A practical guide to cross-cultural and multi-sited data collection in the biological and behavioural sciences.

Researchers in the biological and behavioural sciences are increasingly conducting collaborative, multi-sited projects to address how phenomena vary across ecologies. These types of projects, however, pose additional workflow challenges beyond those typically encountered in single-sited projects. Through specific attention to cross-cultural research projects, we highlight four key aspects of multi-sited projects that must be considered during the design phase to ensure success: (1) project and team management; (2) protocol and instrument development; (3) data management and documentation; and (4) equitable and collaborative practices. Our recommendations are supported by examples from our experiences collaborating on the Evolutionary Demography of Religion project, a mixed-methods project collecting data across five countries in collaboration with research partners in each host country. To existing discourse, we contribute new recommendations around team and project management, introduce practical recommendations for exploring the validity of instruments through qualitative techniques during piloting, highlight the importance of good documentation at all steps of the project, and demonstrate how data management workflows can be strengthened through open science practices. While this project was rooted in cross-cultural human behavioural ecology and evolutionary anthropology, lessons learned from this project are applicable to multi-sited research across the biological and behavioural sciences.

Constructing Causal Life-Course Models: Comparative Study of Data-Driven and Theory-Driven Approaches.

Life-course epidemiology relies on specifying complex (causal) models that describe how variables interplay over time. Traditionally, such models have been constructed by perusing existing theory and previous studies. By comparing data-driven and theory-driven models, we investigated whether data-driven causal discovery algorithms can help in this process. We focused on a longitudinal data set on a cohort of Danish men (the Metropolit Study, 1953-2017). The theory-driven models were constructed by 2 subject-field experts. The data-driven models were constructed by use of the temporal Peter-Clark (TPC) algorithm. The TPC algorithm utilizes the temporal information embedded in life-course data. We found that the data-driven models recovered some, but not all, causal relationships included in the theory-driven expert models. The data-driven method was especially good at identifying direct causal relationships that the experts had high confidence in. Moreover, in a post hoc assessment, we found that most of the direct causal relationships proposed by the data-driven model but not included in the theory-driven model were plausible. Thus, the data-driven model may propose additional meaningful causal hypotheses that are new or have been overlooked by the experts. In conclusion, data-driven methods can aid causal model construction in life-course epidemiology, and combining both data-driven and theory-driven methods can lead to even stronger models.

Training programmes for healthcare professionals in managing postoperative epidural analgesia: A scoping review protocol.

BACKGROUND: Epidural analgesia is an effective technique advocated worldwide for postoperative analgesia after a wide range of surgical procedures. Despite the benefits of epidural analgesia for pain management, systematic education of ward nurses in managing epidural analgesia appears to be lacking. METHODS: The aim of the proposed scoping review is to map the body of evidence and identify training programmes for healthcare professionals in the safe management of postoperative epidural analgesia. The methodology will follow the Preferred Reporting Items for Systematic and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). In addition, the five main steps set forth by Arksey and O'Malley and refined by Levac for guidance of the process will be used. The scoping review will include any study design of any date, design, setting and duration. RESULTS: We will present results descriptively, accompanied with visual presentations as tables and graphs. CONCLUSION: The outlined scoping review will provide an overview of existing training programmes for healthcare professionals in the safe management of postoperative epidural analgesia and map the body of available evidence on the topic. The study may support the development of a training programme for ward nurses caring for patients receiving postoperative epidural analgesia.

Racial/Ethnic Disparities Impact the Real-World Effectiveness of a Multicomponent Maternal Smoking Cessation Program: Findings from the CTTP Cohort.

INTRODUCTION: Smoking during pregnancy adversely affects perinatal outcomes for both women and infants. We conducted a retrospective cohort study of the state-funded Comprehensive Tobacco Treatment Program (CTTP) - the largest maternal tobacco cessation program in San Bernardino County, California - to determine the real-world program effectiveness and to identify variables that can potentially improve effectiveness. METHODS: During 2012-2019, women who smoked during pregnancy were enrolled in CTTP's multicomponent behavioral smoking cessation program that implemented components of known efficacy (i.e., incentives, biomarker testing, feedback, and motivational interviewing). RESULTS: We found that 40.1% achieved prolonged abstinence by achieving weekly, cotinine-verified, 7-day abstinence during 6 to 8 weeks of enrollment. Using intention-to-treat analyses, we computed that the self-reported point prevalence abstinence rate (PPA) at the six-month telephone follow-up was 36.7%. Cohort members achieving prolonged abstinence during the CTTP were five times more likely to achieve PPA six months after CTTP. Several non-Hispanic ethnicities (Black, Native American, White, or More than one ethnicity) in the cohort were two-fold less likely (relative to Hispanics) to achieve prolonged abstinence during CTTP or PPA at six months after CTTP. This disparity was further investigated in mediation analysis. Variables such as quitting during the first trimester and smoking fewer cigarettes at enrollment were also associated with achieving PPA at six months. DISCUSSION: Racial/ethnic health disparities that have long been linked to a higher rate of maternal smoking persist even when the pregnant smoker enrolls in a smoking cessation program.

