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Background: People with disabilities experience perinatal health disparities. This qualitative study examines disabled people's experiences of labour and delivery care from a disability justice lens., Methods: Semi-structured interviews were conducted between July 2019 and February 2020 with 31 women and transgender people aged 18-45 years with physical, sensory, and/or intellectual/developmental disabilities, who were living in in Ontario, Canada and had given birth in the previous five years., Results: People with disabilities described negative experiences of provider-driven, disrespectful, and discriminatory labour and delivery care that can be interpreted as examples of disability injustice and obstetric ableism. People with disabilities also described positive experiences of collaborative, respectful, and disability-affirming labour and delivery care that can be interpreted as examples of disability justice, facilitated by what feminist disability justice scholars and activists call collective access., Conclusions: Collective access to labour and delivery care can improve perinatal health care for people with disabilities and promote disability justice. Reimagining care-related decision-making as an interdependent, collaborative, respectful, and disability-affirming process shared between patients and providers can help to facilitate collective access to labour and delivery care., Competing Interests: Declarations. Ethics approval and consent to participate: This study was reviewed and approved by the Research Ethics Board at the University of Toronto (protocol number 35018); all methods were performed in accordance with relevant guidelines and regulations from the Declarations of Helsinki and the Canadian Tri-Council Policy Statement on Research Ethics. To assess capacity to consent, individuals with IDD were asked additional screening questions. Before each interview, participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Tropical cyclones (TCs) are one of the major natural hazards to island and coastal communities and ecosystems. However, isotopic compositions of TC-derived precipitation (P) in surface water (SW) and groundwater (GW) reservoirs are still lacking. We tested the three main assumptions of the isotope storm "spike" hypothesis (sudden spikes in isotopic ratios). Our database covers 40 TCs and is divided into recent (N = 778; 2012-2023) and archived (N = 236; 1984-1995) rainfall isotope observations and SW/GW isotope monitoring (N = 6013; 2014-2023). Seasonal rainfall contribution from TCs ranged from less than 1% to over 54% (4% on average) between 1984 and 2023. Mean δ 18 O compositions across TCs domains were significantly lower than the regional (noncyclonic) δ 18 O mean (-5.24 ± 4.27‰): maritime (-6.29 ± 3.28‰), coastal (-7.78 ± 4.28‰), and inland (-9.80 ± 5.18‰) values. Coastal and maritime TC convection resulted in large rainfall amounts with high isotope compositions. This could bias past climate reconstructions toward unrealistic drier conditions. Significant δ 18 O and d-excess differences were found between storm intensities. P/SW and P/GW isotope ratios revealed the rapid propagation of TC excursions in freshwater systems. Our findings highlight the potential of TC isotope observations for diagnosing intensity and frequency in paleoproxies beyond idealized TC models., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

The COVID-19 pandemic has had a detrimental impact on sexual and reproductive health (SRH) and rights globally. However, little is known about the experiences of people with disabilities accessing SRH services during the COVID-19 pandemic. In this community-engaged qualitative study, we examined COVID-related impacts on access to SRH services for people with disabilities. We interviewed 61 women and transgender people in Canada from May 2022 to March 2023. Informed by disability reproductive justice, we identified four major themes through constructivist analysis. First, COVID-related changes to SRH service delivery disrupted access to care and caused disability-related health implications. Second, pandemic response measures changed SRH service accessibility: in-person accessibility barriers were amplified, new in-person accessibility barriers were introduced, and the transition to telehealth amplified, as well as mitigated, accessibility barriers. Third, COVID-related social changes (e.g., lockdowns) had disability-related SRH and rights implications. Fourth, disabled people recommended improving SRH services by enhancing funding, provider training, information and communication, disability accommodations, representation, and comprehensive community engagement. Cutting across these themes were disproportionate negative impacts of the COVID-19 pandemic on access to SRH services for racialized women and transgender people with disabilities. Failure to ensure SRH and rights for women and transgender people with disabilities during the COVID-19 pandemic undermined disability reproductive justice. Comprehensive disability community engagement is necessary to inform accessible SRH services and policies, both during and beyond a pandemic.

Background: On June 8, 2021, a new 20-valent pneumococcal conjugate vaccine (PCV20, PREVNAR 20 ® , Pfizer, Inc.) was licensed for use in adults aged ≥ 18 years by the US Food and Drug Administration (FDA)., Objective: To describe reports to the Vaccine Adverse Event Reporting System (VAERS) after administration of the 20-valent pneumococcal conjugate vaccine in adults., Methods: We searched the VAERS for reports of adverse events involving persons aged ≥ 19 years who received PCV20 during October 20, 2021, through December 31, 2023. Our evaluation included automated analysis of reports, clinical review of serious reports and pre-specified events of special interest, empirical Bayesian data mining to assess for disproportionate reporting, and estimation of reporting rates for reports of Guillain-Barré syndrome (GBS)., Results: The VAERS received 1976 reports after PCV20 administration in persons aged ≥ 19 years (6% of reports involved serious events). The most common adverse events among persons aged 19-64 years (n = 798) were injection-site reactions (231, 29%), pain (134, 17%), erythema (118, 15%), and fever (117, 15%). For persons aged ≥ 65 years (n = 1178), the most common adverse events were injection-site reactions (417, 35%), pain (180, 15%), pain in extremity (162, 14%), and erythema (158, 13%). A data mining alert (EB05 = 3.812) for the MedDRA Preferred Term "Guillain-Barre syndrome" was observed for serious reports. Clinical review verified 11 of 20 GBS reports; 7/11 vaccine recipients were aged ≥ 65 years. Among the 11 verified cases, the median time from vaccination to symptom onset was 14 days. Five persons received another vaccine on the same visit. The reporting rate of GBS after PCV20 receipt was 0.5 cases per million doses distributed. No other safety concern was identified., Conclusions: During the period of this post-licensure review of PCV20, we found most reports were non-serious and comprised mostly local and systemic (e.g., fever) reactions consistent with prelicensure studies. In serious reports, we also identified a data mining alert for GBS after receipt of PCV20, which Centers for Disease Control and Prevention and the FDA are investigating further. No other new or unexpected safety concern was identified., Competing Interests: Declarations. Part of this research was presented during the February 29, 2024 meeting of the Advisory Committee on Immunization Practices in Atlanta, Georgia. Funding: No funding from any organization, agency or entity was received for this study. Conflicts of interest: None of the authors have conflicts of interest that are directly relevant to the content of this article. Disclaimer: The findings and conclusions in this manuscript are those of the author and do not necessarily represent the official position of the CDC or FDA. Ethics approval: This activity was reviewed by the CDC and was considered to be consistent with applicable federal law and CDC policy. Informed consent was not obtained for this secondary use of existing information; see 45 CFR part 46.102(l)(2), 21 CFR part 56, 42 USC §241(d), 5 USC §552a, and 44 USC §3501 et seq. Consent for publication and consent to participate: Not applicable Availability of data and materials: Data from the VAERS system is available to everyone through the VAERS Wonder database available at: https://wonder.cdc.gov/vaers.html . Anyone with internet access may use this site and conduct basic analysis to confirm some of the findings described in the manuscript. However there are data in this manuscript which come from review of medical records of the patients who experienced an adverse event. The data cannot be shared openly to protect patient privacy. Code availability: Not applicable Author contributions: PLM and MMO originated the study, supervised its implementation, conducted the analysis, and led the writing of the manuscript summarizing the findings. PM, CE, PB, KW, NN, and MT assisted in one or more aspects, including study design, review of VAERS reports and medical records, technical advice, administrative support, and writing of the report. All authors read and approved the final version., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Epicardial ventricular tachycardia (VT) ablation is an established approach in patients with epicardial arrhythmogenic foci and is most commonly performed via percutaneous access. An alternative approach is via video-assisted thoracoscopic surgery (VATS), although reports of this technique are limited to the use of catheter-based technologies for radiofrequency ablation delivery., Case Summary: A 55-year-old man with non-ischaemic cardiomyopathy presented with recurrent VT despite medical therapy. Twelve-lead ECG and cardiac MRI were suggestive of an epicardial left ventricular lateral wall breakout. Epicardial ablation was successfully performed via VATS using a linear surgical bipolar ablation device with electroanatomical mapping (EAM) integration. Following ablation, VT was non-inducible. Other than six short episodes of non-sustained during initial follow-up (up to 6 weeks), the patient remained free of ventricular arrhythmias at 18 months with minimal anti-arrhythmic therapy., Discussion: Epicardial VT ablation via VATS is feasible and allows for integration of a surgical ablation device within an EAM system. This may serve as an alternative approach in patients with a failed percutaneous ablation, or those with adverse features for a successful percutaneous procedure., Competing Interests: Conflict of interest: J.S. reports an educational grant from Boston Scientific and speaker fees from Atricure. S.H. reports being a consultant and proctor for AtriCure. G.J.K. reports an educational grant from Boston Scientific. M.T.M. and K.W. report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Phillip G. Blanc reports ownership of Community Health Systems, Inc. stock, sold in 2022. No other potential conflicts of interest were disclosed.

