Nevin Manimala

Phys Rev Lett. 2022 Apr 15;128(15):151101. doi: 10.1103/PhysRevLett.128.151101.

ABSTRACT

Perturbations of Kerr spacetime are typically studied with the Teukolsky formalism, in which a pair of gauge invariant components of the perturbed Weyl tensor are expressed in terms of separable modes that satisfy ordinary differential equations. However, for certain applications it is desirable to construct the full metric perturbation in the Lorenz gauge, in which the linearized Einstein field equations take a manifestly hyperbolic form. Here we obtain a set of Lorenz-gauge solutions to the linearized vacuum field equations on Kerr-Newman-Unti-Tamburino spacetimes in terms of homogeneous solutions to the spin-2, spin-1, and spin-0 Teukolsky equations. We also derive Lorenz-gauge completion pieces representing mass and angular momentum perturbations of Kerr spacetime.

PMID:35499892 | DOI:10.1103/PhysRevLett.128.151101

Phys Rev Lett. 2022 Apr 15;128(15):150603. doi: 10.1103/PhysRevLett.128.150603.

ABSTRACT

Thermodynamics as limiting behaviors of statistics is generalized to arbitrary systems with probability a priori where the thermodynamic infinite-size limit is replaced by a multiple-measurement limit. A duality symmetry between Massieu’s and Gibbs’s entropy arises in the limit of infinitely repeated observations, yielding the Gibbs equation and Hill-Gibbs-Duhem equation (HGDE) as a dual pair. If a system has a thermodynamic limit satisfying Callen’s postulate, entropy being an Eulerian function, the symmetry is lost: the HGDE reduces to the Gibbs-Duhem equation. This theory provides a de-mechanized foundation for classical and nanothermodynamics and offers a framework for distilling emergence from large data, free from underlying details.

PMID:35499877 | DOI:10.1103/PhysRevLett.128.150603

JMIR Public Health Surveill. 2022 May 2;8(5):e31847. doi: 10.2196/31847.

ABSTRACT

BACKGROUND: As a young subgroup, college students have become the main users of mobile social networks. Considering that people can indiscriminately access explicit sexual content on the internet, coupled with the increase of HIV infections in male college students, the role of the internet in meeting sexual partners and its correlation to risky sexual behavior has become an important topic.

OBJECTIVE: The aim of this study is to explore the effects of internet exposure on sexual partners and sexual risk behavior among sexually experienced male college students.

METHODS: An institution-based cross-sectional study design was used to collect data through a paper-based questionnaire administered to male college students recruited from colleges and gay organizations in Hangzhou, Zhejiang Province, China. A total of 1045 sexually experienced male students were incorporated in our analysis, with the following information collected: sociodemographic characteristics, sexual intercourse-related behaviors, and sexually transmitted disease (STD) knowledge. Mann-Whitney U and Kruskal-Wallis tests were used to examine differences regarding basic characteristics and sexual risk behaviors between male college students who meet sexual partners via the internet and those who do not. Sequential logistic regression models were employed to examine the influence of meeting sexual partners via the internet on risky sexual behaviors after controlling for other factors.

RESULTS: The mean age of the sexually experienced male students was 21.6 (SD 2.0) years. The likelihood of risky sexual behavior was varied, yet it was the highest for those who aim to meet paid sexual partners (145/192, 75.5% to 19/22, 86.4%), followed by those seeking partners for love or romance (258/435, 59.3%). Compared to non-internet partner seekers, internet partner seekers tended to have more casual intercourse (292/542, 53.9% versus 51/503, 10.1%), paid intercourse (32/542, 5.9% versus 12/503, 2.4%), and intercourse with same-sex partners (349/542, 64.4% versus 41/503, 8.2%); they were also more likely to use psychoactive drugs (125/349, 35.8% versus 5/41, 12.2%) and have more than 2 partners. With the increase of HIV and STD knowledge, the probability of having unprotected intercourse decreased for non-internet partner seekers. However, it increased for internet partner seekers with a rising HIV knowledge score. Sequential logistic regression showed that meeting sexual partners on the internet was statistically associated with sexual risk behaviors with multiple sexual partners (odds ratio 4.434; P<.001).

