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Nathan Yee,1 Emily R Locke,2 Kenneth C Pike,3 Zijing Chen,3 Jungeun Lee,4 Joe C Huang,5 Huong Q Nguyen,6 Vincent S Fan2,7 1Department of Medicine, University of Washington, Seattle, WA, USA; 2Department of Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; 3Department of Child, Family, and Population Health Nursing, School of Nursing, University of Washington, Seattle, WA, USA; 4College of Nursing, University of Rhode Island, Kingston, RI, USA; 5Division of Gerontology & Geriatric Medicine, University of Washington, Seattle, WA, USA; 6Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA; 7Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USACorrespondence: Vincent S FanDepartment of Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, Pulmonary Section, S-111-Pulm, 1660 S. Columbian Way, Seattle, WA 98108, USATel +1 206 764-2504Fax +1 206 764-2659Email Vincent.fan@va.govBackground: Frailty is a complex clinical syndrome associated with vulnerability to adverse health outcomes. While frailty is thought to be common in chronic obstructive pulmonary disease (COPD), the relationship between frailty and COPD-related outcomes such as risk of acute exacerbations of COPD (AE-COPD) and hospitalizations is unclear.Purpose: To examine the association between physical frailty and risk of acute exacerbations, hospitalizations, and mortality in patients with COPD.Methods: A longitudinal analysis of data from a cohort of 280 participants was performed. Baseline frailty measures included exhaustion, weakness, low activity, slowness, and undernutrition. Outcome measures included AE-COPD, hospitalizations, and mortality over 2 years. Negative binomial regression and Cox proportional hazard modeling were used.Results: Sixty-two percent of the study population met criteria for pre-frail and 23% were frail. In adjusted analyses, the frailty syndrome was not associated with COPD exacerbations. However, among the individual components of the frailty syndrome, weakness measured by handgrip strength was associated with increased risk of COPD exacerbations (IRR 1.46, 95% CI 1.09– 1.97). The frailty phenotype was not associated with all-cause hospitalizations but was associated with increased risk of non-COPD-related hospitalizations.Conclusion: This longitudinal cohort study shows that a high proportion of patients with COPD are pre-frail or frail. The frailty phenotype was associated with an increased risk of non-COPD hospitalizations but not with all-cause hospitalizations or COPD exacerbations. Among the individual frailty components, low handgrip strength was associated with increased risk of COPD exacerbations over a 2-year period. Measuring handgrip strength may identify COPD patients who could benefit from programs to reduce COPD exacerbations.Keywords: chronic obstructive pulmonary disease, frailty, weakness, handgrip strength

Nini H Jonkman,1 Heleen Westland,1 Jaap CA Trappenburg,1 Rolf HH Groenwold,2 Erik WMA Bischoff,3 Jean Bourbeau,4 Christine E Bucknall,5 David Coultas,6 Tanja W Effing,7 Michael J Epton,8 Frode Gallefoss,9 Judith Garcia-Aymerich,10–12 Suzanne M Lloyd,13 Evelyn M Monninkhof,2 Huong Q Nguyen,14 Job van der Palen,15,16 Kathryn L Rice,17 Maria Sedeno,4 Stephanie JC Taylor,18 Thierry Troosters,19 Nicholas A Zwar,20 Arno W Hoes,2 Marieke J Schuurmans1 1Department of Rehabilitation, Nursing Science and Sports, 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands; 4Respiratory Epidemiology and Clinical Research Unit, Department of Medicine, McGill University Health Center, McGill University, Montreal, QC, Canada; 5Department of Respiratory Medicine, Glasgow Royal Infirmary, Glasgow, UK; 6Veterans Administration Portland Health Care System and Oregon Health & Science University, Portland, OR, USA; 7Department of Respiratory Medicine, Repatriation General Hospital, Adelaide, SA, Australia; 8Canterbury District Health Board, Respiratory Services, Christchurch Hospital, Christchurch, New Zealand; 9Department of Pulmonary Medicine, Sorlandet Hospital, Kristiansand, Norway; 10Centre for Research in Environmental Epidemiology CREAL, 11Pompeu Fabra University, 12CIBER Epidemiología y Salud Pública CIBERESP, Barcelona, Spain; 13Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK; 14Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA; 15Department of Research Methodology, Measurement and Data Analysis, University of Twente, 16Department of Clinical Epidemiology, Medisch Spectrum Twente, Enschede, the Netherlands; 17Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Minneapolis Veterans Affairs Health Care Service and University of Minnesota, Minneapolis, MN, USA; 18Centre for Primary Care and Public Health, Queen Mary University of London, London, UK; 19Department of Rehabilitation Sciences, Catholic University of Leuven, Leuven, Belgium; 20School of Public Health and Community Medicine, UNSW Australia, Sydney, NSW, Australia Background: Self-management interventions are considered effective in patients with COPD, but trials have shown inconsistent results and it is unknown which patients benefit most. This study aimed to summarize the evidence on effectiveness of self-management interventions and identify subgroups of COPD patients who benefit most.Methods: Randomized trials of self-management interventions between 1985 and 2013 were identified through a systematic literature search. Individual patient data of selected studies were requested from principal investigators and analyzed in an individual patient data meta-analysis using generalized mixed effects models.Results: Fourteen trials representing 3,282 patients were included. Self-management interventions improved health-related quality of life at 12 months (standardized mean difference 0.08, 95% confidence interval [CI] 0.00–0.16) and time to first respiratory-related hospitalization (hazard ratio 0.79, 95% CI 0.66–0.94) and all-cause hospitalization (hazard ratio 0.80, 95% CI 0.69–0.90), but had no effect on mortality. Prespecified subgroup analyses showed that interventions were more effective in males (6-month COPD-related hospitalization: interaction P=0.006), patients with severe lung function (6-month all-cause hospitalization: interaction P=0.016), moderate self-efficacy (12-month COPD-related hospitalization: interaction P=0.036), and high body mass index (6-month COPD-related hospitalization: interaction P=0.028 and 6-month mortality: interaction P=0.026). In none of these subgroups, a consistent effect was shown on all relevant outcomes.Conclusion: Self-management interventions exert positive effects in patients with COPD on respiratory-related and all-cause hospitalizations and modest effects on 12-month health-related quality of life, supporting the implementation of self-management strategies in clinical practice. Benefits seem similar across the subgroups studied and limiting self-management interventions to specific patient subgroups cannot be recommended. Keywords: chronic obstructive pulmonary disease, individual patient data meta-analysis, self-management, subgroup analysis