Background: Several studies demonstrated that burn size calculations by referring clinicians are poor. The purpose of this study was to determine if inaccuracies in burn size estimation have improved with time within the same population, and whether widespread roll-out of a smartphone-based TBSA calculator (in the form of the NSW Trauma App) had an impact on accuracy., Methods: A review of all burn-injured adult patients transferred to Burn Units from August 2015, following the roll out of the NSW Trauma App, to January 2021 was performed. The TBSA determined by the referring centre was compared with the TBSA calculated by the Burn Unit. This was compared to historical data from the same population between January 2009 and August 2013., Results: There were 767 adult burn-injured patients transferred to a Burn Unit between 2015 and 2021. The median overall TBSA was 7%. There were 290 patients (37.9%) who had equivalent TBSA calculations by the referring hospital and the Burn Unit. This was a significant improvement compared to the preceding time period (P < 0.005). Overestimation by the referring hospital occurred in 364 cases (47.5%), which was significantly reduced compared to 2009 - 2013 (P < 0.001). Unlike the earlier time period where changes in estimation accuracy were seen in relation to increasing time after the burn injury, burn size estimation accuracy remained relatively consistent in the contemporary time period with no significant change observed (P = 0.86)., Conclusions: This cumulative, longitudinal study of nearly 1500 adult burn-injured patients over 13 years demonstrates improvements in burn size estimation by referring clinicians over time. It is the largest cohort of patients analysed with respect to burn size estimation and is the first to demonstrate improvements in accuracy of TBSA in association with a smartphone-based app. Adopting this simple strategy into burn retrieval systems will augment early assessment of these injuries and improve outcomes., Competing Interests: Conflict of interest statement The authors declare that there is no source of financial or other support, or any financial or professional relationships which may pose a competing interest., (Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Aim: To understand the postpartum care received by birthing people with disabilities and their newborns, from their own perspectives., Design: A qualitative study with semi-structured interviews., Methods: Between July 2019 and February 2020, in-person and virtual interviews were conducted with 31 people with physical, sensory, and intellectual/developmental disabilities in Ontario, Canada, about the formal inpatient and outpatient services and supports they used in the first few months after they gave birth. Thematic analysis was used identify common themes., Results: We identified three overall themes concerning participants' postpartum care experiences and the different types of formal services received in and out of hospital: (1) lack of adequate care, (2) lack of provider awareness of disability and disability accommodations, and (3) fear of judgement, discrimination, and intrusive surveillance. The identified themes were applicable across disability groups. However, most comments on disability accommodations came from participants with physical or sensory disabilities, while participants with intellectual/developmental disabilities most commonly reported concerns about lack of adequate care and fear of judgement, discrimination, and intrusive surveillance., Conclusion: Findings indicate that postpartum care often fails people with disabilities. This could contribute to negative health consequences for them and their newborns., Impact: Birthing people with disabilities need multidisciplinary, proactive, and strengths-based postpartum care to mitigate risk for health complications. Further, disability-related training and guidelines for health and social service providers is required., Reporting Method: Consolidated criteria for reporting qualitative research (COREQ)., Patient or Public Contribution: Our research team included two peer researchers with physical disabilities who served as co-interviewers and participated in data analysis, contributing their lived experience of disability and interactions with the health care system. All stages of the study were also informed by feedback from the study's Advisory Committee, which comprised women with disabilities (many of whom are parents), disability organization staff, clinicians, and policy representatives., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

We describe the disability-related education and training experiences of perinatal care providers in Ontario. Twenty perinatal care providers (e.g., obstetricians, midwives) participated in semi-structured interviews. Using a content analysis approach, we found most acquired disability-related training through their own initiative as opposed to education through professional training programs. Barriers to training included lack of data on disability and pregnancy and limited experiential learning opportunities. Providers recommended that future training focus on experiential learning and social determinants of health, with people with disabilities involved in developing and delivering training. These efforts are vital to optimize pregnancy outcomes for people with disabilities., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Purpose: Despite widely available safety information for the COVID-19 vaccines, vaccine hesitancy remains a challenge. In some cases, vaccine hesitancy may be related to concerns about the number of reports of death to the Vaccine Adverse Event Reporting System (VAERS). We aimed to provide information and context about reports of death to VAERS following COVID-19 vaccination., Methods: This is a descriptive study evaluating reporting rates for VAERS death reports for COVID-19 vaccine recipients in the United States between December 14, 2020, and November 17, 2021. Reporting rates were calculated as death events per million persons vaccinated and compared to expected all-cause (background) death rates., Results: 9201 death events were reported for COVID-19 vaccine recipients aged 5 years and older (or age unknown). Reporting rates for death events increased with increasing age, and males generally had higher reporting rates than females. For death events within 7 days and 42 days of vaccination, respectively, observed reporting rates were lower than the expected all-cause death rates. Reporting rates for Ad26.COV2.S vaccine were generally higher than for mRNA COVID-19 vaccines, but still lower than the expected all-cause death rates. Limitations of VAERS data include potential reporting bias, missing or inaccurate information, lack of a control group, and reported diagnoses, including deaths, are not causally verified diagnoses., Conclusions: Reporting rates for death events were lower than the all-cause death rates expected in the general population. Trends in reporting rates reflected known trends in background death rates. These findings do not suggest an association between vaccination and overall increased mortality., (© 2023 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Anxiety is commonly experienced by people living with mild cognitive impairment (MCI) and dementia. Whilst there is strong evidence for late-life anxiety treatment using cognitive behavioural therapy (CBT) and delivery via telehealth, there is little evidence for the remote delivery of psychological treatment for anxiety in people living with MCI and dementia. This paper reports the protocol for the Tech-CBT study which aims to investigate the efficacy, cost-effectiveness, usability and acceptability of a technology-assisted and remotely delivered CBT intervention to enhance delivery of anxiety treatment for people living with MCI and dementia of any aetiology., Methods: A hybrid II single-blind, parallel-group randomised trial of a Tech-CBT intervention (n = 35) versus usual care (n = 35), with in-built mixed methods process and economic evaluations to inform future scale-up and implementation into clinical practice. The intervention (i) consists of six weekly sessions delivered by postgraduate psychology trainees via telehealth video-conferencing, (ii) incorporates voice assistant app technology for home-based practice, and (iii) utilises a purpose-built digital platform, My Anxiety Care. The primary outcome is change in anxiety as measured by the Rating Anxiety in Dementia scale. Secondary outcomes include change in quality of life and depression, and outcomes for carers. The process evaluation will be guided by evaluation frameworks. Qualitative interviews will be conducted with a purposive sample of participants (n = 10) and carers (n = 10), to evaluate acceptability and feasibility, as well as factors influencing participation and adherence. Interviews will also be conducted with therapists (n = 18) and wider stakeholders (n = 18), to explore contextual factors and barriers/facilitators to future implementation and scalability. A cost-utility analysis will be undertaken to determine the cost-effectiveness of Tech-CBT compared to usual care., Discussion: This is the first trial to evaluate a novel technology-assisted CBT intervention to reduce anxiety in people living with MCI and dementia. Other potential benefits include improved quality of life for people with cognitive impairment and their care partners, improved access to psychological treatment regardless of geographical location, and upskilling of the psychological workforce in anxiety treatment for people living with MCI and dementia., Trial Registration: This trial has been prospectively registered with ClinicalTrials.gov: NCT05528302 [September 2, 2022]., (© 2023. The Author(s).)

