol and general health in SCD.

Background People living with HIV (PLWH) are at increased risk of re-activation of latent tuberculosis infection (LTBI). Although UK and international guidelines identify this group as a priority for LTBI screening and treatment, data on attitudes of PLWH to this policy recommendation are lacking. Methods A five-point, Likert-style questionnaire was administered to PLWH to assess views and intentions towards accepting LTBI screening and treatment. Subsequent interferon-γ release assay (IGRA) testing was offered, and chemoprophylaxis if required. Influencing demographic and psychological associations with planned, and actual, testing and treatment uptake were assessed using multivariable logistic regression. Results 444 out of 716 (62%) patients responded. 417 out of 437 (95.4%) expressed intention to accept LTBI testing. The only significant association was the perceived importance of testing to the individual (adjusted odds ratio (aOR) 8.98, 95% CI 2.55–31.67). 390 out of 393 (99.2%) accepted appropriate IGRA screening; 41 out of 390 (10.5%) were positive. 397 out of 431 (92.1%) expressed intention to accept chemoprophylaxis, associated with perceived importance of treatment (aOR 3.52, 95% CI 1.46–8.51), a desire to have treatment for LTBI (aOR 1.77, 95% CI 0.99–3.15) and confidence in taking treatment (aOR 3.77, 95% CI 1.84–7.72). Of those offered chemoprophylaxis, 36 out of 37 (97.3%) accepted and 34 out of 36 (94.4%) completed treatment. There were no correlates with actual screening acceptance. Conclusions LTBI is common amongst PLWH, highlighting the importance of robust screening and treatment programmes. This study shows that screening and treatment for LTBI is highly acceptable to PLWH and provides strong, objective evidence for policy-makers developing guidelines in this cohort.

Research background. Legumes are superior sources of macro- and micronutrients which can be further enhanced by fermentation. This can assist in addressing the food security concerns. The present study aims to determine the effect of fermentation by Rhizopus oligosporus on nutritional and antinutritional composition of some commonly consumed legumes. Experimental approach. Chickpea (kabuli and desi), pigeon pea and soybean were fermented with Rhizopus oligosporus (at 34 °C for 52 h), dried at 45 °C for 16-18 h and milled. Antioxidant potential, phenolic composition, antinutrients, mineral composition and FTIR spectra of fermented and unfermented flour samples were evaluated. Results and conclusions. Fermentation significantly (p

Background: Patients with an alcohol use disorder (AUD) have an increased risk of developing complications during their hospital stays; however, how AUD impacts the length of stay (LOS) and the utilization of hospital resources remains inconclusive. Aim: This study aimed to identify the associations between AUD, defined by self-reported alcohol consumption, blood alcohol content (BAC), and hospital LOS (HLOS) including intensive care unit (ICU) LOS in the trauma patient population. Study Design: We conducted a retrospective study analyzing data obtained from 2010 to 2018 at a university-based, level-one trauma emergency department. We identified 1689 adult trauma patients who completed the AUDs identification test (AUDIT) and were admitted to the hospital. We retrieved BAC, age, gender, LOS, and injury severity score (ISS) from the patient charts. The independent samples' median test was used to assess the association of HLOS and ICULOS with ISS, BAC levels, or AUDIT scores. Results: ISS was directly associated with higher HLOS (P < 0.001) and ICULOS (P < 0.001); however there was no statistically significant association between AUDIT scores and ICULOS (P = 0.21) or HLOS (P = 0.86). There was also no statistically significant association between BAC and HLOS (P = 0.09) or ICULOS (P = 0.07). Conclusions: Our study found no associations between AUDIT, BAC, and both hospital and ICU LOS in trauma patients even though the literature supported an increased risk of medical complications in the AUD patients.

Context: Oral cavity offers diverse habitats to various species of different microorganisms; some of them, under certain conditions cause loss of connective tissue and bone, ultimately leading to periodontitis. Once such complex of bacteria often referred to as red complex bacteria consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia have been regarded as those associated with periodontitis. With increasing advances in the field of medicine N-benzoyl-DL-arginine-2-naphthylamide (BANA) test, a modern chair-side paraclinical method has been designed to detect the presence of one or more such bacteria. Aim: The aim of the study was to detect the presence of these bacteria in patients suffering from various forms of periodontitis using BANA test kit. Settings and Design: A total of 1500 patients suffering from various forms of periodontitis were selected for the study. Subjects and Methods: These were divided into three groups: Group I: Mild periodontitis, Group II: Moderate periodontitis, and Group III: Severe periodontitis. Microbial parameters were recorded using BANA test. Statistical analysis used Mann–Whitney test and Pearson's Chi-square test. Results: Group III had significantly greater percentage of BANA-positive sites followed by Group II and Group I. Conclusions: There is a positive correlation between the presence of red complex bacteria and severity of periodontitis.

