The issue of hysteresis in perovskite solar cells has now been convincingly linked to the presence of mobile ions within the perovskite layer. Here we test the limits of the ionic theory by ...attempting to account for a number of exotic characterization results using a detailed numerical device model that incorporates ionic charge accumulation at the perovskite interfaces. Our experimental observations include a temporary enhancement in open-circuit voltage following prolonged periods of negative bias, dramatically S-shaped current-voltage sweeps, decreased current extraction following positive biasing or "inverted hysteresis", and non-monotonic transient behaviours in the dark and the light. Each one of these phenomena can be reproduced and ultimately explained by our models, providing further evidence for the ionic theory of hysteresis as well as valuable physical insight into the factors that coincide to bring these phenomena about. In particular we find that both interfacial recombination and carrier injection from the selective contacts are heavily affected by ionic accumulation, and are essential to explaining the non-monotonic voltage transients and S-shaped J-V curves. Inverted hysteresis is attributed to the occurrence of "positive" ionic accumulation, which may also be responsible for enhancing the stabilized open-circuit voltage in some perovskite cells.
Objective
To compare fall incidence, and visual acuity and refractive status, before surgery and after first and second eye cataract surgery.
Design, setting
Prospective observational study in eight ...tertiary referral ophthalmology clinics in public hospitals in Sydney, Melbourne, and Perth.
Participants
People aged 65 years or more referred for bilateral age‐related cataract surgery during 2013–16, followed for maximum of 24 months after study entry or until six months after second eye surgery, whichever was shorter.
Main outcome measures
Primary outcome: age‐ and sex‐adjusted incidence of falls. Secondary outcomes: visual acuity and refractive error.
Results
The mean age of the 409 included participants was 75.4 years (SD, 5.4 years); 220 were women (54%). Age‐ and sex‐adjusted fall incidence prior to surgery was 1.17 (95% CI, 0.95–1.43) per year, 0.81 (95% CI, 0.63–1.04) per year after first eye surgery, and 0.41 (95% CI, 0.29–0.57) per year after second eye surgery. For the 118 participants who underwent second eye surgery and participated in all follow‐up visits, age‐ and sex‐adjusted incidence before (0.80 95% CI, 0.55–1.15 falls per year) and after first eye surgery (0.81 95% CI, 0.57–1.15 falls per year) was similar, but was lower after second eye surgery (0.32 95% CI 0.21–0.50 falls per year). Mean habitual binocular visual acuity (logMAR) was 0.32 (SD, 0.21) before surgery, 0.15 (SD, 0.17) after first eye surgery, and 0.07 (SD, 0.15) after second eye surgery.
Conclusions
First eye surgery substantially improves vision in older people with cataract, but second eye surgery is required to minimise fall incidence. Timely cataract surgery for both eyes not only optimises vision in older people with cataract, but also reduces their risk of injury from falls.
