A Novel image processing technique for weighted particle size distribution assessment.

The objective of the study was to create a reliable method that could be used to evaluate the particle size distribution of samples and pre-mixes in real-world situations, particularly those consisting of typical formulation blends. The goal was to use this method to assess the uniformity of the samples and ensure that they met the required quality standards. The researchers aimed to create a method that could be easily incorporated into the manufacturing process, providing a practical and efficient solution. This study demonstrates the use of ImageJ software to analyze the particle size distribution (PSD) of powders. The technique produces qualitative data from microscopy images and quantitative data from analysis of parameters including average diameter, D10, D50, D90, and standard deviation. The method was tested with various treatments, showing differentiating outcomes in all cases. The alternate technique provides a rapid and cost-effective method for PSD analysis, surpassing the limitations of sieve analysis. Extensive testing of the method, using a variety of sample types, including typical formulation blends, was performed. The results suggest that the method can effectively assess the morphology of changing materials during batch manufacturing and characterize uniformity in blends. The methodology has the capability to identify attributes related to PSD that are typically required to be monitored during manufacturing. The technique allows for accurate and reliable quantification of the attributes through image capture technology. The technique has future potential and has important implications for material science, powder rheology, pharmaceutical formulation development, and continual process monitoring.

[Figure: see text]A Novel Image Processing Technique for Weighted Particle Size Distribution Assessment.

Early Ultrasound Surveillance of Newly-Created Hemodialysis Arteriovenous Fistula.

Introduction: We assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention. Methods: Consenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling. Results: Of 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9-77.3]; elbow, 66.7% [48.9-84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan's findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data. Conclusion: Early ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation.

The impact of S2 mutations on Omicron SARS-CoV-2 cell surface expression and fusogenicity.

SARS-CoV-2 Omicron subvariants are still emerging and spreading worldwide. These variants contain a high number of polymorphisms in the spike (S) glycoprotein that could potentially impact their pathogenicity and transmission. We have previously shown that the S:655Y and P681H mutations enhance S protein cleavage and syncytia formation. Interestingly, these polymorphisms are present in Omicron S protein. Here, we characterized the cleavage efficiency and fusogenicity of the S protein of different Omicron sublineages. Our results showed that Omicron BA.1 subvariant is efficiently cleaved but it is poorly fusogenic compared to previous SARS-CoV-2 strains. To understand the basis of this phenotype, we generated chimeric S protein using combinations of the S1 and S2 domains from WA1, Delta and Omicron BA.1 variants. We found that the S2 domain of Omicron BA.1 hindered efficient cell-cell fusion. Interestingly, this domain only contains six unique polymorphisms never detected before in ancestral SARS-CoV-2 variants. WA1614G S proteins containing the six individuals S2 Omicron mutations were assessed for their fusogenicity and S surface expression after transfection in cells. Results showed that the S:N856K and N969K substitutions decreased syncytia formation and impacted S protein cell surface levels. However, we observed that "first-generation" Omicron sublineages that emerged subsequently, had convergently evolved to an enhanced fusogenic activity and S expression on the surface of infected cells while "second-generation" Omicron variants have highly diverged and showed lineage-specific fusogenic properties. Importantly, our findings could have potential implications in the improvement and redesign of COVID-19 vaccines.

Targeting malnutrition in patients with COPD in the community.

The number of individuals living with chronic obstructive pulmonary disease (COPD) is increasing, but nutritional care can be inconsistent, especially in those with stable COPD. Historically, poor appetite and weight loss have been considered the norm during the progression of COPD into the later stage. However, it is imperative that nutritional assessment, support and management is undertaken from diagnosis, because malnutrition can lead to exacerbations of COPD and increased hospitalisation. Poor nutrition in individuals with COPD has been shown to predict an increase in mortality and with the care of patients taking place principally in the community, the nutritional aspects of care should be assessed, monitored and managed, in accordance with the latest guidance. The lack of a nutritional Quality Outcome Framework indicator for COPD can leave nutrition overlooked, but evidence shows that screening, assessment and planning can have an overall positive impact.

US National Institutes of Health Prioritization of SARS-CoV-2 Variants.

Since late 2020, SARS-CoV-2 variants have regularly emerged with competitive and phenotypic differences from previously circulating strains, sometimes with the potential to escape from immunity produced by prior exposure and infection. The Early Detection group is one of the constituent groups of the US National Institutes of Health National Institute of Allergy and Infectious Diseases SARS-CoV-2 Assessment of Viral Evolution program. The group uses bioinformatic methods to monitor the emergence, spread, and potential phenotypic properties of emerging and circulating strains to identify the most relevant variants for experimental groups within the program to phenotypically characterize. Since April 2021, the group has prioritized variants monthly. Prioritization successes include rapidly identifying most major variants of SARS-CoV-2 and providing experimental groups within the National Institutes of Health program easy access to regularly updated information on the recent evolution and epidemiology of SARS-CoV-2 that can be used to guide phenotypic investigations.

Modelling the impact of historic landscape change on soil erosion and degradation.