Mei Lu,1 Christopher L Bowlus,2 Keith Lindor,3 Carla V Rodriguez-Watson,4 Robert J Romanelli,5 Irina V Haller,6 Heather Anderson,7 Jeffrey J VanWormer,8 Joseph A Boscarino,9 Mark A Schmidt,10 Yihe G Daida,11 Amandeep Sahota,12 Jennifer Vincent,13 Jia Li,1 Sheri Trudeau,1 Loralee B Rupp,14 Stuart C Gordon15 On Behalf of the FOLD Investigators1Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA; 2University of California Davis School of Medicine, Sacramento, CA, USA; 3College of Health Solutions, Arizona State University, Phoenix, AZ, USA; 4Center for Health Research Kaiser Permanente Mid-Atlantic Research Institute, Rockville, MD; Reagan-Udall Foundation for the FDA, Washington, DC, USA; 5Palo Alto Medical Foundation Research Institute, Palo Alto, CA, USA; 6Essentia Institute of Rural Health, Essentia Health, Duluth, MN, USA; 7Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 8Marshfield Clinic Research Foundation, Marshfield, WI, USA; 9Department of Population Health Sciences, Geisinger Clinic, Danville, PA, USA; 10Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA; 11Center for Integrated Health Care Research, Kaiser Permanente Hawai’i, Honolulu, HI, USA; 12Department of Research and Evaluation, Kaiser Permanente Southern California, Los Angeles, CA, USA; 13Baylor, Scott & White Research Institute, Temple, TX, USA; 14Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA; 15Division of Gastroenterology and Hepatology, Henry Ford Health System; and Wayne State University School of Medicine, Detroit, MI, USACorrespondence: Mei LuDepartment of Public Health Sciences, Henry Ford Health System, 3E One Ford Place, Detroit, MI 48202, USATel +1 313 874 6413Fax +1 313 874 6730Email mlu1@hfhs.orgBackground: Biopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients.Methods: Histological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and > 100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis.Results: Among 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively).Conclusion: An algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients’ cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.Keywords: primary biliary cirrhosis, cholangitis, race/gender/ethnicity, gender, ethnicity, decompensated cirrhosis, ursodeoxycholic acid, UCDA

Summary: Background: Homeless and precarious housed persons are particularly prone to traumatic brain injuries (TBIs), but existent incidence rates are hampered by poor case acquisition. We rigorously documented TBIs in precariously housed persons transitioning in and out of homelessness. Methods: Between December 2016 and May 2018, 326 precariously housed participants enrolled in a longitudinal study in Vancouver, Canada were assessed monthly for TBI occurrences after education on sequelae. Over one participant-year, 2433 TBI screenings were acquired for 326 person-years and variables associated with odds of incident TBI were evaluated. Findings: One hundred participants acquired 175 TBIs, yielding an observed incidence proportion of 30·7% and event proportion of 53·7%. Of the injured, 61% reported one TBI and 39% reported multiple injuries. Acute intoxication was present for more than half of the TBI events assessed. Additionally, 9·7% of TBI events occurred in the context of a drug overdose. Common injury mechanisms were falls (45·1%), assaults (25·1%), and hitting one's head on an object (13·1%). In this community-based but non-randomly recruited sample, exploratory analyses identified factors associated with odds of an incident TBI over one year of follow-up, including: schizophrenia disorders (odds ratio (OR) = 0·43, 95% confidence interval (CI) 0·19, 0·94), role functioning (OR = 0·69, 95% CI 0·52, 0·91), opioid dependence (OR = 2·17, 95% CI 1·27, 3·72) and those reporting past TBIs (OR = 1·99, 95% CI 1·13, 3·52). Interpretation: Given the ubiquity of TBIs revealed in this precariously housed sample, we identify an underappreciated and urgent healthcare priority. Several factors modified the odds of incident TBI, which can facilitate investigations into targeted prevention efforts. Funding: Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, William and Ada Isabelle Steel Research Fund, Simon Fraser University Vice-President Research Undergraduate Student Research Award and Simon Fraser University Psychology Department Research Grant.