Introduction: Modern burn care is centralised, and studies show that early, prompt referral to dedicated burn services improve clinical outcomes. We describe the use of a novel clinical instrument, the burn injury Transfer Feedback Form, to support and educate referring clinicians about the early assessment and management of burn injuries. Since 2005, Transfer Feedback Forms have been completed for all burn-injured patients with inter-hospital transfer to a specialised burn unit in the state of New South Wales (NSW), Australia. The aim of this study was to review physiological, procedural, and system or process issues in the care of both adult and paediatric burn-injured patients needing retrieval and transfer in NSW as identified by the Transfer Feedback Form. Secondary objectives were to determine any significant differences in these parameters between metropolitan and regional or remote referring institutions, and if any improvements occurred in these parameters over time., Methods: This was a retrospective analysis of all patients who were transferred to a burn unit in NSW between July 2005 and July 2021 using their prospectively completed Transfer Feedback Forms. Patients were divided into metropolitan and non-metropolitan referral sources based on geographic location. Clinical issues or deficiencies identified during each patient transfer were then classified into various groups. To determine if transfer-related clinical concerns had changed with time, two distinct periods before and after 2015, when the NSW Trauma App was introduced, were analysed. We compared trends in frequency of transfer-related concerns before and after App introduction by using interrupted time series analysis., Results: A total of 3233 patients had Feedback Forms submitted during the 16-year period. We included 929 children (28.7%) and 2304 adults (71.3%). Transfer-related clinical issues were identified in 904 adults (39.0%) and 484 children (52.0%). In both adult and paediatric patients, the most common transfer-related clinical deficiency was in relation to burn size estimation with 525 patients (43.7%) and 207 patients (30.6%), respectively. Between the time periods analysed, the number of issues arising during inter-hospital transfer fell significantly for both adults (from 46.1% to 26.1%; p < 0.05) and children (from 55.3% to 40.7%; p < 0.05). Segmented regression analysis demonstrated a significant break in the rate of transfer-related clinical issues in 2014 (p < 0.05) and 2015 (p < 0.01) for adults. Accurate body surface area estimations also increased significantly by 53% and 50% for adults and children (p < 0.05 for both), respectively, after 2015., Conclusion: Our analysis indicates that the early care of burn-injured patients undergoing inter-hospital transfer is associated with clinical, technical, and logistical challenges. However, introduction of the burn injury Transfer Feedback Form has been associated with improvements in early burn care by referring centres both temporally and geographically. Smartphone-based applications such as the NSW Trauma App have also probably contributed to these findings. Adopting these simple, inexpensive strategies into burn care systems will augment inter-hospital transfer of burn-injured patients, and improve clinical outcomes., (Copyright © 2022 Elsevier Ltd and ISBI. All rights reserved.)

Objective: To explore the care experiences of childbearing people with physical, sensory, and/or intellectual/developmental disabilities during pregnancy., Design: Descriptive qualitative., Setting: Ontario, Canada, where physician and midwifery care during pregnancy are provided at no direct cost to residents., Participants: Thirty-one people with physical, sensory, and/or intellectual/developmental disabilities (who self-identified as cisgender women [n = 29] and trans or nonbinary persons [n = 2]) who gave birth in the last 5 years., Methods: We recruited childbearing people with disabilities through disability and parenting organizations, social media, and our team's networks. Using a semistructured guide, we conducted in-person and virtual (e.g., telephone or Zoom) interviews with childbearing people with disabilities in 2019 to 2020. We asked participants about the services they accessed during pregnancy and if services met their needs. We used a reflexive thematic analysis approach to analyze interview data., Results: Across disability groups, we identified four common themes: Unmet Accommodation Needs, Lack of Coordinated Care, Ableism, and Advocacy as a Critical Resource. We found that these experiences manifested in unique ways based on disability type., Conclusion: Our findings suggest the need for accessible, coordinated, and respectful prenatal care for people with disabilities, with the requirements of such care depending on the needs of the individual person with a disability. Nurses can play a key role in identifying the needs and supporting people with disabilities during pregnancy. Education and training for nurses, midwives, obstetricians, and other prenatal care providers should focus on disability-related knowledge and respectful prenatal care., (Copyright © 2023 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Background: Emerging research has shown racial and ethnic variations in the magnitude of association between the apolipoprotein ɛ4 (APOE ɛ4) allele and the risk of developing Alzheimer's disease and related dementias (ADRD). Studies researching this association among Hispanic groups within and outside of the United States have produced inconsistent results., Objective: To examine the association between the APOE ɛ4 allele and the risk of developing ADRD in global Hispanic populations from different ethnic regions of origin., Methods: PubMed, Embase, Scopus, and PsycInfo were searched for studies relating to Hispanic/Latin American origin, APOE ɛ4, and ADRD. Odds ratios (OR) of ADRD risk for individuals with APOE ɛ4 versus those without APOE ɛ4 were extracted and calculated using random effects analysis., Results: 20 eligible studies represented Caribbean Hispanic, Mexican, South American, Spanish, and Cuban groups. Overall, APOE ɛ4 was significantly associated with increased risk of ADRD (Odds Ratio [OR] 3.80, 95% CI: 2.38-6.07). The association was only significant in the South American (OR: 4.61, 95% CI: 2.74-7.75) subgroup., Conclusion: There was an association between APOE ɛ4 and increased ADRD risk for the South American subgroup. The strength of this association varied across Hispanic subgroups. Data is limited with more studies especially needed for adjusted analysis on Spanish, Central American, Cuban Hispanic, and Caribbean Hispanic groups. Results suggest additional environmental or genetic risk factors are associated with ethnic variations.

Background: To highlight the unique spectrum of lower extremity firearm injuries seen at a rural, Midwestern level 1 trauma center to provide insight into prevalence, mechanism of injury, and identify modifiable factors that contribute to firearm injuries of the lower extremity. It is our belief that the creation of our database will help future trauma and firearm databases improve documentation and understand the relationship between anatomic location of injury and outcomes., Methods: A retrospective review of lower extremity firearm injuries from a rural, Midwestern level 1 trauma center was collected from January 2011 to December 2019. Data acquired included injury description; demographics, injury mechanism/ description/ location, firearm used, toxicology, and information regarding hospitalization. Data was analyzed using Chi-squared analysis and Fisher's exact test for categorical data and the Wilcoxon rank sum test for continuous data., Results: 69 patients with lower extremity firearm injuries were identified. Average age was 30.14 years, 89.86% were males, and one fatality were identified. 47.83% (33) of these injuries were assaults, followed by unintentional injuries at 42.03% (29). Law enforcement-related and self-inflicted injuries contributed minimally. Handguns were the most common type of firearm, used in 72.5% of cases. Nearly 1/3 of the unintentional firearm injuries occurred during November or December, the active deer hunting months in the community of study., Conclusion: The lower extremity is uniquely vulnerable to both assaults and unintentional injury in our rural environment, differing from what we have previously published regarding the upper extremity. Lower extremity gunshot wounds increased during the winter months, offering a correlation to deer hunting season. Our findings display that not all firearm injuries are created equal, and that there is a need to improve documentation of and additional study in order to optimally tailor firearm prevention measures based on the ruralityurbanicity spectrum. Level of Evidence: III ., (Copyright © The Iowa Orthopaedic Journal 2022.)

Competing Interests: Conflicts of interest Dr Chong is an investigator for Daavlin Corporation, Biogen Incorporated, and Pfizer Incorporated. He is a consultant for Celgene Corporation, Viela Bio, Bristol Meyers Squibb, EMD Serono, and Principia Biopharma. Dr Wan has received research funding from Pfizer, Inc, paid to the University of Pennsylvania. Dr Arkin has received research equipment from Candela, serves as an investigator for Celgene Corporation, and serves as a consultant to Regeneron and Amgen. Drs Brown, Shields, Mir, Hynan, and Kovarik and authors Srivastava and Welsh have no conflicts of interest to declare.