Sara Fleehart,1,* Vincent S Fan,2,3,* Huong Q Nguyen,4 Jungeun Lee,1 Ruth Kohen,3 Jerald R Herting,5 Gustavo Matute-Bello,2,3 Sandra G Adams,6,7 Genevieve Pagalilauan,3 Soo Borson3 1School of Nursing, University of Washington, Seattle, WA, USA; 2VAPuget Sound Health Care Center, Seattle, WA, USA; 3School of Medicine, University of Washington, Seattle, WA, USA; 4Reseach and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA; 5Department of Sociology, University of Washington, Seattle, WA, USA; 6School of Medicine, University of Texas Health Science Center; 7South Texas Veterans Health Care System, San Antonio, TX, USA *These authors contributed equally to this paper Purpose: The purpose of this study was to examine the prevalence and correlates of suicidal ideation (SI) in patients with stable moderate to very severe chronic obstructive pulmonary disease (COPD). Patients and methods: We conducted an exploratory mixed methods analysis of data from participants in a longitudinal observational study of depression in COPD. We measured depression with the Patient Health Questionnaire-9 (PHQ-9), which includes an item on SI. We compared participants with and without SI in relation to sociodemographics, symptoms, anxiety, and healthcare resource use with independent t-tests and chi-square tests. Content analysis was performed on qualitative data gathered during a structured SI safety assessment. Results: Of 202 participants, 121 (60%) had depressive symptoms (PHQ ≥6); 51 (25%) had a PHQ-9 ≥10, indicating a high likelihood of current major depression; and 22 (11%) reported SI. Compared to the 99 depressed participants without SI, those with SI were more likely to be female (59% vs 27%, P=0.004); had worse dyspnea (P=0.009), depression (P

Maayan Agmon,1 Basia Belza,2 Huong Q Nguyen,2,3 Rebecca G Logsdon,2 Valerie E Kelly41The Cheryl Spencer Department of Nursing, Faculty of Social Welfare and Health Studies, University of Haifa, Israel; 2School of Nursing, University of Washington, Seattle, WA, USA; 3Department of Research and Evaluation, Kaiser Permanente, CA, USA; 4School of Medicine, University of Washington, Seattle, WA, USABackground: Injury due to falls is a major problem among older adults. Decrements in dual-task postural control performance (simultaneously performing two tasks, at least one of which requires postural control) have been associated with an increased risk of falling. Evidence-based interventions that can be used in clinical or community settings to improve dual-task postural control may help to reduce this risk.Purpose: The aims of this systematic review are: 1) to identify clinical or community-based interventions that improved dual-task postural control among older adults; and 2) to identify the key elements of those interventions.Data sources: Studies were obtained from a search conducted through October 2013 of the following electronic databases: PubMed, CINAHL, PsycINFO, and Web of Science.Study selection: Randomized and nonrandomized controlled studies examining the effects of interventions aimed at improving dual-task postural control among community-dwelling older adults were selected.Data extraction: All studies were evaluated based on methodological quality. Intervention characteristics including study purpose, study design, and sample size were identified, and effects of dual-task interventions on various postural control and cognitive outcomes were noted.Data synthesis: Twenty-two studies fulfilled the selection criteria and were summarized in this review to identify characteristics of successful interventions.Limitations: The ability to synthesize data was limited by the heterogeneity in participant characteristics, study designs, and outcome measures.Conclusion: Dual-task postural control can be modified by specific training. There was little evidence that single-task training transferred to dual-task postural control performance. Further investigation of dual-task training using standardized outcome measurements is needed.Keywords: physical therapy, balance, walking, motor learning, fall preventionA Letter to the editor has been published for this paper

