Superconducting Diamond on Silicon Nitride for Device Applications

Chemical vapour deposition (CVD) grown nanocrystalline diamond is an attractive material for the fabrication of devices. For some device architectures, optimisation of its growth on silicon nitride is essential. Here, the effects of three pre-growth surface treatments, often employed as cleaning methods of silicon nitride, were investigated. Such treatments provide control over the surface charge of the substrate through modification of the surface functionality, allowing for the optimisation of electrostatic diamond seeding densities. Zeta potential measurements and X-ray photoelectron spectroscopy (XPS) were used to analyse the silicon nitride surface following each treatment. Exposing silicon nitride to an oxygen plasma offered optimal surface conditions for the electrostatic self-assembly of a hydrogen-terminated diamond nanoparticle monolayer. The subsequent growth of boron-doped nanocrystalline diamond thin films on modified silicon nitride substrates under CVD conditions produced coalesced films for oxygen plasma and solvent treatments, whilst pin-holing of the diamond film was observed following RCA-1 treatment. The sharpest superconducting transition was observed for diamond grown on oxygen plasma treated silicon nitride, demonstrating it to be of the least structural disorder. Modifications to the substrate surface optimise the seeding and growth processes for the fabrication of diamond on silicon nitride devices

CLAM-Accelerated K-Nearest Neighbors Entropy-Scaling Search of Large High-Dimensional Datasets via an Actualization of the Manifold Hypothesis

Many fields are experiencing a Big Data explosion, with data collection rates outpacing the rate of computing performance improvements predicted by Moore's Law. Researchers are often interested in similarity search on such data. We present CAKES (CLAM-Accelerated $K$-NN Entropy Scaling Search), a novel algorithm for $k$-nearest-neighbor ($k$-NN) search which leverages geometric and topological properties inherent in large datasets. CAKES assumes the manifold hypothesis and performs best when data occupy a low dimensional manifold, even if the data occupy a very high dimensional embedding space. We demonstrate performance improvements ranging from hundreds to tens of thousands of times faster when compared to state-of-the-art approaches such as FAISS and HNSW, when benchmarked on 5 standard datasets. Unlike locality-sensitive hashing approaches, CAKES can work with any user-defined distance function. When data occupy a metric space, CAKES exhibits perfect recall.Comment: As submitted to IEEE Big Data 202

AI solutions for human problems

Abstract Background Bronchiectasis is a chronic respiratory condition. Persistent bacterial colonisation in the stable state with increased and sometimes altered bacterial burden during exacerbations are accepted as key features in the pathophysiology. The extent to which respiratory viruses are present during stable periods and in exacerbations is less well understood. Methods This study aimed to determine the incidence of respiratory viruses within a cohort of bronchiectasis patients with acute exacerbations at a teaching hospital and, separately, in a group of patients with stable bronchiectasis. In the group of stable patients, a panel of respiratory viruses were assayed for using real time quantitative PCR in respiratory secretions and exhaled breath. The Impact of virus detection on exacerbation rates and development of symptomatic infection was evaluated. Results Routine hospital-based viral PCR testing was only requested in 28% of admissions for an exacerbation. In our cohort of stable bronchiectasis patients, viruses were detected in 92% of patients during the winter season, and 33% of patients during the summer season. In the 2-month follow up period, 2 of 27 patients presented with an exacerbation. Conclusions This pilot study demonstrated that respiratory viruses are commonly detected in patients with stable bronchiectasis. They are frequently detected during asymptomatic viral periods, and multiple viruses are often present concurrently

Osteoarthritis in England: Incidence Trends From National Health Service Hospital Episode Statistics

