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Lipoprotein(a) [Lp(a)] is made up of a low-density lipoprotein (LDL) particle and a specific apolipoprotein(a). The blood concentration of Lp(a) is approximately 90% genetically determined, and the main genetic factor determining Lp(a) levels is the size of the apo(a) isoform, which is determined by the number of KIV2 domain repeats. The size of the apo(a) isoform is inversely proportional to the blood concentration of Lp(a). Lp(a) is a strong and independent cardiovascular risk factor. Elevated Lp(a) levels ≥ 50 mg/dl (≥ 125 nmol/l) are estimated to occur in more than 1.5 billion people worldwide. However, determination of Lp(a) levels is performed far too rarely, including Poland, where, in fact, it is only since the 2021 guidelines of the Polish Lipid Association (PoLA) and five other scientific societies that Lp(a) measurements have begun to be performed. Determination of Lp(a) concentrations is not easy due to, among other things, the different sizes of the apo(a) isoforms; however, the currently available certified tests make it possible to distinguish between people with low and high cardiovascular risk with a high degree of precision. In 2022, the first guidelines for the management of patients with elevated lipoprotein(a) levels were published by the European Atherosclerosis Society (EAS) and the American Heart Association (AHA). The first Polish guidelines are the result of the work of experts from the two scientific societies and their aim is to provide clear, practical recommendations for the determination and management of elevated Lp(a) levels.

Abstract Due to the prolonged inflammatory process induced by infection of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indices of autonomic nervous system dysfunction may persist long after viral shedding. Previous studies showed significant changes in HRV parameters in severe (including fatal) infection of SARS-CoV-2. However, few studies have comprehensively examined HRV in individuals who previously presented as asymptomatic or mildly symptomatic cases of COVID-19. In this study, we examined HRV in asymptomatic or mildly symptomatic individuals 5–7 weeks following positive confirmation of SARS-CoV-2 infection. Sixty-five ECG Holter recordings from young (mean age 22.6 ± 3.4 years), physically fit male subjects 4–6 weeks after the second negative test (considered to be the start of recovery) and twenty-six control male subjects (mean age 23.2 ± 2.9 years) were considered in the study. Night-time RR time series were extracted from ECG signals. Selected linear as well as nonlinear HRV parameters were calculated. We found significant differences in Porta’s symbolic analysis parameters V0 and V2 (p

Introduction In the following study we describe the diagnostic process and further case analysis of a 30-year-old woman admitted with typical COVID-19 symptoms, who subsequently developed additional symptoms suggesting cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL). Material and methods Other than the standard diagnostic procedures, whole genome sequencing (WGS) was used, which led to following findings. A new variant of the NOTCH3 gene, which led to CADASIL-like symptoms, was found, and it had been most likely activated by the SARS-CoV-2 infection. This novel variant in NOTCH3 has not been found in existing databases and has never been mentioned in research concerning CADASIL before. Results Furthermore, after subjecting the patient’s close relatives to WGS it was found that no other examined person demonstrated the same genetic mutation. Conclusions It seems therefore that the new variant of NOTCH3 is of de novo origin in the patient’s genome. Additionally, the relatively early onset of CADASIL and the unexpectedly severe COVID-19 infection suggest that the two occurred simultaneously: the infection with SARS-CoV-2 accelerated development of CADASIL symptoms and the unusual variant of the NOTCH3 gene contributed to the more severe course of COVID-19.

Introduction Atrial fibrillation (AF) is a prevalent disease considerably contributing to the worldwide cardiovascular burden. For patients at high thromboembolic risk (CHA2DS2-VASc ≥3) and not suitable for chronic oral anticoagulation, owing to history of major bleeding or other contraindications, left atrial appendage occlusion (LAAO) is indicated for stroke prevention, as it lowers patient’s ischaemic burden without augmentation in their anticoagulation profile.Methods and analysis Stand-Alone Left Atrial appendage occlusion for throMboembolism prevention in nonvalvular Atrial fibrillatioN DiseasE Registry (SALAMANDER) will be conducted in 10 heart surgery and cardiology centres across Poland to assess the outcomes of LAAO performed by fully thoracoscopic-epicardial, percutaneous-endocardial or hybrid endo-epicardial approach. The registry will include patients with nonvalvular AF at a high risk of thromboembolic and bleeding complications (CHA2DS2-VASc Score ≥2 for males, ≥3 for females, HASBLED score ≥2) referred for LAAO. The first primary outcome is composite procedure-related complications, all-cause death or major bleeding at 12 months. The second primary outcome is a composite of ischaemic stroke or systemic embolism at 12 months. The third primary outcome is the device-specific success assessed by an independent core laboratory at 3–6 weeks. The quality of life (QoL) will be assessed as well based on the QoL EQ-5D-5L questionnaire. Medication and drug adherence will be assessed as well.Ethics and dissemination Before enrolment, a detailed explanation is provided by the investigator and patients are given time to make an informed decision. The patient’s data will be protected according to the requirements of Polish law, General Data Protection Regulation (GDPR) and hospital Standard Operating Procedures. The study will be conducted in accordance with the Declaration of Helsinki. Ethical approval was granted by the local Bioethics Committee of the Upper-Silesian Medical Centre of the Silesian Medical University in Katowice (decision number KNW/0022/KB/284/19). The results will be published in peer-reviewed journals and presented during national and international conferences.Trial registration number NCT05144958.

Objective: This study aimed to investigate the efficacy and safety of convalescent plasma (CP) transfusion in a group of high-risk COVID-19 patients. Methods: This prospective study included 204 patients from a single tertiary-care hospital, hospitalized with COVID-19, of whom 102 were treated with CP administration and standard care (PG) and 102 others who received standard care only (CG). The CG was selected from 336 hospitalized patients using the propensity-score matching (PSM) technique using age, MEWS score, and comorbidities. The primary outcome was mortality rate; secondary outcomes were the requirement of a ventilator, length of ventilator need, length of intensive care unit (ICU) stay, and length of overall hospital confinement. Additionally, parameters predicting death in COVID-19 patients were identified. Results: Findings confirmed a significantly lower mortality rate in the PG versus the CG (13.7% vs. 34.3 %, p = 0.001) and a significant difference in the cumulative incidence of death between the two groups (p

Acute aortic syndrome includes classic aortic dissection, aortic intramural hematoma, and penetrating atherosclerotic ulcer – a group of conditions that are defined by their dynamic evolution and similar clinical manifestation. Accurate diagnosis and prompt treatment are essential as all the aforementioned conditions are a significant threat to a patient’s life. However, acute aortic syndrome and especially aortic intramural hematoma may be challenging diagnostic problems. Intravascular ultrasound imaging is a diagnostic method that can be useful for more thorough evaluation of the aortic lesion and can particularly aid in discerning the different forms of acute aortic syndrome. We present a case of a patient with aortic intramural hematoma that was missed by conventional imaging studies but was successfully visualized with intravascular ultrasound imaging.