Background: Effective provider-patient communication is a key element of quality health care, including perinatal care. What constitutes "effective communication" in perinatal care may vary according to the population seeking care, such as women with intellectual and developmental disabilities (IDD) and sensory disabilities. Research broadly indicates that communication issues are among the barriers to perinatal care experienced by women with disabilities. However, few studies have explicitly explored their communication experiences in this context. The purpose of this study was to understand the communication experiences of birthing people with IDD and/or sensory disabilities in perinatal care., Methods: We conducted semi-structured interviews with 17 people with IDD (e.g., autism, cognitive delay) and/or sensory disabilities (e.g., d/Deaf, blind) in Ontario, Canada, who had recently given birth, to explore barriers to and facilitators of effective communication in perinatal care. A combination of deductive and inductive thematic analysis guided data analysis., Results: We found that birthing people with IDD and/or sensory disabilities encountered multiple barriers to effective communication in perinatal care, namely, lack of policies and guidelines, lack of provider experience, lack of provider effort, as well as ableism and provider assumptions. Facilitators included knowledgeable, aware, and supportive providers; access to communication aids and services; tailoring information to patients' disability-related communication needs; empathic communication; and, communication among providers., Conclusion: Unmet communication needs may contribute to negative health and social outcomes for birthing people with disabilities and their newborns. Accessibility policy implementation and practice change are needed to meet the communication needs of people with IDD and/or sensory disabilities in perinatal care to ensure positive experiences and outcomes., (© 2022. The Author(s).)

Purpose: The purpose of this report from the field is to describe the process by which an multidisciplinary workgroup, selected by the CDC Foundation in partnership with maternal health experts, developed a definition of racism that would be specifically appropriate for inclusion on the Maternal Mortality Review Information Application (MMRIA) form., Description: In the United States Black women are nearly 4 times more likely to experience a pregnancy-related death. Recent evidence points to racism as a fundamental cause of this inequity. Furthermore, the CDC reports that 3 of 5 pregnancy related deaths are preventable. With these startling facts in mind, the CDC created the Maternal Mortality Review Information Application (MMRIA) for use by Maternal Mortality Review Committees (MMRC) to support standardized data abstraction, case narrative development, documentation of committee decisions, and analysis on maternal mortality to inform practices and policies for preventing maternal mortality., Assessment: Charged with the task of defining racism and discrimination as contributors to pregnancy related mortality, the work group established four goals to define their efforts: (1) the desire to create a product that was inclusive of all forms of racism and discrimination experienced by birthing people; (2) an acknowledgement of the legacy of racism in the U.S. and the norms in health care delivery that perpetuate racist ideology; (3) an acknowledgement of the racist narratives surrounding the issue of maternal mortality and morbidity that often leads to victim blaming; and (4) that the product would be user friendly for MMRCs., Conclusion: The working group developed three definitions and a list of recommendations for action to help MMRC members provide suggested interventions to adopt when discrimination or racism were contributing factors to a maternal death. The specification of these definitions will allow the systematic tracking of the contribution of racism to maternal mortality through the MMRIA and allow a greater standardization of its identification across participating jurisdictions with MMRCs that use the form., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cryolipolysis is an increasingly popular nonsurgical fat-reduction procedure. Published treatment guidance and adverse event (AE) management protocols are limited., Objective: A modified Delphi study aimed to establish global expert consensus on the use of CoolSculpting (Allergan Aesthetics, an AbbVie Company, Irvine, CA), a noninvasive cryolipolysis treatment system., Methods: A literature search informed survey topics for an 11-expert Delphi panel. Panelists completed an online 39-question survey. An interim panel discussion, with open-ended questions and yes/no voting, informed a second survey containing 61 statements, for which panelists rated agreement using a 5-point Likert scale. Topics included treatment outcome and responder definitions, patient evaluation and selection, treatment protocols, patient satisfaction, and AEs., Results: Panelists achieved consensus on 38 final guidelines and recommendations. They reached moderate to complete consensus on 4 statements on defining responders (ie, patients with a range of visible improvement) and 6 statements on patient factors contributing to treatment outcomes (eg, how well the applicator conforms to patient body region). Panelists defined minimum numbers of treatment cycles to achieve visible clinical outcomes for 12 body regions, with moderate to complete consensus on 31 statements. They achieved a strong to complete consensus on 7 statements about patient satisfaction (eg, importance of patient expectations, visible improvement, and before-and-after photographs). Panelists defined management strategies for AEs, with moderate to complete consensus on 15 statements., Conclusions: A modified Delphi process yielded multiple guideline recommendations for cryolipolysis, providing a needed resource for the broad range of clinicians who perform this noninvasive fat-reduction procedure., (© 2022 The Aesthetic Society.)

Background: Accessible and quality care during the perinatal period is critical for optimal maternal and neonatal health. Using the socio-ecological model, the purpose of this study was to explore barriers and facilitators that shape the perinatal care experiences of people with intellectual and/or developmental disabilities (IDD)., Methods: Semi-structured interviews were conducted with 10 individuals with IDD in Ontario, Canada, who had given birth within the past 5 years. Interviews focused on care experiences before, during, and after pregnancy. Data were analyzed using a directed content analysis approach, and the socio-ecological model guided analysis., Results: Barriers at the societal (e.g., cultural norms of motherhood), policy/institutional (e.g., child protection policies and practices), interpersonal (e.g., inadequate formal and informal support), and intrapersonal levels (e.g., internalized stigma) contributed to participants having negative perinatal care experiences. Conversely, we identified facilitators on the interpersonal level (e.g., positive interactions with perinatal care providers and familial and social service supports) as positively shaping participants' perinatal care experiences., Conclusions: Findings reveal that the perinatal care experiences of people with IDD are shaped by several interrelated factors that largely stem from societal-level barriers, such as dominant (stigmatizing) discourses of disability. To improve the perinatal care experiences of people with IDD, there is a need for interventions at multiple levels. These include the development of policies to support perinatal care for diverse populations and training care providers to enact policies at the institutional and interpersonal levels., (Copyright © 2021 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

Remote teleoperation of robots can broaden the reach of domain specialists across a wide range of industries such as home maintenance, health care, light manufacturing, and construction. However, current direct control methods are impractical, and existing tools for programming robot remotely have focused on users with significant robotic experience. Extending robot remote programming to end users, i.e., users who are experts in a domain but novices in robotics, requires tools that balance the rich features necessary for complex teleoperation tasks with ease of use. The primary challenge to usability is that novice users are unable to specify complete and robust task plans to allow a robot to perform duties autonomously, particularly in highly variable environments. Our solution is to allow operators to specify shorter sequences of high-level commands, which we call task-level authoring, to create periods of variable robot autonomy. This approach allows inexperienced users to create robot behaviors in uncertain environments by interleaving exploration, specification of behaviors, and execution as separate steps. End users are able to break down the specification of tasks and adapt to the current needs of the interaction and environments, combining the reactivity of direct control to asynchronous operation. In this paper, we describe a prototype system contextualized in light manufacturing and its empirical validation in a user study where 18 participants with some programming experience were able to perform a variety of complex telemanipulation tasks with little training. Our results show that our approach allowed users to create flexible periods of autonomy and solve rich manipulation tasks. Furthermore, participants significantly preferred our system over comparative more direct interfaces, demonstrating the potential of our approach for enabling end users to effectively perform remote robot programming., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Senft, Hagenow, Welsh, Radwin, Zinn, Gleicher and Mutlu.)

Background: Anaphylaxis is a rare, serious allergic reaction. Its identification in large healthcare databases can help better characterize this risk., Objective: To create an ICD-10 anaphylaxis algorithm, estimate its positive predictive values (PPVs) in a post-vaccination risk window, and estimate vaccination-attributable anaphylaxis rates in the Medicare Fee For Service (FFS) population., Methods: An anaphylaxis algorithm with core and extended portions was constructed analyzing ICD-10 anaphylaxis claims data in Medicare FFS from 2015 to 2017. Cases of post-vaccination anaphylaxis among Medicare FFS beneficiaries were then identified from October 1, 2015 to February 28, 2019 utilizing vaccine relevant anaphylaxis ICD-10 codes. Information from medical records was used to determine true anaphylaxis cases based on the Brighton Collaboration's anaphylaxis case definition. PPVs were estimated for incident anaphylaxis and the subset of vaccine-attributable anaphylaxis within a 2-day post-vaccination risk window. Vaccine-attributable anaphylaxis rates in Medicare FFS were also estimated., Results: The study recorded 66,572,128 vaccinations among 21,685,119 unique Medicare FFS beneficiaries. The algorithm identified a total of 190 suspected anaphylaxis cases within the 2-day post-vaccination window; of these 117 (62%) satisfied the core algorithm, and 73 (38%) additional cases satisfied the extended algorithm. The core algorithm's PPV was 66% (95% CI [56%, 76%]) for identifying incident anaphylaxis and 44% (95% CI [34%, 56%]) for vaccine-attributable anaphylaxis. The vaccine-attributable anaphylaxis incidence rate after any vaccination was 0.88 per million doses (95% CI [0.67, 1.16])., Conclusion: The ICD-10 claims algorithm for anaphylaxis allows the assessment of anaphylaxis risk in real-world data. The algorithm revealed vaccine-attributable anaphylaxis is rare among vaccinated Medicare FFS beneficiaries., 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., (Published by Elsevier Ltd.)

