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Background: Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disease resulting from extracellular and intracellular deposits of amyloid-β (Aβ) and neurofibrillary tangles in the brain. Although many clinical studies evaluating pharmacological approaches have been conducted, most have shown disappointing results; thus, innovative strategies other than drugs have been actively attempted. Objective: This study aims to explore low-dose radiation therapy (LDRT) for the treatment of patients with AD based on preclinical evidence, case reports, and a small pilot trial in humans. Methods: This study is a phase II, multicenter, prospective, single-blinded, randomized controlled trial that will evaluate the efficacy and safety of LDRT to the whole brain using a linear accelerator in patients with mild AD. Sixty participants will be randomly assigned to three groups: experimental I (24 cGy/6 fractions), experimental II (300 cGy/6 fractions), or sham RT group (0 cGy/6 fractions). During LDRT and follow-up visits after LDRT, possible adverse events will be assessed by the physician's interview and neurological examinations. Furthermore, the effectiveness of LDRT will be measured using neurocognitive function tests and imaging tools at 6 and 12 months after LDRT. We will also monitor the alterations in cytokines, Aβ42/Aβ40 ratio, and tau levels in plasma. Our primary endpoint is the change in cognitive function test scores estimated by the Alzheimer's Disease Assessment Scale-Korea compared to baseline after 6 months of LDRT. Conclusions: This study is registered at ClinicalTrials.gov [NCT05635968] and is currently recruiting patients. This study will provide evidence that LDRT is a new treatment strategy for AD. [ABSTRACT FROM AUTHOR]

Background: LRRC6 is an assembly factor for dynein arms in the cytoplasm of motile ciliated cells, and when mutated, dynein arm components remained in the cytoplasm. Here, we demonstrate the role of LRRC6 in the active nuclear translocation of FOXJ1, a master regulator for cilia-associated gene transcription. Methods: We generated Lrrc6 knockout (KO) mice, and we investigated the role of LRRC6 on ciliopathy development by using proteomic, transcriptomic, and immunofluorescence analysis. Experiments on mouse basal cell organoids confirmed the biological relevance of our findings. Results: The absence of LRRC6 in multi-ciliated cells hinders the assembly of ODA and IDA components of cilia; in this study, we showed that the overall expression of proteins related to cilia decreased as well. Expression of cilia-related transcripts, specifically ODA and IDA components, dynein axonemal assembly factors, radial spokes, and central apparatus was lower in Lrrc6 KO mice than in wild-type mice. We demonstrated that FOXJ1 was present in the cytoplasm and translocated into the nucleus when LRRC6 was expressed and that this process was blocked by INI-43, an importin α inhibitor. Conclusions: Taken together, these results hinted at the LRRC6 transcriptional regulation of cilia-related genes via the nuclear translocation of FOXJ1. 9eDfA3zLzmCEQkVeGa2G9M Video Abstract [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare breast-related complications between hypofractionated adjuvant postmastectomy radiation therapy (PMRT) and conventional fractionated radiation therapy (RT) in patients with breast cancer undergoing reconstruction by reconstruction surgery type.Methods and Materials: Data from a total of 396 patients with breast cancer who underwent breast reconstruction after mastectomy between 2009 and 2018 were retrospectively reviewed. All patients received adjuvant PMRT according to either a conventional fractionation or hypofractionation schedule. We analyzed breast-related complications according to the timing of breast reconstruction (immediate or delayed). In cases of delayed reconstruction, only PMRT delivered before final delayed reconstruction was included. A major breast complication was defined as a breast-related toxicity that required reoperation or rehospitalization after the end of RT.Results: The median follow-up time was 35.3 months (range, 8.8-122.7 months). Of all patients, 267 received immediate breast reconstruction and 129 received delayed breast reconstruction. In patients with immediate breast reconstruction, 91 were treated with conventional RT and 176 received hypofractionated RT. The occurrence of major breast-related complications did not differ significantly between the 2 fractionation regimens. Hypofractionated RT did not increase major wound problems (infection and dehiscence) compared with conventional RT. Furthermore, major contracture occurred significantly less frequently in hypofractionated RT. Of the patients who had delayed breast reconstruction, 48 received conventional RT and 81 received hypofractionated RT. There was no difference in the incidence of major breast complications between these 2 RT groups, and no difference in major breast complications were reported for either 1- or 2-stage delayed reconstruction. A time interval of >10 months between PMRT and final definitive reconstruction had a significantly lower incidence of major breast complications.Conclusions: Hypofractionated RT appears to be comparable with conventional fractionated RT in terms of breast-related complications in patients with breast cancer undergoing reconstruction, regardless of breast reconstruction type. An ongoing prospective randomized trial should confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Genome‐wide association studies (GWASs) of asthma have identified several risk alleles and loci, but most have been conducted in individuals with European‐ancestry. Studies in Asians, especially children, are still lacking. We aimed to identify susceptibility loci by performing the first GWAS of asthma in Korean children with persistent asthma. Methods: We used a discovery set of 741 children with persistent asthma as cases and 589 healthy children and 551 healthy adults as controls to perform a GWAS. We validated our GWAS findings using UK Biobank data. We then used the Genotype‐Tissue Expression database to identify expression quantitative trait loci of candidate variants. Finally, we quantified proteins of genes associated with asthma. Results: Variants at the 17q12‐21 locus and SNPs in CYBRD1 and TNFSF15 genes were associated with persistent childhood asthma at genome‐wide thresholds of significance. Four SNPs in the TNFSF15 gene were also associated with childhood‐onset asthma in British white participants in the UK Biobank data. The asthma‐associated rs7856856‐C allele, the lead SNP, was associated with decreased TNFSF15 expression in whole blood and in arteries. Korean children with asthma had lower serum TNFSF15 levels than controls, and those with the asthma risk rs7856856‐CC genotype exhibited the lowest serum TNFSF15 levels overall, especially asthmatic children. Conclusions: Our GWAS of persistent childhood asthma with allergic sensitization identified a new susceptibility gene, TNFSF15, and replicated associations at the 17q12‐21 childhood‐onset asthma locus. This novel association may be mediated by reduced expression of serum TNFSF15 and loss of suppression of angiogenesis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare the treatment efficacy and safety of re-irradiation (re-RT) using stereotactic ablative radiotherapy (SABR) and initial SABR for primary, recurrent lung cancer or metastatic lung tumor.Methods: A retrospective review of the medical records of 336 patients who underwent lung SABR was performed. Re-RT was defined as the overlap of the 70% isodose line of second-course SABR with that of the initial radiotherapy, and 20 patients were classified as the re-RT group. The median dose of re-RT using SABR was 54 Gy (range 48-60 Gy), and the median fraction number was 4 (range 4-6). One-to-three case-matched analysis with propensity score matching was used, and 60 patients were included in the initial SABR group of the matched cohort.Results: The 1- and 2-year local control rates for the re-RT group were 73.9% and 63.3% and those for the initial SABR group in the matched cohort were 92.9% and 87.7%, respectively (P = 0.013). There was no difference in distant metastasis-free, progression-free, and overall survival rates. The crude grade ≥ 2 toxicity rates were 40.0% for the re-RT group and 25.0% for the initial SABR group (P = 0.318). Re-RT group had higher acute grade ≥ 2 toxicity rates (25.0% vs 5.0%, P = 0.031). One incident of grade 3 toxicity (pulmonary) was reported in the re-RT group; there was no grade 4‒5 toxicity.Conclusions: The local control rate of the in-field re-RT SABR was lower than that of the initial SABR without compromising the survival rates. The toxicity of re-RT using SABR was acceptable. [ABSTRACT FROM AUTHOR]