Patients in high- and low-revision hospitals have similar outcomes after primary knee arthroplasty: 1-year postoperative results from the Danish prospective multicenter cohort study, SPARK.

PURPOSE: It is well-known that revision rates after primary knee arthroplasty vary widely. However, it is uncertain whether hospital revision rates are reliable indicators of general surgical quality as defined by patients. The SPARK study compared primary knee arthroplasty surgery at three high-volume hospitals whose revision rates differed for unknown reasons. METHODS: This prospective observational study included primary knee arthroplasty patients (total, medial/lateral unicompartmental and patellofemoral) in two low-revision hospitals (Aarhus University Hospital and Aalborg University Hospital Farsø) and one high-revision hospital (Copenhagen University Hospital Herlev-Gentofte). Patients were followed from preoperatively (2016-17) to 1-year postoperatively with patient-reported outcome measures including Oxford Knee Score (OKS), EQ-5D-5L and Copenhagen Knee ROM (range of motion) Scale. The surgical outcomes were compared across hospitals for patients with comparable grades of radiographic knee osteoarthritis and preoperative OKS. Statistical comparisons (parametric and non-parametric) included all three hospitals. RESULTS: 97% of the 1452 patients who provided baseline data (89% of those included and 56% of those operated) responded postoperatively (90% at 1 year). Hospitals' utilization of unicompartmental knee arthroplasties differed (Aarhus 49%, Aalborg 14%, and Copenhagen 22%, p < 0.001). 28 patients had revision surgery during the first year (hospital independent, p = 0.1) and were subsequently excluded. 1-year OKS (39 ± 7) was independent of hospital (p = 0.1), even when adjusted for age, sex, Body Mass Index, baseline OKS and osteoarthritis grading. 15% of patients improved less than Minimal Important Change (8 OKS) (Aarhus 19%, Aalborg 13% and Copenhagen 14%, p = 0.051 unadjusted). Patients with comparable preoperative OKS or osteoarthritis grading had similar 1-year results across hospitals (OKS and willingness to repeat surgery, p ≥ 0.087) except for the 64 patients with Kellgren-Lawrence grade-4 (Aarhus 4-6 OKS points lower). 86% of patients were satisfied, and 92% were "willing to repeat surgery", independent of hospital (p ≥ 0.1). Hospital revision rates differences diminished during the study period. CONCLUSIONS: Patients in hospitals with a history of differing revision rates had comparable patient-reported outcomes 1 year after primary knee arthroplasty, supporting that surgical quality should not be evaluated by revision rates alone. Future studies should explore if revision rate variations may depend as much on revision thresholds and indications as on outcomes of primary surgery. LEVEL OF EVIDENCE: Level II (Prospective cohort study).

Hospital variation in revision rates after primary knee arthroplasty was not explained by patient selection: baseline data from 1452 patients in the Danish prospective multicenter cohort study, SPARK.