Abstract Studies have used extensive clinical information to predict time-to-heart failure (HF) in patients with and without diabetes mellitus (DM). We aimed to determine a screening method using only computed tomography calcium scoring (CTCS) to assess HF risk. We analyzed CTCS scans from 1,998 patients (336 with type 2 diabetes) from a no-charge coronary artery calcium score registry (CLARIFY Study, Clinicaltrials.gov NCT04075162). We used deep learning to segment epicardial adipose tissue (EAT) and engineered radiomic features of calcifications (“calcium-omics”) and EAT (“fat-omics”). We developed models incorporating radiomics to predict risk of incident HF in patients with and without type 2 diabetes. At a median follow-up of 1.7 years, 5% had incident HF. In the overall cohort, fat-omics (C-index: 77.3) outperformed models using clinical factors, EAT volume, Agatston score, calcium-omics, and calcium-and-fat-omics to predict HF. For DM patients, the calcium-omics model (C-index: 81.8) outperformed other models. In conclusion, CTCS-based models combining calcium and fat-omics can predict incident HF, outperforming prediction scores based on clinical factors.Please check article title if captured correctly.YesPlease check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.Yes

ABSTRACT Tuberculosis (TB) remains a significant global health challenge, exacerbated by the emergence of drug-resistant strains, such as those resistant to pyrazinamide (PZA). The current scarcity of affordable and precise quantitative diagnostic tests for PZA resistance underscores the urgent need for more accessible diagnostic tools. We evaluated PZA susceptibility in 264 TB-positive samples by quantifying pyrazinoic acid (POA) production, using both the MODS-Wayne qualitative assay and our newly developed quantitative approach (MODS-WQ). The MODS-WQ was assessed in 7H9 medium (MODS-WQ7H9) or citrate buffer (MODS-WQCB), with POA levels measured via spectrophotometry against a calibration curve. PZA susceptibility determinations were based on a composite reference standard. Associations between POA levels and pyrazinamidase mutations were explored. The composite standard detected PZA resistance in 23.5% of the samples, which accounts for 62.8% of the multidrug-resistant (MDR) samples. The MODS-WQ established specific POA cutoffs of 123.25 µM for MODS-WQ7H9 and 664.7 µM for MODS-WQCB, with sensitivities of 81.3% and 92.3% and specificities of 77.2% and 95.9%, respectively. Notably, samples with mutations in the pyrazinamidase metal-binding site exhibited significantly lower POA levels compared with mutations in the enzyme periphery. Furthermore, a significant correlation was found between POA production and PZA resistance, Bactec Growth Index, and minimum inhibitory concentration (MIC) values. This study presents a novel, direct, and accessible susceptibility test for PZA resistance that quantifies POA, enhancing the detection capabilities for this condition. The citrate-buffered MODS-WQ assay demonstrated high sensitivity and specificity for quantifying POA, confirming that POA production is a reliable indicator of PZA resistance.IMPORTANCEPZA susceptibility testing continues to be a challenge, particularly in countries with high TB incidence. In response to this pressing need, we have developed a quantitative MODS-Wayne (MODS-WQ) assay. This approach offers a direct and cost-effective solution representing a significant advancement in TB diagnostics, particularly benefiting resource-limited laboratories, primarily in developing regions. The MODS-WQ assay stands out for its ability to quantify pyrazinoic acid (POA) production, as a reliable indicator of PZA resistance. Unlike traditional qualitative assays, MODS-WQ eliminates the inherent subjectivity in interpretation, providing more accurate and actionable results. Moreover, the MODS-WQ approach accounts for critical factors influencing PZA resistance, including enzymatic efficiency and efflux pump activity. By integrating these factors into the detection process, our methodology offers a comprehensive understanding of PZA resistance levels, enabling tailored treatment strategies for patients.

This paper presents new methods to analyze a category’s change through a time series of maps, even when the time intervals have inconsistent durations. The methods include an option to facilitate comparison among sites by expressing results as an annual percentage of each site’s unified size. A site’s unified size is the union of where the category exists at any of the site’s time points. The methods also specify gross losses, gross gains, eight trajectories, and three components: Quantity, Exchange, and Alternation. The illustrative application compares maps of the marsh category for three Long-Term Ecological Research sites: Plum Island Ecosystems (PIE), Georgia Coastal Ecosystems (GCE), and the Virginia Coast Reserve (VCR). The application analyzes marsh’s changes during two time intervals that have unequal durations within each site’s distinct temporal extent. Results show that PIE has the fastest change during each site’s temporal extent. Gross change is more than double the quantity change for all sites. Exchange accounts for most of the change in GCE, while Alternation accounts for most of the change in PIE and VCR. The methods provide more information than popular methods that quantify annual net change. Our timeseriesTrajectories R package performs the analysis and is available for free at https://github.com/bilintoh/timeseriesTrajectories.

Abstract Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density). We used novel, hand-crafted calcification features (calcium-omics); Cox time-to-event modeling; elastic net; and up and down synthetic sampling methods for imbalanced data, to assess MACE risk. We used 2457 CT calcium score (CTCS) images enriched for MACE events from our large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were especially important determinants of increased risk, with dense calcification (> 1000HU, stable calcifications) associated with reduced risk Our calcium-omics model with (training/testing, 80/20) gave C-index (80.5%/71.6%) and 2-year AUC (82.4%/74.8%). Although the C-index is notoriously impervious to model improvements, calcium-omics compared favorably to Agatston and gave a significant difference (P

An overview of hydraulic track drive systems employed in mobile rock crushers for the mining industry is provided. A mathematical model was developed to analyse thrust and resistive forces experienced during typical machine operations, including flat-plane tracking, incline climbing, and pivot turning. The model provides a basis for assessing power demands required to transition from hydraulic to electric drive systems by quantifying relevant resistive forces involved. Simulink simulations of the track loading, transverse and longitudinal resistive forces, and frictional forces were performed to evaluate system performance under various operational conditions. Results show that incline tracking climbing a slope generate significantly higher resistive forces than straight tracking or pivot turning tracking. This study addresses the challenges of electrifying large-scale off-road machinery by providing insights into the operational demands of the hydraulic system. The findings offer a foundation for subsequent research into electric alternatives that can deliver comparable power densities, improve energy efficiency, and reduce emissions. Potential areas for further investigation include battery optimisation, advancements in electric motor technology, and hybrid solutions that bridge hydraulic and fully electric systems.