International policies and guidelines often highlight the divide between 'nature' and 'heritage' in landscape management, and the weakness of monodisciplinary approaches. This study argues that historic agricultural practices have played a key role in shaping today's landscapes, creating a heritage which affords opportunities for more sustainable landscape management. The paper develops a new interdisciplinary approach with particular reference to soil loss and degradation over the long term. It presents innovative methods for assessing and modelling how pre-industrial agricultural features can mitigate soil erosion risk in response to current environmental conditions. Landscape archaeology data presented through Historic Landscape Characterisation are integrated in a GIS-RUSLE model to illustrate the impact of varying historic land-uses on soil erosion. The resulting analyses could be used to inform strategies for sustainable land resource planning.

GSK2556286 Is a Novel Antitubercular Drug Candidate Effective In Vivo with the Potential To Shorten Tuberculosis Treatment.

As a result of a high-throughput compound screening campaign using Mycobacterium tuberculosis-infected macrophages, a new drug candidate for the treatment of tuberculosis has been identified. GSK2556286 inhibits growth within human macrophages (50% inhibitory concentration [IC50] = 0.07 µM), is active against extracellular bacteria in cholesterol-containing culture medium, and exhibits no cross-resistance with known antitubercular drugs. In addition, it has shown efficacy in different mouse models of tuberculosis (TB) and has an adequate safety profile in two preclinical species. These features indicate a compound with a novel mode of action, although still not fully defined, that is effective against both multidrug-resistant (MDR) or extensively drug-resistant (XDR) and drug-sensitive (DS) M. tuberculosis with the potential to shorten the duration of treatment in novel combination drug regimens. (This study has been registered at ClinicalTrials.gov under identifier NCT04472897).

A Google Earth Engine-enabled Python approach for the identification of anthropogenic palaeo-landscape features.

The necessity of sustainable development for landscapes has emerged as an important theme in recent decades. Current methods take a holistic approach to landscape heritage and promote an interdisciplinary dialogue to facilitate complementary landscape management strategies. With the socio-economic values of the "natural" and "cultural" landscape heritage increasingly recognised worldwide, remote sensing tools are being used more and more to facilitate the recording and management of landscape heritage. The advent of freeware cloud computing services has enabled significant improvements in landscape research allowing the rapid exploration and processing of satellite imagery such as the Landsat and Copernicus Sentinel datasets. This research represents one of the first applications of the Google Earth Engine (GEE)  Python application programming interface (API) in studies of historic landscapes. The complete free and open-source software (FOSS) cloud protocol proposed here consists of a Python code script developed in Google Colab, which could be adapted and replicated in different areas of the world. A multi-temporal approach has been adopted to investigate the potential of Sentinel-2 satellite imagery to detect buried hydrological and anthropogenic features along with spectral index and spectral decomposition analysis. The protocol's effectiveness in identifying palaeo-riverscape features has been tested in the Po Plain (N Italy).

Surveillance arterioveNous fistulAs using ultRasound (SONAR) trial in haemodialysis patients: a study protocol for a multicentre observational study.

INTRODUCTION: Arteriovenous fistulas (AVFs) are considered the best and safest modality for providing haemodialysis in patients with end-stage renal disease. Only 20% of UK centres achieve the recommended 80% target for achieving dialysis of the prevalent dialysis population via permanent access (as opposed to a central venous catheter). This is partly due to the relatively poor maturation rate of newly created fistulas, with as many as 50% of fistulas failing to mature.The Surveillance Of arterioveNous fistulAe using ultRasound study will examine whether a protocolised programme of Doppler ultrasound (US) surveillance can identify, early after creation, potentially correctable problems in those AVFs that subsequently fail to mature. METHODS AND ANALYSIS: This is a multicentre observational study that will assess newly created AVFs by Doppler US performed at 2, 4, 6 and 10 weeks after creation. The primary outcome measure will be primary fistula patency at week 10. Secondary outcome measures include: successful use of the fistula; clinical suitability for dialysis; creation of new fistula or radiological salvage; fistula thrombosis; secondary fistula patency rate and patient acceptability. ETHICS AND DISSEMINATION: The study has been approved by the Cambridgeshire and Hertfordshire Research Ethics Committee and by the Health Research Authority (REC 18/EE/0234). The results generated from this work will be published as open access, within 3 years of trial commencement. We will also present our findings at key national/international renal meetings, as well as support volunteers at renal patient groups to disseminate the trial outcome. TRIAL REGISTRATION NUMBER: ISRCTN36033877.

Periodic dielectric structures for light-trapping in InGaAs/GaAs quantum well solar cells.

We study dielectric diffraction gratings for light-trapping in quantum well solar cells and compare their performance with plasmonic and Lambertian light-trapping structures. The optimum structural parameters are identified for symmetric uni-periodic, symmetric bi-periodic and asymmetric bi-periodic gratings. The enhancement in short-circuit current density from the quantum well region with respect to a reference cell with no diffraction grating is calculated. The ratio of this enhancement to the maximum achievable enhancement (i.e. no transmission losses) is 33%, 75% and 74%, respectively for these structures. The optimum asymmetric and symmetric bi-periodic structures perform closest to Lambertian light-trapping, while all three optimum grating structures outperform optimum plasmonic light-trapping. We show that the short-circuit current density from the quantum well region is further enhanced by incorporating a rear reflector.

