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Using the dual-pathway framework (Beach et al., 2022a), we tested a Neuro-immune Network (NIN) hypothesis: i.e., that chronically elevated inflammatory processes may have delayed (i.e., incubation) effects on young adult substance use, leading to negative health outcomes. In a sample of 449 participants in the Family and Community Health Study who were followed from age 10 to age 29, we examined a non-self-report index of young adult elevated alcohol consumption (EAC). By controlling self-reported substance use at the transition to adulthood, we were able to isolate a significant delayed (incubation) effect from childhood exposure to danger to EAC (β = −.157, p = .006), which contributed to significantly worse aging outomes. Indirect effects from danger to aging outcomes via EAC were: GrimAge (IE = .010, [.002, .024]), Cardiac Risk (IE = −.004, [−.011, −.001]), DunedinPACE (IE = .002, [.000, .008]). In exploratory analyses we examined potential sex differences in effects, showing slightly stronger incubation effects for men and slightly stronger effects of EAC on aging outcomes for women. Results support the NIN hypothesis that incubation of immune pathway effects contributes to elevated alcohol consumption in young adulthood, resulting in accelerated aging and elevated cardiac risk outcomes via health behavior.
Despite the increased awareness and action towards Equality, Diversity and Inclusion (EDI), the glaciological community still experiences and perpetuates examples of exclusionary and discriminatory behavior. We here discuss the challenges and visions from a group predominantly composed of early-career researchers from the 2023 edition of the Karthaus Summer School on Ice Sheets and Glaciers in the Climate System. This paper presents the results of an EDI-focused workshop that the 36 students and 12 lecturers who attended the summer school actively participated in. We identify common threads from participant responses and distill them into collective visions for the future of the glaciological research community, built on actionable steps toward change. In this paper, we address the following questions that guided the workshop: What do we see as current EDI challenges in the glaciology research community and which improvements would we like to see in the next fifty years? Contributions have been sorted into three main challenges we want and need to face: making glaciology (1) more accessible, (2) more equitable and (3) more responsible.
Epilepsy is a relatively common condition that affects approximately 4–5 per 1000 individuals in Ontario, Canada. While genetic testing is now prevalent in diagnostic and therapeutic care plans, optimal test selection and interpretation of results in a patient-specific context can be inconsistent and provider dependent.
Methods:
The first of its kind, the Ontario Epilepsy Genetic Testing Program (OEGTP) was launched in 2020 to develop clinical testing criteria, curate gene content, standardize the technical testing criteria through a centralized testing laboratory, assess diagnostic yield and clinical utility and increase genetics literacy among providers.
Results:
Here we present the results of the first two years of the program, demonstrating the overall 20.8% diagnostic yield including pathogenic sequence and copy number variation detected by next-generation sequencing panels. Routine follow-up testing of family members enabled the resolution of ambiguous findings. Post-test outcomes were collected as reported by the ordering clinicians, highlighting the clinical benefits of genetic testing.
Conclusion:
This programmatic approach to genetic testing in epilepsy by OEGTP, together with engagement of clinical and laboratory stakeholders, provided a unique opportunity to gather insight into province-wide implementation of a genetic testing program.
Psychologists and psychological research have shaped sleep and circadian science for over a century. Yet, psychology has not fully embraced sleep as a core area of inquiry, and sleep medicine has not distinctly acknowledged the foundational role psychology plays in understanding sleep and circadian rhythms. This Question Paper invites submissions exploring psychology’s profound impact on the study, measurement and intervention strategies in sleep and circadian science, as well as reciprocal influences. Manuscripts may include historiographies of key contributors, laboratory milestones, theoretical advancements and methodological innovations within a historical context. We aim to capture the full scope of sleep psychology from its origins to a vision of its future.
Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.
Aims
To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.
Method
The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).
Results
In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).
Conclusion
Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.
Insomnia’s impact on psychological functioning is known to increase suicide risk. The underlying mechanisms of this association are unclear. This study explored psychological factors including depression, emotion dysregulation, perceived burdensomeness and thwarted belongingness as possible mechanisms in the association between insomnia and suicidal ideation in a nationally representative sample for age, sex and race in the United States. Participants (N = 428) completed a Qualtrics survey of demographics, Insomnia Severity Index, Difficulties in Emotion Regulation Scale, Interpersonal Needs Questionnaire, Frequency of Suicidal Ideation Inventory and PROMIS-Depression and PROMIS-Anxiety short forms. Regression analyses and structural equation modeling were used. Insomnia severity was associated with greater suicidality (p < 0.001, CI = 0.19–0.31). When accounting for depression severity, emotion dysregulation and perceived burdensomeness fully mediated insomnia–suicidal ideation frequency association (β = 0.04, p = 0.045; β = 0.24, p < 0.001). Insomnia has major implications on psychological functioning, which may serve as mechanisms through which insomnia confers risk for suicidality. Our model posits that insomnia prevents regional sleep restoration in brain regions involved in psychological functioning, thereby conferring risk for suicidality. Insomnia may be an ideal upstream target for reducing suicidality and its risk factors, including depression, emotion dysregulation and perceived burdensomeness.