Introduction: A community-based project was developed to support quit attempts and denormalise smoking in Aboriginal communities. This qualitative study evaluates the effectiveness of project strategies, messages and the partnership process, and explores impacts observed by Aboriginal community members, complementing findings from a quantitative evaluation., Methods: The study comprised five focus groups (40 participants) and 14 in-depth interviews (with 15 community members). Data were analysed thematically by manual and NVivo software methods., Results: Results demonstrate that the project attracted community attention, was well recalled and messages were considered convincing and persuasive. Participants reported being more likely to quit and to discuss smoking with family and friends, and noticed that many people were quitting. Participants observed an increase in asking people not to smoke in the home and fewer people smoking at events, but noted that many smokers struggled to stay quit. The partnership and participation of Aboriginal Health Workers were viewed as crucial., Conclusion: The qualitative findings reinforce quantitative evaluation findings suggesting that the project contributed to denormalising smoking and motivating quit attempts., So What: The evaluation provided insight into how the project changed attitudes and motivated community members to make quit attempts and provided ideas to meet the ongoing challenge., (© 2020 Australian Health Promotion Association.)

Objectives: Psychological comorbidities have been associated with asthma in adults and children, but have not been studied in a population of children with severe asthma. The aim of this study was to test the hypothesis that symptoms of anxiety or depression are highly prevalent in pediatric severe asthma and negatively effects asthma control., Methods: Longitudinal assessments of anxiety or depression symptoms (Patient Health Questionnaire-4 [PHQ-4]), asthma control (Asthma Control Test [ACT]), and lung function were performed in a single-center pediatric severe asthma clinic. Participant data were collected during routine clinical care. Primary outcomes were ACT and forced expiratory volume in 1 s per forced vital capacity (FEV1/FVC)., Results: Among 43 subjects (with total 93 observations), 58.1% reported at least one anxious or depressive symptom and 18.6% had a PHQ-4 more than 2, the threshold for an abnormal test result. After adjusting for age, sex, race, and asthma medication step, there was a significant reduction in ACT for girls with PHQ-4 more than 2 (adjusted mean [SE] ACT for PHQ-4 > 2: 13.64 [0.59], ACT for PHQ-4 ≤ 2: 20.64 [1.25], p = .02) but not boys. Moreover, there was a significant differential effect of mental health impairment for girls than boys. ACT for girls with PHQ more than 2: 13.64 (0.59) compared with boys with PHQ-4 more than 2: 17.82 (0.95), adjusted mean difference ACT by sex = 4.18 points; 95% confidence interval, 0.63-7.73; p = .033. In adjusted models, there was no association between PHQ-4 more than 2 and FEV1/FVC., Conclusions: Symptoms of anxiety and depression are common. In children with severe asthma, a PHQ-4 score more than 2 is associated with worse asthma symptom control in girls, but not boys., (© 2020 Wiley Periodicals LLC.)

Background: There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method., Methods: Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis., Results: Our study revealed significant uptrend in AM to PM FT4 ( p  < 0.0001) samples, downtrend in AM to PM TT3 ( p  = 0.0004) and FT3 samples ( p  < 0.0001), and AM to PM uptrend in rT3 samples ( p  < 0.0001). No difference was observed for TT4 between AM and PM. No significant sex differences were seen for any of the five thyroid hormones., Conclusion: When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Under a changing climate, projections estimate that over the next thirty years, extreme Tropical Cyclones (TCs) will increase in frequency, with two to three times more Category 4 and 5 hurricanes in the Atlantic basin between 20°N and 40°N. In recent years, the Caribbean Sea and Atlantic Ocean basins have experienced several extreme TCs, resulting in extensive human, ecological, and economic damage [1], [2], [3]. To improve understanding of TCs and their potential impacts in the face of climate change, physically based understanding of past climate and modern TC dynamics is necessary. Despite the well-known Atlantic hurricane season, surface observations of the isotopic evolution of TC's moisture and the propagation of isotopically distinct pulses across surface and subsurface water reservoirs are lacking. In this data article, we provide novel high frequency sampling of surface rainfall isotope compositions (δ 18 O, δ 2 H, and d -excess in ‰) for Hurricanes Otto (Costa Rica, 2016), Nate (Costa Rica, 2017), Irma (Cuba and The Bahamas, 2017), Maria (Cuba and The Bahamas, 2017), and Dorian (The Bahamas, 2019). These five TCs were characterized by unprecedented impacts during continental and maritime landfalls and passages. In total, 161 surface rainfall samples were collected in passive devices [4] with event-based and daily frequencies, resulting in the first surface isotopic tempestology anatomy across the Caribbean Sea and Atlantic Ocean basins to date. Derived rainfall from TCs often results in large input amounts of isotopically distinct water over an area from few hours to several days, and therefore this unique isotope composition is propagated through surface and shallow subsurface reservoirs. Our data also include spring (N=338) and surface water (N=334) isotope compositions following the impact of Hurricane Otto and Tropical Storm Nate in central Costa Rica. As this region is well-known for its diverse rainfall dynamics and as a climate change 'hot spot' [5], [6], [7], our data provide an opportunity to improve and complement modern and past climate interpretations often derived from satellite products and calcite-δ 18 O paleoclimatic archives in light of climatic forcing, TC rainfall amounts and recharge rates, and the hypothesized climatic-induced decline of past Mesoamerican civilizations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that have, or could be perceived to have, influenced the work reported in this article., (© 2020 The Author(s).)

Introduction : The marine environment is a very promising resource for natural product research, with many of these reaching the market as new drugs, especially in the field of cancer therapy as well as the drug discovery pipeline for new antimicrobials. Exploitation for bioactive marine compounds with unique structures and novel bioactivity such as the isoquinoline alkaloid; trabectedin, the polyether macrolide; halichondrin B, and the peptide; dolastatin 10, requires the use of analytical techniques, which can generate unbiased, quantitative, and qualitative data to benefit the biodiscovery process. Metabolomics has shown to bridge this understanding and facilitate the development of new potential drugs from marine sources and particularly their microbial symbionts. Areas covered : In this review, articles on applied secondary metabolomics ranging from 1990-2018 as well as to the last quarter of 2019 were probed to investigate the impact of metabolomics on drug discovery for new antibiotics and cancer treatment. Expert opinion : The current literature review highlighted the effectiveness of metabolomics in the study of targeting biologically active secondary metabolites from marine sources for optimized discovery of potential new natural products to be made accessible to a R&D pipeline.

Objectives: To evaluate the longer term changes in executive functioning among participants with cardiovascular disease (CVD) risk factors and cognitive impairments with no dementia (CIND) randomized to a diet and exercise intervention., Design: A 2 (Exercise) × 2 (Dietary Approaches to Stop Hypertension [DASH] eating plan) factorial randomized clinical trial., Setting: Academic tertiary care medical center., Participants: Volunteer sample of 160 older sedentary adults with CIND and at least one additional CVD risk factor enrolled in the ENLIGHTEN trial between December 2011 and March 2016., Interventions: Six months of aerobic exercise (AE), DASH diet counseling, combined AE + DASH, or health education (HE) controls., Measurements: Neurocognitive battery recommended by the Neuropsychological Working Group for Vascular Cognitive Disorders including measures of executive function, memory, and language/verbal fluency. Secondary outcomes included the Clinical Dementia Rating-Sum of Boxes (CDR-SB), Six-Minute Walk Distance (6MWD), and CVD risk including blood pressure, body weight, and CVD medication burden., Results: Despite discontinuation of lifestyle changes, participants in the exercise groups retained better executive function 1 year post-intervention (P = .041) compared with non-exercise groups, with a similar, albeit weaker, pattern in the DASH groups (P = .054), without variation over time (P's > .867). Participants in the exercise groups also achieved greater sustained improvements in 6MWD compared with non-Exercise participants (P < .001). Participants in the DASH groups exhibited lower CVD risk relative to non-DASH participants (P = .032); no differences in CVD risk were observed for participants in the Exercise groups compared with non-Exercise groups (P = .711). In post hoc analyses, the AE + DASH group had better performance on executive functioning (P < .001) and CDR-SB (P = .011) compared with HE controls., Conclusion: For participants with CIND and CVD risk factors, exercise for 6 months promoted better executive functioning compared with non-exercisers through 1-year post-intervention, although its clinical significance is uncertain. J Am Geriatr Soc 68:559-568, 2020., (© 2019 The American Geriatrics Society.)