CONCLUSIONS: Meeting sexual partners via the internet is a common behavior among sexually experienced male college students, and those who meet partners on the internet exhibited higher levels of risky sexual behaviors although they had sufficient HIV and STD knowledge; this is especially true for students who aimed to find partners for sexual intercourse. Thus, more attention should be paid to young adults to address the risky sexual behaviors that may contribute to STD spread among this population.

PMID:35499864 | DOI:10.2196/31847

JMIR Med Inform. 2022 May 2;10(5):e33219. doi: 10.2196/33219.

ABSTRACT

BACKGROUND: Systematic reviews (SRs) are central to evaluating therapies but have high costs in terms of both time and money. Many software tools exist to assist with SRs, but most tools do not support the full process, and transparency and replicability of SR depend on performing and presenting evidence according to established best practices.

OBJECTIVE: This study aims to provide a basis for comparing and selecting between web-based software tools that support SR, by conducting a feature-by-feature comparison of SR tools.

METHODS: We searched for SR tools by reviewing any such tool listed in the SR Toolbox, previous reviews of SR tools, and qualitative Google searching. We included all SR tools that were currently functional and required no coding, and excluded reference managers, desktop applications, and statistical software. The list of features to assess was populated by combining all features assessed in 4 previous reviews of SR tools; we also added 5 features (manual addition, screening automation, dual extraction, living review, and public outputs) that were independently noted as best practices or enhancements of transparency and replicability. Then, 2 reviewers assigned binary present or absent assessments to all SR tools with respect to all features, and a third reviewer adjudicated all disagreements.

RESULTS: Of the 53 SR tools found, 55% (29/53) were excluded, leaving 45% (24/53) for assessment. In total, 30 features were assessed across 6 classes, and the interobserver agreement was 86.46%. DistillerSR (Evidence Partners; 26/30, 87%), Nested Knowledge (Nested Knowledge; 25/30, 83%), and EPPI-Reviewer Web (EPPI-Centre; 24/30, 80%) support the most features followed by Giotto Compliance (Giotto Compliance; 23/30, 77%), LitStream (ICF), and SRDB.PRO (VTS Software). Fewer than half of all the features assessed are supported by 7 tools: RobotAnalyst (National Centre for Text Mining), SRDR (Agency for Healthcare Research and Quality), SyRF (Systematic Review Facility), Data Abstraction Assistant (Center for Evidence Synthesis in Health), SR Accelerator (Institute for Evidence-Based Healthcare), RobotReviewer (RobotReviewer), and COVID-NMA (COVID-NMA). Notably, of the 24 tools, only 10 (42%) support direct search, only 7 (29%) offer dual extraction, and only 13 (54%) offer living/updatable reviews.

CONCLUSIONS: DistillerSR, Nested Knowledge, and EPPI-Reviewer Web each offer a high density of SR-focused web-based tools. By transparent comparison and discussion regarding SR tool functionality, the medical community can both choose among existing software offerings and note the areas of growth needed, most notably in the support of living reviews.

PMID:35499859 | DOI:10.2196/33219

Ann Am Thorac Soc. 2022 May 2. doi: 10.1513/AnnalsATS.202103-343OC. Online ahead of print.

