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Objectives: Processing speed is essential to functional independence in later life, such as driving a vehicle. Few studies have examined processing speed and driving mobility in the context of racial differences and social determinants of health (SDoH). This study characterized the longitudinal association between processing speed and driving mobility, and how it varied by race and SDoH. Methods: Using data from the control arm of the Advanced Cognitive Training in Vital Elderly study (n = 581, 24.5% Black), multilevel models examined longitudinal associations between processing speed and driving mobility outcomes (driving space, exposure, and difficulty). Race and SDoH moderations were explored. Results: Decline in processing speed measures was associated with increased self-reported driving difficulty, but only for older adults with below-average to average scores for neighborhood and built environments and social community context SDoH domains. Discussion: Findings emphasize the influence of physical and social environmental characteristics on processing speed and driving mobility.

Decarbonization goals in the United States electricity sector are increasing the levels of renewable energy generation in the electricity supply system, and are driving increased attention to building electrification, which will increase the magnitude and shift the timing of the electricity system peak. These changes are motivating new approaches to coordinate building electricity demand with low-carbon renewable generation, elevating the importance of demand flexibility (DF) in buildings and the need to quantify the temporal impacts of DF. In this paper, we first characterize the hourly predictive accuracy of six commonly used baseline models in an application context of quantifying building-level load shift. Our analysis revealed insights such as hours of the day (afternoons), periods of the week (weekends), and seasons (summer) that were predicted with more accuracy than other time periods. In addition, the analysis showed tendencies toward overprediction or underprediction of load. Secondly, we provide the first published investigation of baseline erosion from repeated dispatch of building load shifting. We observed that as the baseline period is pushed back further from the prediction day, the distribution of errors across baseline model predictions increases, with notable inflection points near the three-week erosion point for two of the three models.

The study objective was to investigate the effects of childhood residential mobility on older adult physical and mental health. In REasons for Geographic and Racial Differences in Stroke (REGARDS) Study, we used linear regression models to investigate if number of moves during childhood predicted mental and physical health (SF-12 MCS, PCS), adjusting for demographic covariates, childhood socioeconomic status (SES), childhood social support, and adverse childhood experiences (ACEs). We investigated interaction by age, race, childhood SES, and ACEs. People who moved more during childhood had poorer MCS scores, β = -0.10, SE = 0.05, p = 0.03, and poorer PCS scores, β = -0.25, SE = 0.06, p < 0.0001. Effects of moves on PCS were worse for Black people compared to White people (p = 0.06), those with low childhood SES compared to high childhood SES (p = 0.02), and high ACEs compared to low ACEs (p = 0.01). As family instability accompanying residential mobility, family poverty, and adversity disproportionately affect health, Black people may be especially disadvantaged.

Background There are ethnic differences, including differences related to indigeneity, in the incidence of first episode psychosis (FEP) and pathways into care, but research on ethnic disparities in outcomes following FEP is limited. Aims In this study we examined social and health outcomes following FEP diagnosis for a cohort of Māori (Indigenous people of New Zealand) and non-Māori (non-Indigenous) young people. We have focused on understanding the opportunities for better outcomes for Māori by examining the relative advantage of non-Māori with FEP. Method Statistics New Zealand's Integrated Data Infrastructure was accessed to describe mental health and social service interactions and outcomes for a retrospective FEP cohort comprising 918 young Māori and 1275 non-Māori aged 13 to 25 at diagnosis. Logistic regression models were used to examine whether social outcomes including employment, benefit receipt, education and justice involvement in year 5 differed by indigeneity. Results Non-Māori young people were more likely than Māori to have positive outcomes in the fifth year after FEP diagnosis, including higher levels of employment and income, and lower rates of benefit receipt and criminal justice system involvement. These patterns were seen across diagnostic groups, and for both those receiving ongoing mental healthcare and those who were not. Conclusions Non-Māori experience relative advantage in outcomes 5 years after FEP diagnosis. Indigenous-based social disparities following FEP urgently require a response from the health, education, employment, justice and political systems to avoid perpetuating these inequities, alongside efforts to address the disadvantages faced by all young people with FEP.