Objective: It is typical in epidemiological research of osteoarthritis (OA) to collect data for the hand, hip, and knee. However, little population‐based data exist for this disease in the foot. Thus, we addressed patterns of OA for the foot compared with the hand, hip, and knee spanning 2000/2001 to 2017/2018 in England. Methods: Secondary‐care data from 3 143 928 patients with OA of the foot, hand, hip, and knee were derived from the National Health Service (NHS) Hospital Episode Statistics (HES) database. Distribution, population prevalence, and incidence of joint‐specific OA were stratified by age and sex. Results: OA incidence increased significantly at the foot [3.8% (95% confidence interval [CI] 3.0, 4.6)], hand [10.9% (10.1, 11.7)], hip [3.8% (2.9, 4.7)], and knee [2.9% (2.2, 3.6)] per year from 2000/2001 to 2017/2018. A higher proportion of women were diagnosed with OA, whereas greater incidence in men was estimated for the hand and hip. Foot OA presented comparable diagnosis numbers to the hand. More recently during 2012/2013 to 2017/2018, a significant rise in hip OA was estimated among younger adults, whereas knee OA decreased across all age groups. Incidence of OA in the foot and hand were particularly significant among the 75 or older age group, though bimodal age distributions were observed for both sites. Conclusion: The significant increase in secondary care records for OA in England underscores the importance of exploring possible causative factors and identifying groups most at risk. Further detailed data may be particularly important for the hip, which represents significant incidence among younger adults. Greater incidence of OA in the foot compared with the knee emphasizes the need for well‐conducted epidemiological research in this area. Monitoring the performance of surgical outcomes at the population‐level for this frequently affected yet understudied site could have substantial potential to reduce the socioeconomic burden it represents to the NHS

Clinical Severity of Clostridium difficile PCR Ribotype 027: A Case-Case Study

BACKGROUND: Clostridium difficile is a leading infectious cause of health care associated diarrhoea. Several industrialised countries have reported increased C. difficile infections and outbreaks, which have been attributed to the emergent PCR ribotype 027 strain. METHODS AND FINDINGS: We conducted a case-case study to compare severity of C. difficile disease for patients with 027 versus non-027 ribotypes. We retrospectively collected clinical information about 123/136 patients with C. difficile infections admitted to hospitals in the East of England region in 2006 and from whom stool isolates were cultured and ribotyped as part of an earlier national survey. We defined severe C. difficile disease as having one or more of shock, paralytic ileus, pseudo membranous colitis or toxic megacolon. Patient median age was 83 years old (range 3 to 98, interquartile range 75 to 89), 86% were prescribed antibiotics in the eight weeks before illness onset, 41% had ribotype 027 and 30-day all cause mortality during hospital admission was 21%. Severe disease occurred in 24% (95%CI 13% to 37%) and 17% (95%CI 9% to 27%) of patients with PCR ribotype 027 and non-027 ribotypes respectively. In a multivariable model, ribotype 027 was not associated with severe disease after adjusting for sex, discharge from hospital prior to 60 days of current admission, gastroenteritis on admission, number of initiator antibiotics for C. difficile disease, and hospital where the patient was admitted. CONCLUSIONS: Our study found no evidence to support previous assertions that ribotype 027 is more virulent than other PCR ribotypes. This finding raises questions about the contribution of this strain to the recent increase in C. difficile disease throughout North America and Europe

Reliability, familiarization effect, and comparisons between a predetermined and a self-determined isometric-squat testing protocol

Purpose: This study examined the interday reliability of a predetermined and a self-determined isometric-squat test among youth soccer players. Familiarization effects were evaluated to determine the minimum number of trials necessary to obtain consistent outputs. Finally, differences between protocols were evaluated.Methods: Thirty-one youth soccer players (mean [SD] age: 13.2 [1.0] y; body mass: 54.1 [3.4] kg; stature: 166.3 [11.2] cm; percentage of estimated adult height: 92.6% [3.6%]) from a top-tier professional academy completed 4 experimental sessions for each protocol: familiarization 1, familiarization 2, test, and retest sessions. Peak force; relative peak force; impulse from 0 to 50 milliseconds, 0 to 100 milliseconds, 0 to 150 milliseconds, and 0 to 200 milliseconds; and rate of force development from 0 to 50 milliseconds, 0 to 100 milliseconds, 0 to 150 milliseconds, and 0 to 200 milliseconds were measured. Results: Both protocols displayed acceptable (intraclass correlation coefficient >=.75 and coefficient of variation ≤10%) reliability statistics for all metrics apart from rate of force development of any time epoch. Differences were found between familiarization 2 and both test and retest sessions for peak force (P = .034 and .021, respectively) and relative peak force (P = .035 and .005, respectively) across both protocols. Conclusions: The isometric-squat test is a reliable test among youth soccer players. Two familiarization sessions seem to be sufficient to ensure data stabilization. Outputs between the self-determined and predetermined are comparable; however, the latter seems preferable due to improved testing time efficiency