The declaration of the COVID-19 pandemic necessitated rapid implementation of telehealth across all neurological subspecialties. Transitioning to telehealth technology can be challenging for physicians and health care facilities with no prior experience. Here, we describe our experience at the Neurology and Sleep Disorders Clinic at the University of Missouri-Columbia of successful transition of all in-person clinic visits to telehealth visits within a span of 2 weeks with a collaborative effort of clinic staff and the leadership. Within a month of launch, 18 clinic providers with no prior telehealth experience conducted 1451 telehealth visits, which was the 2nd highest number of telehealth visits conducted by any department at the University of Missouri-Columbia Health Care system. Lack of connectivity, poor video/audio quality, and unavailability of smart devices among rural populations were the important shortcomings identified during our telehealth experience. Our study highlighted the need for expansion of high-speed internet access across rural Missouri. We hope our experience will help other health care facilities to learn and incorporate telehealth technology at their facilities, overcome the associated challenges, and serve patient needs while limiting the spread of the COVID-19.

Objective: Iaccarino et al. (2016) [1] exposed 1 h of light flickering at 40 Hz to awake 5XFAD Alzheimer’s Disease (AD) mouse models, generating action potentials at 40 Hz, activating ∼54% of microglia to colocalize with Aβ plaque, acutely, and clearing ∼ 50% of Aβ plaque after seven days, but only in the visual cortex. Hypothesis: Transcranially delivered, focused ultrasound (tFUS) can replicate the results of Iaccarino et al. (2016) [1] but throughout its area of application. Methods: We exposed sedated 5XFAD mice to tFUS (2.0 MHz carrier frequency, 40 Hz pulse repetition frequency, 400 μs-long pulses, spatial peak pulse average value of 190 W/cm2). Acute studies targeted tFUS into one hemisphere of brain centered on its hippocampus for 1 h. Chronic studies targeted comparable brain in each hemisphere for 1 h/day for five days. Results: Acute application of tFUS activated more microglia that colocalized with Aβ plaque relative to sham ultrasound (36.0 ± 4.6% versus 14.2 ± 2.6% [mean ± standard error], z = 2.45, p

Background and purpose — There is a large volume of heterogeneous studies across all Enhanced Recovery After Surgery (ERAS®) components within total hip and total knee replacement surgery. This multidisciplinary consensus review summarizes the literature, and proposes recommendations for the perioperative care of patients undergoing total hip replacement and total knee replacement with an ERAS program. Methods — Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials, and large prospective cohort studies that evaluated the efficacy of individual items of the perioperative treatment pathway to expedite the achievement of discharge criteria. A consensus recommendation was reached by the group after critical appraisal of the literature. Results — This consensus statement includes 17 topic areas. Best practice includes optimizing preoperative patient education, anesthetic technique, and transfusion strategy, in combination with an opioid-sparing multimodal analgesic approach and early mobilization. There is insufficient evidence to recommend that one surgical technique (type of approach, use of a minimally invasive technique, prosthesis choice, or use of computer-assisted surgery) over another will independently effect achievement of discharge criteria. Interpretation — Based on the evidence available for each element of perioperative care pathways, the ERAS® Society presents a comprehensive consensus review, for the perioperative care of patients undergoing total hip replacement and total knee replacement surgery within an ERAS® program. This unified protocol should now be further evaluated in order to refine the protocol and verify the strength of these recommendations.