PURPOSE: Revision rates following primary knee arthroplasty vary by country, region and hospital. The SPARK study was initiated to compare primary surgery across three Danish regions with consistently different revision rates. The present study investigated whether the variations were associated with differences in the primary patient selection. METHODS: A prospective observational cohort study included patients scheduled Sep 2016 Dec 2017 for primary knee arthroplasty (total, medial/lateral unicompartmental or patellofemoral) at three high-volume hospitals, representing regions with 2-year cumulative revision rates of 1, 2 and 5%, respectively. Hospitals were compared with respects to patient demographics, preoperative patient-reported outcome measures, motivations for surgery, implant selection, radiological osteoarthritis and the regional incidence of primary surgery. Statistical tests (parametric and non-parametric) comprised all three hospitals. RESULTS: Baseline data was provided by 1452 patients (89% of included patients, 56% of available patients). Patients in Copenhagen (Herlev-Gentofte Hospital, high-revision) were older (68.6 ± 9 years) than those in low-revision hospitals (Aarhus 66.6 ± 10 y. and Aalborg (Farsø) 67.3 ± 9 y., p = 0.002). In Aalborg, patients who had higher Body Mass Index (mean 30.2 kg/m2 versus 28.2 (Aarhus) and 28.7 kg/m2 (Copenhagen), p < 0.001), were more likely to be male (56% versus 45 and 43%, respectively, p = 0.002), and exhibited fewer anxiety and depression symptoms (EQ-5D-5L) (24% versus 34 and 38%, p = 0.01). The preoperative Oxford Knee Score (23.3 ± 7), UCLA Activity Scale (4.7 ± 2), range of motion (Copenhagen Knee ROM Scale) and patient motivations were comparable across hospitals but varied with implant type. Radiological classification ≥ 2 was observed in 94% (Kellgren-Lawrence) and 67% (Ahlbäck) and was more frequent in Aarhus (low-revision) (p ≤ 0.02), where unicompartmental implants were utilized most (49% versus 14 (Aalborg) and 23% (Copenhagen), p < 0.001). In the Capital Region (Copenhagen), the incidence of surgery was 15-28% higher (p < 0.001). CONCLUSION: Patient-reported outcome measures prior to primary knee arthroplasty were comparable across hospitals with differing revision rates. While radiographic classifications and surgical incidence indicated higher thresholds for primary surgery in one low-revision hospital, most variations in patient and implant selection were contrary to well-known revision risk factors, suggesting that patient selection differences alone were unlikely to be responsible for the observed variation in revision rates across Danish hospitals. LEVEL OF EVIDENCE: II, Prospective cohort study.

Implementation and Outcomes of a Maternal Smoking Cessation Program for a Multi-ethnic Cohort in California, USA, 2012-2019.

Smoking during pregnancy remains one of the most significant risk factors for poor birth outcomes. During 2012-2019, the Loma Linda University Health Comprehensive Tobacco Treatment Program (CTTP) used a multicomponent behavioral intervention for tobacco cessation for 1402 pregnant smokers with components of known efficacy (i.e., incentives, biomarker testing, feedback, and motivational interviewing). The CTTP cohort includes a multi-ethnic sample of pregnant women with a mean age of 27 years referred by collaborating community-based healthcare providers in San Bernardino county. Evaluation of program outcomes from 7 years of follow-up (2012-2019) creates a rich cohort dataset for implementation science research to examine the real-world effectiveness of the program. In this report, we provide a cohort profile, and 8-week prolonged abstinence (8-week PA) and relapse findings from the first year of follow-up (n = 233). We found: (1) 28.4% achieved 8-week PA, (2) At a median of 6.2 months of follow-up after achieving 8-week PA, 23.2% of enrolled subjects reported tobacco cessation, and (3) a high rate of loss to follow-up (44%). In addition, our modeling indicated that the odds of relapse/smoking after enrollment was significantly higher in young mothers, non-Hispanic mothers (White, Black/African-American), mothers in the first and third trimester, and rural mothers. Formative quantitative and qualitative research on the CTTP cohort will consider the effects of a range of implementation science (number of intervention sessions, addition of a mHealth component, distance to care) and individual (partner/household smoking, birth outcomes, NICU) outcome measures for the purpose of scaling up the CTTP model.

Data-Driven Model Building for Life-Course Epidemiology.

Life-course epidemiology is useful for describing and analyzing complex etiological mechanisms for disease development, but existing statistical methods are essentially confirmatory, because they rely on a priori model specification. This limits the scope of causal inquiries that can be made, because these methods are suited mostly to examine well-known hypotheses that do not question our established view of health, which could lead to confirmation bias. We propose an exploratory alternative. Instead of specifying a life-course model prior to data analysis, our method infers the life-course model directly from the data. Our proposed method extends the well-known Peter-Clark (PC) algorithm (named after its authors) for causal discovery, and it facilitates including temporal information for inferring a model from observational data. The extended algorithm is called temporal PC. The obtained life-course model can afterward be perused for interesting causal hypotheses. Our method complements classical confirmatory methods and guides researchers in expanding their models in new directions. We showcase the method using a data set encompassing almost 3,000 Danish men followed from birth until age 65 years. Using this data set, we inferred life-course models for the role of socioeconomic and health-related factors on development of depression.