ABSTRACT

Background: To inform an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guideline, this systematic review evaluated existing interstitial lung disease (ILD) literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic nintedanib. Methods: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using nintedanib to treat patients with PPF. Mortality, disease progression, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Results: Two relevant studies were selected. The annual decline in FVC was less in the nintedanib arm in the overall study population [mean difference (MD) 107 milliliters (mL)/year (yr) (95% CI 65.4-148.5 mL/yr)] and in the subgroups with usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis [MD 128.2 mL/yr (95% CI 70.8-185.6 mL/yr)], non-UIP patterns of pulmonary fibrosis [MD 75.3 mL/yr (95% CI 15.5-135.0 mL/yr)], fibrotic connective tissue disease-related ILD [MD 106.2 mL/yr (95% CI 10.6-201.9 mL/yr)], fibrotic idiopathic non-specific interstitial pneumonia [MD 141.7 mL/yr (95% CI 46.0-237.4 mL/yr)], and fibrotic occupational ILD [MD 252.8 mL/yr (95% CI 79.2-426.5 mL/yr)], but not fibrotic hypersensitivity pneumonitis [MD 72.9 mL/yr (95% CI -8.9-154.7 mL/yr)], fibrotic sarcoidosis [MD -20.5 mL/yr (95% CI -337.1-296.1 mL/yr)], or unclassified fibrotic ILD [MD 68.5 mL/yr (95% CI -31.3-168.4 mL/yr)] when compared to placebo. Gastrointestinal (GI) side effects were common. Quality of evidence for the outcomes ranged from very low to moderate GRADE. Conclusions: Nintedanib use in patients with PPF is associated with a statistically significant decrease in disease progression but increase in GI side effects regardless of the radiographic pattern of pulmonary fibrosis. However, limitations in the available evidence lead to low certainty in these effect estimates and make definitive conclusions about the differential effects by subtype of ILD difficult to determine.

PMID:35499854 | DOI:10.1513/AnnalsATS.202103-343OC

Ann Am Thorac Soc. 2022 May 2. doi: 10.1513/AnnalsATS.202103-342OC. Online ahead of print.

ABSTRACT

Background: To inform an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guideline, this systematic review evaluated existing interstitial lung disease literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic pirfenidone. Methods: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using pirfenidone to treat patients with PPF. Mortality, disease progression, lung function, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Results: Two studies met inclusion criteria. Meta-analyses revealed changes in FVC % predicted [mean difference (MD) 2.3% (95% CI 0.5-4.1)], FVC in mL [MD 100.0 mL (95% CI 98.1-101.9)], and 6MWD in meters [MD 25.2 m (95% CI 8.3-42.1)] all favored pirfenidone to placebo. Change in DLCO in mmol/kPa/min [MD 0.40 mmol/kPa/min (95% CI 0.10-0.70)] and risk of DLCO declining more than 15% [relative risk (RR) 0.27 (95% CI 0.08-0.95)] also favored pirfenidone. The risks of gastrointestinal discomfort [RR 1.83 (95% CI 1.29-2.60)] and photosensitivity [RR 4.88 (95% CI 1.09-21.83)] were higher with pirfenidone. The quality of evidence was low or very low GRADE, depending on the outcome. Conclusions: Pirfenidone use in patients with PPF is associated with statistically significant decrease in disease progression and protection in lung function. However, there is very low certainty in the estimated effects due to limitations in the available evidence.

PMID:35499847 | DOI:10.1513/AnnalsATS.202103-342OC

Invest Ophthalmol Vis Sci. 2022 May 2;63(5):1. doi: 10.1167/iovs.63.5.1.

ABSTRACT

PURPOSE: To investigate the phenotypic changes of mature corneal epithelial cells (MCECs) that cocultured with limbal niche cells (LNCs) in three-dimensional Matrigel (3D Matrigel) in vitro.

METHODS: MCECs were isolated from central corneas, and limbal epithelial progenitor cells (LEPCs) were isolated from limbal segments with Dispase II. LNCs were isolated and cultured from limbal niche using the collagenase A digestion method and identified with PCK/VIM/CD90/CD105/SCF/PDGFRβ. MCECs were cultured on 3D Matrigel (50%, v/v) with or without LNCs for 10 days. Expression of CK12 and p63α and clone formation test were used to compare the progenitor phenotypic changes for MCECs before and after induction using LEPCs as control.