There is growing interest in fluorinated electrolytes due to their high-voltage stability. We use full electrochemical characterization based on concentrated solution theory to investigate the underpinnings of conductivity and transference number in tetraglyme/LiTFSI mixtures (H4) and a fluorinated analog, C8-DMC, mixed with LiFSI (F4). Conductivity is significantly lower in F4 than in H4, and F4 exhibits negative cation transference numbers, while that of H4 is positive at most salt concentrations. By relating Stefan-Maxwell diffusion coefficients, which quantify ion-solvent and cation-anion frictional interactions, to conductivity and transference number, we determine that at high salt concentrations, the origin of differences in transference number is differences in anion-solvent interactions. We also define new Nernst-Einstein-like equations relating conductivity to Stefan-Maxwell diffusion coefficients. In H4 at moderate to high salt concentrations, we find that all molecular interactions must be included. However, we demonstrate another regime, in which conductivity is controlled by cation-anion interactions. The applicability of this assumption is quantified by a pre-factor, β+-} which is similar to the "ionicity"pre-factor that is often included in the Nernst-Einstein equation. In F4, β+-} is unity at all salt concentrations, indicating that ionic conductivity is entirely controlled by the Stefan-Maxwell diffusion coefficient quantifying cation-anion frictional interactions.

Imposing a steady ionic current through an electrolyte results in the formation of salt concentration gradients that compromise battery performance. The limiting current is usually defined as the current at which the salt concentration at the cathode approaches zero. Higher currents cannot be imposed on the cell as larger concentration gradients are unsustainable. We study the limiting current in electrolytes comprising a perfluorinated oligomer, C8-DMC, and lithium bis(fluorosulfonyl)imide salt in symmetric lithium cells. The time-dependence of the potential, which increases as salt concentration gradients develop, was also measured. Both steady-state and transient behaviors are modeled using Newman's concentrated solution theory; transport and thermodynamic parameters needed to perform the calculations were measured independently. The limiting current is a nonmonotonic function of salt concentration in both theory and experiment. The model shows that at low salt concentrations (below 0.88 mol/kg solvent), the concentration at the cathode approaches zero at limiting current. In contrast, at high salt concentrations (above 0.88 mol/kg solvent), the concentration at the anode approaches the solubility limit (2.03 mol/kg solvent). The experimentally determined salt concentration at which the limiting current is maximized is in excellent agreement with theoretical predictions made without resorting to any adjustable parameters.

Purpose: The mechanical properties and functional load performance of implant restorations coupled with metal abutments have been studied widely. However, the fatigue performance of the newly introduced ceramic implant abutments has not been reported. This study investigated the load fatigue performance of four implant systems and their corresponding zirconia ceramic abutments at the manufacturers' recommended torque levels. Materials and Methods: Three different diameters (narrow, regular, and wide) of the Replace Select and Brånemark systems and two different diameters (4.1 mm and 5.0 mm) of the Osseotite NT and Osseotite NT Certain systems provided 10 implant-abutment test groups. The abutments tested were Procera zirconia, Zireal posts, and Certain ZiReal posts. Each group had a sample size of five. A rotational load fatigue machine applied a 21-N load to the specimens at an angle of 45 degrees to produce an effective bending moment of 35 Ncm at a test frequency of 10 Hz. The number of cycles to failure was recorded. Results: Twenty-nine of the 50 implant-abutment combinations tested failed. Eighteen abutments fractured. Seven implant fractures and 16 abutment screw fractures were seen, along with some damage to the implant platform in some specimens. No significant difference was seen between the implant systems, but significant differences were observed between the implant diameters. A subsequent one-way analysis of variance revealed statistically significant differences between the 10 implant-abutment test groups. Conclusions: Rotational load fatigue testing performance of zirconia abutments is dependent on the abutment diameter. Failure modes varied according to system design characteristics. [ABSTRACT FROM AUTHOR]

Background: Recurrence is a major cause of treatment failure after allogeneic transplantation for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), and treatment options are very limited. Azacitidine is a DNA methyltransferase inhibitor with activity in myeloid disease. The authors hypothesized that low-dose azacitidine administered after transplant would reduce recurrence rates, and conducted a study to determine a safe dose/schedule combination.Methods: Forty-five high-risk patients were treated. Median age was 60 years; median number of comorbidities was 3; 67% were not in remission. By using a Bayesian adaptive method to determine the best dose/schedule combination based on time to toxicity, the authors investigated combinations of 5 daily azacitidine doses, 8, 16, 24, 32, and 40 mg/m2, and 4 schedules: 1, 2, 3, or 4 cycles, each with 5 days of drug and 25 days of rest. Cycle 1 started on Day +40.Results: Reversible thrombocytopenia was the dose-limiting toxicity. The optimal combination was 32 mg/m2 given for 4 cycles. Median follow-up was 20.5 months. One-year event-free and overall survival were 58% and 77%, justifying further studies to estimate long-term clinical benefit. No dose significantly affected DNA global methylation.Conclusions: Azacitidine at 32 mg/m2 given for 5 days is safe and can be administered after allogeneic transplant for at least 4 cycles to heavily pretreated AML/MDS patients. The trial also suggested that this treatment may prolong event-free and overall survival, and that more cycles may be associated with greater benefit. [ABSTRACT FROM AUTHOR]