A comparison of the outcomes of one-stage and two-stage brachiobasilic arteriovenous fistulas.

OBJECTIVE: The brachiobasilic arteriovenous fistula (BBAVF) can be formed in one or two stages. This study examined the failure rates and functional patencies of one-stage vs two-stage brachiobasilic transposition fistulas to compare the two surgical techniques. METHODS: We retrospectively identified all the patients who underwent BBAVF access surgery at King's College Hospital between January 1, 2009, and December 31, 2011 (3 years). Patients were divided into two groups according to one-stage or two-stage procedure. All patients were seen in the access clinic 4 to 6 weeks postoperatively, and their fistulas were scanned (duplex). The surveillance of fistulas consists of duplex scans every 6 months to assess volume flow. RESULTS: During the study interval, 149 brachiobasilic transpositions (65 one-stage and 84 two-stage) were performed in 141 patients. Patients undergoing the two-stage procedure had a smaller mean preoperative vein diameter (4.0 ± 1.1 vs 3.6 ± 1.3 mm; P = .041) and tended to be older (58 ± 15 vs 63 ± 15 years; P = .062). Mean overall follow-up was 559 ± 333 days. There was no difference in primary failure between the two groups (45% vs 42%; P = .718). At 1 year, the two-stage BBAVFs had significantly better primary (71% vs 87%; P = .034), assisted primary (77% vs 95%; P = .017), and secondary functional (79% vs 95%; P = .026) patencies. The same applied to 2-year primary (53% vs 75%; P = .034), assisted primary (57% vs 77%; P = .017), and secondary functional (57% vs 77%; P = .026) patencies. Multivariate Cox regression showed that the one-stage procedure was 3.2 times more likely to fail (P = .028). Men were 2.7 times more likely to lose their access (P = .054). CONCLUSIONS: This study describes a large series of BBAVFs and makes an extensive comparison between the one-stage and two-stage operations. Significantly improved overall functional patency is demonstrated for the two-stage operation.

Management of the incus body in ossiculoplasty.

OBJECTIVE: (1) Evaluate the sound transfer impact of removal of the incus body in ossicular chain reconstruction (OCR) using an incus strut prosthesis. (2) Provide basic science data to assist clinical decision making in ossiculoplasty. STUDY DESIGN: Basic science. SETTING: Cadaveric temporal bone research laboratory. SUBJECTS AND METHODS: Ossicular chain reconstruction with an incus strut prosthesis was performed on 7 human temporal bones with and without the incus body. The difference in round window membrane (RWM) peak-to-peak displacements (90-dB sound pressure level, 250-8000 Hz) using single-point laser Doppler vibrometry (LDV) was compared with observed baseline, intact ossicular chain values. RESULTS: Comparing OCR using an incus strut prosthesis to an intact ossicular chain across all 7 temporal bones, the largest differences in RWM velocity occurred at 1011 and 2011 Hz. With increasing frequencies, RWM velocities of the OCR approached the intact ossicular chain. Using a Wilcoxon rank-sum test comparing the ossicular chain with and without the incus body showed no statistically significant difference across all frequencies (P = .925). Removing the incus body resulted in improved median RWM velocity (× 10(-2) mm/s) by 0.6 at 1011 Hz and a decrease of 0.6 at 2011 Hz. A rank-sum test to evaluate the difference at 1011 and 2011 Hz did not demonstrate statistical significance. CONCLUSION: Removal of the incus body in OCR using an incus strut prosthesis did not significantly change sound transfer function of the middle ear relative to its preservation. Our data suggest the impact of the retained mass in OCR to be minimal.

A randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents.

Cognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings.

The "duty to warn" a patient's family members about hereditary disease risks.

Genetic tests for adult-onset disorders, including common forms of cancer, are now commercially available, and tests for genetic polymorphisms that predict drug effects or toxicity after treatment are under development. For each of these circumstances, testing of 1 individual may imply an increased risk to his/her relative. The obligation, if any, to warn family members of the identification of a genetic mutation has generated concerns regarding the conflict between the physician's ethical obligations to respect the privacy of genetic information vs the potential liabilities resulting from the physician's failure to notify at-risk relatives. A duty to warn relatives about risks due to some infectious agents has been assumed by state and local health agencies, and the duty to breach confidentiality to warn of imminent harm has been the subject of case law. In general, the special nature of genetic tests has been viewed as a barrier to physicians' breaching the confidentiality of personal genetic information. However, the failure to warn family members about hereditary disease risks has already resulted in 3 lawsuits against physicians in the United States. While the findings of case law and the state and federal statutes that bear on the issue of "duty to warn" of inherited health risk are still being defined, we believe that health care professionals have a responsibility to encourage but not to coerce the sharing of genetic information in families, while respecting the boundaries imposed by the law and by the ethical practice of medicine.