RESULTS: Homogeneous LNCs were isolated and identified as spindle shape and adherent to a plastic surface coated with 5% Matrigel. Double immunostaining of the fourth-passage LNCs was uniformly PCK-/VIM+/CD90+/CD105+/SCF+/PDGFRβ+. Reverse transcription and quantitative real-time polymerase chain reaction (RT-qPCR) revealed the decrease of PCK expression from the second passage and elevation of Vim, CD90, CD105, SCF, and PDGFRβ transcripts from the third passage, and the transcription level of Vim, CD90, CD105, SCF, and PDGFRβ was elevated statistically in the fourth passage compared to the first passage (P < 0.01). Both immunofluorescence (IF) staining for cross section and cytospin cells demonstrated that MCECs expressed higher CK12 while lower p63α than LEPCs (P < 0.01). Sphere growth formation was noticed as early as 24 hours in the MCEC + LNC group, 48 hours in the LEPC group, and 72 hours in the MCEC group. The diameters of the spheres were the biggest in the MCEC + LNC group (182.24 ± 57.91 µm), smaller in the LEPC group (125.71 ± 41.20 µm), and smallest in the MCEC group (109.39 ± 34.85 µm) by the end of the 10-day culture (P < 0.01). Double immunostaining with CK12/p63α showed that cells in the sphere formed from MCECs expressed CK12 but not p63α; in contrast, some cells in the MCEC + LNC group expressed CK12, but most of them expressed p63α. RT-qPCR revealed a significant reduction of CK12 transcript but elevation of p63α, Oct4, Nanog, Sox2, and SSEA4 (P < 0.05). Holoclone composed of cubic epithelial cells could be generated in the MCEC + LNC group but not in the other two groups.

CONCLUSIONS: The data shows that human MCEC cell phenotype could be induced to the dedifferentiation stage when cocultured with LNCs in 3D Matrigel that simulated the microenvironment of limbal stem cells in vitro.

PMID:35499835 | DOI:10.1167/iovs.63.5.1

JAMA Intern Med. 2022 May 2. doi: 10.1001/jamainternmed.2022.1449. Online ahead of print.

ABSTRACT

IMPORTANCE: Observational evidence suggests that higher physical activity is associated with slower kidney function decline; however, to our knowledge, no large trial has evaluated whether activity and exercise can ameliorate kidney function decline in older adults.

OBJECTIVE: To evaluate whether a moderate-intensity exercise intervention can affect the rate of estimated glomerular filtration rate per cystatin C (eGFRCysC) change in older adults.

DESIGN, SETTING, AND PARTICIPANTS: This ancillary analysis of the Lifestyle Interventions and Independence For Elders randomized clinical trial enrolled 1199 community-dwelling, sedentary adults aged 70 to 89 years with mobility limitations and available blood specimens. The original trial was conducted across 8 academic centers in the US from February 2010 through December 2013. Data for this study were analyzed from March 29, 2021, to February 28, 2022.

INTERVENTIONS: Structured, 2-year, partially supervised, moderate-intensity physical activity and exercise (strength, flexibility) intervention compared with a health education control intervention with 2-year follow-up. Physical activity was measured by step count and minutes of moderate-intensity activity using accelerometers.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in eGFRCysC. Rapid eGFRCysC decline was defined by the high tertile threshold of 6.7%/y.

RESULTS: Among the 1199 participants in the analysis, the mean (SD) age was 78.9 (5.2) years, and 800 (66.7%) were women. At baseline, the 2 groups were well balanced by age, comorbidity, and baseline eGFRCysC. The physical activity and exercise intervention resulted in statistically significantly lower decline in eGFRCysC over 2 years compared with the health education arm (mean difference, 0.96 mL/min/1.73 m2; 95% CI, 0.02-1.91 mL/min/1.73 m2) and lower odds of rapid eGFRCysC decline (odds ratio, 0.79; 95% CI, 0.65-0.97).