The primary purpose of this secondary analysis was to determine whether 103 participants with chronic obstructive pulmonary disease rated the affective dimension of dyspnea (dyspnea-related anxiety and dyspnea-related distress) separately from the sensory dimension (intensity) during baseline exercise testing conducted as part of a randomized clinical trial. A secondary purpose was to determine if dyspnea-related anxiety and distress were rated distinctly different from other measurements of anxiety. At the end of a 6-minute walk and an incremental treadmill test, participant ratings of the magnitude of dyspnea-related anxiety and distress on the Modified Borg Scale were significantly different from their ratings of the intensity of dyspnea. Dyspnea-related anxiety and distress also appeared to be concepts independent from measures of state anxiety, negative affect, and anxiety before a treadmill test. © 2009 Wiley Periodicals, Inc. Res Nurs Health 33:4-19, 2010 [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the associations between depression and the likelihood of enrollment in a health plan-sponsored physical activity program and pattern of program participation over 2 years; a secondary aim was to examine the association between participation dose and depression risk. There are no published studies on how depression influences participation in health plan-sponsored physical activity programs and how participation affects depression risk in older adults in nonresearch settings.Methods: This study used administrative data from a Medicare Advantage plan. Participants (n=4766) were enrolled in the plan for at least 1 year prior to participating in the plan-sponsored health club benefit (Silver Sneakers). Controls were age- and gender-matched to participants (n=9035). Members were identified as having depression based on ICD-9-CM codes. Multivariate regression and generalized estimating equations models were used. Data were collected between 1998 and 2003 and analyzed in 2008.Results: Members who had a history of depression were as likely to participate in Silver Sneakers as nondepressed members (OR: 1.03; 95% CI=0.89, 1.20; p=0.67). The risk of lapse in Silver Sneakers attendance was 28%-55% (p<0.05) higher for depressed participants during months 15-24. For nondepressed Silver Sneakers participants, attendance of at least 2 visits/week during Year 1 was significantly associated with lower risk of depression in Year 2 (OR=0.54; 95% CI=0.37, 0.79; p=0.002); a similar but statistically nonsignificant association was observed for previously depressed participants (OR=0.51; 95% CI=0.26, 1.02; p=0.06).Conclusions: While depressed older adults are as likely to enroll in a health plan-sponsored physical activity as nondepressed members, they were at higher risk of attendance lapses. Greater participation in the physical activity program was associated with lower depression risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE: During December 2002 to January 2003, a varicella outbreak occurred in an elementary school in Maine. Just 1 month before detecting the outbreak, Maine implemented varicella vaccine requirements for child care but did not require vaccination for school entry. We investigated this outbreak to examine reasons for its occurrence, including vaccine failure. METHODS: A self-administered questionnaire was sent to all students' parents to determine student disease status, medical conditions, and vaccination status, which was further confirmed by review of medical records. Parental reporting of chickenpox/varicella that occurred since September 1, 2002, in a student who attended the school was used to define a case. Parents of cases were interviewed by telephone about disease characteristics. Disease severity was classified on the basis of the number of skin lesions and the occurrence of complications. Vaccine effectiveness was calculated by comparing varicella attack rates for any disease, for moderate to severe disease, and for severe disease among vaccinated and unvaccinated students. RESULTS: We obtained complete information for 296 (81%) of 364 students. Varicella vaccine coverage was 74% overall and decreased by grade, from 90% in kindergarten to 60% in third grade. Attack rates increased significantly from 14% in kindergarten to 37% in third grade. Of the 53 varicella cases, 36 (68%) were unvaccinated, 12 (22%) were vaccinated, and 5 (10%) had previous disease history. Vaccine effectiveness was 89% (95% confidence interval [CI]: 79-94%) against disease of any severity, 96% (95% CI: 88-99%) against moderate to severe disease, and 100% (95% CI: undefined) against severe disease. Twenty-two percent of unvaccinated students had severe disease and 1 was hospitalized for a skin infection, whereas none of the vaccinated cases reported severe disease. CONCLUSION: This outbreak was attributable primarily to failure to vaccinate, especially among children in grades 1 through 3. Catch-up vaccination of susceptible older children and adolescents is especially important to prevent accumulation of susceptibility in these groups, in which the natural disease is more severe. School entry requirements will contribute to a more rapid implementation of the existing recommendations for vaccination. [ABSTRACT FROM AUTHOR]