Introduction: The mechanical response of brain tissue to high-speed forces in the blast and blunt traumatic brain injury is poorly understood. Object-to-object variation and interspecies differences are current limitations in animal and cadaver studies conducted to study damage mechanisms. Biofidelic and transparent tissue simulants allow the use of high-speed optical diagnostics during a blast event, making it possible to observe deformations and damage patterns for comparison to observed injuries seen post-mortem in traumatic brain injury victims., Methods: Material properties of several tissue simulants were quantified using standard mechanical characterization techniques, that is, shear rheometric, tensile, and compressive testing., Results: Polyacrylamide simulants exhibited the best optical and mechanical property matching with the fewest trade-offs in the design of a cranial test object. Polyacrylamide gels yielded densities of ~1.04 g/cc and shear moduli ranging 1.3-14.55 kPa, allowing gray and white matter simulant tuning to a 30-35% difference in shear for biofidelity., Conclusions: These materials are intended for use as layered cranial phantoms in a shock tube and open field blasts, with focus on observing phenomena occurring at the interfaces of adjacent tissue simulant types or material-fluid boundaries. Mechanistic findings from these studies may be used to inform the design of protective gear to mitigate blast injuries., (Published by Oxford University Press on behalf of Association of Military Surgeons of the United States 2020.)

Introduction: A partnership between three Aboriginal Community Controlled Organisations and a mainstream health service was formed to develop, implement and evaluate a comprehensive and culturally appropriate social marketing project which aimed to encourage smokers to quit smoking. The project also supported quit attempts and promoted denormalisation of smoking., Methods: The project was evaluated through baseline (n = 427) and follow-up (n = 611) surveys carried out face-to-face with Aboriginal and/or Torres Strait Islander participants 18 years and older recruited through convenience sampling at community events and venues during 2010-2011 and 2015., Results: The proportion of participants who had made one or more quit attempts increased significantly between baseline and follow-up surveys (54%, 101 out of 187; vs 64%, 189 out of 297; P < 0.05). Participants who had intended to quit within 6 months (AOR, 3.29; 95% CI 1.90-5.68; P < 0.01); and participants disagreeing with the statement "I don't mind if people smoke inside my home" (AOR, 1.74; 95% CI 1.06-2.84; P < 0.05) were significantly more likely to have made one or more quit attempts compared to the respective reference groups., Conclusion: Study findings demonstrate that the project was associated with increased quit attempts. Intention to quit and attitude were found to be the predictors of making a quit attempt. SO WHAT?: Many studies suggest the need to denormalise smoking; this study demonstrated both change in attitudes and an increase in quit attempts. It is recognised that many quit attempts may be needed for long-term smoking cessation., (© 2019 Australian Health Promotion Association.)

Competing Interests: Conflict of interest statement: The author(s) declare that there is no conflict of interest.

The Mesoamerican and Caribbean (MAC) region is characterized by tropical cyclones (TCs), strong El Niño-Southern Oscillation events, and climate variability that bring unique hazards to socio-ecological systems. Here we report the first characterization of the isotopic evolution of a TC (Hurricane Otto, 2016) in the MAC region. We use long-term daily rainfall isotopes from Costa Rica and event-based sampling of Hurricanes Irma and Maria (2017), to underpin the dynamical drivers of TC isotope ratios. During Hurricane Otto, rainfall exhibited a large isotopic range, comparable to the annual isotopic cycle. As Hurricane Otto organized into a Category 3, rapid isotopic depletion coupled with a decrease in d-excess indicates efficient isotopic fractionation within ~200 km SW of the warm core. Our results shed light on key processes governing rainfall isotope ratios in the MAC region during continental and maritime TC tracks, with applications to the interpretation of paleo-hydroclimate across the tropics.

Objective: Accurate measurement of steroid hormones remains challenging. Mass spectrometry affords a reliable means for quantitating steroid profiles accurately. Our objective was to establish and define (1) the extent of diurnal fluctuations in steroid concentrations that potentially necessitate strict adherence to time of sample acquisition and (2) time-dependent steroid reference intervals., Design: Nine steroid markers were examined in couplets in males and females., Methods: Using isotope dilution high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis, we developed a multi-steroid profile requiring only a minimal volume of serum (0.1 mL). Couplet (AM and PM) measurements of steroid hormones for 120 healthy females (F) and 62 healthy males (M) were obtained. Patients were recruited from several participating centers., Results: The following diurnal values were noted to be significantly different in both females and males: cortisone, cortisol, corticosterone, 11 deoxycortisol (11 DOC), androstenedione, 17a-hydroxyprogesterone (17 OHP) and dehydroepiandrosterone (DHEA). Testosterone was only found to have significant diurnal variance in males. Progesterone showed no significant difference in AM and PM values for either groups and thus may provide an internal control., Conclusions: When diagnosing endocrine disorders, it is imperative to acknowledge the 24-h diurnal variation of the biochemical steroid markers. We highlight the importance of standardization of collection times and appropriate implementation of reference intervals., Precis: We identify diurnal fluctuations in steroid concentrations with time of day and emphasize the importance of adhering to firm time of sample acquisition.

Objectives: Older adults often display postoperative cognitive decline (POCD) after surgery, yet it is unclear to what extent functional connectivity (FC) alterations may underlie these deficits. We examined for postoperative voxel-wise FC changes in response to increased working memory load demands in cardiac surgery patients and nonsurgical controls., Experimental Design: Older cardiac surgery patients (n = 25) completed a verbal N-back working memory task during MRI scanning and cognitive testing before and 6 weeks after surgery; nonsurgical controls with cardiac disease (n = 26) underwent these assessments at identical time intervals. We measured postoperative changes in degree centrality, the number of edges attached to a brain node, and local coherence, the temporal homogeneity of regional functional correlations, using voxel-wise graph theory-based FC metrics. Group × time differences were evaluated in these FC metrics associated with increased N-back working memory load (2-back > 1-back), using a two-stage partitioned variance, mixed ANCOVA., Principal Observations: Cardiac surgery patients demonstrated postoperative working memory load-related degree centrality increases in the left dorsal posterior cingulate cortex (dPCC; p < .001, cluster p-FWE < .05). The dPCC also showed a postoperative increase in working memory load-associated local coherence (p < .001, cluster p-FWE < .05). dPCC degree centrality and local coherence increases were inversely associated with global cognitive change in surgery patients (p < .01), but not in controls., Conclusions: Cardiac surgery patients showed postoperative increases in working memory load-associated degree centrality and local coherence of the dPCC that were inversely associated with postoperative global cognitive outcomes and independent of perioperative cerebrovascular damage., (© 2017 Wiley Periodicals, Inc.)