OBJECTIVES:. Accumulating basic science data, early clinical findings and various feasibility considerations have provided rationales for administering ketamine as a proposed rescue medication for midazolam-resistant status epilepticus (SE) in the logistically challenging prehospital environment. This report details the multiyear experience of paramedics managing midazolam-resistant SE following the introduction of a ketamine-rescue protocol. DESIGN:. A 7-year, population-based, observational study was conducted to evaluate outcomes of patients treated with IV, intraosseous, intramuscular, or intranasal ketamine for SE despite sufficient midazolam dosings. Tracked outcomes included: 1) rapid/sustained termination of clinical seizures in adults while under paramedics’ care; 2) corresponding evaluations in children/adolescents; 3) any concerning observations regarding need for assisted ventilation, intubation, or other active interventions post-ketamine; and 4) any identifiable associations between outcomes and circumstances, demographics, or medical history. SETTING:. Emergency response 9-1-1 system serving a large, diverse U.S. county (jurisdictional population, 961,000/1,769 sq miles). PATIENTS:. Those receiving ketamine from paramedics for persistent seizures. INTERVENTIONS:. Adults and adolescents: 100 mg ketamine IV/intraosseous/intramuscular/intranasal; children: 1 mg/kg intramuscular/intranasal. MEASUREMENTS AND MAIN RESULTS:. Among 81 total cases, 57 involved adults (18–86 yr old) receiving the SE-midazolam + ketamine protocol. Ketamine rapidly terminated convulsions in 56 (98.2%) without recurrence during prehospital and hospital arrival phases. For approved reasons, paramedics administered ketamine directly (no midazolam) in eight adults and one child, terminating convulsions in every case. Among 15 childhood/adolescent cases treated per protocol, ketamine rapidly terminated SE activity in 11, but only mitigated it in four, including two retrospectively judged to involve nonseizure activity and two involving intranasal administration. Among all 81 ketamine-treated cases, there were no identifiable clinically significant complications attributable to ketamine, particularly the need for any additional active interventions. CONCLUSIONS:. Ketamine appeared to be consistently effective in treating adults with ongoing out-of-hospital seizures that were resistant to sufficient dosings of midazolam. Similar results were observed in children/adolescents.

ABSTRACT Alterations to lipid storage, and the consequent effects on liver structure, need to be considered when replacing wild‐derived fish meal (wd‐FM) with alternative ingredients in formulated diets for commercially aquacultured species. The replacement of wd‐FM is likely to alter the available level of precursors for bile acid production, potentially impacting the absorption of dietary lipids and fat‐soluble vitamins. In this 252‐day study, Yellowtail Kingfish, Seriola lalandi (2.52 ± 0.25 kg; 546 ± 20 mm [fork length; mean ± standard deviation]) were fed five different diets. A 30% wd‐FM diet served as a control. Dietary wd‐FM inclusions were reduced to 20% and 10%, replaced with FM by‐product meal. In addition, dietary wd‐FM levels were reduced to 20% and replaced with poultry meal (PM) or soy protein concentrate (SPC) in two other separate diets. Fat deposition in the liver was similar amongst all treatment groups with bile duct proliferation and periductular fibrosis observed in the livers of fish fed diets with wd‐FM replacement with 10% PM or 10% SPC. Fish fed FM by‐product meal at 10% and 20% replacement displayed similar liver structures to control fish. Yellowtail Kingfish fed a 30% wd‐FM diet may have the FM replaced by up to 66.67% FM by‐product, 33.3% PM or 33.3% SPC without any significant impact on total bile acid synthesis, storage and excretion and liver lipid storage. This research expands our ability to deliver cost‐effective nutritional solutions in support of Yellowtail Kingfish culture.