The primary purpose of this study was to determine if there are three distinct factors representing ratings of dyspnea during laboratory exercise, clinical ratings of dyspnea, and pulmonary function in patients with moderate to severe chronic obstructive pulmonary disease (COPD) (n = 92) using factor analysis. Subjects (mean age 66 +/- 7 yrs; FEV1% predicted 44.7 +/- 14.0) were randomly assigned to one of three treatment groups to test the effects of three education and exercise training programs. Outcomes were evaluated at baseline and at 2 months after the intervention. Dyspnea ratings with laboratory exercise (SOB) were measured during incremental (ITT) and endurance (ETT) treadmill tests, and a six-minute walk (6MW) using the modified Borg scale. Clinical measures of dyspnea were measured with the Baseline and Transitional Dyspnea Index (BDI/TDI), UCSD Shortness of Breath Questionnaire (SOBQ), Medical Research Council Dyspnea Scale (MRC), Dyspnea subscale of the Chronic Respiratory Questionnaire (CRQ-D), and a global dyspnea question. Pulmonary function parameters included FEV1% predicted, FEV1/FVC, and RV/TLC. The factor analysis yielded three factors that accounted for 58.7% of the total variance in the data: Factor 1, "Dyspnea with Laboratory Exercise" comprised ETT SOB end, ETT SOB isotime, ITTSOB end, ITT SOB isotime, ITT SOB/Time and ETT SOB/Time. Factor 2, "Clinical Dyspnea," comprised 6MW SOB, 6MW SOB/Feet, BDI, SOBQ, MRC, Global SOB, CRQ-D. Measures of airway resistance (FEV1% predicted, FEV1/FVC) and hyperinflation (RV/TLC) loaded on a third factor, "Pulmonary Function." An additional post hoc factor analysis with post-intervention data provided similar results. The Global SOB question and ITT SOB isostage variables were relatively more sensitive to change compared to the other outcome variables. We conclude that pulmonary function, clinical ratings of dyspnea, and laboratory ratings of dyspnea are three separate and independent factors and should be included in the routine clinical evaluation of patients with COPD. [ABSTRACT FROM AUTHOR]

Precise measurement of magnetic fields is essential for various applications, such as fundamental physics, space exploration, and biophysics. Although recent progress in quantum engineering has assisted in creating advanced quantum magnetometers, there are still ongoing challenges in improving their efficiency and noise resistance. This study focuses on using symmetric graph state resources for quantum magnetometry to enhance measurement precision by analyzing the estimation theory under time-homogeneous and time-inhomogeneous noise models. The results show a significant improvement in estimating both single and multiple Larmor frequencies. In single Larmor frequency estimation, the quantum Fisher information spans a spectrum from the standard quantum limit to the Heisenberg limit within a periodic range of the Larmor frequency, and in the case of multiple Larmor frequencies, it can exceed the standard quantum limit for both noisy cases. This study highlights the potential of graph state-based methods for improving magnetic field measurements under noisy environments., (© 2024. The Author(s).)

Rivers represent one of the main conduits for the delivery of plastics to the sea, while also functioning as reservoirs for plastic retention. In tropical regions, rivers are exposed to both high levels of plastic pollution and invasion of water hyacinths. This aquatic plant forms dense patches at the river surface that drift due to winds and currents. Recent work suggests that water hyacinths play a crucial role in influencing plastic transport, by efficiently trapping the majority of surface plastic within their patches. However, a comprehensive understanding of the interaction between water hyacinths and plastics is still lacking. We hypothesize that the properties relevant to plastic transport change due to their trapping in water hyacinth patches. In particular, the length scale, defined as the characteristic size of the transported material, is a key property in understanding how materials move within rivers. Here, we show that water hyacinth patches trap on average 54%-77% of all observed surface plastics at the measurement site (Saigon river, Vietnam). Both temporally and spatially, we found that plastic and water hyacinth presence co-occur. The formation of plastic-plant aggregates carries significant implications for both clean-up and monitoring purposes, as these aggregates can be detected from space and need to be jointly removed. In addition, the length scale of trapped plastics (∼4.0 m) was found to be forty times larger than that of open water plastics (∼0.1 m). The implications of this increased length scale for plastic transport dynamics are yet to be fully understood, calling for further investigation into travel distances and trajectories. The effects of plastic trapping likely extend to other key properties of plastic-plant aggregates, such as effective buoyancy and mass. Given the prevalence of plant invasion and plastic pollution in rivers worldwide, this research offers valuable insights into the complex environmental challenges faced by numerous rivers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The generation time, representing the interval between infections in primary and secondary cases, is essential for understanding and predicting the transmission dynamics of seasonal influenza, including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially post the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023. More than 200 individuals who tested positive for influenza and their household contacts were enrolled within 7 days of the first illness in the household. All participants were prospectively followed for 10 days completing daily symptom diaries and collecting nasal swabs, which were tested for influenza via RT-PCR. We analyzed these data by modifying a previously published Bayesian data augmentation approach that imputes infection times of cases to obtain both intrinsic (assuming no susceptible depletion) and realized (observed within household) generation times. We assessed the robustness of the generation time estimate by varying the incubation period, and generated estimates of the proportion of transmission before symptomatic onset, infectious period, and latent period. We estimated a mean intrinsic generation time of 3.2 (95% credible interval, CrI: 2.9-3.6) days, with a realized household generation time of 2.8 (95% CrI: 2.7-3.0) days. The generation time exhibited limited sensitivity to incubation period variation. Estimates of the proportion of transmission that occurred before symptom onset, the infectious period, and the latent period were sensitive to variation in incubation periods. Our study contributes to the ongoing efforts to refine estimates of the generation time for influenza. Our estimates, derived from recent data following the COVID-19 pandemic, are consistent with previous pre-pandemic estimates, and will be incorporated into real-time Rt estimation efforts.