Abstract Background This study aims to evaluate the feasibility and acceptability of the PhunkyFoods Programme, a primary school-based intervention to promote healthy nutrition and physical activity knowledge and behaviours to assess outcomes to inform a phase 3 trial. Methods The cluster randomised feasibility trial recruited eight primary schools from the North of England. Elibility criteria included all primary schools in one town, excluding independent and special schools and schools that comprised of only key stage 2 pupils (years 3–6). Eight schools agreed to participate. Randomisation to intervention or control arms was in a 1:1 ratio. Intervention schools received PhunkyFoods over 17 months. Control schools continued with usual curriculum. Assessors were blinded to group assignment. Measures comprised of a Healthy Lifestyle Knowledge Questionnaire and Synchronised Nutrition and Activity Program to assess diet and physical activity, height, weight, and psychological wellbeing. Feasibility outcomes were recruitment, attrition rates, interviews with teaching staff, focus groups with pupils to explore the acceptability of outcome measures, implementation, intervention content, and programme fidelity. Results Three hundred fifty-eight pupils, aged 6–9 years from eight schools were recruited at baseline (control n = 170, intervention n = 188); 337 (94.1%) at 6 months (control n = 163, intervention n = 181); and 331 (92.5%) at 18 months (control n = 152, intervention n = 179), and 6 pupils opted out. Trends in increased knowledge of healthy lifestyle behaviours, healthier eating, and liking of fruit and vegetables were reported in the intervention compared to the control group. Year 4 intervention pupils had significantly higher healthy balanced diet knowledge scores compared to control pupils, mean difference 5.1 (95% CI 0.1 to 10.1, p=0.05). At 18 months, the mean percentage of vegetables liked was higher (intervention 53.9% vs. 43.0% control). Similarly, percentage of fruits liked was also higher (intervention 76.9% vs. 67.2% control). Qualitative data showed that delivery of the intervention was feasible and acceptable to teachers and pupils. Lessons were learned to inform the phase 3 trial around the dietary assessment measure and timing of recruitment. Conclusions Whilst the study was not powered to detect a definitive effect, results suggest a potential to increase knowledge of healthy lifestyle behaviours and dietary behaviours, suggesting that with minor changes, a phase 3 trial is likely to be deliverable. Trial registration ISRCTN, ISRCTN15641330. Registered 8 May 2015—retrospectively registered, https://doi.org/10.1186/ISRCTN15641330

In this work, a nano-polycrystalline Ag-doped ZnO-based threshold switching (TS) selector via a facile co-sputtering technique is investigated without using an Ag active metal layer. The effects of the Ag concentration with respect to OFF-state leakage current (Ioff) were studied, and the results demonstrate that by regulating the Ag doping concentration in the switching layer (SL), an electroforming-free switching with an Ion/Ioff ratio of ∼108 could be achieved, having an extremely low Ioff value of ∼10−13 A. Furthermore, cycling endurance can also be improved as the formation of a laterally thick and stable filament does not happen promptly with consequent measurements when there is a limited amount of Ag in the SL. The selector device performance enhancement is attributed to the doping-based polycrystalline structure that facilitates enhanced control on filament formation due to the restricted availability and anisotropic diffusion of Ag ions in the polycrystalline ZnO SL, thereby trimming down the overall stochasticity during metallic filament growth. The present study demonstrates that a doping-based polycrystalline SL structure can be implemented in a selector device to augment TS characteristics, i.e., device variances and cycling endurance for adoption in ultra-high density memory applications.

This study aimed to compare the screening performance of genome-wide cfDNA testing for chromosomal abnormalities between two periods where additional findings were reported and not reported. Data were obtained from consecutive pregnant women with a singleton pregnancy at ≥10 weeks who requested cfDNA testing during 2015–2019. The performance of screening of the cfDNA test was determined by calculating the concordance rate, detection rate, and false-positive rate. Data from 3981 women were included. The no-result rates were similar between the two reporting periods (2.04% vs. 2.08%). Concordance rates for trisomy 21 and 18 were 100% and 100%, respectively. There were two cases tested high risk for trisomy 13, with a concordance rate of 0%. In total, 12 cases were high risk for any sex chromosome aneuploidy with an overall concordance of 75%, and 15 cases tested high risk for any rare autosomal trisomy, with a 13.3% concordance rate. The detection rates for trisomy 21 and 18 were 100% and 100%, respectively. For any SCA, the detection rate was 90%. For the two reporting periods, the combined false-positive rates were 0.93% and 0.17%, which were significantly different (p = 0.002). Restricting the reporting of additional findings from genome-wide cfDNA analysis has reduced the false-positive rate but without a reduction in the no-result rate.

BackgroundSystemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy–based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA.MethodsSerum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation.ResultsUsing PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p

Background: Pubic rami fragility fractures are common in older people and result in significant morbidity and increased mortality. Co-existing fractures of the sacrum are common, but routinely missed. The aim of the study was to explore the perceptions in the assessment and treatment of pubic rami and sacral fragility fractures amongst healthcare professionals. Methods: We interviewed 14 participants about their experience in the assessment and treatment of patients presenting with pubic rami fragility fractures. Data was analyzed using an inductive thematic approach. Results: The majority of patients presenting with a pubic rami fragility fracture were managed by geriatricians. However, many of the geriatricians were not aware that these fractures have a high association with co-existing sacral fragility fractures. Furthermore, they were not aware of the limitations of standard x-ray imaging, nor of the potential benefits of surgical intervention for sacral fragility fractures. Spinal surgeons recommended that early, more specialist imaging in patients with pubic rami fragility fractures failing to mobilize, would change clinical management, if found to have a coexisting sacral fragility fracture, amenable to surgical intervention. Conclusions: The awareness, assessment and management of sacral fragility fractures in patients presenting with pubic rami fragility fractures is poor amongst healthcare professionals in geriatric medicine. Spinal surgeons in this study advocate early further imaging and surgical intervention in patients confirmed to have a concomitant sacral fragility fracture who are failing to mobilize.