Social media use has potential to facilitate the rapid dissemination of research evidence to busy health and social care practitioners. This study aims to quantitatively synthesize evidence of the ...between- and within-group effectiveness of social media for dissemination of research evidence to health and social care practitioners. It also compared effectiveness between different social media platforms, formats, and strategies. We searched electronic databases for articles in English that were published between January 1, 2010, and January 10, 2023, and that evaluated social media interventions for disseminating research evidence to qualified, postregistration health and social care practitioners in measures of reach, engagement, direct dissemination, or impact. Screening, data extraction, and risk of bias assessments were carried out by at least 2 independent reviewers. Meta-analyses of standardized pooled effects were carried out for between- and within-group effectiveness of social media and comparisons between platforms, formats, and strategies. Certainty of evidence for outcomes was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. In total, 50 mixed-quality articles that were heterogeneous in design and outcome were included (n=9, 18% were randomized controlled trials RCTs). Reach (measured in number of practitioners, impressions, or post views) was reported in 26 studies. Engagement (measured in likes or post interactions) was evaluated in 21 studies. Direct dissemination (measured in link clicks, article views, downloads, or altmetric attention score) was analyzed in 23 studies (8 RCTs). Impact (measured in citations or measures of thinking and practice) was reported in 13 studies. Included studies almost universally indicated effects in favor of social media interventions, although effect sizes varied. Cumulative evidence indicated moderate certainty of large and moderate between-group effects of social media interventions on direct dissemination (standardized mean difference SMD 0.88; P=.02) and impact (SMD 0.76; P<.001). After social media interventions, cumulative evidence showed moderate certainty of large within-group effects on reach (SMD 1.99; P<.001), engagement (SMD 3.74; P<.001), and direct dissemination (SMD 0.82; P=.004) and low certainty of a small within-group effect on impacting thinking or practice (SMD 0.45; P=.02). There was also evidence for the effectiveness of using multiple social media platforms (including Twitter, subsequently rebranded X; and Facebook), images (particularly infographics), and intensive social media strategies with frequent, daily posts and involving influential others. No included studies tested the dissemination of research evidence to social care practitioners. Social media was effective for disseminating research evidence to health care practitioners. More intense social media campaigns using specific platforms, formats, and strategies may be more effective than less intense interventions. Implications include recommendations for effective dissemination of research evidence to health care practitioners and further RCTs in this field, particularly investigating the dissemination of social care research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. The accumulation of the substrates; ...cholesterol esters and triglycerides, significantly impacts cellular function. Untreated patients die within the first 12 months of life. Clinically, patients present severely malnourished, with diarrhoea and hepatosplenomegaly, many have an inflammatory phenotype, including with hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplant (HCT) had been historically the only treatment available but has a high procedure-related mortality because of disease progression and disease-associated morbidities. More recently, enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) has significantly improved patient survival. However, ERT is life long, expensive and its utility is limited by anti-drug antibodies (ADA) and the need for central venous access.
We describe five Wolman disease patients diagnosed in infancy that were treated at Royal Manchester Children's Hospital receiving ERT with DSR then HCT-multimodal therapy. In 3/5 an initial response to ERT was attenuated by ADA with associated clinical and laboratory features of deterioration. 1/5 developed anaphylaxis to ERT and the other patient died post HCT with ongoing HLH. All patients received allogeneic HCT. 4/5 patients are alive, and both disease phenotype and laboratory parameters are improved compared to when they were on ERT alone. The gastrointestinal symptoms are particularly improved after HCT, with reduced diarrhoea and vomiting. This allows gradual structured normalisation of diet with improved tolerance of dietary fat. Histologically there are reduced cholesterol clefts, fewer foamy macrophages and an improved villous structure. Disease biomarkers also show improvement with ERT, immunotherapy and HCT. Three patients have mixed chimerism after HCT, indicating a likely engraftment-defect in this condition.
We describe combined ERT, DSR and HCT, multimodal treatment for Wolman disease. ERT and DSR stabilises the sick infant and reduces the formerly described prohibitively high, transplant-associated mortality in this condition. HCT abrogates the problems of ERT, namely attenuating ADA, the need for continuing venous access, and continuing high cost drug treatment. HCT also brings improved efficacy, particularly evident in improved gastrointestinal function and histology. Multimodal therapy should be considered a new paradigm of treatment for Wolman disease patients where there is an attenuated response to ERT, and for all patients where there is a well-matched transplant donor, in order to improve long term gut function, tolerance of a normal diet and quality of life.
Sebelipase alfa (KanumaR) is approved for patients with Wolman disease (WD) at a dosage of 3-5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting ...more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials. We recruited 3 patients receiving Sebelipase alfa 5 mg/kg twice weekly. We measured LAL activity in leukocytes and plasma oxysterol concentration in two patients and LAL activity in fibroblasts in one patient. Clinical follow up was also assessed. Analyses of LAL activity and oxysterols demonstrate that there is short-lived enzyme activity post-dosing which is associated with the release of stored lipids. Clinical data demonstrate that 5 mg/kg twice weekly dosing is well tolerated and effective. 5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the 'trough' periods before the next dosing, even with this intensive regimen.