Background: The standard treatment for de novo metastatic hormone-sensitive prostate cancer (mHSPC) involves androgen deprivation therapy (ADT) combined with next-generation hormonal agents and/or docetaxel. While the standard dose (STD) of abiraterone is 1,000 mg administered while fasting, recent evidence suggests that a low dose (LOW) of 250 mg taken with a low-fat meal may achieve comparable pharmacokinetic outcomes., Objectives: This study aimed to evaluate the failure-free survival (FFS) and safety of LOW and STD in de novo high-risk mHSPC patients., Materials and Methods: We conducted a retrospective analysis of males with de novo high-risk mHSPC treated with ADT plus abiraterone (250 mg with a low-fat meal or 1000 mg fasting) at the Vietnam National Cancer Hospital from January 2019 to May 2024. The primary endpoint was FFS, assessed using Kaplan-Meier and multivariate Cox regression analyses., Results: The study included 183 patients, with 91 in the LOW group and 92 in the STD group. The rates of patients who achieved undetectable PSA (PSA < 0.2 ng/ml) were 52.7% in the LOW group and 47.8% in the STD group. The median time to undetectable PSA was 6.9 months in the LOW group and 6.4 months in the STD group. The median overall FFS was 28.1 months (95% CI: 21.1 to 35.0) in the LOW group and 25.4 months (95% CI: 15.5 to 35.3) in the STD group (P = .286). Multivariate analysis indicated that visceral metastases and detectable PSA (PSA ≥ 0.2 ng/ml) were significant negative predictors of FFS in both groups. The incidence of grade 3 and grade 4 adverse events was similar between the LOW group and the STD group., Conclusions: The LOW group and STD group showed effectiveness and safety in de novo high-risk mHSPC. The use of low-dose abiraterone in de novo mHSPC can significantly reduce treatment costs., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chronic compression of the left common iliac vein (CIV) by the right common iliac artery (CIA) or May-Thurner syndrome is rare and could be challenging to diagnose. The phenomenon results in chronic left lower extremity vein thrombosis. In this report, we present a 33-year-old female with pain and swelling in her left inner thigh for 2 days. She denied any systemic signs or any remarkable past medical history. Doppler ultrasonography revealed large blood clots extending from the left femoral and great saphenous veins to the upper part of the external iliac vein, causing a nearly complete obstruction. CT venography showed compression of the left CIV near the confluence by the right CIA and the lumbar vertebrae L4. She was managed by catheter-directed thrombolysis with alteplase via a superior vena cava catheter. Subsequently, a left CIV self-expanding stent was successfully placed. Follow-up demonstrated a positive outcome without any complications., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Nanozymes based on manganese oxide (MnO 2 ) are demonstrated to be promising probes in colorimetric sensing applications. In this study, the r-MnO 2 /β-MnO 2 heterophase nanostructure was simply prepared by a calcination process with controllable temperature. The characterization of the nanostructured material was confirmed by SEM, UV-vis spectroscopy, Raman, TGA-DSC, and XRD analysis. The r-MnO 2 /β-MnO 2 exhibits a remarkably good catalytic activity in the oxidation process of 3,3',5,5'-tetramethylbenzidine (TMB) compared with the r-MnO 2 or Mn 2 O 3 nanostructure owing to its heterophase junctions. The enhanced performance of the colorimetric sensor for ascorbic acid (AA) detection was investigated using the r-MnO 2 /β-MnO 2 heterophase nanostructure as probe. The r-MnO 2 /β-MnO 2 material enhanced the monitoring of AA in the wide linear range from 1 µM to 50 μM with a limit of detection of 0.84 µM. This work presents a promising and straightforward approach for the construction of MnO 2 -based colorimetric sensor and their practical application in plant growth monitoring., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Cognitive impairment and dementia are frequently under-recognized. Health system strategies anchored in primary care are essential to address gaps in timely, comprehensive diagnosis. The goal of this paper is to describe the adaptation of a tablet-based brain health assessment (TabCAT-BHA) intervention and the study protocol to test its effectiveness in improving the detection of cognitive impairment, including dementia., Methods: This mixed-methods, pragmatic, cluster randomized, hybrid effectiveness-implementation trial is being conducted in two 18-month waves with 26 Kaiser Permanente Southern California primary care clinics, with 13 serving as intervention clinics and 13 as usual care clinics. Patients 65 years and older with memory concerns (n ~ 180,000) receiving care at the 26 clinics will be included in the analyses. Primary care clinics are provided the following practice supports as part of the TabCAT-BHA intervention: brief education and training on neurocognitive disorders and study workflows; digital tools to assess cognitive function and support clinician decision making and documentation; and registered nurse support during the work-up and post-diagnosis periods for primary care providers, patients, and families. The intervention was adapted based on engagement with multiple levels of clinical and operational leaders in the healthcare system. Effectiveness outcomes include rates of cognitive impairment diagnosis in primary care and rates of completed standardized cognitive assessments and specialist referrals with incident diagnoses. Implementation outcomes include acceptability-appropriateness-feasibility, adoption, and fidelity., Results: We identified seven themes organized by system-, provider-, and patient-level domains that were used to adapt the TabCAT-BHA intervention. Accordingly, changes were made to the provider education, diagnostic work-up, and post-diagnostic support. Results will be reported in fall of 2027., Conclusions: Our engagement with multiple primary and specialty care clinical and operational leaders to adapt the TabCAT-BHA intervention to these primary care clinics has informed the protocol to evaluate the intervention's effectiveness for improving the detection of cognitive impairment, including dementia, in an integrated healthcare system., Trial Registation: Clinicaltrials.gov: NCT06090578 (registered 10/24/23)., (© 2024. The Author(s).)

