Combined First-Principles and Experimental Investigation into the Reactivity of Codeposited Chromium-Carbon under Pressure.

High-pressure synthesis in the diamond anvil cell suffers from the lack of a general approach for the control of precursor stoichiometry and homogeneity. Here, we present results from a new method we have developed that uses magnetron cosputtering to prepare stoichiometrically precise and atomically mixed amorphous films of Cr:C. Laser-heated diamond anvil cell experiments carried out on a flake of this sample at pressures between 13.5 and 24.3 GPa lead to the observation of Cr3C (Pnma) over the entire pressure range-in good agreement with our in-house theoretical predictions-but also reveal two other metastable phases that were not expected: a novel monoclinic chromium carbide phase and the NaCl-type CrC (Fm3̅m) phase. The unexpected stability of CrC is investigated by using first-principles methods, revealing a large stabilizing effect tied to substoichiometry at the carbon site. These results offer an important case study into the current limitations of crystal structure prediction methods with regard to phase complexity and bolster the growing need for advanced theoretical approaches that can more completely survey experimentally unexplored phase space.

Understanding the experiences of ketogenic metabolic therapy for people living with varying levels of depressive symptoms: a thematic analysis.

Background: Evidence suggests that a ketogenic diet (KD) may help to alleviate psychiatric symptoms, including depression and anxiety. Positive changes have been reported such as improvements in cognition, concentration, and sleep, a reduction in hunger, and an increase in well-being, energy, confidence, and resilience. This research aims to understand the impact of a non-calorie-restricted KD on depression and aspects of psychological well-being in those with varying degrees of depressive symptoms. Though there are a few studies directly exploring the experiences of those following a KD, this will be the first study to explore the narrative from a mental health and psychological well-being viewpoint. Method: A sample of nine participants who had followed a non-calorie restricted KD intervention of 50 g of carbohydrates or less per day for at least 12 weeks were recruited. Participants were split into 'healthy adults' group who had no to low depressive symptoms and 'depressive symptoms' group who had mild to moderate depressive symptoms. A reflexive thematic analysis was considered suitable for this study. Findings: Five core themes and 24 subthemes were created. These were, (1) Poor health prior to program; (2) Hunger and cravings-the food and mood connection; (3) Psychological well-being improvements; (4) It becomes a lifestyle; and (5) Implementation difficulties. Participants experienced mental health improvements such as increased self-esteem, confidence, motivation, and achievement. Some experienced more control in life and a greater sense of reward. Those with depressive symptoms who initially reported low self-worth and hopelessness later reported increased self-esteem and renewed meaning and purpose in life. The findings from this study reflect the previous reports that the diet implementation can be difficult initially, but soon becomes easy to follow and turns into a lifestyle. Conclusion: In the literature, there are very few qualitative studies that explore the accounts and lived experiences of those following a KD. From the participants' accounts in this study, it appears that the benefits and positive outcomes of this diet outweigh any negative side-effects experienced. This is encouraging for those who are looking for adjunctive therapies to address and improve their depressive symptoms and overall mental health.

High-Pressure Synthesis and Recovery of Single Crystals of the Metastable Manganese Carbide, MnCx.

Transition metal carbides find widespread use throughout industry due to their high strength and resilience under extreme conditions. However, they remain largely limited to compounds formed from the early d-block elements, since the mid-to-late transition metals do not form thermodynamically stable carbides. We report here the high-pressure bulk synthesis of large single crystals of a novel metastable manganese carbide compound, MnCx (P63/mmc), which adopts the anti-NiAs-type structure with significant substoichiometry at the carbon sites. We demonstrate how synthesis pressure modulates the carbon loading, with ~40 % occupancy being achieved at 9.9 GPa.

Temporally dense monitoring of pathogen occurrence at four drinking-water well sites - Insights and Implications.