Background: Anaemia is a common but treatable condition that predicts adverse clinical outcomes. However, standards of anaemia management vary considerably. Aim: To estimate the prevalence of anaemia and extent of screening for common underlying causes in the healthcare system in the Republic of Ireland. Design & setting: We conducted a retrospective cohort study of 112 181 adult patients, aged ≥18 years, who had a full blood count performed in 2013, using data from the National Kidney Disease Surveillance System. Method: The prevalence of anaemia was determined across demographic and clinical subgroups, according to World Health Organization (WHO) definitions. The proportion screened for iron, vitamin B12, and folate deficiency was determined within a 3-month follow-up period and the corresponding prevalence for each deficiency determined. Results: The overall prevalence of anaemia was 12.0% (95% confidence interval [CI] = 11.8% to 12.2%) and was higher in women than men (13.2% versus 10.5%, P75 years) and worsening kidney function (8.2%, 10.9%, 33.2%, and 63.8% for each estimated glomerular filtration rate [eGFR] categories >90, 60–89, 30–59 and

Summary: Chagas disease, caused by the protozoan Trypanosoma cruzi, is a highly overlooked parasitic infection within the United States. It affects an estimated 300,000 individuals, often remaining asymptomatic for years before triggering severe complications such as cardiomyopathy in 30-40% of cases. While many contract the disease in Latin America, its transmission by local vectors in the southern U.S. presents a significant challenge. Unfortunately, limited access to diagnosis and treatment persists, alongside unresolved gaps in healthcare systems and disease pathogenesis. In this viewpoint, we discuss the need for focused research and public health initiatives, with U.S. research institutions playing a crucial role in developing new treatments and identifying biomarkers. Furthermore, investigating the genetic variations of T. cruzi between North and South America is vital for improving diagnostic and treatment strategies. Urgent action is required to implement national and local programs, bolstering healthcare responses and advancing research efforts.

For over 100 years there has been an academic pursuit of understanding and applying the principals of sport psychology to improve athletic performance. How is it that certain athletes do their best when it means the most while others “choke”? Meeting and exceeding the challenges that are presented can completely change the trajectory of any athlete's career. What is it that separates the good from the great and the great from the superstars? Is it motivation, preparation, determination, discipline, commitment, natural talent, physical strength, or work ethic? Maybe it is a combination of all of these characteristics. Without the right mentality everything can fall apart. In Alcoholics Anonymous, it is said, “you don't have a drinking problem – you have a thinking problem.” The evidence is quite clear that the mental game can have a substantial impact, both for the better and for the worse, on performance. In this perspectives and viewpoints, we share our own insights from our experience for athletes to obtain the ultra-mentality and maximise their athletic performance. We have attempted to take simple words to briefly explain complicated concepts.

Abstract Background Genomic heterozygosity has been shown to confer a health advantage in humans and play a protective role in complex diseases. Given osteoarthritis (OA) is a highly polygenic disease, we set out to determine if an association exists between OA and genomic heterozygosity. Results End-stage knee and hip OA patients and healthy controls were recruited from the Newfoundland and Labrador (NL) population. The Arthritis Research UK Osteoarthritis Genetics (arcOGEN) consortium database was utilized as a replication cohort. DNA was extracted from blood samples and genotyped. Individual rates of observed heterozygosity (HetRate) and heterozygosity excess (HetExcess) relative to the expected were mathematically derived, and standardized to a z-score. Logistic regression modeling was used to examine the association between OA and HetRate or HetExcess. A total of 559 knee and hip OA patients (mean age 66.5 years, body mass index (BMI) 33.7 kg/m2, and 55% females) and 118 healthy controls (mean age 56.4 years, BMI 29.5 kg/m2, and 59% female) were included in the NL cohort analysis. We found that OA had an inverse relationship with HetRate and HetExcess with odds ratios of 0.64 (95% CI: 0.45–0.91) and 0.65 (95% CI: 0.45–0.93) per standard deviation (SD), respectively. The arcOGEN data included 2,019 end-stage knee and hip OA patients and 2,029 healthy controls, validating our findings with HetRate and HetExcess odds ratios of 0.60 (95% CI: 0.56–0.64) and 0.44 (95% CI: 0.40–0.47) per SD, respectively. Conclusions Our results are the first to clearly show evidence, from two separate cohorts, that reduced genomic heterozygosity confers a risk for the future development of OA.

Basal‐like breast cancer (BBC) and glioblastoma multiforme (GBM) are aggressive cancers associated with poor prognosis. BBC and GBM have stem cell‐like gene expression signatures, which are in part driven by forkhead box O (FOXO) transcription factors. To gain further insight into the impact of FOXO1 in BBC, we treated BT549 cells with AS1842856 and performed RNA sequencing. AS1842856 binds to unphosphorylated FOXO1 and inhibits its ability to directly bind to DNA. Gene Set Enrichment Analysis indicated that a set of WNT pathway target genes, including lymphoid enhancer‐binding factor 1 (LEF1) and transcription factor 7 (TCF7), were robustly induced after AS1842856 treatment. These same genes were also induced in GBM cell lines U87MG, LN18, LN229, A172, and DBTRG upon AS1842856 treatment. By contrast, follow‐up RNA interference (RNAi) targeting of FOXO1 led to reduced LEF1 and TCF7 gene expression in BT549 and U87MG cells. In agreement with RNAi experiments, CRISPR Cas9‐mediated FOXO1 disruption reduced the expression of canonical WNT genes LEF1 and TCF7 in U87MG cells. The loss of TCF7 gene expression in FOXO1 disruption mutants was restored by exogenous expression of the DNA‐binding‐deficient FOXO1‐H215R. Therefore, FOXO1 induces TCF7 in a DNA‐binding‐independent manner, similar to other published FOXO1‐activated genes such as TCF4 and hes family bHLH transcription factor 1. Our work demonstrates that FOXO1 promotes canonical WNT gene expression in examined BBC and GBM cells, similar to results found in Drosophila melanogaster, T‐cell development, and murine acute myeloid leukemia models.