Introduction: The optimal salvage treatment strategies for lymph node-positive (LNP) patients after radical surgery have not been clearly defined in prostate cancer with biochemical recurrence or persistence of elevated prostate-specific antigen (PSA). In this study, we compared the clinical outcomes of two different salvage treatments, androgen deprivation therapy (ADT) alone versus ADT with radiotherapy (RT). We also investigated prognostic factors that could support the use of ADT with RT in LNP prostate cancer. Materials and methods: We retrospectively reviewed 94 LNP prostate cancer patients who underwent radical prostatectomy (RP) followed by salvage treatment between 2004 and 2018. Salvage treatments involved either ADT alone or ADT with RT according to the clinical judgment of the physician. We analyzed clinicopathological and treatment factors related to 2nd biochemical failure (2nd BCF), clinical progression (CP), and progression-free survival (PFS). The cumulative failure after salvage treatment was defined as including both 2nd BCF and CP. Results: The median duration of follow-up was 55 months (interquartile range, 35–97 months). Thirty-seven (39.4%) patients were treated with ADT alone, and 57 patients (60.6%) were treated with a combination of ADT with RT. During follow-up period, the incidence of failure after salvage treatment in the ADT alone group and the combined treatment group was 89.2% and 45.6%, respectively (HR, 22.4; 95% CI 5.43–92.1; P < 0.001). The combination of ADT with RT was associated with better 2nd BCF and PFS than ADT alone (P = 0.007 and P = 0.015, respectively). In multivariate analyses, number of positive LN ≥ 2 and PSA nadir ≥ 0.005 ng/ml after RP were associated with poor 2nd BCF, CP, and PFS after salvage treatment. Salvage by combined ADT plus RT showed better 2nd BCF and PFS than ADT alone. Specifically, patients with number of positive LN ≥ 2 or PSA nadir ≥ 0.005 ng/ml after RP showed better 2nd BCF (P = 0.004) or PFS (P = 0.011) when treated with ADT plus RT rather than ADT alone. Conclusions: In patients with LNP prostate cancer, salvage ADT plus RT improved 2nd BCF and PFS compared to ADT alone. In particular, when the patients had more than two positive lymph nodes or PSA nadir ≥ 0.005 ng/ml after RP, ADT with RT seems to be a more beneficial salvage treatment resulting in better 2nd BCF and PFS. [ABSTRACT FROM AUTHOR]

Preclinical studies have shown that radiation therapy modulates antitumor immune responses. However, circulating T-cell responses after radiation therapy in patients with cancer have been poorly characterized. This study aims to explore the changes in circulating T cells after stereotactic body radiation therapy (SBRT). Peripheral blood samples of 30 patients with breast cancer who underwent SBRT for bone metastasis were analyzed using multicolor flow cytometry. Phenotypes of PD-1+ CD8+ T cells and regulatory T (T REG) cells were examined. Additionally, plasma protein levels were analyzed using a bead-based immunoassay. Circulating PD-1+ CD8+ T cells, which are enriched for tumor-specific clonotypes, were activated at 1 week after SBRT. However, circulating T REG cells were also activated after SBRT; this pattern was also evident among effector Foxp3hiCD45RA− T REG cells. We observed no difference in T-cell responses according to the fraction size and number. Notably, activation of T REG cells was more prominent in patients who experienced greater activation of PD-1+ CD8+ T cells. Plasma level changes in TGF-β1, soluble CTLA-4, and soluble 4-1BB at 1 week after SBRT were associated with PD-1+ CD8+ T-cell responses. Activation of T REG cells at 1 week after SBRT was associated with worse progression-free survival. Clinical factors including molecular subtype were not associated with the T-cell responses. SBRT induced activation of both potentially tumor-specific CD8+ T cells and T REG cells, which were tightly associated with each other. These results may support the use of T REG cell-modulating strategies with SBRT to improve the antitumor immune response. [ABSTRACT FROM AUTHOR]