Category: Other; Midfoot/Forefoot Introduction/Purpose: Charcot-Marie-Tooth (CMT) disease is an inherited peripheral neuropathy known to cause progressive sensory and motor impairment. Patients often develop foot structure abnormalities, including pes cavus, due to intrinsic muscle weakness. These deformities, paired with the disease’s typical sensory and motor symptoms, can increase the risk of falls. Ankle foot orthoses (AFOs) are commonly used with the intent of reducing fall risk and restoring a more normal gait. The Timed Up and Go (TUG) test is widely used as a clinical screening tool to identify patients at risk of falling. No previous study has applied the TUG test in the setting of CMT fall risk assessment. The purpose of this study was to assess the overall predictive value of TUG on fall risk in CMT. Methods: Existing data from patients seen at the at the University of Iowa Hospitals and Clinics, as part of research with the Inherited Neuropathy Consortium (INC), were used for this investigation. Patients in the INC return to clinic on an annual basis and data from each patient’s most recent evaluation were included for analysis. All CMT sub-types were included. Clinical outcome measures were taken from the CMT Functional Outcome Measure (CMT-FOM) and the CMT Health Index (CMT-HI). Timed up and go (TUG) and patient reported ankle-foot orthoses (AFO) use was recorded as part of the CMT-FOM. The CMT-HI provides patient perspective on the impact of various health related topics, including difficulty getting up from the floor or ground, falling, and difficulty rising from a seated position. Kruskal-Wallis and Wilcoxon Rank Sum tests were utilized for statistical analysis and pair-wise group comparisons. Results: In total, 126 patients of 4,971 available records were included for analysis. The remainder were excluded due to missing data, unconfirmed CMT diagnosis, or statistical outliers. TUG scores ranged from 3.4s to 26.0s (mean 9.70s). Responses to the CMT-HI Falls question included no effect, little effect, moderate effect, and severely effecting, and poorer responses were correlated with a slower average TUG (p< 0.0001). Participants who reported AFO use had a average TUG score of 11.29 seconds while non-users averaged 10.0 seconds (p=0.0015). 117/126 (93%) patients reported foot deformity: 106 pes cavus, 6 pes planus, 5 “other”, 7 reported none, and 2 unreported. Of the 117 with reported deformities, those with pes planus averaged a TUG of 9.76 seconds compared to 9.45 seconds with pes cavus. Conclusion: This is the first study to identify a significant correlation between patient-reported fall risk and average TUG in CMT patients. This observation of slower TUG times in individuals with greater fall risk is consistent with findings available for other at-risk falls populations, such as stroke patients. The most predominant deformity was pes cavus. However, neither the presence nor absence of foot deformities showed a substantial difference in TUG results. Patients who wore Ankle-foot orthoses had, on average, slower times in the TUG test than non-users. This is likely due to greater a dependency on AFOs with increased disease progression.

BackgroundChronic lymphocytic leukaemia (CLL) typically presents with asymptomatic, early-stage disease that is monitored until disease progression (‘treatment-naïve’ CLL). The objective of this pilot study was to assess the feasibility and preliminary safety of an exercise program in treatment-naïve CLL. We also sought to preliminarily assess the impact of the exercise program on disease activity, as it has been proposed that exercise training may reduce disease outgrowth in treatment-naïve CLL.MethodsA total of 40 treatment-naïve CLL patients were recruited into this randomised-controlled pilot study, and after screening, n = 28 were randomised into a 16-week, home-based, partially supervised, personalised, progressive exercise intervention (n = 14: mean ± SD: age = 62 ± 12 years) or 16 weeks of usual care, control group (n = 14: mean ± SD: age = 61 ± 10 years). The primary outcome measures were safety (number and severity of adverse events) and feasibility (uptake, retention, and adherence to the trial). Disease activity (CD5+/CD19+ CLL cells clonally restricted to kappa or lambda) and other immune cell phenotypes, with a principal focus on T cells, were measured by flow cytometry. Other secondary outcomes included DEXA-derived body composition, cardiorespiratory and functional fitness, resting cardiovascular measures.ResultsTrial uptake was 40%, and the overall retention rate was 86%, with 79% of the exercise group and 93% of the control group completing the trial. Adherence to the exercise intervention was 92 ± 8%. One serious adverse event was reported unrelated to the trial, and one adverse event related to the trial was reported. The exercise intervention elicited a 2% increase in DEXA-derived lean mass in the exercise group compared with a 0.4% decrease in the control group (p = 0.01). No between-group differences were observed over time for whole-body mass, BMI, bone mineral density, body fat, blood pressure resting heart rate, or measures of cardiorespiratory or functional fitness (all p > 0.05). No between-group differences were observed over time for clonal CLL cells and CD4+ or CD8+ T-cell subsets (all p > 0.05).ConclusionThe exercise training program used in this study was feasible in people with treatment-naïve CLL who passed pre-trial screening, and we preliminarily conclude that the exercise training program was safe and also resulted in an increase in lean mass.Clinical trial registrationhttps://doi.org/10.1186/ISRCTN55166064, identifier ISRCTN 55166064.