Abstract Background Abnormalities of serum sodium are associated with increased mortality risk in hospitalised patients, but it is unclear whether, and to what extent other factors influence this relationship. We investigated the impact of dysnatraemia on total and cause-specific mortality in the Irish health system while exploring the concurrent impact of age, kidney function and designated clinical work-based settings. Methods A retrospective cohort study of 32,666 participants was conducted using data from the National Kidney Disease Surveillance System. Hyponatraemia was defined as 145 mmol/L with normal range 135–145 mmol/L. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR’s) and 95% Confidence Intervals (CIs) while penalised spline models further examined patterns of risk. Results There were 5,114 deaths (15.7%) over a median follow up of 5.5 years. Dysnatraemia was present in 8.5% of patients overall. In multivariable analysis, both baseline and time-dependent serum sodium concentrations exhibited a U-shaped association with mortality. Hyponatremia was significantly associated with increased risk for cardiovascular [HR 1.38 (1.18–1.61)], malignant [HR: 2.49 (2.23–2.78)] and non-cardiovascular/non-malignant causes of death [1.36 (1.17–1.58)], while hypernatremia was significantly associated with cardiovascular [HR: 2.16 (1.58–2.96)] and non-cardiovascular/ non-malignant deaths respectively [HR: 3.60 (2.87–4.52)]. The sodium-mortality relationship was significantly influenced by age, level of kidney function and the clinical setting at baseline (P

Abstract Background and Aim Acute severe ulcerative colitis (ASUC) remains a significant cause of morbidity and healthcare utilization. This study aimed to characterize the total healthcare costs of ASUC, explore factors associated with significant cost over the 12 months following an index admission, and document outcomes including corticosteroid exposure. Methods Patients admitted from January 2016 until January 2021 for ASUC to a tertiary inflammatory bowel disease (IBD) center in Australia were identified via retrospective chart review. Costs were calculated over a 12‐month period following index admission. Results Seventy‐two patients (30 [42%] female, median age 39 [IQR 27–54] years) were included. The median length of stay of index admission was 6 days (IQR 5–10 days). The median cost of index admission was 7829 AUD, which was driven by the initial length of stay (P

This manuscript provides guidance concerning how to use the Total Operating Characteristic (TOC) when (1) analyzing change through time, (2) ranking a categorical independent variable, and (3) constraining the extent for a gaining category. The illustrative variable is the marsh land-cover category in the Plum Island Ecosystems of northeastern Massachusetts, USA. The data are an elevation map and maps showing the land categories of water, marsh, and upland in 1938, 1971, and 2013. There were losses and gains near the edge of the marsh between 1938 and 1972 and between 1972 and 2013. The TOC curves show that marsh gained most intensively at intermediate elevations during the first time interval and then had a weaker association with elevation during the second time interval. Marsh gains more intensively from water than from upland during both time intervals. The TOC curves also demonstrate that the marsh gains occurred where marsh was previously lost, a phenomenon called Alternation. Furthermore, eliminating far distances and extreme elevations from the spatial extent decreased the area under the curve (AUC) for distance and increased the AUC for elevation. We invite scientists to use the TOC because the TOC is easier to interpret and shows more information than the Relative Operative Characteristic.

Tomato spotted wilt orthotospovirus (TSWV) causes substantial economic loss to tomato production, and the Sw-5b resistance gene is widely deployed for management. Here, we show (i) the emergence of resistance-breaking (RB) TSWV strains in processing and fresh market tomato production in California over the past ten years, and (ii) evolutionary relationships with RB strains from other areas. A specific RT-PCR test was used to show the C118Y RB strain that emerged in Fresno County in 2016 quickly became predominant in the central production area and remained so through this study. In 2021, the C118Y strain was detected in the Northern production area, and was predominant in 2022. However, in 2023, the C118Y strain was unexpectedly detected in fewer spotted wilt samples from resistant varieties. This was due to emergence of the T120N RB strain, previously known to occur in Spain. A specific RT-PCR test was developed and used to show that the T120N RB strain was predominant in Colusa and Sutter counties (detected in 75-80% of samples), and detected in ~50% of samples from Yolo County. Pathogenicity tests confirmed California isolates of the T120N strain infected Sw-5b tomato varieties and induced severe symptoms. Another RB strain, C118F, was associated with spotted wilt samples of Sw-5 varieties from fresh market tomato production in southern California. Phylogenetic analyses with complete NSm sequences revealed that the C118Y and T120N RB strains infecting resistant processing tomato in California emerged locally, whereas those from fresh market production were more closely related to isolates from Mexico. Thus, widespread deployment of this single dominant resistance gene in California has driven the local emergence of multiple RB strains in different tomato production areas and types. These results further emphasize the need for ongoing monitoring for RB strains, and identification of sources of resistance to these strains.

Conclusion: EBD is a highly effective and safe procedure in both de novo and anastomotic strictures < 4 cm that can prevent or delay the need for surgical treatment.

Objective: Simulation exercises are meant to provide an opportunity for health care workers to improve teamwork and develop clinical skills, among other goals. The objective of this systematic review was to determine whether simulated interdisciplinary activities in the health care or clinical setting improve interprofessional collaboration within health care teams that include respiratory therapists. Methods: A systematic literature search of PubMed, EMBASE and CINAHL was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline to find relevant articles using both MeSH terms and free text. Filters were applied to include English-language studies; studies published within the last 10 years (2011–2021), and studies involving human participants. Studies were excluded if they did not assess the effects of simulation on aspects of teamwork, if participants were students, if teams did not include respiratory therapists, or if the training did not involve a simulated experience in a clinical setting. The search identified 312 articles, 75 of which were advanced to full-text review. Of those 75 articles, 62 were eliminated for not measuring teamwork in their outcomes. Two articles were excluded for being published before 2011, and one was eliminated for poor methodological quality. A risk of bias assessment using standardized qualitative and quantitative appraisal checklists was conducted on each of the remaining 10 studies selected for inclusion. Results: A total of 10 studies met the inclusion criteria for this review (eight prospective, pre/post-test studies and two prospective observational studies). Randomization and participant/researcher blinding were not present in the majority of the studies and reporting bias was also found to be a concern throughout the literature. However, all of the studies noted increased teamwork scores post-intervention, though they differed in the tools used to evaluate this outcome. Discussion: Collectively, the studies included in this review demonstrate that interprofessional simulation experiences including respiratory therapists enhance teamwork. The various tools used to assess change in teamwork had evidence of validity; however, studies varied in their outcomes measured, making quantitative analysis inappropriate. There are challenges involved in creating and assessing these simulations, particularly when performed within a clinical environment, which make it difficult to fully remove bias from the study design. It is unclear if the teamwork improvement can strictly be attributed to the simulation intervention or in part due to the general development of team members’ competencies throughout the research period. Additionally, the permanency of the effects cannot be evaluated based on the studies included and could be an area for future research. Conclusion: Despite the limited number and methodological precision of studies included in this review along with the differing outcome evaluation methods, the authors conclude that positive teamwork improvement results are generalizable and agree with the broader base of research of the effectiveness of simulation on teambuilding.

