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Our Paper In Thomson, Hanson and McLanahan (1994), we investigated the relative importance of two types of parental resources--time and money--for explaining the association between family structure and children's academic [...]

This article examines the prevalence, predictors and outcomes of unmarried mothers' repartnering patterns following a nonmarital birth. Results indicate that, within five years after a birth, approximately two-thirds of unmarried mothers end their relationship with the focal child's biological father, and more than half of these mothers enter new partnerships. Among those who repartnered, 60 percent of mothers formed unions with men who had higher economic capabilities than their former partners, 20 percent formed unions with men of similar capabilities, and 20 percent formed unions with men who had lower capabilities. This pattern holds for both nonresidential and coresidential unions. Our findings are consistent with marriage market, learning and evolutionary biology theories about union formation, and they provide support for qualitative evidence that unmarried mothers have high standards for new partners. While many mothers find new partners who seem to offer a higher level of economic security, many other mothers remain unpartnered, likely due (at least in part) to the limited pool of potential partners with relatively high levels of economic promise., Introduction The dramatic increase in nonmarital childbearing over the past four decades represents an important change in family demography. Rather than signaling a decline in the importance of marriage, however, [...]

The social and economic burden of long-term illness and chronic conditions is not equitably distributed: Most people have moderate health care needs, and the personal cost of meeting these needs [...]

Most states enroll individuals with disabilities who receive Supplemental Security Income (SSI) in Medicaid managed care plans. The impact of managed care on these individuals, especially those with substance abuse disorders, is not well understood. A review of the literature related to substance abuse, disability, and Medicaid managed care suggests that substance abuse is a serious issue for individuals with disabilities. More research is needed to determine how the substance abuse treatment needs of individuals with disabilities can be met through Medicaid managed care. The authors identified topics for a research agenda on the needs of individuals with disabilities who also experience co-occurring substance abuse disorders. Implications for social work policy and practice are discussed. Key words disability Medicaid managed care policy substance abuse, Nearly 7 million Americans with disabilities receive federally sponsored cash support and health care benefits from the Supplemental Security Income (SSI) program (U.S. House of Representatives, 2000). These individuals experience [...]

Abstract We used data from the National Survey of Families and Households to investigate economic resources and parental behavior explanations for family structure effects on children. The economic explanation received considerable support in terms of single-mother disadvantage and accounted for a smaller proportion of disadvantage associated with mother-partner families. Parental behaviors, particularly maternal and paternal support, accounted for much smaller proportions of disadvantages found in mother-stepfather as well as mother-partner families. Parental behaviors did not appear to mediate any of the economic resource effects on children., During the past decade, a considerable body of research has shown that (1) children raised by both original parents are advantaged in several domains of well-being compared to children whose [...]

A key element of the Patient Protection and Affordable Care Act (known as the Affordable Care Act or the ACA) (P.L. 111-148) is the provision relating to the creation of [...]

In the past 2 decades, modern radiological methods, such as multiple detector computed tomography (MDCT), MDCT-angiography, and cardiac magnetic resonance imaging (MRI) were introduced into postmortem practice for investigation of sudden death (SD), including cases of sudden cardiac death (SCD). In forensic cases, the underlying cause of SD is most frequently cardiovascular with coronary atherosclerotic disease as the leading cause. There are many controversies about the role of postmortem imaging in establishing the cause of death and especially the value of minimally invasive autopsy techniques. This paper discusses the state of the art for postmortem radiological evaluation of the heart compared to classical postmortem examination, especially in cases of SCD. In SCD cases, postmortem CT is helpful to estimate the heart size and to visualize haemopericardium and calcified plaques and valves, as well as to identify and locate cardiovascular devices. Angiographic methods are useful to provide a detailed view of the coronary arteries and to analyse them, especially regarding the extent and location of stenosis and obstruction. In postsurgical cases, it allows verification and documentation of the patency of stents and bypass grafts before opening the body. Postmortem MRI is used to investigate soft tissues such as the myocardium, but images are susceptible to postmortem changes and further work is necessary to increase the understanding of these radiological aspects, especially of the ischemic myocardium. In postsurgery cases, the value of postmortem imaging of the heart is reportedly for the diagnostic and documentation purposes. The implementation of new imaging methods into routine postmortem practice is challenging, as it requires not only an investment in equipment but, more importantly, investment in the expertise of interpreting the images. Once those requirements are implemented, however, they bring great advantages in investigating cases of SCD, as they allow documentation of the body, orientation of sampling for further analyses and gathering of other information that cannot be obtained by conventional autopsy such as a complete visualization of the vascular system using postmortem angiography.Key points There are no established guidelines for the interpretation of postmortem imaging examination of the heart At present, postmortem imaging methods are considered as less accurate than the autopsy for cardiac deaths Postmortem imaging is useful as a complementary tool for cardiac deaths There is still a need to validate postmortem imaging in cardiac deaths by comparing with autopsy findings