Even though many oral glucose-lowering or lipid-lowering agents have already been reported to improve hepatic steatosis to some degree, which drug had a more beneficial effect on hepatic steatosis among those drugs has not been precisely explored. We analysed the effect of empagliflozi, a selective sodium-glucose cotransporter 2 inhibitor, and ezetimibe on developing hepatic steatosis. Using 4005,779 patients with type 2 diabetes mellitus (T2DM) or dyslipidemia provided by the Korean National Health Insurance Service (NHIS) between January 2015 and December 2015, we analyzed the odds ratio (OR) of fatty liver development (fatty liver index [FLI] >60). Additionally, we examined the metabolic effects of ezetimibe and empagliflozin in mice fed with a choline-deficient high-fat diet, mimicking the features of human NAFLD. The experiment for agents was performed for the non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) mouse models independently. In the NHIS data, ORs for the development of fatty liver were significantly lower in all treatment groups than in the reference group, which did not receive ezetimibe or empagliflozin. (Ezetimibe therapy; OR=0.962, empagliflozin therapy; OR=0.527, ezetimibe plus empagliflozin; OR=0.509 compared to reference therapy). Unlike non-alcoholic steatohepatitis mouse model, ezetimibe, empagliflozin, and combination therapy also reduced liver steatosis in the non-alcoholic fatty liver mouse model. Compared with other agents, empagliflozin and/or ezetimibe treatment reduced the risk of developing hepatic steatosis. Our data suggest that empagliflozin or ezetimibe can be primarily considered in type 2 DM or dyslipidemia patients to prevent hepatic steatosis. • There are no ideal treatments for people with T2DM or dyslipidemia who also have NAFLD. • Patients with T2DM or dyslipidemia (< 5 years) and the NAFL mouse model appeared to benefit from combination therapy the most. • Combination therapy might be beneficial for the first treatment of T2DM and/or dyslipidemia patients to stop the progression of the NAFLD. [ABSTRACT FROM AUTHOR]

UV-curable coatings have numerous advantages, including environmental sustainability due to 100% solid content, economic feasibility attributable to relatively fast curing time, decent appearance, mechanical properties, chemical resistance, and abrasion resistance. However, UV-curable polyurethane acrylate coatings on metals apparently restrict their engineering applications owing to low mechanical properties and poor thermal stability, giving UV-curable coatings less flexibility and formability. In this study, we evaluated the property change of films according to the type of reactive diluents that lowers the viscosity of UV-curing coatings for pre-coated metal and has a substantial effect on the curing rate, viscoelastic properties, adhesive properties, and flexibility of the film. Moreover, there are many changes in the properties of coatings according to varied curing conditions in order to evaluate the oxygen inhibition phenomenon during the curing process in the atmosphere. In particular, to evaluate the effect of reactive diluents on forming formability, which is the most crucial property for the pre-coated metal, this study used conventional formability tests, such as t-bending or the Erichsen test. Moreover, a cross-die cup drawing mold with a similar form as failure and Safety Zone was utilized in order to obtain clearer information on its actual formability. The analysis on the effect of failure and safety zone on the material used in press forming was conducted by assessing limit punch height and forming a limit diagram of the manufactured film according to varied reactive diluents. [ABSTRACT FROM AUTHOR]

Motivation: Inferring lengths of inherited microsatellite alleles with single base pair resolution from short sequence reads is challenging due to several sources of noise caused by the repetitive nature of microsatellites and the technologies used to generate raw sequence data.Results: We have developed a program, GenoTan, using a discretized Gaussian mixture model combined with a rules-based approach to identify inherited variation of microsatellite loci from short sequence reads without paired-end information. It effectively distinguishes length variants from noise including insertion/deletion errors in homopolymer runs by addressing the bidirectional aspect of insertion and deletion errors in sequence reads. Here we first introduce a homopolymer decomposition method which estimates error bias toward insertion or deletion in homopolymer sequence runs. Combining these approaches, GenoTan was able to genotype 94.9% of microsatellite loci accurately from simulated data with 40x sequence coverage quickly while the other programs showed <90% correct calls for the same data and required 5∼30× more computational time than GenoTan. It also showed the highest true-positive rate for real data using mixed sequence data of two Drosophila inbred lines, which was a novel validation approach for genotyping.Availability: GenoTan is open-source software available at http://genotan.sourceforge.net.Contact: garner@vbi.vt.eduSupplementary Information: Supplementary data are available at Bioinformatics online [ABSTRACT FROM PUBLISHER]

This work presents a new four-tier hierarchical change-point algorithm designed to detect land-cover change from satellite data. We tested the algorithm using Global Inventory Modelling and Mapping Studies (GIMMS) data for eastern Africa. Using a unique sequence of four statistical change-point detection methods, we identified significant increases or decreases in normalized difference vegetation index (NDVI), estimated the approximate time of change, and characterized the likely forms of change (i.e. linear trend, abrupt mean and/or variability change, and hockey-stick shaped change). Our method allows not just the identification of the change point but also the manner of change, and it can provide considerable insights into land-cover trajectories. In that sense, our approach has a significant advantage over other types of change-detection methods commonly reported in the remote-sensing literature. Although we demonstrated our algorithm using annual averages for coarse resolution data, our method can be easily adapted to finer spatial or temporal scale data, assuming assumptions of normality and independence are met. Overall, the changes detected by the algorithm are consistent with changes observed by other authors for the East Africa study area. We have demonstrated a powerful new tool for the detection of land-cover change using multi-temporal satellite data. [ABSTRACT FROM AUTHOR]