Background: Early extubation (EE), within 8 h of cardiac surgery, is associated with improved resource utilization. Studies have demonstrated that for patients receiving low-dose, fast-track opioid cardiac anesthesia (FTCA) protocols, EE is as safe as conventional care. To date, it is unclear when the earliest timepoints for safe extubation might be. Additionally, some authors pointed out that certain patients receiving FTCA protocols frequently experience delays during extubation attempts. Understanding the factors associated with delayed extubation is crucial for perioperative planning and resource management. This review seeks to 1) determine whether immediate extubation (IE) in the operating room is as safe as EE and 2) identify factors associated with delayed extubation. Methods: MEDLINE, Cochrane Library, EMBASE and CINAHL (up to March 2022) were searched. Studies pertaining to FTCA, IE, EE or factors associated with delayed extubation were included. All authors extracted, appraised and synthesized data. The primary outcome measures were treatment results and factors associated with delayed extubation. Results: Six studies investigated treatment outcomes associated with FTCA and IE. One randomized controlled trial reported that outcomes associated with IE were comparable to those with EE. Five observational studies reported incidence for 19 treatment outcomes associated with IE, but no comparisons were made to EE. Six observational studies assessed pre- and intraoperative factors associated with delayed extubation in FTCA patients. In at least one study, 37 factors were investigated and 22 were identified. The most frequently reported factors were pre-existing cardiac insufficiency or renal disease, time on pump and cross-clamp time. Obesity and stroke were investigated but were not associated with delayed extubation. No study examined the influence of race, ethnicity or gender on outcomes. Discussion and conclusion: Evidence pertaining to treatment outcomes associated with FTCA and IE is weak. Observational studies cannot determine causation. Large multicentre randomized control trials are required to determine the safety of IE. Although numerous factors have been associated with delayed extubation, several studies do not describe how or which factors were selected for examination. Therefore, certain factors may have yet to be evaluated. Future studies should comprehensively define all factors under investigation.

Direct visualization of the structural transformation from pre-pore to pore of the mammalian immune defense complex perforin-2 (PFN2) reveals a clockwise hand-over-hand mechanism that propagates at ~15 subunits per second.

Perforin is a pore-forming protein that plays a crucial role in the immune system by clearing virus-infected or tumor cells. It is released from cytotoxic granules of immune cells and forms pores in targeted lipid membranes to deliver apoptosis-inducing granzymes. It is a very cytotoxic protein and is therefore adapted not to act in producing cells. Its activity is regulated by the requirement for calcium ions for optimal activity. However, the exact affinity of perforin for calcium ions has not yet been determined. We conducted a molecular dynamics simulation in the absence or presence of calcium ions that showed that binding of at least three calcium ions is required for stable perforin binding to the lipid membrane. Biophysical studies using surface plasmon resonance and microscale thermophoresis were then performed to estimate the binding affinities of native human and recombinant mouse perforin for calcium ions. Both approaches showed that mouse perforin has a several fold higher affinity for calcium ions than that of human perforin. This was attributed to a particular residue, tryptophan at position 488 in mouse perforin, which is replaced by arginine in human perforin. This represents an additional mechanism to control the activity of human perforin.

The western United States (U.S.) has been experiencing more severe wildfires, in part due to climate change, but the underlying synoptic patterns and their modulation in driving fire weather is unclear. Here we investigated the relationship between weather regimes (WRs) and fire weather indices, specifically vapor pressure deficit (VPD) and the Canadian Forest Fire Weather Index. By identifying five singular WRs using k-means clustering, we found that a particular regime (WR-2), one characterized by a distinct tripolar wave train pattern over the continental U.S., has exhibited an increased frequency since 1980. The ascribed WR-2 regime was found to be mainly responsible for rising trends in the fire weather indices, especially VPD. Further, the average fire indices of the WR-2 regime played a more important role than the frequency in shaping the rising trends in the fire weather indices. The increased frequency of the WR-2 WR was mainly attributed to anthropogenic forcing and, the year-to-year variation of the frequency was associated with sea surface temperature anomalies over the subtropical eastern Pacific. Human-induced climate change might have furthered the exacerbation of wildfire danger in the western U.S. by modulating the behaviors of WRs and fire weather indices.

Background and Aims: Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to prevent chemotherapy induced infertility are urgently needed. Here we investigate whether pharmacological elevation of nicotinamide adenine dinucleotide (NAD+) ameliorates chemotherapy induced female infertility in mice. Method: 8-week-old C57BL6 female mice were treated +/- chemotherapy (doxorubicin, Dox; 10 mg/kg) and +/- nicotinamide mononucleotide (NMN; 200 mg/kg i.p. once and 2 g/L in drinking water on-going), an orally bioavailable metabolic precursor to NAD+. Effects on fertility were measured by impact on ovarian reserve and folliculogenesis, ovulation rates and breeding performance. Effects on the ovarian NAD+ metabolome were assessed by mass spectrometry. A potential adverse effect of NMN on the efficiency of chemotherapy was assessed using a xenograft model of mammary cancer. Results: NMN treatment did not prevent a decline in the ovarian reserve caused by chemotherapy but did maintain the health of the remaining primordial follicle and total follicle populations, leading to a restoration in oocyte yield in chemo-treated mice (Dox vs Dox+NMN; P