Yearlong, event based, microbiological and chemical sampling was conducted at four public water supply well sites spanning a range of geologic settings and well depths to look for correlation between precipitation events and microbial occurrence. Near-continuous monitoring using autosamplers occurred just before, during, and after 5-7 sampling events triggered by rainfall and/or snowmelt. Microbial genetic material was noted at all four locations during all but one sampling event, but was exceedingly variable in time, where one sample would have no detections and the next sample could be a relatively high concentration. The highest microbial sums (microbial concentrations summed over an event) were observed during months in which precipitation exceeded historical averages. Extended wet conditions through the spring thaw resulted in the highest percentage of microbial positive samples, though at relatively low concentrations. Sampling events that followed drier than normal periods showed longer lag times between the onset of precipitation and microbial occurrence, as well as lower microbial detection rates. Although a general lag time pattern was observed at each site, the largest offset in time was observed at the site with the greatest depth to water. The study's temporally dense representation of drinking water pathogen characterization suggests that single event or infrequent periodic sampling of a drinking water supply cannot provide a representative characterization of the probability that pathogens are present, which likely has ramifications for calculating health risk assessments.

Stable Clinical and Radiological Outcomes at Medium and over 5 Year Follow Up of Calcaneus Fracture Open Reduction Internal Fixation Using a Sinus Tarsi Approach.

The sinus tarsi approach is increasingly growing in popularity for open reduction internal fixation of calcaneus fractures. Multiple studies have demonstrated favorable short-term results compared to the traditional extensile L incision, however long-term data over 5 years is currently limited to a single retrospective case series. Following local ethical approval, all patients who had completed a minimum 5 years from time of operation were contacted with a Standardized Telephone Questionnaire completed. This followed a previous retrospective chart review, with follow up telephone or clinic consultation performed by Davey et al. of this cohort at mean 35 months. Thirty-four fractures (31 patients) completed minimum 5 year follow up from the eligible group of 54 fractures (49 patients). Regarding functional outcomes, a significant improvement in mean Maryland Foot Score was observed between short- (mean 35.8 months) and medium-term (mean 81.9 months) of 77.6 (SD 15.0) to 86 (SD 7.9) (p = .0082). There was no significant difference in postoperative and long term radiographic Bohler's angle (p = .9683). Eleven feet (32%) proceeded to require reoperation, with removal of metal performed in 10 (29%), fusion in 2 (6%), and skin grafting following wound breakdown for 1 (3%). Four feet (12.9%) experienced post operative wound complications, including 3 (9.68%) cases of infection and 2 (6.45%) of delayed wound healing. This study demonstrated stable clinical and radiographic outcomes over 5 years following Calcaneus Fracture Open Reduction Internal Fixation using a sinus tarsi approach, supporting its continued usage when treating intraarticular calcaneus fractures for which operative intervention is indicated.

High-Pressure Polymorphism in Silver Ferrite Delafossite, AgFeO2.

The delafossites are a class of layered metal oxides that are notable for being able to exhibit optical transparency alongside an in-plane electrical conductivity, making them promising platforms for the development of transparent conductive oxides. Pressure-induced polymorphism offers a direct method for altering the electrical and optical properties in this class, and although the copper delafossites have been studied extensively under pressure, the silver delafossites remain only partially studied. We report two new high-pressure polymorphs of silver ferrite delafossite, AgFeO2, that are stabilized above ∼6 and ∼14 GPa. In situ X-ray diffraction and vibrational spectroscopy measurements are used to examine the structural changes across the two phase transitions. The high-pressure structure between 6 and 14 GPa is assigned as a monoclinic C2/c structure that is analogous to the high-pressure phase reported for AgGaO2. Nuclear resonant forward scattering reveals no change in the spin state or valence state at the Fe3+ site up to 15.3(5) GPa.

Risk factors for Cryptosporidium contamination in Minnesota public supply wells.

In a recent monitoring study of Minnesota's public supply wells, Cryptosporidium was commonly detected with 40% of the wells having at least one detection. Risk factors for Cryptosporidium occurrence in drinking water supply wells, beyond surface water influence, remain poorly understood. To address this gap, physical and chemical factors were assessed as potential predictors of Cryptosporidium occurrence in 135 public supply wells in Minnesota. Univariable analysis, regression techniques, and classification trees were used to analyze the data. Many variables were identified as significant risk factors in univariable analysis and several remained significant throughout the succeeding analysis techniques. These factors fell into general categories of well use and construction, aquifer characteristics, and connectedness to the land surface, well capture zones, and land use therein, existence of potential contaminant sources within 200-feet of the well, and variability in the chemical and isotopic parameters measured during the study. These risk categories, and the specific variables and threshold values we have identified, can help guide future research on factors influencing Cryptosporidium contamination of wells and can be used by environmental health programs to develop risk-based sampling plans and design interventions that reduce associated health risks.

Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure.

The HIV-1 capsid has emerged as a tractable target for antiretroviral therapy. Lenacapavir, developed by Gilead Sciences, is the first capsid-targeting drug approved for medical use. Here, we investigate the effect of lenacapavir on HIV capsid stability and uncoating. We employ a single particle approach that simultaneously measures capsid content release and lattice persistence. We demonstrate that lenacapavir's potent antiviral activity is predominantly due to lethal hyperstabilisation of the capsid lattice and resultant loss of compartmentalisation. This study highlights that disrupting capsid metastability is a powerful strategy for the development of novel antivirals.

Cone-Beam Computed Tomography Assessment of Prevalence of Procedural Errors in Maxillary Posterior Teeth.

A range of procedural errors can occur when performing endodontic treatment on posterior teeth. These errors may decrease the success rate in endodontic practice. This study assessed the prevalence of procedural errors and the quality of endodontic treatments in maxillary molars and premolars using cone-beam computed tomography (CBCT). CBCT scans from two private radiology centers were assessed retrospectively to ensure the same calculated sample size of 327 teeth for each of the four maxillary posterior tooth types (a total of 1,308 endodontically treated teeth). Image sets were evaluated for procedural errors categorized as follows: obturation length (overfilling or underfilling by >2 mm short of the root apex), missed canals, perforations, strip perforations (with extrusion of material into the furcation area), separated instruments in the root canal space, and root fracture. Data were analyzed with SPSS version 20 (SPSS Inc., Chicago, IL, USA), and frequency data was assessed using the Monte Carlo test at the 0.05 level of significance. The procedural errors most commonly reported in the present study were from most frequent to least frequent: underfilled canals (50.0%), missed canals (27.5%), overfilled canals (12.5%), apical perforations (5.0%), separated instruments (3.1%), and root fractures (1.9%). No strip perforations (with extrusion of material into the furcation area) were seen in the study (0%). Underfilled and missed root canals were the most frequent procedural errors identified in the present study. These findings underline the importance of more consideration of critical working length management during all stages of root canal treatment, greater awareness of root canal anatomy, and the use of imaging and diagnostic devices that enhance the ability to identify and treat root canals both safely and effectively.

Posttraumatic stress moderates return intentions: a factorial survey experiment with internally displaced persons in Nigeria.

Background: Persons displaced by conflict often consider returning to their area of origin. Lack of reliable information about conditions in the area of origin makes this decision more difficult. Displaced persons address this by seeking information from other sources, but must then assess the credibility of these sources.Objective: This study examines the role of symptoms of posttraumatic stress as a moderator of how information from a trustworthy source influences return intentions among displaced persons.Method: We test our hypotheses with a factorial survey experiment, drawing participants (N = 822) from residents of internally displaced person (IDP) camps in northeastern Nigeria.Results: Information from a more trustworthy source led to increased return intentions. However, the more participants reported symptoms of posttraumatic stress, the smaller the effect source trustworthiness had on their return intentions.Conclusions: Findings highlight how traumatic experiences during wartime can undermine the effectiveness of the provision of information from a trustworthy source about good conditions in displaced persons' areas of origin, and suggest that interventions addressing posttraumatic stress could have downstream effects on safe, durable, and dignified return.

Examines the impact of posttraumatic stress on the decision-making process of internally displaced persons in Nigeria.Credible information from trustworthy sources can positively influence return intentions, but this effect is diminished by symptoms of posttraumatic stress.Highlights the importance of addressing both information needs and mental health concerns to support displaced persons in making informed decisions about their future.

Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy.

Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease. Here, we show that ablation of retinal microglia ameliorates visual dysfunction and neurodegeneration in a type I diabetes mouse model. We also provide evidence of enhanced microglial contact and engulfment of amacrine cells, ultrastructural modifications, and transcriptome changes that drive inflammation and phagocytosis. We show that CD200-CD200R signaling between amacrine cells and microglia is dysregulated during early DR and that targeting CD200R can attenuate high glucose-induced inflammation and phagocytosis in cultured microglia. Last, we demonstrate that targeting CD200R in vivo can prevent visual dysfunction, microglia activation, and retinal inflammation in the diabetic mouse. These studies provide a molecular framework for the pivotal role that microglia play in early DR pathogenesis and identify a potential immunotherapeutic target for treating DR in patients.

Vitamin D: determinants of status, indications for testing and knowledge in a convenience sample of Irish adults.

Vitamin D deficiency is common in Irish adults, though there is limited research on its determinants, knowledge of vitamin D or indications for testing. We aimed to explore the determinants of vitamin D status in adults and examine knowledge and reasons for testing. The study population comprised adults who had serum 25-hydroxyvitamin D tested by general practitioners request at a Dublin Hospital in 2020. Questionnaires detailing dietary intake, sun exposure, ethnicity, biophysical factors and vitamin D knowledge were sent to a sample stratified by age, sex and vitamin D status. In total, there were 383 participants, mean age 56·0 (sd 16·6) years. Wintertime deficiency disproportionally affected non-white v. white (60 % v. 24 %, P < 0·001). The greatest predictors of deficiency were low vitamin D intake (< 10 µg/d) (P < 0·001) and non-white ethnicity (P = 0·006), followed by sun avoidance (P = 0·022). It was also more prevalent in those with lower body exposure when outdoors. The majority (86 %) identified vitamin D as important for bone health. However, 40 % were tested for non-clinical indications and half were not aware of the recommended daily allowance (RDA). Low vitamin D intake was the most important determinant of deficiency, but ethnicity and sun exposure habits were also significant predictors. The majority had no clear indication for testing and were not aware of the RDA. Public health policies to improve knowledge and vitamin D intake, especially for those of non-white ethnicity and with reduced sun exposure, should be considered.

An approach for determining the reliability of manual and digital scoring of sleep stages.

STUDY OBJECTIVES: Inter-scorer variability in sleep staging is largely due to equivocal epochs that contain features of more than one stage. We propose an approach that recognizes the existence of equivocal epochs and evaluates scorers accordingly. METHODS: Epoch-by-epoch staging was performed on 70 polysomnograms by six qualified technologists and by a digital system (Michele Sleep Scoring [MSS]). Probability that epochs assigned the same stage by only two of the six technologists (minority score) resulted from random occurrence of two errors was calculated and found to be <5%, thereby indicating that the stage assigned is an acceptable variant for the epoch. Acceptable stages were identified in each epoch as stages assigned by at least two technologists. Percent agreement between each technologist and the other five technologists, acting as judges, was determined. Agreement was considered to exist if the stage assigned by the tested scorer was one of the acceptable stages for the epoch. Stage assigned by MSS was likewise considered in agreement if included in the acceptable stages made by the technologists. RESULTS: Agreement of technologists tested against five qualified judges increased from 80.8% (range 70.5%-86.4% among technologists) when using the majority rule, to 96.1 (89.8%-98.5%) by the proposed approach. Agreement between unedited MSS and same judges was 90.0% and increased to 92.1% after brief editing. CONCLUSIONS: Accounting for equivocal epochs provides a more accurate estimate of a scorer's (human or digital) competence in scoring sleep stages and reduces inter-scorer disagreements. The proposed approach can be implemented in sleep-scoring training and accreditation programs.

Fixed-intensity exercise tests to measure exertional dyspnoea in chronic heart and lung populations: a systematic review.