Abstract: We develop a likelihood ratio test for an abrupt change point in Weibull hazard functions with covariates, including the two-piece constant hazard as a special case. We first define the log-likelihood ratio test statistic as the supremum of the profile log-likelihood ratio process over the interval which may contain an unknown change point. Using local asymptotic normality (LAN) and empirical measure, we show that the profile log-likelihood ratio process converges weakly to a quadratic form of Gaussian processes. We determine the critical values of the test and discuss how the test can be used for model selection. We also illustrate the method using the Chronic Granulomatous Disease (CGD) data. [Copyright &y& Elsevier]

Abstract: Quantitative trait loci (QTL) mapping has been a standard means in identifying genetic regions harboring potential genes underlying complex traits. Likelihood ratio test (LRT) has been commonly applied to assess the significance of a genetic locus in a mixture model content. Given the time constraint in commonly used permutation tests to assess the significance of LRT in QTL mapping, we study the behavior of the LRT statistic in mixture model when the proportions of the distributions are unknown. We found that the asymptotic null distribution is stationary Gaussian process after suitable transformation. The result can be applied to one-parameter exponential family mixture model. Under certain condition, such as in a backcross mapping model, the tail probability of the supremum of the process is calculated and the threshold values can be determined by solving the distribution function. Simulation studies were performed to evaluate the asymptotic results. [Copyright &y& Elsevier]

We consider a test for an abrupt change in a Weibull hazard function with unknown scale parameter when the data are subject to staggered entry and Type I censoring. We formulate the profile log-likelihood ratio test statistic as a function of the change point and show that it converges weakly to an Ornstein-Uhlenbeck process. We determine critical values from an approximation to the tail probability of the supremum of the process. We study the power of the test through simulation, and demonstrate its applicability using real data from a clinical study for the treatment of chronic granulomatous disease. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Methods and results Conclusions The TRANSFORM‐HF trial demonstrated no significant outcome differences between torsemide and furosemide following hospitalization for heart failure (HF), but may have been impacted by non‐adherence to the randomized diuretic. The current study sought to determine the treatment effect of torsemide versus furosemide using an on‐treatment analysis inclusive of all randomized patients except those confirmed non‐adherent to study diuretic.TRANSFORM‐HF was an open‐label, pragmatic randomized trial of 2859 patients hospitalized for HF from June 2018 through March 2022. Patients were randomized to a loop diuretic strategy of torsemide versus furosemide with investigator‐selected dosage. This post‐hoc on‐treatment analysis included all patients alive with either known or unknown diuretic status, and excluded patients confirmed to be non‐adherent to study diuretic. This modified on‐treatment definition was applied separately at time of hospital discharge and 30‐day follow‐up. All‐cause mortality and hospitalization outcomes were assessed over 12 months. Overall, 2570 (89.9%) and 2374 (83.0%) patients were included in on‐treatment analyses at discharge and 30‐day follow‐up, respectively. There was no significant difference in all‐cause mortality between torsemide and furosemide in patients on‐treatment at discharge (17.5% vs. 17.8%; hazard ratio [HR] 1.01 [95% confidence interval [CI] 0.83–1.22], p = 0.96) and at 30‐day follow‐up (14.5% vs. 15.0%; HR 1.02 [95% CI 0.81–1.27], p = 0.90). All‐cause mortality or all‐cause hospitalization was similar between torsemide and furosemide in patients who were on‐treatment at discharge (58.3% vs. 61.3%; HR 0.92 [95% CI 0.82–1.03]) and 30‐day follow‐up (60.9% vs. 64.4%; HR 0.93 [95% CI 0.82–1.05]). In patients who were on‐treatment at 30‐day follow‐up, there were 677 total hospitalizations in the torsemide group and 686 total hospitalizations in the furosemide group (rate ratio 0.99 [95% CI 0.86–1.14], p = 0.87).In TRANSFORM‐HF, a post‐hoc on‐treatment analysis did not meaningfully differ from the original trial results. Among those deemed compliant with the assigned diuretic, there remained no significant difference in mortality or hospitalization after HF hospitalization with a strategy of torsemide versus furosemide.Clinical Trail Registration: ClinicalTrials.gov Identifier: NCT03296813. [ABSTRACT FROM AUTHOR]

Consider the choice of outcome for overall treatment benefit in a clinical trial which measures the first time to each of several clinical events. We describe several new variants of the win ratio that incorporate the time spent in each clinical state over the common follow‐up, where clinical state means the worst clinical event that has occurred by that time. One version allows restriction so that death during follow‐up is most important, while time spent in other clinical states is still accounted for. Three other variants are described; one is based on the average pairwise win time, one creates a continuous outcome for each participant based on expected win times against a reference distribution and another that uses the estimated distributions of clinical state to compare the treatment arms. Finally, a combination testing approach is described to give robust power for detecting treatment benefit across a broad range of alternatives. These new methods are designed to be closer to the overall treatment benefit/harm from a patient's perspective, compared to the ordinary win ratio. The new methods are compared to the composite event approach and the ordinary win ratio. Simulations show that when overall treatment benefit on death is substantial, the variants based on either the participants' expected win times (EWTs) against a reference distribution or estimated clinical state distributions have substantially higher power than either the pairwise comparison or composite event methods. The methods are illustrated by re‐analysis of the trial heart failure: a controlled trial investigating outcomes of exercise training. [ABSTRACT FROM AUTHOR]