Objective Simulation exercises are meant to provide an opportunity for health care workers to improve teamwork and develop clinical skills, among other goals. The objective of this systematic review was to determine whether simulated interdisciplinary activities in the health care or clinical setting improve interprofessional collaboration within health care teams that include respiratory therapists. Methods A systematic literature search of PubMed, EMBASE and CINAHL was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline to find relevant articles using both MeSH terms and free text. Filters were applied to include English-language studies; studies published within the last 10 years (2011--2021), and studies involving human participants. Studies were excluded if they did not assess the effects of simulation on aspects of teamwork, if participants were students, if teams did not include respiratory therapists, or if the training did not involve a simulated experience in a clinical setting. The search identified 312 articles, 75 of which were advanced to full-text review. Of those 75 articles, 62 were eliminated for not measuring teamwork in their outcomes. Two articles were excluded for being published before 2011, and one was eliminated for poor methodological quality. A risk of bias assessment using standardized qualitative and quantitative appraisal checklists was conducted on each of the remaining 10 studies selected for inclusion. Results A total of 10 studies met the inclusion criteria for this review (eight prospective, pre/post-test studies and two prospective observational studies). Randomization and participant/researcher blinding were not present in the majority of the studies and reporting bias was also found to be a concern throughout the literature. However, all of the studies noted increased teamwork scores post-intervention, though they differed in the tools used to evaluate this outcome. Discussion Collectively, the studies included in this review demonstrate that interprofessional simulation experiences including respiratory therapists enhance teamwork. The various tools used to assess change in teamwork had evidence of validity; however, studies varied in their outcomes measured, making quantitative analysis inappropriate. There are challenges involved in creating and assessing these simulations, particularly when performed within a clinical environment, which make it difficult to fully remove bias from the study design. It is unclear if the teamwork improvement can strictly be attributed to the simulation intervention or in part due to the general development of team members' competencies throughout the research period. Additionally, the permanency of the effects cannot be evaluated based on the studies included and could be an area for future research. Conclusion Despite the limited number and methodological precision of studies included in this review along with the differing outcome evaluation methods, the authors conclude that positive teamwork improvement results are generalizable and agree with the broader base of research of the effectiveness of simulation on teambuilding.

Abstract Background Reverse total shoulder arthroplasty (RTSA) has emerged as a successful surgery with expanding indications. Outcomes may be influenced by post-operative rehabilitation; however, there is a dearth of research regarding optimal rehabilitation strategy following RTSA. The primary purpose of this study is to compare patient reported and clinical outcomes after RTSA in two groups: in one group rehabilitation is directed by formal, outpatient clinic-based physical therapists (PT group) as compared to a home therapy group, in which patients are instructed in their rehabilitative exercises by surgeons at post-operative appointments (HT group). Secondary aims include comparisons of complications, cost of care and quality of life between the two groups. Methods This randomised controlled trial has commenced at seven sites across the United States. Data is being collected on 200 subjects by clinical research assistants pre-operatively and post-operatively at 2, 6, and 12 weeks, 6 months, 1 and 2 year visits. The following variables are being assessed: American Shoulder and Elbow Surgeons (ASES), pain level using the numeric pain scale, the Single Assessment Numeric Evaluation (SANE) score, and shoulder active and passive range of motion for analysis of the primary aim. Chi square and t-tests will be used to measure differences in baseline characteristics of both groups. Repeated measures linear mixed effects modeling for measurement of differences will be used for outcomes associated with ASES and SANE and scores, and range of motion measures. Secondary aims will be analyzed for comparison of complications, cost, and quality of life assessment scores using data obtained from the PROMIS 29 v. 2, questionnaires administered at standard of care post-operative visits, and the electronic health record. Subjects will be allowed to crossover between the PT and HT groups, and analysis will include both intention-to-treat including patients who crossed over, and a second with cross-over patients removed, truncated to the time they crossed over. Discussion RTSA is being performed with increasing frequency, and the optimal rehabilitation strategy is unclear. This study will help clarify the role of formal physical therapy with particular consideration to outcomes, cost, and complications. In addition, this study will evaluate a proposed rehabilitation strategy. Trial registration This study is registered as NCT03719859 at ClincialTrials.gov .

Background Early extubation (EE), within 8 h of cardiac surgery, is associated with improved resource utilization. Studies have demonstrated that for patients receiving low-dose, fast-track opioid cardiac anesthesia (FTCA) protocols, EE is as safe as conventional care. To date, it is unclear when the earliest timepoints for safe extubation might be. Additionally, some authors pointed out that certain patients receiving FTCA protocols frequently experience delays during extubation attempts. Understanding the factors associated with delayed extubation is crucial for perioperative planning and resource management. This review seeks to 1) determine whether immediate extubation (IE) in the operating room is as safe as EE and 2) identify factors associated with delayed extubation. Methods MEDLINE, Cochrane Library, EMBASE and CINAHL (up to March 2022) were searched. Studies pertaining to FTCA, IE, EE or factors associated with delayed extubation were included. All authors extracted, appraised and synthesized data. The primary outcome measures were treatment results and factors associated with delayed extubation. Results Six studies investigated treatment outcomes associated with FTCA and IE. One randomized controlled trial reported that outcomes associated with IE were comparable to those with EE. Five observational studies reported incidence for 19 treatment outcomes associated with IE, but no comparisons were made to EE. Six observational studies assessed pre- and intraoperative factors associated with delayed extubation in FTCA patients. In at least one study, 37 factors were investigated and 22 were identified. The most frequently reported factors were pre-existing cardiac insufficiency or renal disease, time on pump and cross-clamp time. Obesity and stroke were investigated but were not associated with delayed extubation. No study examined the influence of race, ethnicity or gender on outcomes. Discussion and conclusion Evidence pertaining to treatment outcomes associated with FTCA and IE is weak. Observational studies cannot determine causation. Large multicentre randomized control trials are required to determine the safety of IE. Although numerous factors have been associated with delayed extubation, several studies do not describe how or which factors were selected for examination. Therefore, certain factors may have yet to be evaluated. Future studies should comprehensively define all factors under investigation.

Background: Prior studies have suggested significant underutilization of statins in women and worse cardiovascular outcomes. Data examining the impact of real-world coronary artery calcium (CAC) scoring to improve utilization of preventive therapies and outcomes is limited. Methods: In a prospective registry study of low cost or no-cost CAC scoring between 2014 and 19 (CLARIFY Study, Clinicaltrials.gov NCT04075162), we sought to study the association of CAC scoring on statin utilization, blood lipids (LDL, total cholesterol, triglycerides), downstream ischemic testing (coronary angiography and stress testing), coronary revascularization and outcomes (MI, stroke, death) in women compared with men. Eligibility for statin initiation was defined as atherosclerotic cardiovascular disease pooled cohort equation (ASCVD-PCE) ≥ 7.5% and CAC≥100/≥75th percentile. Results: A total of 52,151 patients (26,336 women and 25,815 men) were enrolled. Women were more likely to have CAC 0 (51% vs 30%, P