Dihydroazulene-Azobenzene-Dihydroazulene Triad Photoswitches.

Photoswitch triads comprising two dihydroazulene (DHA) units in conjugation with a central trans-azobenzene (AZB) unit were prepared in stepwise protocols starting from meta- and para-disubstituted azobenzenes. The para-connected triad had significantly altered optical properties and lacked the photoactivity of the separate photochromes. In contrast, for the meta-connected triad, all three photochromes could be photoisomerized to generate an isomer with two vinylheptafulvene (VHF) units and a cis-azobenzene unit. Ultrafast spectroscopy of the photoisomerizations revealed a fast DHA-to-VHF photoisomerization and a slower trans-to-cis AZB photoisomerization. This meta triad underwent thermal VHF-to-DHA back-conversion with a similar rate of all VHFs, independent of the identity of the neighboring units, and in parallel thermal cis-to-trans AZB conversion. The experimental observations were supported by computation (excitation spectra and orbital analysis of the transitions).

H2O2-induced cataract as a model of age-related cataract: Lessons learned from overexpressing the proteasome activator PA28αß in mouse eye lens.

Cataract, the world-leading cause of blindness, is formed when crystallin aggregates cloud the eye lens. We overexpressed PA28αß, a proteasome activator with properties protective against aggregation and oxidative stress, and examined whether they are less prone to develop cataract arisen from aging and/or hydrogen peroxide (H2O2) treatment. Another objective of this work was to compare the H2O2-induced cataracts of mouse lenses ex vivo to cataracts formed upon aging in mice. As part of an aging study of F2 hybrid C57BL/6NxBALB/c mice, ocular lenses of mature adult (7 months), middle-aged (15 months), and old (22 months of age) PA28αOE mice and their wildtype littermates (n = 22-44 lenses per group) were dissected and evaluated with regard to their cataractous state. In parallel, ocular lenses from 3 to 4 months old PA28αOE and wildtype C57BL/6 N littermates were treated with 100 µM H2O2 every 24 h for 7 days, with progression of cataract and physical appearance monitored daily. Lenses from both studies were also subjected to analysis of oxidative protein damage (carbonylation) and protein solubility. We found that overexpression of PA28αß had no effect on neither age-related nor H2O2-induced cataract and conclude that overexpression of PA28αß does not protect mice from developing cataract. The inefficiency of PA28αß against cataract could be due to its anti-aggregation activity being already excessively present in the eye lens, exerted by crystallins. Crystallins are likely also constituting the 20-25 kDa proteins that were the dominant carbonyl targets in the eye lens irrespective of cataractous state. Assessment of H2O2-induced cataract in relation to age-related cataract demonstrated that high molecular weight protein carbonylation correlates to cataract both in vivo and ex vivo, while reduced protein solubility is more pronounced in age-related cataract. Furthermore, this work highlights vast dissimilarities in the physical manifestations of cataract upon aging and H2O2 ex vivo treatment. Age-related cataract initiation can take various forms, as a vague general blurriness or as a barely visible demarcated opacity, while H2O2-induced cataractogenesis seems to follow a specific scheme. In mice, this scheme begins with relatively opaque peripheral areas emerging that clear up later on as the lenses start to display a hat-like appearance. This transformation takes place synchronous to swelling of the eye lens, and is likely a result of osmotic disturbances causing a phase separation between the viscous lens cortex and the more solid fibers of the lens nucleus.

Smoke-Free Home Intervention in Permanent Supportive Housing: A Multifaceted Intervention Pilot.