Aim: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all‐cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half‐life, but direct supportive evidence is lacking. Methods and results: The TRANSFORM‐HF trial randomized patients hospitalized for HF to a long‐term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post‐hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30–<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ‐CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30–<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all‐cause mortality and all‐cause (re)‐hospitalizations, both when assessing eGFR categorically or continuously (p‐value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ‐CSS (p‐value for interaction all >0.052) when assessing eGFR categorically or continuously. Conclusion: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient‐reported outcomes between torsemide and furosemide, irrespective of renal function. [ABSTRACT FROM AUTHOR]

Abstract: Research to find out an optimum decomposition process for CF4, one of the most stable gases among PFCs, have conducted with the steam plasma processing which elevates decomposition rate for high reactivity of steam itself. Before performing experiment, thermodynamic equilibrium calculations are done for the condition of 1atm and 300K–5000K by a software program to check the concentration based on the composition at equilibrium. CF4 is injected at atmospheric pressure and analyzed quantitatively and qualitatively by using GC (Gas Chromatography). HF (hydrogen fluoride), a byproduct, is extracted from the device by a vacuum aspirator and changed into fluorite or others as it passes through scrubbers containing NaOH (sodium hydroxide) and CaCO3 (calcium carbonate). We study the effects of reaction time, quenching condition, additive gas dilution, input power, and etc. on decomposition of CF4 and achieve more than 90% of the CF4 removal rate. [Copyright &y& Elsevier]

We develop a likelihood-ratio based procedure for testing for a change in the hazard rate of the patients' survival distribution when the patients enter the trial at random times. We show that the profile log-likelihood ratio process converges weakly to a non-stationary Gaussian process and obtain the upper percentiles of the supremum of the limiting process using an approximation for the tail distribution of the supremum of the Ornstein–Uhlenbeck process. We also discuss the power of the test. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the effect of radiation dose rate in patients with hematolymphoid malignancies undergoing myeloablative conditioning with total body irradiation (TBI), for hematopoietic stem cell transplantation.Methods: The incidence of pulmonary toxicity (PT) and treatment efficacy were compared between the conventional (≥ 6 cGy/min) and reduced dose rate (< 6 cGy/min). Seventy-seven patients receiving once-daily TBI between 2000 and 2016 were reviewed. We compared the cumulative rate of PT, overall survival (OS), relapse, and transplantation-related mortality (TRM) between conventional (n = 54) and reduced (n = 23) groups. Factors associated with PT were assessed in the presence of competing risks.Results: The median follow-up time was 40.7 months, and PT occurred in 50 patients (64.9%). On multivariate analyses, the groups classified by the dose rate (P = 0.010), total dose (P = 0.025), and conditioning regimen (P = 0.029) were significant factors for the development of PT. OS was significantly reduced when PT occurred (P < 0.001). However, the OS, relapse, and TRM were not different between the two groups.Conclusions: In summary, about two-thirds of the patients undergoing daily TBI experienced PT, which affected OS. Therefore, reducing the dose rate (less than 6 cGy/min) of TBI can decrease the risk of PT, without compromising the treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. Methods: TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0–100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0–6; score ≥3 supporting evaluation for depression) over 12 months. Results: Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27–60) in the torsemide group and 40 (24–59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, –2.26 to 2.37]; P =0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: P =0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, –0.64 to 3.36]; P =0.18) and 6-month follow-up (adjusted mean difference, –0.37 [95% CI, –2.52 to 1.78]; P =0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. Conclusions: Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296813. [ABSTRACT FROM AUTHOR]

Background Context: It has been reported that newly developed osteoporotic vertebral compression fractures (OVCFs) occur at a relatively high frequency after treatment. While there are many reports on possible risk factors, these have not yet been clearly established.Purpose: The purpose of this study was to investigate the risk factors for newly developed OVCFs after treatment by vertebroplasty (VP), kyphoplasty (KP), or conservative treatment.Study Design/setting: A retrospective comparative study.Patient Sample: One hundred thirty-two patients who had radiographic follow-up data for one year or longer among 356 patients who were diagnosed with OVCF and underwent VP, KP or conservative treatment between March 2007 and February 2016.Outcome Measures: All records were examined for age, sex, body mass index (BMI), rheumatoid arthritis and other medical comorbidities, osteoporosis medication, bone mineral density (BMD), history of vertebral and nonvertebral fractures, treatment methods used, level of fractures, and presence of multiple fracture sites.Methods: Patients were divided into those who manifested new OVCF (Group A) and those who did not (Group B). For the risk factor analysis, student's t-tests and chi-square tests were used in univariate analysis. Multivariate logistic regression analysis was carried out on variables with a p<.1 in the univariate analysis.Results: Newly developed OVCFs occurred in 46 of the 132 patients (34.8%). Newly developed OVCF increased significantly with factors such as average age (p=.047), low BMD T-score of the lumbar spine (p=.04) and of the femoral neck (p=.046), advanced age (>70 years) (p=.011), treatment by cement augmentation (p=.047) and low compliance with osteoporosis medication (p=.029). In multivariate regression analysis, BMD T-score of the lumbar spine (p=.009) and treatment by cement augmentation (p=.044) showed significant correlations with the occurrence of new OVCFs with a predictability of 71.4%.Conclusion: Osteoporotic vertebral compression fracture patients with low BMD T-score of the lumbar spine and those who have been treated by cement augmentation have an increased risk of new OVCFs after treatment and, therefore, require especially careful observation and attention. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does torsemide reduce all-cause mortality compared with furosemide in patients with heart failure following hospitalization? Findings: In this randomized clinical trial of 2859 patients, 26.1% of patients randomized to torsemide and 26.2% randomized to furosemide died over a median follow-up of 17.4 months without a significant difference between groups. Meaning: Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months; however, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. Importance: Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide. Objective: To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure. Design, Setting, and Participants: TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022. Interventions: Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage. Main Outcomes and Measures: The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide. Results: TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction. Conclusions and Relevance: Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. Trial Registration: ClinicalTrials.gov Identifier: NCT03296813 This clinical trial compares the efficacy of torsemide vs furosemide in decreasing the risk of death from any cause among patients hospitalized for heart failure (regardless of ejection fraction). [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is becoming an important tool for the investigation of emerging infectious diseases in animal models. Usually, PET imaging is performed after intravenous (IV) radiotracer administration. However, IV injections are difficult to perform in some small animals, such as golden hamsters. This challenge is particularly evident in longitudinal imaging studies, and even more so in maximum containment settings used to study high-consequence pathogens. We propose the use of intramuscular (IM) administration of 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) for PET imaging of hamsters in a biosafety level 4 (BSL-4) laboratory setting. After [18F]F-FDG administration via IM or IV (through surgically implanted vascular access ports), eight hamsters underwent static or dynamic PET scans. Time–activity curves (TACs) and standardized uptake values (SUVs) in major regions of interest (ROIs) were used to compare the two injection routes. Immediately after injection, TACs differed between the two routes. At 60 min post-injection, [18F]F-FDG activity for both routes reached a plateau in most ROIs except the brain, with higher accumulation in the liver, lungs, brain, and nasal cavities observed in the IM group. IM delivery of [18F]F-FDG is an easy, safe, and reliable alternative for longitudinal PET imaging of hamsters in a BSL-4 laboratory setting. [ABSTRACT FROM AUTHOR]

