Sculpturing of photonic crystals by ion beam lithography: towards complete photonic bandgap at visible wavelengths

Three dimensional (3D) ion beam lithography (IBL) is used to directly pattern 3D photonic crystal (PhC) structures in crystalline titania. The process is maskless and direct write. The slanted pore 3D structures with pore diameters of 100 nm having aspect ratio of 8 were formed. It is shown that chemical enhancement of titania removal up to 5.2 times is possible in XeF2 gas for the closest nozzle-to-sample distance; the enhancement was similar to 1.5 times for the actual 3D patterning due to a sample tilt. Tolerances of structural parameters and optimization of IBL processing required for the fabrication of PhCs with full photonic bandgap in visible spectral range in rutile are outlined. Application potential of 3D-IBL is discussed. (c) 2011 Optical Society of Americ

Ion beam lithography for Fresnel zone plates in X-ray microscopy

Fresnel Zone Plates (FZP) are to date very successful focusing optics for X-rays. Established methods of fabrication are rather complex and based on electron beam lithography (EBL). Here, we show that ion beam lithography (IBL) may advantageously simplify their preparation. A FZP operable from the extreme UV to the limit of the hard X-ray was prepared and tested from 450 eV to 1500 eV. The trapezoidal profile of the FZP favorably activates its 2nd order focus. The FZP with an outermost zone width of 100 nm allows the visualization of features down to 61, 31 and 21 nm in the 1st, 2nd and 3rd order focus respectively. Measured efficiencies in the 1st and 2nd order of diffraction reach the theoretical predictions

Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden

IMPORTANCE: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication. OBJECTIVE: To evaluate phenotypic features across genetic burden for POAG. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023. MAIN OUTCOMES AND MEASURES: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits. RESULTS: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4% (3005 of 40 644) vs 1.3% (544 of 40 795) in lowest decile (P < .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95% CI, -0.11 to -0.07; P < .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 μm and macular ganglion cell complex (GCC) of 0.26 μm (P < .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95% CI, 0.012-0.014; P < .001 for both). A total of 22 of 5193 fundus photographs (0.4%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5%) had suspicious optic disc features compared with 9 of 5158 (0.2%) and 10 of 5219 (0.2%), respectively, in decile 1 (P < .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P < .001). CONCLUSION AND RELEVANCE: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice

The organisation and delivery of health improvement in general practice and primary care: a scoping study

Background This project examines the organisation and delivery of health improvement activities by and within general practice and the primary health-care team. The project was designed to examine who delivers these interventions, where they are located, what approaches are developed in practices, how individual practices and the primary health-care team organise such public health activities, and how these contribute to health improvement. Our focus was on health promotion and ill-health prevention activities. Aims The aim of this scoping exercise was to identify the current extent of knowledge about the health improvement activities in general practice and the wider primary health-care team. The key objectives were to provide an overview of the range and type of health improvement activities, identify gaps in knowledge and areas for further empirical research. Our specific research objectives were to map the range and type of health improvement activity undertaken by general practice staff and the primary health-care team based within general practice; to scope the literature on health improvement in general practice or undertaken by health-care staff based in general practice and identify gaps in the evidence base; to synthesise the literature and identify effective approaches to the delivery and organisation of health improvement interventions in a general practice setting; and to identify the priority areas for research as defined by those working in general practice. Methods We undertook a comprehensive search of the literature. We followed a staged selection process involving reviews of titles and abstracts. This resulted in the identification of 1140 papers for data extraction, with 658 of these papers selected for inclusion in the review, of which 347 were included in the evidence synthesis. We also undertook 45 individual and two group interviews with primary health-care staff. Findings Many of the research studies reviewed had some details about the type, process or location, or who provided the intervention. Generally, however, little attention is paid in the literature to examining the impact of the organisational context on the way services are delivered or how this affects the effectiveness of health improvement interventions in general practice. We found that the focus of attention is mainly on individual prevention approaches, with practices engaging in both primary and secondary prevention. The range of activities suggests that general practitioners do not take a population approach but focus on individual patients. However, it is clear that many general practitioners see health promotion as an integral part of practice, whether as individual approaches to primary or secondary health improvement or as a practice-based approach to improving the health of their patients. Our key conclusion is that there is currently insufficient good evidence to support many of the health improvement interventions undertaken in general practice and primary care more widely. Future Research Future research on health improvement in general practice and by the primary health-care team needs to move beyond clinical research to include delivery systems and be conducted in a primary care setting. More research needs to examine areas where there are chronic disease burdens – cancer, dementia and other disabilities of old age. Reviews should be commissioned that examine the whole prevention pathway for health problems that are managed within primary care drawing together research from general practice, pharmacy, community engagement, etc

Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice

<p>Abstract</p> <p>Background</p> <p>Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.</p> <p>Methods</p> <p>Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.</p> <p>Results</p> <p>Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.</p> <p>Conclusions</p> <p>Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.</p

Cost-effectiveness analysis of smoking cessation interventions in the United Kingdom accounting for major neuropsychiatric adverse events

Objectives Smoking is a leading cause of death worldwide. Cessation aids include varenicline, bupropion, nicotine replacement therapy (NRT), and e-cigarettes at various doses (low, standard and high) and used alone or in combination with each other. Previous cost-effectiveness analyses have not fully accounted for adverse effects nor compared all cessation aids. The objective was to determine the relative cost-effectiveness of cessation aids in the United Kingdom. Methods An established Markov cohort model was adapted to incorporate health outcomes and costs due to depression and self-harm associated with cessation aids, alongside other health events. Relative efficacy in terms of abstinence and major adverse neuropsychiatric events was informed by a systematic review and network meta-analysis. Base case results are reported for UK-licensed interventions only. Two sensitivity analyses are reported, one including unlicensed interventions and another comparing all cessation aids but removing the impact of depression and self-harm. The sensitivity of conclusions to model inputs was assessed by calculating the expected value of partial perfect information. Results When limited to UK-licensed interventions, varenicline standard-dose and NRT standard-dose were most cost-effective. Including unlicensed interventions, e-cigarette low-dose appeared most cost-effective followed by varenicline standard-dose + bupropion standard-dose combined. When the impact of depression and self-harm was excluded, varenicline standard-dose + NRT standard-dose was most cost-effective, followed by varenicline low-dose + NRT standard-dose. Conclusion Although found to be most cost-effective, combined therapy is currently unlicensed in the United Kingdom and the safety of e-cigarettes remains uncertain. The value-of-information analysis suggested researchers should continue to investigate the long-term effectiveness and safety outcomes of e-cigarettes in studies with active comparators

Causes of genome instability: the effect of low dose chemical exposures in modern society.

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis

Strategies for improving patient recruitment to focus groups in primary care: a case study reflective paper using an analytical framework

<p>Abstract</p> <p>Background</p> <p>Recruiting to primary care studies is complex. With the current drive to increase numbers of patients involved in primary care studies, we need to know more about successful recruitment approaches. There is limited evidence on recruitment to focus group studies, particularly when no natural grouping exists and where participants do not regularly meet. The aim of this paper is to reflect on recruitment to a focus group study comparing the methods used with existing evidence using a resource for research recruitment, PROSPeR (Planning Recruitment Options: Strategies for Primary Care).</p> <p>Methods</p> <p>The focus group formed part of modelling a complex intervention in primary care in the Resources for Effective Sleep Treatment (REST) study. Despite a considered approach at the design stage, there were a number of difficulties with recruitment. The recruitment strategy and subsequent revisions are detailed.</p> <p>Results</p> <p>The researchers' modifications to recruitment, justifications and evidence from the literature in support of them are presented. Contrary evidence is used to analyse why some aspects were unsuccessful and evidence is used to suggest improvements. Recruitment to focus group studies should be considered in two distinct phases; getting potential participants to contact the researcher, and converting those contacts into attendance. The difficulty of recruitment in primary care is underemphasised in the literature especially where people do not regularly come together, typified by this case study of patients with sleep problems.</p> <p>Conclusion</p> <p>We recommend training GPs and nurses to recruit patients during consultations. Multiple recruitment methods should be employed from the outset and the need to build topic related non-financial incentives into the group meeting should be considered. Recruitment should be monitored regularly with barriers addressed iteratively as a study progresses.</p

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

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