INTRODUCTION: Smoke-free homes (SFHs), the voluntary adoption of home smoking restrictions, are associated with reduced secondhand smoke exposure. However, SFHs are uncommon in permanent supportive housing (PSH) for formerly homeless adults, who have fivefold higher smoking rates than the general population. We pilot-tested a brief intervention to increase voluntary adoption of SFHs among PSH residents in the San Francisco Bay Area. AIMS AND METHODS: We pilot-tested a brief intervention to increase voluntary adoption of SFHs among PSH residents in the San Francisco Bay Area. Rest of the methods, PSH residents (n = 100) and staff (n = 62) from 15 PSH sites participated in the intervention between October 2017 and February 2018. Research staff provided counseling to PSH residents on how to adopt an SFH and trained PSH staff on how to counsel residents on smoking cessation. The primary outcome was self-reported voluntary adoption of an SFH for ≥90 days, and the secondary outcome was carbon monoxide-verified PPA at 6-month follow-up. PSH staff completed the Smoking Knowledge, Attitudes, and Practices survey at baseline and 3-month follow-up. RESULTS: At 6 months, 31.3% of PSH residents had adopted an SFH (vs. 13.0% at baseline) and 16.9% reported carbon monoxide-verified PPA. A positive attitude toward an SFH policy was associated with increased odds of SFH adoption (adjusted odds ratio = 8.68, 95% confidence interval: 2.42, 31.17). Voluntary SFH adoption was associated with increased PPA (adjusted odds ratio = 26.27, 95% confidence interval: 3.43, 201.30). PSH staff reported improved attitudes toward and self-efficacy in delivering cessation care, and decreased barriers to discussing smoking cessation among PSH residents between baseline and 3-month follow-up. CONCLUSIONS: In this single-arm study, a brief intervention increased SFH adoption and PPA among PSH residents. IMPLICATIONS: To date, few interventions have addressed SFHs and their association with tobacco use among PSH residents. A "ground-up" approach that relies on buy-in from residents and that promotes voluntary SFHs is an innovative way to increase smoke-free living environments in PSH. This approach could pave a pathway for smoke-free policy implementation in these sites. PSH can play a role in reducing the burden of tobacco use by empowering its residents to adopt voluntary SFHs, which could increase smoking cessation among residents.

Measurement properties of UCLA Activity Scale for hip and knee arthroplasty patients and translation and cultural adaptation into Danish.

Background and purpose - The UCLA Activity Scale (UCLA) is a questionnaire assessing physical activity level from 1 (low) to 10 (high) in patients undergoing hip or knee arthroplasty (HA/KA). After translation and cultural adaptation, we evaluated the measurement properties of the Danish UCLA.Patients and methods - After dual panel translation, cognitive interviews were performed among 55 HA/KA patients. An orthopedic surgeon and a physiotherapist estimated UCLA scores for 80 KA patients based on short interviews. Measurement properties were evaluated in 130 HA and 134 KA patients preoperatively and 1-year postoperatively.Results - To suit Danish patients of today, several adaptations were required. Prior to interviews, 4 patients were excluded, and 11 misinterpreted the answer options. Examiners rated the remaining 65 patients (mean age 67 years) 0.2-1.6 UCLA levels lower than patients themselves. The 130 HA and 134 KA patients (mean age 71/68 years) changed from 4.3 (SD 1.9)/4.5 (1.8) preoperatively to 6.6 (1.8)/6.2 (1.0) at 1-year follow-up. 103 (79%) HA and 89 (66%) KA patients reported increased activity. Effect sizes were large (1.2/0.96). Knee patients reaching minimal important change (MIC, ≥ 8 Oxford Knee Score points) had higher 1-year UCLA scores than patients not reaching MIC.Interpretation - Original scale development was undocumented. Content validity was questionable, and there was discrepancy between patient and examiner estimates. UCLA appears valuable for measuring change in self-reported physical activity on a group level. 4 out of 5 HA patients and 2 out of 3 KA patients were more physically active 1 year after joint replacement surgery.

Demographic Shifts, Case Mix, Activity, and Outcome for Elderly Patients Admitted to Adult General ICUs in England, Wales, and Northern Ireland.