Background: Kaiser Permanente Southern California began offering a 4-week supplemental benefit of home-delivered meals to Medicare Advantage members after discharge from a hospitalization for heart failure and other medical conditions in 2021. The purpose of this study is to explore the associations between socioeconomic disadvantage and food insecurity with patient uptake of and satisfaction with the meals., Methods: Data for this cross-sectional study were drawn from survey and electronic medical record data for members referred for the meals benefit (n = 6169) and linked to a hospitalization encounter (n = 2254) between January and December 2021. Uptake was assessed using vendor records; measures of socioeconomic status included the neighborhood deprivation index (NDI) and prior receipt of medical financial assistance (MFA) from the health system. Patients were invited to complete an email or phone survey about their satisfaction with the meals and food insecurity. Multivariable log-binomial regression models were used to examine the association between socioeconomic disadvantage and food insecurity with meals uptake and satisfaction., Results: Sixty-two percent of patients referred for the benefit accepted the meals (mean age: 79 ± 9, 59% people of color). While there was no significant relationship between NDI and meals uptake (RR: 0.99, 95% CI: 0.92-1.07, p = 0.77), patients who received prior MFA were more likely to accept the meals (RR: 1.09, 95% CI: 1.02-1.16, p < 0.01). Sixty-nine percent of patients who completed the survey (23% response rate) reported that meals were very or extremely helpful. Patients with food insecurity (29% of survey respondents) were more likely to report that the meals were helpful for their recovery compared to food secure patients (RR: 1.21, 95% CI: 1.09-1.35, p < 0.01)., Conclusions: The home-delivered meals appeared to be particularly utilized by and helpful to patients with greater financial strain and/or food insecurity, suggesting that supplemental benefits could be more targeted toward addressing unmet needs of vulnerable adults., (© 2024 The American Geriatrics Society.)

The level of tumor and circulating CXCR1/2-expressing neutrophils and CXCR1/2 ligands correlate with poor patient outcomes, inversely correlate with tumoral lymphocyte content, and predict immune checkpoint inhibitor (ICI) treatment failure. Accordingly, CXCR2-selective and CXCR1/2 dual inhibitors exhibit activity both as single agents and in combination with ICI treatment in mouse tumor models. Based on such reports, clinical trials combining CXCR1/2 axis antagonists with ICI treatment for cancer patients are underway. It has been assumed that CXCR1/2 blockade impacts tumors by blocking neutrophil chemotaxis and reducing neutrophil content in tumors. Here, we show that while CXCR2 antagonism does slow tumor growth, it does not preclude neutrophil recruitment into tumor. Instead, CXCR1/2 inhibition alters neutrophil function by blocking the polarization of transcriptional programs toward immune suppressive phenotypes and rendering neutrophils incapable of suppressing lymphocyte proliferation. This is associated with decreased release of reactive oxygen species and Arginase-1 into the extracellular milieu. Remarkably, these therapeutics do not impact the ability of neutrophils to phagocytose and kill ingested bacteria. Taken together, these results mechanistically explain why CXCR1/2 inhibition has been active in cancer but without infectious complications., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Valbenazine is a highly potent and selective inhibitor of synaptic vesicular monoamine transporter 2. The current therapeutic doses of valbenazine for tardive dyskinesia (TD) are 40, 60, or 80 mg capsules, given orally, once daily (QD). While 40 and 80 mg were investigated in phase 3 KINECT ® 3 trial and initially approved, the approval of valbenazine 60 mg was based on the analysis utilizing the Model-informed drug development (MIDD) approach, facilitated through the US Food and Drug Administration's MIDD Pilot Program. This study aimed to demonstrate the efficacy of 60 mg QD dose through model simulations using an established exposure-response (E-R) relationship between valbenazine active metabolite [+]-α-dihydrotetrabenazine exposure and the change from baseline in Abnormal Involuntary Movement Scale total score (AIMS-CFB). A longitudinal E-R model was constructed based on the 40 and 80 mg data from the KINECT 3 trial. The final E max model adequately predicted dose-dependent improvement in the primary endpoint and was used to interpolate AIMS-CFB for 60 mg at week 6. The efficacy of the unstudied 60 mg dose regimen is expected to be within the range of doses studied clinically with predicted mean AIMS-CFB (95% confidence interval) of -2.69 (-3.30, -2.13) between observed mean AIMS-CFB for 40 mg of -1.92 and 80 mg of -3.39. Results from this analysis provided the key evidence to establish efficacy of 60 mg QD without the need for an additional clinical trial. The availability of valbenazine 60 mg dose fills an existing medical need for patients with TD who could benefit from this third effective dose., (© 2024 The Author(s). The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Rationale: Physical activity, lung function, and grip strength are associated with exacerbations, hospitalizations, and mortality in people with chronic obstructive pulmonary disease (COPD). We tested whether baseline inflammatory biomarkers were associated with longitudinal outcomes of these physiologic measurements., Methods: The COPD Activity: Serotonin Transporter, Cytokines, and Depression (CASCADE) study was a prospective observational study of individuals with COPD. A total of 14 inflammatory biomarkers were measured at baseline. Participants were followed for 2 years. We analyzed associations between baseline biomarkers and forced expiratory volume in 1 second (FEV 1 ), physical activity, and grip strength. We used a hierarchical hypothesis testing procedure to reduce type I error. We used Pearson correlations to test associations between baseline biomarkers and longitudinal changes in the outcomes of interest. We used Fisher's linear discriminant analysis to test if linear combinations of baseline biomarkers predict rapid FEV 1 decline. Finally, we used linear mixed modeling to test associations between baseline biomarkers and outcomes of interest at baseline, year 1, and year 2; models were adjusted for age, smoking status, baseline biomarkers, and FEV 1 ., Results: A total of 302 participants (age 67.5 ± 8.5 years, 19.5% female, 28.5% currently smoking) were included. Baseline biomarkers were not associated with longitudinal changes in grip strength, physical activity, or rapid FEV 1 decline. Higher interleukin-6 and C-reactive protein were associated with lower physical activity at baseline and these relationships persisted at year 1 and year 2., Conclusion: Baseline inflammatory biomarkers did not predict changes in lung function or physical activity, but higher inflammatory biomarkers were associated with persistently low levels of physical activity., (JCOPDF © 2024.)