INTRODUCTION: Exertional dyspnoea is the primary diagnostic symptom for chronic cardiopulmonary disease populations. Whilst a number of exercise tests are used, there remains no gold standard clinical measure of exertional dyspnoea. The aim of this review was to comprehensively describe and evaluate all types of fixed-intensity exercise tests used to assess exertional dyspnoea in chronic cardiopulmonary populations and, where possible, report the reliability and responsiveness of the tests. METHODS: A systematic search of five electronic databases identified papers that examined 1) fixed-intensity exercise tests and measured exertional dyspnoea, 2) chronic cardiopulmonary populations, 3) exertional dyspnoea reported at isotime or upon completion of fixed-duration exercise tests, and 4) published in English. RESULTS: Searches identified 8785 papers. 123 papers were included, covering exercise tests using a variety of fixed-intensity protocols. Three modes were identified, as follows: 1) cycling (n=87), 2) walking (n=31) and 3) other (step test (n=8) and arm exercise (n=2)). Most studies (98%) were performed on chronic respiratory disease patients. Nearly all studies (88%) used an incremental exercise test. 34% of studies used a fixed duration for the exercise test, with the remaining 66% using an exhaustion protocol recording exertional dyspnoea at isotime. Exertional dyspnoea was measured using the Borg scale (89%). 7% of studies reported reliability. Most studies (72%) examined the change in exertional dyspnoea in response to different interventions. CONCLUSION: Considerable methodological variety of fixed-intensity exercise tests exists to assess exertional dyspnoea and most test protocols require incremental exercise tests. There does not appear to be a simple, universal test for measuring exertional dyspnoea in the clinical setting.

Vitamin D intake and status in Ireland: a narrative review.

Vitamin D is crucial for musculoskeletal health, with evidence suggesting non-skeletal benefits. Cutaneous vitamin D synthesis is limited in Ireland due to its northern latitude (52-55°N) and the population is dependent on dietary sources, yet intakes are inadequate. No study to-date has comprehensively examined vitamin D intakes and status in Ireland (Northern Ireland and the Republic). We aimed to review the evidence since 2010 and summarise the results in subgroups of the Irish population. We found that in the largest studies prevalence of deficiency [25-hydroxyvitamin D (25(OH)D) < 30 nm/l] was 15-17% in pregnancy, 15-23% in children and 13% in adults. Approximately half the population had 25(OH)D < 50 nm/l. There were only four small studies in an ethnic population with the largest in Southeast Asians finding that 67% were deficient. All studies found higher rates of deficiency and levels <50 nm/l in winter v. summer. Vitamin D intake was lowest in children (mean 2⋅3-4⋅2 µg/d) and pregnant women (mean 1⋅9-5⋅1 µg/d) and highest in older adults (6⋅9 µg/d), with over 90% of the population not meeting the recommended daily allowance. This review indicates that low vitamin D status and dietary vitamin D intake are widespread with children, adolescents, younger adults, pregnant women and ethnic minorities most at-risk. However, data are sparse in at-risk groups including the Travelling community, non-Europeans and institutionalised adults. Given the significant prevalence of deficiency, public health policies to promote better awareness of recommended vitamin D intakes and explore the options of food fortification are needed to address this issue.

Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19: A Randomized, Placebo-Controlled Dosing Clinical Trial.