Gram-negative bacterial pathogens inject type III secreted effectors (T3SEs) directly into host cells to promote pathogen fitness by manipulating host cellular processes. Despite their crucial role in promoting virulence, relatively few T3SEs have well-characterized enzymatic activities or host targets. This is in part due to functional redundancy within pathogen T3SE repertoires as well as the promiscuity of individual T3SEs that can have multiple host targets. To overcome these challenges, we generated and characterized a collection of yeast strains stably expressing 75 T3SE constructs from the plant pathogen Pseudomonas syringae. This collection is devised to facilitate heterologous genetic screens in yeast, a non-host organism, to identify T3SEs that target conserved eukaryotic processes. Among 75 T3SEs tested, we identified 16 that inhibited yeast growth on rich media and eight that inhibited growth on stress-inducing media. We utilized Pathogenic Genetic Array (PGA) screens to identify potential host targets of P. syringae T3SEs. We focused on the acetyltransferase, HopZ1a, which interacts with plant tubulin and alters microtubule networks. To uncover putative HopZ1a host targets, we identified yeast genes with genetic interaction profiles most similar (i.e., congruent) to the PGA profile of HopZ1a and performed a functional enrichment analysis of these HopZ1a-congruent genes. We compared the congruence analyses above to previously described HopZ physical interaction datasets and identified kinesins as potential HopZ1a targets. Finally, we demonstrated that HopZ1a can target kinesins by acetylating the plant kinesins HINKEL and MKRP1, illustrating the utility of our T3SE-expressing yeast library to characterize T3SE functions.

Abstract BackgroundBreast augmentation-mastopexy can yield an aesthetically attractive breast, but the 1-stage procedure is prone to unsatisfactory outcomes, including poor wound healing. ObjectivesThe authors evaluated whether postsurgical application of a polyurethane bra cup coated with oxygen-enriched olive oil (NovoX Cup; Moss SpA, Lesa, Novara, Italy) would decrease pain associated with augmentation-mastopexy and improve the quality of the surgical scar. MethodsThis retrospective study was conducted at a single center from January 2016 to June 2019. All patients underwent 1-stage augmentation-mastopexy with the inverted T incision. For 2 weeks postsurgically, wounds were dressed either with the oxygen-enriched olive oil bra or with Fitostimoline (Farmaceutici Damor SpA, Naples, Italy). Patients indicated their pain intensity on postoperative days 2, 3, and 10, and patients and independent observers scored scar quality on the Patient and Observer Scar Assessment Scale (POSAS) 6 and 12 months after the procedure. ResultsA total of 240 women (120 per study arm) completed the study. All the patients had satisfactory aesthetic results, and there were no tolerability concerns with either postoperative dressing. Compared with patients in the Fitostimoline group, patients who received the oxygen-enriched olive oil bra cup had significantly lower pain levels, and their surgical scars were given better scores on the POSAS. ConclusionsThe results suggest that maintenance of the surgical wound in a film of oxygen-enriched olive oil for 2 weeks is a safe, effective modality for suppressing pain and promoting healing following augmentation-mastopexy. Level of Evidence: 2

Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling.