Objective: Low-dose cardiac-gated chest CTs allow for simultaneous evaluation of coronary artery calcification and aortic size. We sought to evaluate the prevalence of thoracic aortic dilation (TAD) and thoracic aortic aneurysm (TAA) in a large cohort of patients undergoing coronary artery calcium (CAC) screening. Methods: We reviewed all patients from a large, prospective no-charge CAC screening program (CLARIFY, Clinicaltrials.gov NCT04075162) for whom measurements of the ascending aorta were available. TAD was defined as an ascending aortic diameter ≥4.0cm, while TAA was defined as ascending aortic diameter ≥ 4.5cm. We explored associations between patient characteristics, CAC, and the prevalence of TAD/TAA. Results: A total of 36,356 patients enrolled in the CLARIFY program underwent analysis for TAD/TAA. 3,130 patients (8.6%) had TAD and 237 (0.7%) had TAA. Patients with TAA were older (63±8 vs 59±10 years, p

Background and Purpose: Although quantitative image biomarkers (radiomics) show promising value for cancer diagnosis, prognosis, and treatment assessment, these biomarkers still lack reproducibility. In this systematic review, we aimed to assess the progress in radiomics reproducibility and repeatability in the recent years. Methods and materials: Four hundred fifty-one abstracts were retrieved according to our search pattern criteria, with the publication dates ranging from 2017/05/01 to 2020/12/01. Each abstract including the keywords was independently screened by four observers. Forty-two full-text articles were selected for further analysis. Patient population data, radiomic feature classes, feature extraction software, image preprocessing, and reproducibility results were extracted from each article. To support the community with a standardized reporting strategy, we propose a specific reporting checklist to evaluate the feasibility to reproduce each study. Results: Many studies continue to under-report essential reproducibility information: all but one clinical and all but two phantom studies missed to report at least one important item reporting image acquisition. The studies included in this review indicate that all radiomic features are sensitive to image acquisition, reconstruction, tumor segmentation, and interpolation. However, the amount of sensitivity is feature dependent, for instance, textural features were, in general, less robust than statistical features. Conclusions: Radiomics repeatability, reproducibility, and reporting quality can substantially be improved regarding feature extraction software and settings, image preprocessing and acquisition, cutoff values for stable feature selection. Our proposed radiomics reporting checklist can serve to simplify and improve the reporting and, eventually, guarantee the possibility to fully replicate and validate radiomic studies.

The Flow matrix is a novel method to describe and extrapolate transitions among categories. The Flow matrix extrapolates a constant transition size per unit of time on a time continuum with a maximum of one incident per observation during the extrapolation. The Flow matrix extrapolates linearly until the persistence of a category shrinks to zero. The Flow matrix has concepts and mathematics that are more straightforward than the Markov matrix. However, many scientists apply the Markov matrix by default because popular software packages offer no alternative to the Markov matrix, despite the conceptual and mathematical challenges that the Markov matrix poses. The Markov matrix extrapolates a constant transition proportion per time interval during whole-number multiples of the duration of the calibration time interval. The Markov extrapolation allows at most one incident per observation during each time interval but allows repeated incidents per observation through sequential time intervals. Many Markov extrapolations approach a steady state asymptotically through time as each category size approaches a constant. We use case studies concerning land change to illustrate the characteristics of the Flow and Markov matrices. The Flow and Markov extrapolations both deviate from the reference data during a validation time interval, implying there is no reason to prefer one matrix to the other in terms of correspondence with the processes that we analyzed. The two matrices differ substantially in terms of their underlying concepts and mathematical behaviors. Scientists should consider the ease of use and interpretation for each matrix when extrapolating transitions among categories.

ObjectiveThe timing and nature of surgical intervention for semisolid abnormalities are dependent upon distinguishing between adenocarcinoma-in-situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (INV). We sought to develop and evaluate a quantitative imaging method to determine invasiveness of small, ground-glass lesions on computed tomography (CT) chest scans.MethodsThe study comprised 268 patients from 4 institutions with resected (

Abstract Aim Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea. Methods and results Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO2) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO2 (p = 0.02, p = 0.03). Conclusion Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea.

Conventional computed tomography (CT) plays an important role in detection of lung nodules. However, further characterization is usually limited requiring additional imaging and invasive work up. Spectral Detector CT (SDCT) is an upcoming novel modality that not only allows morphological evaluation but also provides insight into prediction of malignant behavior of lung nodules. Additional quantification capabilities available from the same scan make it a more comprehensive imaging option in oncology patients. This is a first case report demonstrating the potential of single SDCT to provide necessary information for lung cancer diagnosis and preoperative planning, comparable to standard of care imaging.

Many studies find a strong association between press freedom and corruption perceptions (Adsera, Boix, & Payne, 2003; Brunetti & Weder, 2003; Freille, Haque, & Kneller, 2007). However, it is possible that this relationship is driven by experts’ belief that limits on press freedom are associated with corruption. This article tests the association between press freedom and corruption perceptions using objective measures of corruption from the World Bank’s Enterprise Surveys, a series of representative surveys of the owners and top managers of private firms in the manufacturing and service sectors. Our findings suggest that there is a reputational premium associated with press freedom: Holding corruption experiences constant, corruption perceptions are improved by greater press freedom. Moreover, we find that the developed world is best placed to avail of this premium, as it is most evident in countries with low to moderate levels of corruption by global standards.

ObjectiveThe disease COVID-19 has caused a widespread global pandemic with ~3. 93 million deaths worldwide. In this work, we present three models—radiomics (MRM), clinical (MCM), and combined clinical–radiomics (MRCM) nomogram to predict COVID-19-positive patients who will end up needing invasive mechanical ventilation from the baseline CT scans.MethodsWe performed a retrospective multicohort study of individuals with COVID-19-positive findings for a total of 897 patients from two different institutions (Renmin Hospital of Wuhan University, D1 = 787, and University Hospitals, US D2 = 110). The patients from institution-1 were divided into 60% training, D1T (N = 473), and 40% test set D1V (N = 314). The patients from institution-2 were used for an independent validation test set D2V (N = 110). A U-Net-based neural network (CNN) was trained to automatically segment out the COVID consolidation regions on the CT scans. The segmented regions from the CT scans were used for extracting first- and higher-order radiomic textural features. The top radiomic and clinical features were selected using the least absolute shrinkage and selection operator (LASSO) with an optimal binomial regression model within D1T.ResultsThe three out of the top five features identified using D1T were higher-order textural features (GLCM, GLRLM, GLSZM), whereas the last two features included the total absolute infection size on the CT scan and the total intensity of the COVID consolidations. The radiomics model (MRM) was constructed using the radiomic score built using the coefficients obtained from the LASSO logistic model used within the linear regression (LR) classifier. The MRM yielded an area under the receiver operating characteristic curve (AUC) of 0.754 (0.709–0.799) on D1T, 0.836 on D1V, and 0.748 D2V. The top prognostic clinical factors identified in the analysis were dehydrogenase (LDH), age, and albumin (ALB). The clinical model had an AUC of 0.784 (0.743–0.825) on D1T, 0.813 on D1V, and 0.688 on D2V. Finally, the combined model, MRCM integrating radiomic score, age, LDH and ALB, yielded an AUC of 0.814 (0.774–0.853) on D1T, 0.847 on D1V, and 0.771 on D2V. The MRCM had an overall improvement in the performance of ~5.85% (D1T: p = 0.0031; D1Vp = 0.0165; D2V: p = 0.0369) over MCM.ConclusionThe novel integrated imaging and clinical model (MRCM) outperformed both models (MRM) and (MCM). Our results across multiple sites suggest that the integrated nomogram could help identify COVID-19 patients with more severe disease phenotype and potentially require mechanical ventilation.