Sleep disturbances, including insomnia and excessive daytime sleepiness, are highly prevalent in patients with ischemic stroke (IS), which severely impacts recovery and rehabilitation efforts. However, how IS induces sleep disturbances is unclear. Three experiments were performed on middle-aged C57BL/6J mice, instrumented with sleep recording electrodes and/or subjected to 1 h of middle cerebral artery (MCAO; Stroke group) or sham (Sham group) occlusion to induce IS. After 48 h of reperfusion (a) experiment 1 verified sensorimotor deficit (using Garcia scale) and infarction (using TTC staining) in this mouse model; (b) experiment 2 examined the effects of IS on the quality (sleep latency and NREM delta power) and quantity (duration) of sleep; and (c) experiment 3 determined the effects of IS on sleep homeostasis using sleep deprivation (SD) and recovery sleep (RS) paradigm. Stroke mice display (a) a significant correlation between sensorimotor deficit and cerebral infarction; (b) insomnia-like symptoms (increased sleep latency, reduced NREM duration and delta power) during the light (inactive) period and daytime sleepiness-like symptoms during the dark (active) period mimicking sleep in IS patients; and (c) impairments in the markers of sleep pressure (during SD) and sleep dissipation (during RS). Our results suggest that IS disrupts sleep homeostasis to cause sleep disturbances.

Abstract Objectives To investigate how personal protective equipment (PPE) guidance altered the facial hair of hospital doctors and explore the wider impact and implications of these changes. Methods A single site uncontrolled before‐after survey study examining change in facial hairstyles, and wider implications on doctor's cultural, religious, and personal wellbeing. Outcome measures included change in facial hair between January and April 2020 and whether these changes adhered to guidance set by Public Health England. Participants were also asked about the wider impact of these changes which were thematically analyzed using an inductive approach. Results Of those who completed the survey, 257 participants met the inclusion criteria. 68% (n = 67) of doctors who could grow facial hair changed their facial hairstyle during the COVID‐19 pandemic and 96% (n = 64) reported that the change was in response to PPE guidance. The odds of having a facial hairstyle that complied with PPE guidance before the pandemic was 0.32, which rose to 2.77 after guidance was released, giving an odds ratio of 8.54 (95% CI 4.49‐16.23, P

Abstract Background Children’s centres in the UK provide a setting for public health programmes; offering support to families living in the most disadvantaged areas where obesity prevalence is at its highest. Health, Exercise and Nutrition in the Really Young (HENRY) is an eight-week obesity prevention programme currently delivered in children’s centres across the UK. However, low participant engagement in some local authorities threatens its potential reach and impact. This study aimed to explore the factors influencing participant engagement with HENRY to describe where local intervention may support engagement efforts. Method A focused ethnography study was undertaken in five children’s centres delivering HENRY across the UK. One hundred and ninety hours of field observations, 22 interviews with staff (commissioners, HENRY co-ordinators, managers and facilitators) and six focus groups (36 parents), took place over five consecutive days in each centre. The Consolidated Framework for Implementation Research (CFIR) was used to guide the observations and analysis of the data. Results Three overarching themes described the factors influencing participant engagement with HENRY: local authority decision making around children’s centre programmes; children’s centre implementation of HENRY; and the participant experience of HENRY. The results indicate that factors influencing participant engagement with public health programmes begin at the commissioning body level, influencing children’s centre implementation and subsequently the experience of participants. Local authority funding priorities and constraints influence availability of places and who these places are offered to, with funding often targeted towards those deemed most at need. This was perceived to have a detrimental effect on participant experience of the programme. Conclusion In summary, participant engagement is affected by multiple factors, working at different levels of the children’s centre and local authority hierarchy, most of which are at play even before participants decide whether or not they choose to enrol and maintain attendance. For programmes to achieve their optimal reach and impact, factors at the commissioning and local implementation level need to be addressed prior to addressing participant facing issues.