OBJECTIVES: Major increases in the proportion of elderly people in the population are predicted worldwide. These population increases, along with improving therapeutic options and more aggressive treatment of elderly patients, will have major impact on the future need for healthcare resources, including critical care. Our objectives were to explore the trends in admissions, resource use, and risk-adjusted hospital mortality for older patients, admitted over a 20-year period between 1997 and 2016 to adult general ICUs in England, Wales, and Northern Ireland. DESIGN: RETROSPECTIVE ANALYSIS OF NATIONAL CLINICAL AUDIT DATABASE. SETTING: The Intensive Care National Audit & Research Centre Case Mix Programme Database, the national clinical audit for adult general ICUs in England, Wales, and Northern Ireland. PATIENTS: All adult patients 16 years old or older admitted to adult general ICUs contributing data to the Case Mix Programme Database between January 1, 1997, and December 31, 2016. MEASUREMENTS AND MAIN RESULTS: The annual number, trends, and outcomes for patients across four age bands (16-64, 65-74, 75-84, and 85+ yr) admitted to ICUs contributing to the Case Mix Programme Database from 1997 to 2016 were examined. Case mix, activity, and outcome were described in detail for the most recent cohort of patients admitted in 2015-2016. Between 1997 to 2016, the annual number of admissions to ICU of patients in the older age bands increased disproportionately, with increases that could not be explained solely by general U.K. demographic shifts. The risk-adjusted acute hospital mortality decreased significantly within each age band over the 20-year period of the study. Although acute severity at ICU admission was comparable with that of the younger age group, apart from cardiovascular and renal dysfunction, older patients received less organ support. Older patients stayed longer in hospital post-ICU discharge, and hospital mortality increased with age, but the majority of patients surviving to hospital discharge returned home. CONCLUSIONS: Over the past two decades, elderly patients have been more commonly admitted to ICU than can be explained solely by the demographic shift. Importantly, as with the wider population, outcomes in elderly patients admitted to ICU are improving over time, with most patients returning home.

What Is the Causal Interpretation of Sibling Comparison Designs?

Sibling comparison designs have long been used to assess causal effects of exposures for which randomized studies are impossible and measurement of all relevant confounding is unobtainable. The idea is to utilize the fact that siblings often share a lot of unobserved variables. Therefore, it is proposed that in certain cases, comparing siblings is equivalent to comparing exchangeable individuals, which is the foundation for causal inference based on randomized controlled trials (RCTs). However, this intuition-and the publication of highly important sibling studies-vastly predate modern causal inference theory. Full causal descriptions of sibling comparison designs are essentially nonexistent, and therefore it is not clear exactly how or if we can interpret their estimated effects as causal. We fill this theoretical gap by proposing a counterfactual-based framework for sibling comparison designs. Moreover, we employ this framework to derive precise causal interpretations for three commonly used sibling model estimators stemming from fixed-effects ordinary least squares (OLS), conditional logistic regression, and stratified Cox regression. We establish that, for the latter two, the obtained effect parameter describes a causal effect on the full sibling group, not the individuals, and thus it does not correspond to the prevailing intuition from the RCT analogue. For fixed-effects OLS estimation, the parameter describes a causal effect on an individual, but may depend on an intervention on the whole sibling group. OLS estimation thus results in an estimator that can be given a simple causal interpretation that is similar, but not equal to, the RCT parallel. See video abstract at, http://links.lww.com/EDE/B618.

Multi-Photochromic Molecules Based on Dihydroazulene Units.

Multi-photochromic systems incorporating individually addressable switching units are attractive for development of advanced data storage devices. Here, we present the synthesis and properties of a selection of such molecular systems incorporating the dihydroazulene/vinylheptafulvene (DHA/VHF) photo-/thermoswitch. The influence of the linker (meta-phenylene vs. azulene-1,3-diyl vs. thiophene-2,5-diyl) separating two DHA units on the switching properties was investigated. An azulene-1,3-diyl spacer largely inhibited both the DHA-to-VHF photoisomerizations and the thermal VHF-to-DHA back-reactions; the latter occurred ten times slower than for the related compound with a meta-phenylene spacer. A DHA trimer containing three DHA units around a central benzene ring was found to undergo stepwise DHA-to-VHF photoisomerizations, whereas the thermal back-reactions occurred at similar rates for the three VHF entities. A meta-phenylene-bridged DHA dimer was subjected to further structural modifications at position C-1 of each DHA, having strong implications for the switching events, and synthetic steps for further functionalizations at position C-7 of each DHA were investigated. Finally, the molecular structure (from X-ray crystallographic analysis) between the meta-phenylene-bridged DHA dimer and CuI is presented.

Establishing linear-free-energy relationships for the quadricyclane-to-norbornadiene reaction.

The kinetics of the thermal quadricyclane-to-norbornadiene (QC-to-NBD) isomerization reaction was studied for a large selection of derivatives where the one NBD double bond contains a cyano and aryl substituent of either electron-withdrawing or -donating character. While the kinetics data did not satisfy a linear-free-energy-relationship for all the derivatives based on Hammett σ values, we found individual linear relationships for derivatives containing either electron-withdrawing or electron-donating para substituents on the aryl group; with the most electron-witdrawing substituent in the one series and with the most electron-donating substituent in the other providing the fastest reaction (corresponding to opposite slopes of the Hammett plots). All data were well described, however, by a linear relationship when using Creary radical values; the correlation could be slightly improved by using a combination of σ and values (used in ratio of 0.104 : 1). The results imply a combination of polar and free radical effects for the isomerization reaction of this specific class of derivatives, with the latter playing the most significant role. The NBD derivatives were prepared by Diels-Alder cycloaddition reactions between cyclopentadiene and 3-arylpropiolonitriles, and in the case of bromophenyl derivatives further cyanation and Sonogashira coupling reactions were performed.