Objective: During Dignity Therapy a trained provider guides a patient to share their life story and legacy. Providers can demonstrate empathy through empathic self-disclosure (ESD), sharing something substantial and personal about themselves in response to the patient. The current study aims to identify the topics of ESDs and determine whether ESD frequency varied by patient and/or provider characteristics. Methods: Two coders analyzed 203 audio-recorded, transcribed Dignity Therapy sessions of palliative care patients (M = 65.78 years; SD = 7.43 years, 65.69% women) for ESD. Topic modeling characterized themes of ESD and multilevel modeling examined ESD frequency based on several patient and provider characteristics. Results: ESD occurred in 37% of interviews (M = 0.59, SD = 1.21). Topic modeling revealed five main themes: family, memory, school, geographical experiences, and values/beliefs. Multilevel modeling indicated patient-level differences, including greater rates of ESD when patients were men and older. Conclusion: ESD seems to be dependent on the context of the patient rather than individual communication style differences. Providers may use ESD in multiple instances, including when similar and different from patients. Innovation: This study introduces and defines the novel concept of ESD. It is among the first to examine patient-provider communication during Dignity Therapy, and the first to specifically examine self-disclosure.

Multiple myeloma is a haematological cancer characterised by the accumulation of clonal plasma cells in the bone marrow and is commonly treated with daratumumab, an anti-CD38 monoclonal antibody immunotherapy. Daratumumab often fails to induce stringent complete responses, due in part to resistance to antibody-dependent cellular cytotoxicity (ADCC) exerted by natural killer (NK)-cells and monocytes. Exercise bouts undertaken by healthy people induce lymphocytosis in blood, including to NK-cells and B-cells, but the effects of exercise are unknown in myeloma patients. In addition, whether exercise mobilises plasma cells has not been adequately investigated, and as such the potential impact of exercise on daratumumab treatment is unclear. In this exploratory pilot study, n = 16 smouldering multiple myeloma participants enrolled and n = 9 completed the study which comprised a bout of cycling 15% above anaerobic threshold for ∼30-min, with blood samples collected pre-, immediately post-, and 30-min post-exercise. Peripheral blood mononuclear cells were isolated from blood samples and incubated with the RPMI-8226 plasmacytoma cell line, with or without the presence of daratumumab to determine specific lysis using a calcein-release assay. Daratumumab-mediated cell lysis increased from 18.8% to 23.2% pre- to post-exercise, respectively (p 0.05). Notably, we observed a 305% increase in NK-cells expressing CD38, the daratumumab target antigen, which might render NK-cells more susceptible to daratumumab-mediated fratricide – whereby NK-cells initiate ADCC against daratumumab-bound NK-cells. In conclusion, exercise modestly improved the efficacy of daratumumab-mediated ADCC in vitro. However, plasma cells were largely unchanged, and NK-cells expressing CD38 – the daratumumab target antigen – increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis.

Objectives There are health disparities and inequities in the outcomes of critical illness survivors related to the influence of social determinants of health on recovery. The purpose of this study was to describe the relationship between critical illness recovery and the intermediary social determinants of health in the Canadian context. Because Canadian healthcare is provided within a universal publicly funded system, this analysis sheds light on the role of social determinants of health in the context of universal health services and a relatively robust social safety net.Design In this qualitative interpretive description study, data from semi-structured interviews with intensive care unit survivors, family caregivers and healthcare providers were analysed using thematic and constant comparative methods.Setting Western Canadian Hospital serving a population of 900 000 people.Participants The 74 study participants included 30 patients (mean age 58 years, 18 men and 12 women) and 25 family caregivers (mean age 55 years, 8 men and 17 women), representing 37 cases, as well as 19 healthcare providers.Results Challenges with employment and finances, home set-up, transportation, food and nutrition, medications and social support complicated and hindered critical illness recovery. Critical illness sequelae also altered these social determinants of health, suggesting a reciprocal relationship. Furthermore, individuals experiencing socioeconomic disadvantage before critical illness described being at a greater disadvantage following their critical illness, which interfered with their recovery and suggests an accumulation of risk for some.Conclusions Our findings underscore the significant influence of social determinants of health on critical illness recovery, highlighting the importance of creating and evaluating comprehensive approaches to health and well-being that address health inequities.