Summary: The Standardized Precipitation Index (SPI) has become a popular measure of drought across the globe. Several techniques have been employed in attempts to estimate the time at which any changes in drought patterns occur using categories defined by SPI values. Log-linear models, odds ratios and multiple confidence intervals have all been used while trying to estimate such changepoints and have met with varying degrees of success, in part due to small cell counts and the large number of inferences that must be carried out. The purpose of this paper is to provide an alternative method for the detection of a changepoint in SPI data, specifically in the matrix of transitions from one drought class to another. A resampling algorithm is provided that both detects a potential changepoint and determines its significance under the assumption that at most one changepoint is present. Simulation results are provided to validate the method as well as the suggested metrics for detection. Data from Kenya is used to provide four examples where the technique is implemented on observed rainfall data. [Copyright &y& Elsevier]

Importance: Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis.Objective: To assess the effect of antimicrobial therapy on clinical outcomes.Design, Setting, and Participants: Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020).Interventions: Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if ≥50 kg, n = 126). No placebo was administered in the usual care alone group.Main Outcomes and Measures: The primary end point was time to first nonelective respiratory hospitalization or all-cause mortality.Results: Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care group, with no significant difference between groups (adjusted HR, 1.04 [95% CI, 0.71-1.53; P = .83]. There was no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary end point (adjusted HR, 1.15 [95% CI 0.68-1.95] in the co-trimoxazole group vs 0.82 [95% CI, 0.46-1.47] in the doxycycline group; P = .66). Serious adverse events occurring at 5% or greater among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%) and infections (2.8% vs 6.6%); adverse events of special interest included diarrhea (10.2% vs 3.1%) and rash (6.7% vs 0%).Conclusions and Relevance: Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease.Trial Registration: ClinicalTrials.gov Identifier: NCT02759120. [ABSTRACT FROM AUTHOR]

In addition, the results of this study will be strengthened by comparing the current data with those for the microbiome of patients with Crohn's disease and CKD, and CKD patients without IBD. The causal link between inflammatory bowel disease (IBD) and chronic kidney disease (CKD) is not clear; therefore, we aimed to investigate the role of gut microbiota in decreasing renal function in patients with IBD. [Extracted from the article]

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120. [ABSTRACT FROM AUTHOR]

Background: The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries.Objectives: The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data.Methods: Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis.Results: A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation-positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion.Conclusions: The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers. [ABSTRACT FROM AUTHOR]

This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. [ABSTRACT FROM AUTHOR]

Context: Horticultural therapy (HT) is a subgroup of occupational therapy (OT). Both HT and OT have been successful as adjunctive treatment modalities in substance abuse treatment. Studies have indicated that gardening promotes neuroendocrine and affective restoration from stress.Objectives: The study intended to assess the effect of HT versus nonhorticultural OT on cortisol levels, depression, symptoms of posttraumatic stress disorder (PTSD), alcohol cravings, and quality of life.Methods: The research team designed a randomized pilot study.Setting: The study was open for participation from July 2012-October 2012. It took place during multiple occurrences of a 28-d treatment programs for substance use disorder at a Veterans Affairs medical center. Participants • Participants were 49 veterans, averaging 46.4 y old (SD = 11.9); the dropout rate was 37%.Intervention: Participants were randomly assigned to the HT or the OT group. They attended supervised HT and OT groups 5 h/d for 3 wk. Outcome Measures • Pre- and posttreatment, participants completed the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), the Alcohol Craving Questionnaire (ACQ-NOW), the Posttraumatic Stress Disorder Checklist Civilian Version (PCLC), and the Center for Epidemiologic Studies Depression Scale (CES-D). Salivary cortisol samples were taken at wk 1, 2, and 3.Results: A repeated measures analysis of variance (ANOVA) (F2,20 = 0.878) revealed that the HT performed was associated with a 12% reduction in salivary cortisol levels from wk 1 to wk 3, but the difference was not statistically significant (P = .43). Separate 1-way analyses of covariance (ANCOVAs) revealed no statistically significant differences in the self-administered tests, although both the Q-LES-Q-SF and CES-D showed a trend toward improving quality of life and depressive symptoms in the HT group compared with the OT group. Additional analysis of the nonbiologic tests suggests that most participants in the HT and OT had some benefit from the programmed activities.Conclusions: The trends suggest that HT may modulate stress in veterans, as evidenced by decreased cortisol levels and depressive symptoms, and may improve quality of life more than the programs in which the OT group participated. Further investigation with larger samples, including a nontreatment control group, is needed to determine whether the observed trends are treatment effects or due to abstinence. [ABSTRACT FROM AUTHOR]