Differential Methylation as a Biomarker of Response to Etanercept in Patients With Rheumatoid Arthritis

Objective: Biologic drug therapies represent a huge advance in the treatment of rheumatoid arthritis (RA). However, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority. We undertook this study to test our hypothesis that differential DNA methylation patterns may provide biomarkers predictive of response to tumor necrosis factor inhibitor (TNFi) therapy in patients with RA. Methods: An epigenome-wide association study was performed on pretreatment whole blood DNA from patients with RA. Patients who displayed good response (n = 36) or no response (n = 36) to etanercept therapy at 3 months were selected. Differentially methylated positions were identified using linear regression. Variance of methylation at differentially methylated positions was assessed for correlation with cis-acting single-nucleotide polymorphisms (SNPs). A replication experiment for prioritized SNPs was performed in an independent cohort of 1,204 RA patients. Results: Five positions that were differentially methylated between responder groups were identified, with a false discovery rate of <5%. The top 2 differentially methylated positions mapped to exon 7 of the LRPAP1 gene on chromosome 4 (cg04857395, P = 1.39 × 10−8 and cg26401028, P = 1.69 × 10−8). The A allele of the SNP rs3468 was correlated with higher levels of methylation for both of the top 2 differentially methylated positions (P = 2.63 × 10−7 and P = 1.05 × 10−6, respectively). Furthermore, the A allele of rs3468 was correlated with European League Against Rheumatism nonresponse in the discovery cohort (P = 0.03; n = 56) and in the independent replication cohort (P = 0.003; n = 1,204). Conclusion: We identify DNA methylation as a potential biomarker of response to TNFi therapy, and we report the association between response and the LRPAP1 gene, which encodes a chaperone of low-density lipoprotein receptor–related protein 1. Additional replication experiments in independent sample collections are now needed

Post-Disaster Housing Reconstruction in Sri Lanka: What Methodology?

Research methodology is the procedural framework within which the research is conducted. This includes the overall approach to a problem that could be put into practice in a research process, from the theoretical underpinning to the collection and analysis of data. Choice of methodology depends on the primary drivers: topic to be researched and the specific research questions. Hence, methodological perspectives of managing stakeholder expectations of PDHR context are composed of research philosophies, research strategy, research design, and research techniques. This research belonged to social constructivism or interpretivism within a philosophical continuum. The nature of the study was more toward subjectivism where human behavior favored voluntary stance. Ontological, methodological, epistemological, and axiological positioning carried the characteristics of idealism, ideographic, anti-positivism, and value laden, respectively. Data collection comprises two phases, preliminary and secondary. Exploratory interviews with construction experts in the United Kingdom and Sri Lanka were carried out to refine the interview questions and identify the case studies. Case study interviews during the secondary phase took place in Sri Lanka. Data collected at the preliminary stage were used to assess the attributes of power, legitimacy/proximity, and urgency of stakeholders to the project using Stakeholder Circle™ software. Moreover, the data collected at secondary phase via case studies will be analyzed with NVivo 8. This article aims to discuss these methodological underpinnings in detail applied in a post-disaster housing reconstruction context in Sri Lanka

Bitter Taste Receptor Agonists Mitigate Features of Allergic Asthma in Mice.

Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma. Asthma was induced in mice using intranasal house dust mite or aerosol ova-albumin challenge, and chloroquine or quinine were tested in both prophylactic and treatment models. Allergen challenge resulted in airway inflammation as evidenced by increased immune cells infiltration and release of cytokines and chemokines in the lungs, which were significantly attenuated in TAS2R agonists treated mice. TAS2R agonists attenuated features of airway remodeling including smooth muscle mass, extracellular matrix deposition and pro-fibrotic signaling, and also prevented mucus accumulation and development of AHR in mice. Mechanistic studies using human neutrophils demonstrated that inhibition of immune cell chemotaxis is a key mechanism by which TAS2R agonists blocked allergic airway inflammation and exerted anti-asthma effects. Our comprehensive studies establish the effectiveness of TAS2R agonists in mitigating multiple features of allergic asthma