Background: Chronic rhinosinusitis with and without nasal polyps (CRSwNP and CRSsNP respectively) can be difficult to treat and biologics offer potential as a future therapeutic intervention. CRS and severe asthma often co-exist. Omalizumab is currently licenced for the treatment of severe allergic asthma. Objective: The aim was to determine which blood biomarkers and treatment variables were associated with clinical response for sinonasal symptoms in patients with allergic CRSsNP and CRSwNP who were treated with omalizumab for severe allergic asthma. Methods: Sinonasal outcome test (SNOT)-22 scores were recorded in a cohort of patients with allergic CRSsNP (n=10) or CRSwNP (n=15) treated with omalizumab for severe asthma according to UK guidelines. Using a linear modelling approach, the improvement in the SNOT-22 score as the treatment variable against several disease and treatment predictor variables was modelled. Results: SNOT-22 significantly decreased with omalizumab treatment. Increased blood eosinophil count and omalizumab dosing every two weeks (as opposed to every 4 weeks) were associated with greater reductions in SNOT-22 after 16 weeks of omalizumab treatment. Conclusion: Our study confirms that omalizumab is an effective treatment for CRS, and suggests that improvements are greater in those with eosinophilic disease. Further studies are required to determine long term efficacy and whether this treatment could reduce the need for surgery.

Abstract Background Chronic rhinosinusitis (CRS) has a high prevalence of anxiety and depression. It is currently uncertain if treatment in patients with CRS with or without nasal polyps (CRSwNP and CRSsNP) has any impact on improving mental health outcomes. The aims here were to document anxiety and depression in patients with severe CRS and asthma already treated with appropriate medical therapy. We then evaluated whether further maximal treatment with omalizumab improved anxiety and/or depression alongside improvements in CRS and coassociated asthma. Methods Hospital Anxiety and Depression Scale (HADS) scores along with measures of CRS and asthma severity were recorded according to CRSwNP and CRSsNP status in n = 95 patients with severe CRS and asthma. Of this group, a further n = 23 had omalizumab for associated allergic asthma. Follow‐up measures were collected 16 weeks after omalizumab treatment. Results HADS anxiety and depression prevalence in CRS were 49.47 % and 38.95%, respectively. Within the CRSwNP and CRSsNP group 53.06% and 45.66% had raised HADS‐anxiety scores. Abnormal HADS‐depression scores were present in 40.82% and 36.95% of the CRSwNP and CRSsNP groups, respectively. Correlations for sinonasal outcome test‐22 (SNOT‐22) versus HADS total was r = 0.59 p

Objective To explore the acceptability of different bisphosphonate regimens for the treatment of osteoporosis among patients, clinicians and managers, payers and academics.Design A systematic review of primary qualitative studies. Seven databases were searched from inception to July 2019. Screening, data extraction and quality assessment of full-articles selected for inclusion were performed independently by two authors. A framework synthesis was applied to extracted data based on the theoretical framework of acceptability (TFA). The TFA includes seven domains relating to sense-making, emotions, opportunity costs, burden, perceived effectiveness, ethicality and self-efficacy. Confidence in synthesis findings was assessed.Setting Any developed country healthcare setting.Participants Patients, healthcare professionals, managers, payers and academics.Intervention Experiences and views of oral and intravenous bisphosphonates.Results Twenty-five studies were included, mostly describing perceptions of oral bisphosphonates. We identified, with high confidence, how patients and healthcare professionals make sense (coherence) of bisphosphonates by balancing perceptions of need against concerns, how uncertainty prevails about bisphosphonate perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to bisphosphonates. We identified, with moderate confidence, that bisphosphonate taking induces concern, but has the potential to engender reassurance, and that both side effects and special instructions for taking oral bisphosphonates can result in treatment burden. Finally, we identified with low confidence that multimorbidity plays a role in people’s perception of bisphosphonate acceptability.Conclusion By using the lens of acceptability, our findings demonstrate with high confidence that a theoretically informed, whole-system approach is necessary to both understand and improve adherence. Clinicians and patients need supporting to understand the need for bisphosphonates, and clinicians need to clarify to patients what constitutes bisphosphonate treatment success. Further research is needed to explore perspectives of male patients and those with multimorbidity receiving bisphosphonates, and patients receiving intravenous treatment.PROSPERO registration number CRD42019143526.

Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results.