ABSTRACT Both land-cover/land-use change ( LCLUC) and greenhouse gas ( GHG) concentrations have been shown to influence regional climate, albeit at different spatial scales. In East Africa, climate changes due to changing GHG concentrations are broadly projected to be warmer and wetter. LCLUC projections include trends towards both agricultural intensification and agricultural expansion into savannas, which may result in complex climate interactions and impacts. The primary objective of this study was to examine the regional responses to future GHG, LCLUC, and their combined effects in East Africa, and to better understand how hydrometeorological mechanisms might be altered by LCLUC in future scenarios. In this study, we present high-resolution decadal simulations from a regional climate model that compare the relative and combined effects of projected LCLUC and GHG. This research suggests that taken separately, these two climate forcings may significantly alter regional precipitation patterns both temporally and spatially but in potentially different and independent ways. In combination, some portions of the region exhibit responses dominated by either LCLUC or GHG effects, but certain areas show complex effects resulting from the combined influence of these two forcings. Perhaps most importantly, the results suggest that projected precipitation changes around major population areas may be as strongly influenced by LCLUC as by GHG effects. [ABSTRACT FROM AUTHOR]

Anterior lumbar interbody fusion (ALIF) is a widely accepted tool for management of painful degenerative disc disease. Recently, the modern laparoscopic surgical technique has been combined with ALIF procedure, with good early postoperative results being reported. However, the benefit of laparoscopic fusion is poorly defined compared with its open counterpart. This study aimed to compare perioperative parameters and minimum 2-year follow-up outcome for laparoscopic and open anterior surgical approach for L5–S1 fusion. The data of 54 consecutive patients who underwent anterior lumbar interbody fusion (ALIF) of L5–S1 from 1997 to 1999 were collected prospectively. More than 2-years’ follow-up data were available for 47 of these patients. In all cases, carbon cage and autologous bone graft were used for fusion. Twenty-five patients underwent a laparoscopic procedure and 22 an open mini-ALIF. Three laparoscopic procedures were converted to open ones. For perioperative parameters only, the operative time was statistically different (P=0.001), while length of postoperative hospital stay and blood loss were not. The incidence of operative complications was three in the laparoscopic group and two in the open mini-ALIF group. After a follow-up period of at least 2 years, the two groups showed no statistical difference in pain, measured by visual analog scale, in the Oswestry Disability Index or in the Patient Satisfaction Index. The fusion rate was 91% in both groups. The laparoscopic ALIF for L5–S1 showed similar clinical and radiological outcome when compared with open mini-ALIF, but significant advantages were not identified, despite its technical difficulty. [ABSTRACT FROM AUTHOR]

Respiratory behaviors provide useful measures of lung health. The current methods have limited capabilities of continuous characterization of respiratory behaviors, often required to assess respiratory disorders and diseases. This work presents a system equipped with a machine learning algorithm, capable of continuously monitoring respiratory behaviors. The system, consisting of two wireless wearable sensors, accurately extracts and classifies the features of respiratory behaviors of subjects within various postures, wirelessly transmitting the temporal respiratory behaviors to a laptop. The sensors were attached on the midway of the xiphoid process and the costal margin, and 1 cm above the umbilicus, respectively. The wireless wearable sensor, consisting of ultrasound emitter, ultrasound receiver, data acquisition and wireless transmitter, has a small footprint and light weight. The sensors correlate the mechanical strain at wearing sites to lung volume by measuring the local circumference changes of the chest and abdominal walls simultaneously. Eleven subjects were recruited to evaluate the wireless wearable sensors. Three different random forest classifiers, including generic, individual, and weighted-adaptive classifiers, were used to process the wireless data of the subjects at four different postures. The results demonstrate the respiratory behaviors are individual- and posture-dependent. The generic classifier merely reaches the accuracy of classifying postures of 21.9 ± 1.7% while individual and weighted-adaptive classifiers mark substantially high, up to 98.9 ± 0.6% and 98.8 ± 0.6%, respectively. The accurate monitoring of respiratory behaviors can track the progression of respiratory disorders and diseases, including chronic respiratory obstructive disease (COPD), asthma, apnea, and others for timely and objective approaches for control. • Continuously monitor and extract features of respiratory behaviors completely and accurately. • Machine-learning enabled study of individuality of respiratory behaviors. • Postures recognition based on general respiration contributing to monitor posture-related respiratory diseases, like apnea. [ABSTRACT FROM AUTHOR]