Background: Continuing advances in the understanding of Alzheimer's disease progression have inspired development of disease-modifying therapeutics intended for use in preclinical populations. However, identification of clinically meaningful cognitive and functional outcomes for individuals who are, by definition, asymptomatic remains a significant challenge. Clinical trials for prevention and early intervention require measures with increased sensitivity to subtle deficits in instrumental activities of daily living (IADL) that comprise the first functional declines in prodromal disease. Validation of potential endpoints is required to ensure measure sensitivity and reliability in the populations of interest., Objectives: The present research validates use of the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) for performance-based assessment of IADL functioning in older adults (age 55+) with subjective cognitive decline., Design: Cross-sectional validation study., Setting: All participants were evaluated on-site at NeuroCog Trials, Durham, NC, USA., Participants: Participants included 245 healthy younger adults ages 20-54 (131 female), 247 healthy older adults ages 55-91 (151 female) and 61 older adults with subjective cognitive decline (SCD) ages 56-97 (45 female)., Measures: Virtual Reality Functional Capacity Assessment Tool; Brief Assessment of Cognition App; Alzheimer's Disease Cooperative Study Prevention Instrument Project - Mail-In Cognitive Function Screening Instrument; Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living - Prevention Instrument, University of California, San Diego Performance-Based Skills Assessment - Validation of Intermediate Measures; Montreal Cognitive Assessment; Trail Making Test- Part B., Results: Participants with SCD performed significantly worse than age-matched normative controls on all VRFCAT endpoints, including total completion time, errors and forced progressions (p≤0001 for all, after Bonferonni correction). Consistent with prior findings, both groups performed significantly worse than healthy younger adults (age 20-54). Participants with SCD also performed significantly worse than controls on objective cognitive measures. VRFCAT performance was strongly correlated with cognitive performance. In the SCD group, VRFCAT performance was strongly correlated with cognitive performance across nearly all tests with significant correlation coefficients ranging from 0.3 to 0.7; VRFCAT summary measures all had correlations greater than r=0.5 with MoCA performance and BAC App Verbal Memory (p<0.01 for all)., Conclusions: Findings suggest the VRFCAT provides a sensitive tool for evaluation of IADL functioning in individuals with subjective cognitive decline. Strong correlations with cognition across groups suggest the VRFCAT may be uniquely suited for clinical trials in preclinical AD, as well as longitudinal investigations of the relationship between cognition and function., Competing Interests: AS Atkins is a full-time employee of NeuroCog Trials, Durham, NC, USA, and has received support from National Institute of Mental Health and National Institute on Aging. A Khan is a full-time employee of NeuroCog Trials, Durham, NC, USA, and has received support from National Institute of Mental Health, Janssen, Celgene, Teva Pharmaceuticals, and Stanley Medical Research Foundation. D Ulshen, A Vaughn and D Balentin are full-time employees of NeuroCog Trials, Durham, NC, USA, H. Dickerson as a NeuroCog employee. LE Liharska is a consultant to NeuroCog Trials. B Plassman currently or in the past 3 years has received funding from the National Institute on Aging and the National Institute of Environmental Health Sciences, and has served as a consultant for Takeda. K Welsh-Bohmer is a consultant to NeuroCog Trials. She currently or in the past 3 years has received funding from the National Institute on Aging and has received honoraria, served as a consultant, or advisory board member for Takeda, Biogen, Roche, T3D Therapeutics, Diffusion Pharmaceutical company, and Merck. RSE Keefe currently or in the past 3 years has received investigator-initiated research funding support from the Department of Veteran’s Affair, Feinstein Institute for Medical Research, GlaxoSmithKline, National Institute of Mental Health, National Institute on Aging, Novartis, Psychogenics, Research Foundation for Mental Hygiene, Inc., and the Singapore National Medical Research Council. Dr. Richard Keefe currently or in the past 3 years has received honoraria, served as a consultant, speaker, or advisory board member for Abbvie, Acadia, Aeglea, Akebia, Akili, Alkermes, ArmaGen, Astellas, Avanir, AviNeuro/ChemRar, Axovant, Biogen, Boehringer-Ingelehim, Cerecor, CoMentis, Critical Path Institute, FORUM, Global Medical Education (GME), GW Pharmaceuticals, Intracellular Therapeutics, Janssen, Lundbeck, Lysogene, MedScape, Mentis Cura, Merck, Minerva Neurosciences Inc., Mitsubishi, Monteris, Moscow Research Institute of Psychiatry, Neuralstem, Neuronix, Novartis, NY State Office of Mental Health, Otsuka, Pfizer, Regenix Bio, Reviva, Roche, Sangamo, Sanofi, Sunovion, Takeda, Targacept, University of Moscow, University of Texas Southwest Medical Center, and WebMD. Dr. Keefe receives royalties from versions of the BAC testing battery, the MATRICS Battery (BACS Symbol Coding), and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT). He is also a shareholder in NeuroCog Trials, Inc. and Sengenix

Objectives: To evaluate the reliability of normal Thyroid Stimulating Hormone (TSH) as a thyroid function test and assess the effect of Adrenocorticotropic Hormone (ACTH) on serum TSH concentration., Design and Methods: Patients presenting to the National Institutes of Health Department of Endocrinology outpatient clinic with symptoms consistent with hypothyroidism were identified. Thyroid hormone concentrations were measured by liquid chromatography/tandem mass spectrometry and immunoassay. Patients with normal TSH concentrations were assessed for both clinical and biochemical hypothyroidism.We evaluated the effect of ACTH stimulation (performed on patients for assessment of adrenal function) on TSH concentration., Results: Patients with symptoms consistent with hypothyroidism but with normal TSH values in the range of 1-4 IU/mL and normal free T4 (FT4) values by immunoassay measurements were confirmed to be biochemically hypothyroid following measurements of thyroid hormones by mass spectrometry. We present case studies of two patients, a 76-year-old male and a 58-year-old female. Improvement in the male patient's hypothyroid symptoms, including afternoon fatigue, constipation, alopecia, dry skin and high cholesterol, was documented after initiating thyroid hormone replacement.ACTH stimulation resulted in an average decrease of 17% in TSH between time 0 and 60 minutes post stimulation., Conclusion: Although measurement of TSH is a convenient screen for thyroid function, it is influenced by many factors which may affect its overall reliability. We believe thyroid function should be assessed by more than a single test. We recommend measurement of thyroid hormone concentrations by mass spectrometry if the patient's clinical presentation is discordant with their TSH levels.

Introduction: The neuropsychological battery of the Uniform Data Set (UDSNB) was implemented in 2005 by the National Institute on Aging (NIA) Alzheimer Disease Centers program to measure cognitive performance in dementia and mild cognitive impairment due to Alzheimer Disease. This paper describes a revision, the UDSNB 3.0., Methods: The Neuropsychology Work Group of the NIA Clinical Task Force recommended revisions through a process of due diligence to address shortcomings of the original battery. The UDSNB 3.0 covers episodic memory, processing speed, executive function, language, and constructional ability. Data from 3602 cognitively normal participants in the National Alzheimer Coordinating Center database were analyzed., Results: Descriptive statistics are presented. Multivariable linear regression analyses demonstrated score differences by age, sex, and education and were also used to create a normative calculator available online., Discussion: The UDSNB 3.0 neuropsychological battery provides a valuable non proprietary resource for conducting research on cognitive aging and dementia.

Objective: The aim of the study was to determine the relationship of lifestyle factors and neurocognitive functioning in older adults with vascular risk factors and cognitive impairment, no dementia (CIND)., Methods: One hundred sixty adults (M [SD] = 65.4 [6.8] years) with CIND completed neurocognitive assessments of executive function, processing speed, and memory. Objective measures of physical activity using accelerometry, aerobic capacity determined by exercise testing, and dietary habits quantified by the Food Frequency Questionnaire and 4-Day Food Diary to assess adherence to the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets were obtained to assess direct effects with neurocognition. Potential indirect associations of high-sensitivity C-reactive protein and the Framingham Stroke Risk Profile also were examined., Results: Greater aerobic capacity (β = 0.24) and daily physical activity (β = 0.15) were associated with better executive functioning/processing speed and verbal memory (βs = 0.24; 0.16). Adherence to the DASH diet was associated with better verbal memory (β = 0.17). Greater high-sensitivity C-reactive protein (βs = -0.14; -0.21) and Framingham Stroke Risk Profile (β = -0.18; -0.18) were associated with poorer executive functioning/processing speed and verbal memory. Greater stroke risk partially mediated the association of aerobic capacity with executive functioning/processing speed, and verbal memory and greater inflammation partially mediated the association of physical activity and aerobic fitness, with verbal memory., Conclusions: Higher levels of physical activity, aerobic fitness, and adherence to the DASH diet are associated with better neurocognitive performance in adults with CIND. These findings suggest that the adoption of healthy lifestyle habits could reduce the risk of neurocognitive decline in vulnerable older adults., Clinical Trial Registration: NCT01573546.