Introduction: Anti-tumor necrosis factor (TNF) dose intensification represents an effective method of overcoming secondary loss of response (LOR); however, a subset of patients may not respond (tertiary non-response), or fail to demonstrate durable response (tertiary LOR) to intensified dosing. This systematic review and meta-analysis aimed to evaluate these outcomes to determine the clinical effectiveness of empiric dose intensification in Crohn’s disease. Methods: Multiple databases including MEDLINE and EMBASE were interrogated to identify studies that reported outcomes following anti-TNF dose intensification to address secondary LOR in Crohn’s disease. Studies that used anti-TNF levels as the primary basis for dose intensification were excluded. Studies that reported (1) tertiary response and tertiary non-response within 6 months or (2) tertiary response and tertiary LOR beyond 6 months, were pooled using a random effects model with risk ratio (RR) derived, quantifying the effect of each comparison. Results: Twenty-six studies reported outcomes following anti-TNF dose intensification to address secondary LOR. Short-term response within 12 weeks of any dose-intensification strategy was 33–90%, while sustained response (⩾48 weeks) was achieved in 25–85%. Tertiary non-response occurred in up to 45% of intensified patients within 6 months of anti-TNF dose intensification, while tertiary LOR beyond 6 months occurred in up to 64% of patients. Tertiary response was more likely than tertiary non-response within 6 months (RR 2.58, 95% CI (1.76, 3.79), I 2 = 82%, 12 studies), while sustained response beyond 6 months compared to tertiary LOR (RR 1.10 (0.75, 1.61) I 2 = 85%, 7 studies) was less convincing. Conclusion: Although anti-TNF dose intensification is clinically effective in patients with Crohn’s disease, particularly within the first 6 months, a proportion of patients will fail to demonstrate short-term and/or sustained clinical response. Hence, clinical reassessment following anti-TNF dose intensification, particularly beyond 6 months, remains important to differentiate between effective and ineffective dose-intensification strategies.

Electron density measured at high latitudes by the Swarm satellites was compared with measurements by the incoherent scatter radars at Resolute Bay and Poker Flat. Overall, the ratio of Swarm-based electron density to that measured by the radars was about 0.5–0.6. Smaller ratios were observed at larger electron densities, usually during the daytime. At low electron densities less than 3 × 1010 m−3, the ratios were typically above 1, indicating an overestimation effect. The overestimation effect was stronger at night and for Swarm B. It was more evident at lower solar activity when the electron densities in the topside ionosphere were lower.

Background During shoulder arthroplasty with substantial bone and soft tissue loss, reverse shoulder arthroplasty (RSA) with a tumor prosthesis may restore function, reduce pain, and improve implant fixation. Methods Thirteen adult patients undergoing RSA using a tumor prosthesis system were retrospectively reviewed. Preoperative visual analog score (VAS), single assessment numeric evaluation (SANE), American Shoulder and Elbow Surgeons (ASES) score, simple shoulder test (SST), and forward flexion were compared to latest follow up. Postoperative radiographs and complications were recorded. Results Mean age at surgery was 68.4 years. Eight patients had undergone at least 1 prior operation on the indicated shoulder. Six patients required wide excision of proximal humerus tumor. At mean of 34 months postoperatively, significant improvements were noted in VAS ( P = .03) and ASES score ( P = .04). Active forward elevation was 81.1 degrees. For all patients, postoperative radiographs demonstrated satisfactory alignment. Complications occurred in 38% of patients, with 31% requiring reoperation. Conclusion In cases of failed shoulder arthroplasty with excessive bone and soft tissue loss or substantial tumor burden, RSA with a tumor prosthesis can reduce pain levels and improve functional outcomes. However, forward elevation remains limited, and postoperative complications are a concern.

In a conventional phased array radar system (PAR), a transmit beam is slowly steered through a sector to illuminate targets sequentially, leaving the radar blind to threats when the transmit beam is pointed in other directions. On the other, multiple input, multiple output (MIMO) radar systems transmit orthogonal waveforms from each antenna element to illuminate the entire field of view (FOV) of the radar simultaneously, providing uninterrupted situational awareness. However, MIMO radar systems are more challenging to implement because of the added orthogonality requirements between its channels and the drastic increase in the required digital signal processing. This paper uses commercially-available cutting-edge software-defined radios (SDRs) to build a reconfigurable 8 × 8 MIMO radar with a 64-element virtual array operating in C-band (NATO G-band). Measurements indicate that the radar can detect and localize multiple targets in all 3-dimensions, including bearing, range, and Doppler, with an angular resolution of 5.5 and a range resolution of 0.9 m. The MIMO radar operates in real-time with a refresh rate of only 3 s and can switch between TDM and CDM multiplexing modes.

Our group recently documented that male mice containing a deletion for one copy of the glutaredoxin-2 (Grx2) gene were completely protected from developing diet-induced obesity (DIO). Objectives: Here, we conducted a similar investigation but with female littermates. Results: In comparison to our recent publication using male mice, exposure of WT and GRX2+/- female mice to a HFD from 3-to-10 weeks of age did not induce any changes in body mass, circulating blood glucose, food intake, hepatic glycogen levels, or abdominal fat pad mass. Examination of the bioenergetics of muscle mitochondria revealed no changes in the rate of superoxide (O2●−)/hydrogen peroxide (H2O2) or O2 consumption under different states of respiration or alterations in lipid peroxidation adduct levels regardless of mouse strain or diet. Additionally, we measured the bioenergetics of mitochondria isolated from liver tissue and found that partial loss of GRX2 augmented respiration but did not alter ROS production. Discussion: Overall, our findings demonstrate there are sex differences in the protection of female GRX2+/- mice from DIO, fat accretion, intrahepatic lipid accumulation, and the bioenergetics of mitochondria from muscle and liver tissue.