The purpose of this study is to develop a solid dispersion system with improved dissolution, absorption, and patient compliance of poorly water-soluble celecoxib (CXB). Instead of sodium lauryl sulfate (SLS), an anionic surfactant used in the marketed product (Celebrex®), solubilization was performed using non-ionic surfactants with low toxicity. Cremophor RH40 (Cre-RH) was selected as the optimal solubilizer. Granules and tablets containing CXB and Cre-RH were prepared via fluid-bed and tableting processes, respectively. The morphology, crystallinity, flowability, dissolution, and pharmacokinetics for CXB-solid dispersion granules (SDGs) and the hardness and friability for CXB-solid dispersion tablets (SDTs) were evaluated. The solubility of CXB was found to be increased by about 717-fold when using Cre-RH. The dissolution of granules containing Cre-RH was found to be increased greatly compared with CXB API and Celebrex® (66.9% versus 2.3% and 37.2% at 120 min). The improvement of the dissolution was confirmed to be the same as that of granules in tablets. The CXB formulation resulted in 4.6- and 4.9-fold higher AUCinf and Cmax of CXB compared with those of an oral dose of CXB powder in rats. In short, these data suggest that the solid dispersion based on Cre-RH—a non-toxic solubilizer, non-ionic surfactant— may be an effective formulation for CXB to enhance its oral bioavailability and safety. [ABSTRACT FROM AUTHOR]

Introduction: The Hypertrophic Cardiomyopathy Registry (HCMR) is a NHLBI-funded study of 2764 HCM patients recruited from 44 sites worldwide. Baseline clinical evaluation included echo, cardiac magnetic resonance imaging (CMR), and blood drawn for genetic and biomarker analysis. Follow-up is 1.5 years to date. CMR protocol included short axis cines, pre-and post-contrast T1 mapping, and late gadolinium enhancement (LGE). Hypothesis: We hypothesized that demographic factors may relate to extent of LGE (replacement fibrosis) and T1 mapping (interstitial fibrosis). Methods: LGE assessed visually was categorized as none, >0-5, >5-10, >10-15 and >15% of LV mass. LGE relationship to continuous demographic variables was assessed by one-way analysis of variance. The relationship of native T1 (by field strength) and extracellular volume (ECV) with baseline variables were assessed by Pearson correlations, unpaired t-tests, or analysis of variance. Results: Of 2764 patients, 2556 (92%) had valid LGE values and 50% had any LGE. (Table) Only 2% of patients had LGE >15% of LV mass. Age was similar across LGE categories, but BMI declined with greater LGE extent. There were smaller % of whites and blacks with >15% LGE, but a larger % of other races (primarily Asian). With more LGE, a family history of HCM was more likely and hypertension less likely. The greater the LGE extent, the lower the LVEF. 2122 patients (77%) had valid native T1 and 1988 (72%) valid ECV measures. There was no relationship between age, BMI, or race with either T1 or ECV. Females had longer native T1 at 1.5T (p < 0.001), but not at 3T (p = 0.168). Females had higher ECV values (0.32±0.06 vs. 0.30±0.06, p<0.001). Conclusions: Baseline data from HCMR demonstrate that 2% of patients have LGE >15% of LV mass. These patients have more family history of HCM, are less often black or white, have less hypertension, lower BMI, and lower LVEF. These data suggest that extensive LGE, a risk factor for sudden cardiac death, may be more typical of familial, rather than sporadic or secondary disease. Ongoing genetic analysis may shed additional light. Interstitial fibrosis is greater in females with HCM. Longer follow-up is needed to demonstrate whether these baseline findings are associated with adverse cardiovascular outcome. [ABSTRACT FROM AUTHOR]

Study Design: Validation of a translated, culturally adapted questionnaire.Objectives: To translate and culturally adapt a Korean version of the Oswestry Disability Index (ODI) and to validate its use in Korean patients.Summary Of Background Data: The ODI is one of the most widely used and validated instruments for measuring disability in spinal disorders. However, no validated Korean version of the index was available at the time our study was initiated.Methods: The study was carried out in three phases: the first was translation into Korean and cultural adaptation of the questionnaire; the second was a pilot study to assess the comprehensibility of the prefinal version and modification; the third was a reliability and validity study of the final version. The Korean version was tested on 206 patients with lumbar spinal disorders who had undergone operations at the authors' institute. Test-retest reliability, internal consistency, concurrent validity, and construct validity were investigated. Follow-up questionnaires were obtained from 39 patients at the 3-month postoperative follow-up meeting. Differences in the ODI, visual analog scale (VAS), and World Health Organization (WHO) quality of life assessment (WHOQOL-BREF) between preoperative and follow-up questionnaires were evaluated. The correlation of the postoperative ODI with the pain rating on a visual analog scale and WHOQOL-BREF was also analyzed.Results: Test-retest reliability was assessed with 88 patients in a time interval of 48 hours. The intraclass correlation coefficient of test-retest reliability was 0.9167. Reliability estimated by the internal consistency reached a Cronbach's alpha of 0.84. The correlation of the preoperative ODI with the pain rating on a visual analog scale (100 mm) was r = 0.425 (P = 0.0001). The correlation between three of the WHOQOL-BREF domains (physical health, psychological health, and environment) and the ODI was statistically significant. The correlation coefficient between the ODI and physical health domain of the WHOQOL-BREF was r = -0.48 (P < 0.05). The correlations with psychological health and environment domains were low with r = -0.192 and -0.160, respectively, even though statistically significant (P < 0.05). The correlation of the postoperative ODI with the pain rating on a visual analog scale (100 mm) was r = 0.626 (P = 0.0001). The correlation between all four domains of the WHOQOL-BREF and the postoperative ODI was statistically significant.Conclusions: The results of this study indicate that the Korean version of the ODI is a reliable and valid instrument for the measurement of disability in Korean patients with lower back problems. The authors recommend this Korean version of the ODI for use in future clinical studies in Korea. [ABSTRACT FROM AUTHOR]