Post-procedural antimicrobial prophylaxis is not recommended by professional guidelines but is commonly prescribed. We sought to reduce use of post-procedural antimicrobials after common endoscopic urologic procedures.
Design:
A before-after, quasi-experimental trial with a baseline (July 2020–June 2022), an implementation (July 2022), and an intervention period (August 2022–July 2023).
Setting:
Three participating medical centers.
Intervention:
We assessed the effect of a bundled intervention on excess post-procedural antimicrobial use (ie, antimicrobial use on post-procedural day 1) after three types of endoscopic urologic procedures: ureteroscopy and transurethral resection of bladder tumor or prostate. The intervention consisted of education, local champion(s), and audit-and-feedback of data on the frequency of post-procedural antimicrobial-prescribing.
Results:
1,272 procedures were performed across all 3 sites at baseline compared to 525 during the intervention period; 644 (50.6%) patients received excess post-procedural antimicrobials during the baseline period compared to 216 (41.1%) during the intervention period. There was no change in the use of post-procedural antimicrobials at sites 1 and 2 between the baseline and intervention periods. At site 3, the odds of prescribing a post-procedural antimicrobial significantly decreased during the intervention period relative to the baseline time trend (0.09; 95% CI 0.02–0.45). There was no significant increase in post-procedural unplanned visits at any of the sites.
Conclusions:
Implementation of a bundled intervention was associated with reduced post-procedural antimicrobial use at one of three sites, with no increase in complications. These findings demonstrate both the safety and challenge of guideline implementation for optimal perioperative antimicrobial prophylaxis.
This trial was registered on clinicaltrials.gov, NCT04196777.
The U.S. Centers for Disease Control and Prevention encourages nurses to evaluate penicillin allergies as part of hospital-based antibiotic stewardship programs. We evaluated the feasibility of an implementation strategy to improve nurses’ comprehensive documentation of penicillin allergies. We defined feasibility as the uptake and acceptability of documentation procedures.
Outpatient surgical areas of an academic medical center located in the U.S.
Intervention:
The implementation strategy was guided by the Capability, Opportunity, Motivation Model for Behavior Change and included, building an interdisciplinary coalition to iteratively evaluate the implementation effort, educational meetings with surgical prescribers and perioperative nurses, the development and distribution of educational pocket cards, and structured communication messages in the electronic medical record.
Results:
A total of 426 patients with 487 penicillin allergy records (216 records pre-implementation period, 271 records post-implementation period) were analyzed. Penicillin allergy documentation contained the following information in the pre- versus post-implementation period: symptoms of the reaction (87% vs 87%), timing/years since reaction (8% vs 26%), onset of reaction in relation to taking penicillin (0% vs 21%), how symptoms resolved (0% vs 21%), and penicillin re-exposure (3% vs 21%). Focus groups revealed nurses perceived documentation procedures as highly acceptable. Major drivers of acceptability included the perceived effectiveness of a detailed allergy history and self-efficacy in conducting a detailed allergy history.
Conclusions:
Nurses perceived the comprehensive documentation of penicillin allergy history intervention as acceptable, and uptake improved following a theory-informed implementation strategy. We offer implementation strategy components to facilitate nurses’ engagement in penicillin allergy evaluation.
This Element outlines the origins and evolution of an international award-winning development intervention, index-based livestock insurance (IBLI), which scaled from a small pilot project in Kenya to a design that underpins drought risk management products and policies across Africa. General insights are provided on i) the economics of poverty, risk management, and drylands development; ii) the evolving use of modern remote sensing and data science tools in development; iii) the science of scaling; and iv) the value and challenges of integrating research with operational implementation to tackle development and humanitarian challenges in some of the world's poorest regions. This title is also available as Open Access on Cambridge Core.
Fructose-containing sugars can exaggerate postprandial lipaemia and stimulate hepatic de novo lipogenesis (DNL) when compared to glucose-based carbohydrates(1). Galactose has recently been shown to increase postprandial lipaemia compared to glucose(2), but mechanisms remain uncharacterised. The aim of this study was to assess the effect and mechanisms of lactose-induced lipaemia.