At a meeting of the EU/US/Clinical Trials in Alzheimer's Disease (CTAD) Task Force in December 2016, an international group of investigators from industry, academia, and regulatory agencies reviewed lessons learned from ongoing and planned prevention trials, which will help guide future clinical trials of AD treatments, particularly in the pre-clinical space. The Task Force discussed challenges that need to be addressed across all aspects of clinical trials, calling for innovation in recruitment and retention, infrastructure development, and the selection of outcome measures. While cognitive change provides a marker of disease progression across the disease continuum, there remains a need to identify the optimal assessment tools that provide clinically meaningful endpoints. Patient- and informant-reported assessments of cognition and function may be useful but present additional challenges. Imaging and other biomarkers are also essential to maximize the efficiency of and the information learned from clinical trials., Competing Interests: P. Aisen: NeuroPhage, Eli Lilly, Merck, Roche, Amgen, Abbvie, Pfizer, Novartis, Janssen, Lundbeck, Biogen, iPerian, Probiodrug, Anavex, Cohbar, Cytox, aTyr, Avanir; R. Bateman: Abbvie, AstraZeneca, Biogen, Eisai, Eli Lilly and Co., Hoffman La-Roche Inc., Janssen, Pfizer, Sanofi-Aventi; N. Fox: Janssen, Roche, Eli Lilly, Novartis, GSK, Biogen; S. Gauthier: Eli Lilly, TauRx, Roche, Eisai, Lundbeck, Schwabe; L. Schneider: Eli Lilly, Novartis, Roche/Genentech, Takeda; P. Tariot: Roche, Novartis, Amgen, Abbvie, Eli Lilly, AstraZeneca, Lundbeck, AC Immune, Merck, Takeda, Boehringer-Ingelheim; K. Welsh-Bohmer: Takeda, Merck, Biogen, Roche, J and J; B. Vellas: Biogen, Eli Lilly, Roche, Nestlé, Merck; R. Sperling: Avid/Lilly, Janssen, Bracket, Genetech, Sanofi, Roche, Abbvie, Lundbeck, Otsuka, Merck. S. Henrix: Pentara Corporation; R. Doody: Genentech/Roche; C. Ho, J. Breitner, R. Amariglio, M. Grundman, R. Raman, M. Isaac: No conflict of interest. The Task Force was partially funded by registration fees from industrial participants. These corporations placed no restrictions on this work.

Objectives: To look for changes in intrinsic functional brain connectivity associated with postoperative changes in cognition, a common complication in seniors undergoing major surgery, using resting-state functional magnetic resonance imaging., Design: Objective cognitive testing and functional brain imaging were prospectively performed at preoperative baseline and 6 weeks after surgery and at the same time intervals in nonsurgical controls., Setting: Academic medical center., Participants: Older adults undergoing cardiac surgery (n = 12) and nonsurgical older adult controls with a history of coronary artery disease (n = 12); no participants had cognitive impairment at preoperative baseline (Mini-Mental State Examination score >27)., Measurements: Differences in resting-state functional connectivity (RSFC) and global cognitive change relationships were assessed using a voxel-wise intrinsic connectivity method, controlling for demographic factors and pre- and perioperative cerebral white matter disease volume. Analyses were corrected for multiple comparisons (false discovery rate P < .01)., Results: Global cognitive change after cardiac surgery was significantly associated with intrinsic RSFC changes in regions of the posterior cingulate cortex and right superior frontal gyrus-anatomical and functional locations of the brain's default mode network (DMN). No statistically significant relationships were found between global cognitive change and RSFC change in nonsurgical controls., Conclusion: Clinicians have long known that some older adults develop postoperative cognitive dysfunction (POCD) after anesthesia and surgery, yet the neurobiological correlates of POCD are not well defined. The current results suggest that altered RSFC in specific DMN regions is positively correlated with global cognitive change 6 weeks after cardiac surgery, suggesting that DMN activity and connectivity could be important diagnostic markers of POCD or intervention targets for potential POCD treatment efforts., Competing Interests: Elements JNB MB TBH PJS WM TLB JHA JGG KWB MFN JPM Financial/Personal Conflicts No No No No No No No No No No No Employment or Affiliation a Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Grants/Funds b Yes No Yes No No Yes No No No No Yes Honoraria No No No No No No No No No No No Speaker Forum No No No No No No No No No No No Consultant No No No No No No No No No No No Stocks No No No No No No No No No No No Royalties No No No No No No No No No No No Expert Testimony No No No No No No No No No No No Board Member No No No No No No No No No No No Patents No No No No No No No No No No No Personal Relationship No No No No No No No No No No No a All coauthors share employment affiliation with Duke University Medical Center (DUMC). Authors MB, MW, MFN and JPM share department affiliation with DUMC Anesthesiology, while authors JNB and KWB share department affiliation with DUMC Psychiatry. b Coauthors JNB, TBH, TLB and JPM derived direct salary support from NHLBI grant (HL109971), which partially funded this research effort and manuscript., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Members of the Inhibitor of APoptosis (IAP) protein family suppress apoptosis within tumor cells, particularly in the context of immune cell-mediated killing by the tumor necrosis factor (TNF) superfamily cytokines. Most IAPs are opposed endogenously by the second mitochondrial activator of caspases (SMAC), which binds to selected baculovirus IAP repeat (BIR) domains of IAPs to displace interacting proteins. The development of SMAC mimetics as novel anticancer drugs has gained impetus, with several agents now in human clinical trials. To further understand the cellular mechanisms of SMAC mimetics, we focused on IAP family members cIAP1 and cIAP2, which are recruited to TNF receptor complexes where they support cell survival through NF-κB activation while suppressing apoptosis by preventing caspase activation. We established fluorescence polarization (FP) assays for the BIR2 and BIR3 domains of human cIAP1 and cIAP2 using fluorochrome-conjugated SMAC peptides as ligands. A library of SMAC mimetics was profiled using the FP assays to provide a unique structure activity relationship (SAR) analysis compared to previous assessments of binding to XIAP. Potent compounds displayed mean inhibitory binding constants (Ki) of 9 to 27 nM against the BIR3 domains of cIAP1 and cIAP2, respectively. Selected compounds were then characterized using cytotoxicity assays in which a cytokine-resistant human tumor cell line was sensitized to either TNF or lymphotoxin-α (LT-α). Cytotoxicity correlated closely with cIAP1 and cIAP2 BIR3 binding activity with the most potent compounds able to reduce cell viability by 50%. Further testing demonstrated that active compounds also inhibit RIP1 binding to BIR3 of cIAP1 and cIAP2 in vitro and reduce steady-state cIAP1 protein levels in cells. Altogether, these data inform the SAR for our SMAC mimetics with respect to cIAP1 and cIAP2, suggesting that these IAP family members play an important role in tumor cell resistance to cytotoxicity mediated by TNF and LT-α., Competing Interests: The authors have declared that no competing interests exist.

Issue addressed Tobacco consumption contributes to health disparities among Aboriginal Australians who experience a greater burden of smoking-related death and diseases. This paper reports findings from a baseline survey on factors associated with smoking, cessation behaviours and attitudes towards smoke-free homes among the Aboriginal population in inner and south-western Sydney. Methods A baseline survey was conducted in inner and south-western Sydney from October 2010 to July 2011. The survey applied both interviewer-administered and self-administered data collection methods. Multiple logistic regression was performed to determine the factors associated with smoking. Results Six hundred and sixty-three participants completed the survey. The majority were female (67.5%), below the age of 50 (66.6%) and more than half were employed (54.7%). Almost half were current smokers (48.4%) with the majority intending to quit in the next 6 months (79.0%) and living in a smoke-free home (70.4%). Those aged 30-39 years (AOR 3.28; 95% CI: 2.06-5.23) and the unemployed (AOR 1.67; 95% CI: 1.11-2.51) had higher odds for current smoking. Participants who had a more positive attitude towards smoke-free homes were less likely to smoke (AOR 0.79; 95% CI: 0.74-.85). Conclusions A high proportion of participants were current smokers among whom intention to quit was high. Age, work status and attitudes towards smoke-free home were factors associated with smoking. So what? The findings address the scarcity of local evidence crucial for promoting cessation among Aboriginal tobacco smokers. Targeted promotions for socio-demographic subgroups and of attitudes towards smoke-free homes could be meaningful strategies for future smoking-cessation initiatives.

Development of emotion regulation strategy use involves a transition from reliance on suppression during childhood to greater use of reappraisal in adolescence and adulthood-a transition that parallels developmental changes in executive functions. We evaluated the relationship between emotion regulation strategy use and executive functioning in the everyday life of 70 typically developing adolescents who completed the Emotion Regulation Questionnaire for Youth and the Behavior Rating Inventory of Executive Function-Self-Report. Results indicated that greater reliance on reappraisal was associated with better executive functions, while reliance on suppression was related to poorer executive functions. Findings suggest that adolescents who rely on reappraisal may have more cognitive resources to help them remain attentive and well regulated in their daily lives. On the other hand, if better executive functions facilitate the use of reappraisal, adolescents' ability to regulate their emotions could potentially be enhanced via supports for executive functions.