BACKGROUND: Bone marrow mesenchymal stem cell (BM-MSC)-derived extracellular vesicles (ExoFlo) convey the immunomodulatory and regenerative properties of intact BM-MSCs. This study aimed to determine the safety and efficacy of ExoFlo as treatment for moderate to severe ARDS in patients with severe COVID-19. RESEARCH QUESTION: Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo? STUDY DESIGN AND METHODS: A prospective phase 2 multicenter double-anonymized randomized placebo-controlled dosing trial was conducted at five sites across the United States with infusions of placebo, 10 mL of ExoFlo, or 15 mL of ExoFlo on days 1 and 4. Patients (N = 102) with COVID-19-associated moderate to severe ARDS were enrolled and randomized to treatment. Adverse events were documented throughout the study. The primary outcome measure was all-cause 60-day mortality rate. Secondary outcomes included time to death (overall mortality); the incidence of treatment-emergent serious adverse events; proportion of discharged patients at 7, 30, and 60 days; time to hospital discharge; and ventilation-free days. RESULTS: No treatment-related adverse events were reported. Mortality (60-day) in the intention-to-treat population was reduced with 15 mL ExoFlo mixed with 85 mL normal saline (ExoFlo-15) compared with placebo (not significant, χ2, P = .1343). For the post hoc subgroup analyses, 60-day mortality was decreased with ExoFlo-15 compared with placebo (relative risk, 0.385; 95% CI, 0.159-0.931; P = .0340; n = 50). With ExoFlo-15, a relative risk of 0.423 (95% CI, 0.173-1.032; P = .0588; n = 24) was determined for participants aged 18 to 65 years with moderate to severe ARDS. Ventilation-free days improved with ExoFlo-15 (P = .0455; n = 50) for all participants aged 18 to 65 years. INTERPRETATION: The 15 mL dose of ExoFlo was found to be safe in patients with severe or critical COVID-19-associated respiratory failure. In participants aged 18 to 65 years, the risk reduction in 60-day mortality was further improved from subjects of all ages in the intention-to-treat population after two doses of 15 mL of ExoFlo compared with placebo. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04493242; URL: www. CLINICALTRIALS: gov.

Degradation and toxicity of bisphenol A and S during cold atmospheric pressure plasma treatment.

Bisphenols are widely recognised as toxic compounds that potentially threaten the environment and public health. Here we report the use of cold atmospheric pressure plasma (CAP) to remove bisphenol A (BPA) and bisphenol S (BPS) from aqueous systems. Additionally, methanol was added as a radical scavenger to simulate environmental conditions. After 480 s of plasma treatment, 15-25 % of BPA remained, compared to > 80 % of BPS, with BPA being removed faster (-kt = 3.4 ms-1, half-life = 210 s) than BPS (-kt = 0.15 ms-1, half-life 4700 s). The characterisation of plasma species showed that adding a radical scavenger affects the formation of reactive oxygen and nitrogen species, resulting in a lower amount of ˙OH, H2O2, and NO2- but a similar amount of NO3-. In addition, a non-target approach enabled the elucidation of 11 BPA and five BPS transformation products. From this data, transformation pathways were proposed for both compounds, indicating nitrification with further cleavage, demethylation, and carboxylation, and the coupling of smaller bisphenol intermediates. The toxicological characterisation of the in vitro HepG2 cell model has shown that the mixture of transformation products formed during CAP is less toxic than BPA and BPS, indicating that CAP is effective in safely degrading bisphenols.

Recurrent chondroblastoma of the talus: A case report and literature review of recurrent lesions in the foot and ankle.

INTRODUCTION AND IMPORTANCE: Chondroblastoma is a benign cartilaginous tumour that usually presents in the epiphysis of long bones in patients aged 10-20 years old. Only 4 % of primary chondroblastoma occur in the talus. Recurrence is rare, especially in the foot and ankle and there is no consensus regarding how it is best managed. This unique case and literature review add to a limited evidence base. CASE PRESENTATION: A 21-year-old male was referred to our elective orthopaedic clinic with persistent anterior ankle pain exacerbated by weight-bearing. Radiographs and MRI revealed a 2.5 cm non-homogenous mass in the anteromedial talus with expansion of overlying bone consistent with chondroblastoma-ABC. Our patient was initially managed by intralesional curettage and autologous bone grafting but had recurrence 4.5 months postoperatively. Subsequent en bloc resection of the talar neck with talonavicular and calcaneocuboid joint fusion resulted in excellent functional outcomes and disease-free survival at 2 years follow-up. CLINICAL DISCUSSION: There are few reports discussing treatment options for recurrence in the foot and ankle. Successful treatment of primary and recurrent lesions depends on complete local resection. Repeat curettage or en bloc resection are effective options depending on tumour size and location. Type of bone graft or void filler should be considered on a case-by-case basis. Novel therapies (e.g. phenol instillation) may be beneficial. CONCLUSION: This case details successful management of recurrent chondroblastoma with en bloc resection of the talar neck and hindfoot reconstruction. We review the efficacy and outcomes of all previously reported recurrent chondroblastoma in the foot and ankle. We highlight multiple potential treatment options.