CONCLUSIONS AND RELEVANCE: Results of this ancillary analysis of a randomized clinical trial showed that when compared with health education, a physical activity and exercise intervention slowed the rate of decline in eGFRCysC among community-dwelling sedentary older adults. Clinicians should consider targeted recommendation of physical activity and moderate-intensity exercise for older adults as a treatment to slow decline in eGFRCysC.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01072500.

PMID:35499834 | DOI:10.1001/jamainternmed.2022.1449

JAMA Netw Open. 2022 May 2;5(5):e229712. doi: 10.1001/jamanetworkopen.2022.9712.

ABSTRACT

IMPORTANCE: The factors associated with the failure of nonoperative management of appendicitis and the differences in patient-reported outcomes between successful and unsuccessful nonoperative management remain unknown.

OBJECTIVES: To investigate factors associated with the failure of nonoperative management of appendicitis and compare patient-reported outcomes between patients whose treatment succeeded and those whose treatment failed.

DESIGN, SETTING, AND PARTICIPANTS: This study was a planned subgroup secondary analysis conducted in 10 children’s hospitals that included 370 children aged 7 to 17 years with uncomplicated appendicitis enrolled in a prospective, nonrandomized clinical trial between May 1, 2015, and October 31, 2018, with 1-year follow-up comparing nonoperative management with antibiotics vs surgery for uncomplicated appendicitis. Statistical analysis was performed from November 1, 2019, to February 12, 2022.

INTERVENTIONS: Nonoperative management with antibiotics vs surgery.

MAIN OUTCOMES AND MEASURES: Failure of nonoperative management and patient-reported outcomes. The relative risk (RR) of failure based on sociodemographic and clinical characteristics was calculated. Patient-reported outcomes were compared based on the success or failure of nonoperative management.

RESULTS: Of 370 patients (34.6% of 1068 total patients; 229 boys [61.9%]; median age, 12.3 years [IQR, 10.0-14.6 years]) enrolled in the nonoperative group, treatment failure occurred for 125 patients (33.8%) at 1 year, with 53 patients (14.3%) undergoing appendectomy during initial hospitalization and 72 patients (19.5%) experiencing delayed treatment failure after hospital discharge. Higher patient-reported pain at presentation was associated with increased risk of in-hospital treatment failure (RR, 2.1 [95% CI, 1.0-4.4]) but not delayed treatment failure (RR, 1.3 [95% CI, 0.7-2.3]) or overall treatment failure at 1 year (RR, 1.5 [95% CI, 1.0-2.2]). Pain duration greater than 24 hours was associated with decreased risk of delayed treatment failure (RR, 0.3 [95% CI, 0.1-1.0]) but not in-hospital treatment failure (RR, 1.2 [95% CI, 0.5-2.7]) or treatment failure at 1 year (RR, 0.7 [95% CI, 0.4-1.2]). There was no increased risk of treatment failure associated with age, white blood cell count, sex, race, ethnicity, primary language, insurance status, transfer status, symptoms at presentation, or imaging results. Health care satisfaction at 30 days and patient-reported, health-related quality of life at 30 days and 1 year were not different. Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs 27.0; difference, 1.0 [95% CI, 0.01-2.0]) and 1 year (28.1 vs 27.0; difference, 1.1 [95% CI, 0.2-2.0]).

CONCLUSIONS AND RELEVANCE: This analysis suggests that a higher pain level at presentation was associated with a higher risk of initial failure of nonoperative management and that a longer duration of pain was associated with lower risk of delayed treatment failure. Although satisfaction was high in both groups, satisfaction with the treatment decision was higher among patients with successful nonoperative management at 1 year.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02271932.

PMID:35499827 | DOI:10.1001/jamanetworkopen.2022.9712

Ann Surg Oncol. 2022 May 2. doi: 10.1245/s10434-022-11758-z. Online ahead of print.

ABSTRACT

BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes.

METHODS: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS).

RESULTS: For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND.

CONCLUSION: This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

PMID:35499783 | DOI:10.1245/s10434-022-11758-z