Background On 15 March 2019, a white supremacist gunman sequentially attacked two mosques in Christchurch, New Zealand, killing 51 people aged from 3 to 77 years and bullet-injuring 40 more. Approximately 250 people survived the atrocity, and many more family and community members have been directly or indirectly affected. Aim To develop an understanding of the personal experiences of some of those affected, including effects on daily life and well-being, in the 18–30 months following the attacks. Method Qualitative thematic analysis of semi-structured interviews with 21 men and women from September 2020 to August 2021 was performed. Participants were drawn from a larger quantitative study and included injured, bereaved, witnesses, family members and those from the wider Muslim community in Christchurch. Results Four superordinate themes were identified: being overwhelmed in the midst of chaos; experiencing silent and enduring impact; living similarly, but differently; and gaining meaning and growth. These themes captured ongoing distress inclusive of physical symptoms, family and community relationship dynamics and connectedness, secondary stressors, and diversity in coping and growth. For most, the centrality of Islam as a faith tradition was woven throughout. Conclusion Consistent with previous literature, post-trauma reactions were pervasive and varied. This appeared to be compounded by secondary stressors in this cohort, such as sociopolitical circumstances, demographic diversity, the COVID-19 pandemic and justice processes. Findings also revealed a strong spiritual thread in the experiences of this minority faith community, shedding light on a complex interaction between recovery and post-traumatic growth.

Background There is strong interest in the evaluation of longer‐term outcome metrics for congenital heart diseases (CHDs); however, registries focus on postoperative metrics. Methods and Results Informed by user online discussion forums and scoping of national data, we selected sentinel CHDs and long‐term outcome metrics suitable for routine monitoring. We then developed sentinel CHD phenotypes and algorithms for identifying treatment pathway procedures using clinical codes. Finally, we calculated the metrics within a retrospective national cohort analysis. The 9 selected sentinel CHDs had a higher‐than‐average prevalence, typically involved surgery in infancy, and were associated with an increased risk of late mortality. The selected metrics of survival and reinterventions at 1, 5, and 10 years were both important and feasible. The cohort included 29 319 (41.3% of all operated CHD births) English and Welsh children born with sentinel CHDs in 2000 to 2022. Example metrics at age 10 years included: survival—hypoplastic left heart syndrome: 57.6% (95% CI, 54.9%–60.4%), functionally univentricular heart: 86.7% (95% CI, 84.6%–88.9%), transposition of the great arteries: 93.1% (95% CI, 92.2%–93.9%), pulmonary atresia: 81.0% (95% CI, 79.1%–82.9%), atrioventricular septal defect: 88.5% (95% CI, 87.5%–89.5%), tetralogy of Fallot: 95.1% (95% CI, 94.4%–95.8%), aortic stenosis: 94.4% (95% CI, 93.3%–95.6%), coarctation: 96.7% (95% CI, 96.2%–97.3%), and ventricular septal defect: 96.9% 95% CI, (96.4%–97.3%); and (2) cumulative incidence of reintervention—hypoplastic left heart syndrome : 54.5% (95% CI, 51.5%–57.3%), functionally univentricular heart: 57.3% (95% CI, 53.9%–60.5%), transposition of the great arteries: 20.9% (95% CI, 19.5%–22.3%), pulmonary atresia: 66.8% (95% CI, 64.2%–69.1%), atrioventricular septal defect: 21.6% (20.3%–23.0%), tetralogy of Fallot: 26.6% (95% CI, 25.2%–28.0%), aortic stenosis: 31.2% (95% CI, 28.8%–33.6%), coarctation: 19.8% (95% CI, 18.6%–21.1%), and ventricular septal defect: 6.1% (95% CI, 5.5%–6.8%). Conclusions It is feasible to report important long‐term outcomes of survival and reintervention for sentinel CHDs using routinely collected procedure records, adding value to national audit.

Aerial images are increasingly adopted and widely used in various research areas. In marine mammal studies, these imagery surveys serve multiple purposes: determining population size, mapping migration routes, and gaining behavioral insights. A single aerial scan using a drone yields a wealth of data, but processing it requires significant human effort. Our research demonstrates that deep learning models can significantly reduce human effort. They are not only able to detect marine mammals but also track their behavior using continuous aerial (video) footage. By distinguishing between different age classes, these algorithms can inform studies on population biology, ontogeny, and adult-calf relationships. To detect beluga whales from imagery footage, we trained the YOLOv7 model on a proprietary dataset of aerial footage of beluga whales. The deep learning model achieved impressive results with the following precision and recall scores: beluga adult = 92%—92%, beluga calf = 94%—89%. To track the detected beluga whales, we implemented the deep Simple Online and Realtime Tracking (SORT) algorithm. Unfortunately, the performance of the deep SORT algorithm was disappointing, with Multiple Object Tracking Accuracy (MOTA) scores ranging from 27% to 48%. An analysis revealed that the low tracking accuracy resulted from identity switching; that is, an identical beluga whale was given two IDs in two different frames. To overcome the problem of identity switching, a new post-processing algorithm was implemented, significantly improving MOTA to approximately 70%. The main contribution of this research is providing a system that accurately detects and tracks features of beluga whales, both adults and calves, from aerial footage. Additionally, this system can be customized to identify and analyze other marine mammal species by fine-tuning the model with annotated data.