Hyperpolarized
C-MRI is an emerging tool for probing tissue metabolism by measuring
C-label exchange between intravenously injected hyperpolarized 1-
Cpyruvate and endogenous tissue lactate. Here, we ...demonstrate that hyperpolarized
C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric
H-MRI and hyperpolarized
C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter
and lactate dehydrogenase A (
), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of
and the hypoxia marker
was associated with reduced relapse-free and overall survival. Hyperpolarized
C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.
The needs of thin-film solar cells are a significant driver in transparent conductor research, making it vital that these requirements are properly understood. Here we demonstrate that the oft-quoted ...need for sheet resistances less than 10 Omega sq super(-1) arises only when the addition of a metal grid is unfeasible, and for cells of a particular size. In addition we show that the performance of a highly transparent layer with a metal grid is generally superior to that of a single layer fulfilling the 10 Omega sq super(-1) requirement without a grid. In order to clarify these issues we introduce simple measures of electrode performance which correspond directly to cell efficiency. These specialized figures of merit can be applied to electrodes with or without a metal grid, and also to those embedded in a tandem cell where good electrode performance is often imperative. By comparison we show that the ratio of DC to optical conductivity, the most widely used figure of merit for transparent conductors, is a bad predictor of performance in a solar cell. Our work jointly motivates the development of scalable techniques for incorporating thin metal wires into front-side electrodes, and research into transparent conductors which prioritize transparency over sheet resistance.
Organometal halide perovskite-based solar cells have rapidly achieved high efficiency in recent years. However, many fundamental recombination mechanisms underlying the excellent performance are ...still not well understood. Here we apply confocal photoluminescence microscopy to investigate the time and spatial characteristics of light-induced trap de-activation in CH3NH3PbI3 perovskite films. Trap de-activation is characterized by a dramatic increase in PL emission during continuous laser illumination accompanied by a lateral expansion of the PL enhancement far beyond the laser spot. These observations are attributed to an oxygen-assisted trap de-activation process associated with carrier diffusion. To model this effect, we add a trap de-activation term to the standard semiconductor carrier recombination and diffusion models. With this approach we are able to reproduce the observed temporal and spatial dependence of laser induced PL enhancement using realistic physical parameters. Furthermore, we experimentally investigate the role of trap diffusion in this process, and demonstrate that the trap de-activation is not permanent, with the traps appearing again once the illumination is turned off. This study provides new insights into recombination and trap dynamics in perovskite films that could offer a better understanding of perovskite solar cell performance.
Patients with phenylketonuria (PKU) are reliant on special low protein foods (SLPFs) as part of their dietary treatment. In England, several issues regarding the accessibility of SLPFs through the ...national prescribing system have been highlighted. Therefore, prescribing patterns and expenditure on all SLPFs available on prescription in England (
= 142) were examined. Their costs in comparison to regular protein-containing (
= 182) and
products (
= 135) were also analysed. Similar foods were grouped into subgroups (
= 40). The number of units and costs of SLPFs prescribed in total and per subgroup from January to December 2020 were calculated using National Health Service (NHS) Business Service Authority (NHSBSA) ePACT2 (electronic Prescribing Analysis and Cost Tool) for England. Monthly patient SLPF units prescribed were calculated using patient numbers with PKU and non-PKU inherited metabolic disorders (IMD) consuming SLPFs. This was compared to the National Society for PKU (NSPKU) prescribing guidance. Ninety-eight percent of SLPF subgroups (
39/40) were more expensive than regular and
food subgroups. However, costs to prescribe SLPFs are significantly less than theoretical calculations. From January to December 2020, 208,932 units of SLPFs were prescribed (excluding milk replacers), costing the NHS £2,151,973 (including milk replacers). This equates to £962 per patient annually, and prescribed amounts are well below the upper limits suggested by the NSPKU, indicating under prescribing of SLPFs. It is recommended that a simpler and improved system should be implemented. Ideally, specialist metabolic dietitians should have responsibility for prescribing SLPFs. This would ensure that patients with PKU have the necessary access to their essential dietary treatment, which, in turn, should help promote dietary adherence and improve metabolic control.
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