Developing Tobacco Control Interventions in Permanent Supportive Housing for Formerly Homeless Adults.

Smoke-free policies are effective population-based strategies to reduce tobacco use yet are uncommon in permanent supportive housing (PSH) for formerly homeless individuals who have high rates of smoking. In this study, we partnered with six supportive housing agencies in the San Francisco Bay Area to examine the implementation of smoke-free policies and cessation services. We administered a questionnaire and conducted in-depth, semistructured interviews with agency directors (n = 6), property management staff (n = 23), and services staff (n = 24) from 23 PSH sites on the barriers to implementing tobacco control interventions. All properties restricted smoking in indoor shared areas, but only two had policies restricting smoking in living areas. While there was staff consensus that smoke-free policies were important to reduce tobacco-related harm, participants disagreed on whether smoke-free policies were aligned with PSH's harm reduction framework. Residents' comorbid mental illness and substance use and the lack of appropriate enforcement tools were barriers to implementation. Using these formative findings, we present a framework for a toolkit of strategies to increase implementation of smoke-free policies and cessation interventions in PSH. Successful implementation of indoor smoke-free policies in PSH will require concurrent cessation services to support smoking cessation efforts and address the mental health and substance use needs of residents.

Does intraoperative contamination during primary knee arthroplasty affect patient-reported outcomes for patients who are uninfected 1 year after surgery? A prospective cohort study of 714 patients.

Background and purpose - It is well recognized that some knee arthroplasty (KA) patients present with prolonged postoperative inflammation and some develop persistent pain. It can reasonably be speculated that some of these problems develop because of low-grade infections with low virulence bacteria caused by intraoperative contamination. This prospective study was performed to investigate whether intraoperative contamination results in lower patient-reported outcomes (PRO) for patients who were clinically uninfected in the first year after surgery. Patients and methods - We combined data from 2 major prospective studies on patients undergoing primary KA at 2 Danish hospitals between September 2016 and January 2018. Pre- and postoperative (1.5, 3, 6, and 12 months) PROs and intraoperative microbiological cultures were obtained on a total of 714 patients who were included in the study. Based on the microbiological cultures, the patients were divided into 2 groups, contaminated and non-contaminated, and differences in PROs between the 2 groups were analyzed. Results - 84 of 714 (12%) patients were intraoperatively contaminated; none of the 714 patients developed clinical infection. The preoperative Oxford Knee Score was 24 and 23 for contaminated and non-contaminated patients, respectively, improving to 40 and 39 at 1 year (p = 0.8). 1-year AUC for Oxford Knee Score and absolute improvement at each postoperative time point for Forgotten Joint Score and EQ-5D-5L also were similar between contaminated and non-contaminated patients. Interpretation - Patient-reported outcomes from 714 patients do not indicate that intraoperative contamination affects the knee-specific or general health-related quality of life in primary KA patients who are clinically uninfected 1 year after surgery.

Gas-Phase Ion Fluorescence Spectroscopy of Tailor-made Rhodamine Homo- and Heterodyads: Quenching of Electronic Communication by π-Conjugated Linkers.

While many key photophysical features are understood for electronic communication between chromophores in neutral compounds, there is limited information on the effect of charges in practically relevant ionic chromo/fluorophores. Here we have chosen positively charged rhodamines and prepared a selection of homo- and heterodimers with alkyl or π-conjugated, acetylenic bridges. Protonated molecules were transferred as isolated ions to gas phase where there is no solvent screening of charges, and fluorescence spectra were measured with a custom-made ion-trap setup. Our work reveals strong polarization of the π-spacer (induced dipole/quadrupole) when it experiences the electric field from one/ two dyes. Hence, π-spacers provide efficient shielding of charges by reducing the Coulomb interaction, whereas two dye cations polarize each other when connected by an alkyl. The screening influences the Förster resonance energy transfer efficiency that relies on the dipole-dipole interaction.