Individuals who are deaf and use American Sign Language (ASL) as their primary mode of communication experience unique negative life experiences, such as lack of communication, limited access to services, marginalization, and discrimination, that can adversely impact resilience and psychological well-being. In addition, deaf individuals experience higher rates of intimate partner violence, polyvictimization, sexual, physical, and emotional abuse, and unemployment. These negative life experiences can sometimes be accompanied by maladaptive behaviors, such as substance use. Resilience and a positive sense of well-being can help to mitigate adverse life events. This survey research utilizes a sample of 206 deaf participants, whose primary language is ASL, and hearing participants to examine the relationships between negative life experiences, substance use, resilience, and well-being. Findings indicate: (1) deaf participants reported experiencing several negative life events significantly more often than their hearing counterparts, specifically being sent to jail or prison, having a serious physical illness, and sexual abuse by a partner than hearing participants; (2) deaf participants reported more experiences of having an abortion or miscarriage and parental separation or divorce as children than their hearing counterparts; (3) deaf individuals reported higher marijuana use than their hearing counterparts, but less use of stimulants, inhalants, and prescription drug abuse; (4) experiences of mental illness was significantly associated with resilience and well-being; and (5) deaf and hearing participants had similar scores in resilience and well-being. The author identifies strengths and limitations of the study and discusses implications for future research.

BackgroundPain is associated with cognitive decline among older adults, but few studies have investigated bidirectional associations between pain and cognitive decline, especially in older Hispanic populations. Our objective was to assess the bidirectional association between pain interference and cognitive performance in a sample of older Puerto Rican adults.MethodsData came from baseline and 4-year follow-up of the Puerto Rican Elderly: Health Conditions Study, a longitudinal representative study of Puerto Rican older adults aged 60 and older. Pain and cognitive performance were assessed at each wave. A pain interference variable was created using the sum of pain status (yes/no) and pain interference (yes/no; range 0-2). Global cognitive performance was assessed with the Mini-Mental Cabán. We tested bidirectional associations using a path model with concurrent and cross-lagged paths between pain and cognitive performance, adjusting for sociodemographic and health factors (n = 2 349).ResultsBaseline pain interference was not associated with baseline cognitive performance (p = .636) or with cognitive performance at follow-up (p = .594). However, increased pain interference at follow-up was associated with greater cognitive decline at follow-up (β = -0.07, standard error [SE] = 0.02, p = .003). Greater baseline cognitive performance was associated with lower pain interference at follow-up (β = -0.07, SE = 0.02, p = .007).ConclusionsThese findings highlight the importance of worsening pain interference as a potentially modifiable risk factor for cognitive decline, as pain treatment options exist. Additionally, better baseline cognitive performance may be a protective factor for pain, providing further evidence of the dynamic relationship between pain and cognitive performance.

Children and adolescents with intellectual and developmental disabilities (IDD) are more likely to engage in challenging and interfering behavior than their typically developing peers, which has been linked to many negative outcomes. The most effective interventions to address challenging and interfering behavior incorporate function-based assessments, which are used to develop individualized behavior interventions. Functional communication training (FCT) is an evidence-based practice to decrease challenging and interfering behavior that can be taught to parents using behavioral parent training (BPT); however, there are limited skilled professionals who can develop interventions and train parents. Telehealth can enable greater access to these professionals. This study used withdrawal designs to determine whether high parent treatment fidelity resulted in decreased challenging and interfering behavior and increased appropriate replacement behavior. Three participants (8-17 years) were included in the study, and their parents served as interventionists during mealtime, toothbrushing, and room cleaning. Data were analyzed using visual analysis. Each parent achieved high treatment fidelity with one session of BPT and bug-in-ear coaching. All participants had a decrease in challenging and interfering behavior and an increase in functional communication responses (FCRs) upon the introduction of the intervention with reliable reversals. All parents reported high social validity. Results and implications for practice and future research are discussed.

BackgroundCyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.MethodsWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.ResultsHigh-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss.ConclusionThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.