Twenty-four non-obese adults (12 male and 12 female) completed three trials in a randomised, crossover design (28 ± 7-day washout). During trials, participants consumed test drinks containing 50 g fat with 100 g of carbohydrate. The control carbohydrate was a glucose polymer (maltodextrin), the experimental carbohydrate was galactose-containing carbohydrate (lactose) and the active comparator was fructose-containing carbohydrate (sucrose). Hepatic DNL was assessed by the 2H2O method and [U-13C]-palmitate was added to the test drink to trace the fate of the ingested fat. Blood and breath samples were taken to determine plasma metabolite and hormone concentrations, in addition to plasma and breath 2H and 13C enrichments. Data were converted into incremental under the curve (iAUC) and were checked for normality by visual inspection of residuals. Differences between trials were assessed by one-way ANOVA. Where a main effect of trial was detected, post- hoc t-tests were performed to determine which trials differed from lactose according to the principle of closed-loop testing.
The plasma triacylglycerol iAUC (mean ± SD) in response to maltodextrin was 51 ± 68 mmol/L*360 min. Following lactose ingestion, plasma triacylglycerol iAUC increased to 98 ± 88 mmol/L*360 min (p<0.001 vs maltodextrin), which was comparable to sucrose [90 ± 95 mmol/L*360 min (p=0.41 vs lactose)]. Hepatic DNL in response to maltodextrin was 6.6 ± 3.0%. Following ingestion of lactose, hepatic DNL increased to 12.4 ± 6.9% (p=0.02 vs maltodextrin), which was comparable to sucrose [12.2 ± 6.9% (p=0.96 vs lactose)]. Exhaled 13CO2 in response to maltodextrin was 10.4 ± 4.1 mmol/kgFFM*360 min. Following ingestion of lactose, exhaled 13CO2 was 8.8 ± 4.9 mmol/kgFFM*360 min (p=0.09 vs maltodextrin), which was lower than sucrose [11.1 ± 3.9 mmol/kgFFM*360 min (p=0.01 vs lactose)].
These data are consistent with the hypothesis that hepatic de novo lipogenesis contributes to both lactose and sucrose-induced lipaemia and provide a rationale to investigate the longer-term effects of lactose and sucrose on metabolism.
For the Western Indian Ocean region, there is a significant knowledge gap regarding marine turtle nesting on the continental coast of East Africa. Here we present results from a long-term (2000–2020) community-based monitoring programme in and around Watamu Marine National Park, Kenya, covering 30 km of coastline (c. 6% of the national total). Conservation actions effectively protected nesting turtles and resulted in a near-total cessation of illegal egg harvesting in Watamu Marine National Park. Collected data indicate this is an important marine turtle nesting index site in Kenya and the wider region. Green turtle Chelonia mydas nests were most common (95%), followed by olive ridley turtles Lepidochelys olivacea (4%), with occasional nests of hawksbill Eretmochelys imbricata and leatherback turtles Dermochelys coriacea. Clutches per season increased significantly over the 20-year monitoring period for green turtles (50%) and showed a positive trend for olive ridley turtles. Watamu remains an area at risk from human pressures such as coastal development. Clutch distribution along the Watamu Marine National Park beach has shifted over time, probably because of coastal development and disturbance. Illegal take of adults and eggs continues in areas north and south of the Watamu Marine National Park, possibly slowing rates of recovery. Clutches deemed at risk were moved to a safe location within the National Park, and hatching success was high. Continued conservation efforts, including wider engagement with stakeholders to reduce human pressures, are needed to ensure the perpetuation of this nesting site.
Characterize antibiotic prescribing behaviors at an Indian palliative care center after the initiation of the Antibiotic Order Form (AOF): an antibiotic stewardship program involving a paper form to track antibiotic use and to provide prescription guidelines.
Design:
Retrospective chart review.
Setting:
Trivandrum Institute of Palliative Sciences (TIPS) is a palliative care organization in Kerala, India.
Methods:
Antibiotic prescription data and patient data were collected for adult patients treated at TIPS between January 1, 2017, and October 31, 2019. Descriptive statistics and a Zero-Inflated Poisson regression model were used to analyze antibiotic prescriptions. AOF completion and prescription concordance with institutional guidelines were also evaluated.
Results:
Out of 7,450 unique patients, 675 (9%) were prescribed 1,448 antibiotics. Age was the strongest factor in determining the number of antibiotic courses with each additional year of age decreasing the expected antibiotic prescription count by 2% per year. The most common antibiotics prescribed were topical metronidazole (44%) and penicillins (29%). Among patients who died, 5% were prescribed antibiotics within the final month of life. In total, 32% of antibiotic prescriptions were documented in AOFs, and 18% were concordant with all institutional antibiotic prescribing guidelines.
Conclusions:
This study is the first to analyze an antibiotic stewardship intervention in a palliative care setting within a low- and middle-income country. This retrospective study provides a benchmark of antibiotic use within Indian palliative care and highlights areas for future stewardship research including topical metronidazole use within palliative care and higher rates of antibiotic use among younger palliative care patients.
Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.
Aims
To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.
Method
This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.
Results
The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.
Conclusions
Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
We surveyed clinicians to evaluate the perceived usefulness of a mnemonic, STORY, to improve penicillin allergy evaluation. Survey responses indicated that the perceived usefulness of STORY was high, and support for nurses’ involvement in penicillin allergy assessment was high. Future research may evaluate the feasibility of STORY implementation in clinical care.
The Goethe Yearbook is a publication of the Goethe Society of North America, encouraging North American Goethe scholarship by publishing original English-language contributions to the understanding of Goethe and other authors of the Goethezeit while also welcoming contributions from scholars around the world. Volume 21 contains eleven articles, including contributions by leading scholars David Wellbery and Katharina Mommsen; innovative work on the reception of Goethe's works around 1900, on women writers, and on Goethe's contemporary Albrecht von Haller; theoretically sophisticated interpretations, including articles on concepts of space in Alexis and Doraand on notions of sacrifice in Faust; and interdisciplinary pieces ranging from a discussion of contemporary psychological and medical theories of ill humor in relation to Goethe's Werther and an economic reading of Goethe's Faust to an analysis of illustrations of Goethe's works. The review section collects responses by eminent scholars to a wide swath of recent books on Goethe and his age, both in German and English. Contributors: Liesl Allingham, William H. Carter, Sarah Vandegrift Eldridge, John B. Lyon, Waltraud Maierhofer, Catherine Minter, Katharina Mommsen, David Pan, Michael Saman, Leif Weatherby, David E. Wellbery. Adrian Daub is Associate Professor of German at Stanford. Elisabeth Krimmer is Professor of German at the University of California Davis. Book review editor Birgit Tautz is Associate Professor of German at Bowdoin College.
Relational event models (REMs) for the analysis of social interaction were first introduced 15 years ago. Since then, a number of important substantive and methodological contributions have produced their progressive refinement and hence facilitated their increased adoption in studies of social and other networks. Today REMs represent a well-established class of statistical models for relational processes. This special issue of Network Science demonstrates the standing and recognition that REMs have achieved within the network analysis and networks science communities. We wrote this brief introductory editorial essay with four main objectives in mind: (i) positioning relational event data and models in the larger context of contemporary network science and social network research; (ii) reviewing some of the most important recent developments; (iii) presenting the innovative studies collected in this special issue as evidence of the empirical value of REMs, and (iv) identifying open questions and future research directions.
Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the “Lifespan and Life Course Research: integrating strategies” “Un-Meeting” to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.
Identification of evidence-based factors related to status of the clinical research professional (CRP) workforce at academic medical centers (AMCs) will provide context for National Center for Advancing Translational Science (NCATS) policy considerations and guidance. The objective of this study is to explore barriers and opportunities related to the recruitment and retention of the CRP workforce.
Materials and Methods:
Qualitative data from a series of Un-Meeting breakout sessions and open-text survey questions were analyzed to explore barriers and recommendations for improving AMC CRP recruitment, retention and diversity.
Results:
While certain institutions have established competency-based frameworks for job descriptions, standardization remains generally lacking across CTSAs. AMCs report substantial increases in unfilled CRP positions leading to operational instability. Data confirmed an urgent need for closing gaps in CRP workforce at AMCs, especially for attracting, training, retaining, and diversifying qualified personnel. Improved collaboration with human resource departments, engagement with principal investigators, and overcoming both organizational and resource challenges were suggested strategies, as well as development of outreach to universities, community colleges, and high schools raising awareness of CRP career pathways.
Discussion:
Based on input from 130 CRP leaders at 35 CTSAs, four National Institute of General Medical Sciences’ Institutional Development Award (IDeA) program sites, along with industry and government representatives, we identified several barriers to successful recruitment and retention of a highly trained and diverse CRP workforce. Results, including securing institutional support, champions, standardizing and adopting proven national models, improving local institutional policies to facilitate CRP hiring and job progression point to potential solutions.
Political borders profoundly influence outcomes central to international politics. Accordingly, a growing literature shows that historical boundaries affect important macro-outcomes such as patterns of interstate disputes and trade. To explain these findings, existing theories posit that borders have persistent effects on individual-level behavior, but the literature lacks empirical evidence of such effects. Combining spatial data on centuries of border changes in Europe with a wide range of contemporary survey evidence, we show that historical border changes have persistent effects on two of the most politically significant aspects of behavior: individuals’ political and social trust. We demonstrate that in areas where borders frequently changed, individuals are, on average, less trusting of others as well as their governments. We argue that this occurs because border changes disrupt historical state-building processes and limit the formation of interpersonal social networks, which leads to lower levels of trust.