Asymptomatic influenza virus infection occurs but may vary by factors such as age, influenza vaccination status, or influenza season. We examined the frequency of influenza virus infection and associated symptoms using data from two case-ascertained household transmission studies (conducted from 2017-2023) with prospective, systematic collection of respiratory specimens and symptoms. From the 426 influenza virus infected household contacts that met our inclusion criteria, 8% were asymptomatic, 6% had non-respiratory symptoms, 23% had acute respiratory symptoms, and 62% had influenza-like illness symptoms. Understanding the prevalence of asymptomatic and mildly symptomatic influenza cases is important for implementing effective influenza prevention strategies and enhancing the effectiveness of symptom-based surveillance systems., Competing Interests: Competing Interest Statement: EAB receives research support from CSL Seqirus unrelated to the current work. HQN receives research support unrelated to this work from CSL Seqirus, GSK, ModernaTX Inc, and honorarium for participating in a consultancy group for Moderna outside the submitted work. Dr. Grijalva has received consulting fees from Merck, and research support from SyneosHealth, NIH, FDA and AHRQ.

Despite longstanding excitement and progress toward understanding liquid-liquid phase separation in natural and artificial membranes, fundamental questions have persisted about which molecules are required for this phenomenon. Except in extraordinary circumstances, the smallest number of components that has produced large-scale, liquid-liquid phase separation in bilayers has stubbornly remained at three: a sterol, a phospholipid with ordered chains, and a phospholipid with disordered chains. This requirement of three components is puzzling because only two components are required for liquid-liquid phase separation in lipid monolayers, which resemble half of a bilayer. Inspired by reports that sterols interact closely with lipids with ordered chains, we tested whether phase separation would occur in bilayers in which a sterol and lipid were replaced by a single, joined sterol-lipid. By evaluating a panel of sterol-lipids, some of which are found in bacteria, we discovered a minimal bilayer of only two components (PChemsPC and diPhyPC) that robustly demixes into micron-scale, liquid phases. It suggests a new role for sterol-lipids in nature, and it reveals a membrane in which tie-lines (and, therefore, the lipid composition of each phase) are straightforward to determine and will be consistent across multiple laboratories., Significance Statement: A wide diversity of bilayer membranes, from those with hundreds of lipids (e.g., vacuoles of living yeast cells) to those with very few (e.g., artificial vesicles) phase separate into micron-scale liquid domains. The number of components required for liquid-liquid phase separation has been perplexing: only two should be necessary, but more are required except in extraordinary circumstances. What minimal set of molecular characteristics leads to liquid-liquid phase separation in bilayer membranes? This question inspired us to search for single, joined "sterol-lipid" molecules to replace both a sterol and a phospholipid in membranes undergoing liquid-liquid phase separation. By producing phase-separating membranes with only two components, we mitigate experimental challenges in determining tie-lines and in maintaining constant chemical potentials of lipids.

Microscopy-based spatially resolved omic methods are transforming the life sciences. However, these methods rely on high numerical aperture objectives and cannot resolve crowded molecular targets, limiting the amount of extractable biological information. To overcome these limitations, here we develop Deconwolf, an open-source, user-friendly software for high-performance deconvolution of widefield fluorescence microscopy images, which efficiently runs on laptop computers. Deconwolf enables accurate quantification of crowded diffraction limited fluorescence dots in DNA and RNA fluorescence in situ hybridization images and allows robust detection of individual transcripts in tissue sections imaged with ×20 air objectives. Deconvolution of in situ spatial transcriptomics images with Deconwolf increased the number of transcripts identified more than threefold, while the application of Deconwolf to images obtained by fluorescence in situ sequencing of barcoded Oligopaint probes drastically improved chromosome tracing. Deconwolf greatly facilitates the use of deconvolution in many bioimaging applications., (© 2024. The Author(s).)