Background: In the United States, hepatitis C virus (HCV) diagnoses among reproductive-aged women are increasing amidst the ongoing opioid and drug overdose epidemic. While previous studies document racial and ethnic disparities in HCV testing and treatment in largely male populations, to our knowledge no national studies analyze these outcomes in reproductive-aged women with opioid use disorder (OUD)., Methods: We analyzed data from a cohort of reproductive-aged women (aged 15-44 years) with diagnosed OUD captured in the TriNetX Research Network, a network of electronic health records from across the United States. Using a log-binomial model, we assessed differences in achieving HCV cascade of care stages (HCV antibody testing, HCV infection [positive HCV RNA test result], linkage to care, and HCV treatment) by race and ethnicity., Results: From 2014 to 2022, 44.6% of the cohort were tested for HCV antibody. Asian and black/African American individuals had a lower probability of having an HCV antibody test than white individuals (risk ratio, 0.77 [95% confidence interval, .62-.96] and 0.76 [.63-.92], respectively). Among those with HCV infection, only 9.1% were treated with direct-acting antivirals. Hispanic/Latinx individuals had a higher probability of treatment than non-Hispanic/Latinx individuals (risk ratio, 1.63 [95% confidence interval, 1.01-2.61])., Conclusions: Few reproductive-aged women with OUD are tested or treated for HCV. Disparities by race and ethnicity in HCV testing further exacerbate the risk of perinatal transmission and disease progression among minoritized communities. Interventions are needed to improve overall rates of and equity in HCV screening and treatment for reproductive-aged women., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Limited data exist on educational programs for people using insulin pump (IP) therapy or those considering its initiation, and the influence of individual characteristics on their educational pathway remains unclear. Our aim was to analyze the characteristics of people with type 1 diabetes (T1D) referred for IP therapy and how these characteristics may influence their educational process. A retrospective descriptive observational study was carried out on people with T1D referred for participation in a structured pre-IP educational program in a hospital setting. Educational, sociodemographic and clinical variables were collected and analyzed. Participants were followed up 5 years after IP placement. Seventy-one people finalized the educational program, of whom 10 experienced major barriers to completing it. People with lower educational level required more sessions and weeks to complete it compared to those with higher educational levels. People referred due to suboptimal metabolic control and hypoglycemia also required more time to complete the process. It is essential for diabetes educators to recognize the diversity of characteristics, needs and challenges among the participants in an educational program. Based on this, they must adapt strategies to provide more effective, person-centered diabetes education and support, fostering positive and sustained outcomes and engagement for participants., (© The Author(s) 2024. Published by Oxford University Press.)

Competing Interests: Conflict of interest: none declared.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on nuclear factor-κB signaling. Nine rare, potentially deleterious variants were found in 8 of 21 patients, located in the IL17RC, IFNA10, or NLRP12 gene. Unlike the wild type NLRP12 protein, which inhibits nuclear factor-κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C., Competing Interests: Potential conflict of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: To explore the perceptions of outpatients with hypertension regarding the conflicting results between their self-reported medication adherence and chemical adherence testing., Methods and Results: An exploratory generic qualitative study design with semi-structured interviews was conducted. Thirteen adult patients being treated with antihypertensives were interviewed. Patients had a negative chemical adherence test for at least one prescribed antihypertensive, while they reported adhering to their medication. Audio-recorded interviews were thematically analysed. Six themes emerged: (1) becoming frustrated with medication intake, (2) being uncomfortable with addressing medication nonadherence, (3) feeling ashamed and angry about their nonadherence, (4) feeling falsely accused of nonadherence, (5) experiencing results as a wake-up call, and (6) wanting to be heard and listened to. Participants reacted differently to the adherence test results. Two distinct groups were identified among the participants: the first group felt shameful, disappointed, and angry at themselves for being nonadherent; the second group felt falsely accused and rejected the adherence test results. No differences between both groups were found in their reasons for becoming frustrated with medication intake and their behaviour after the adherence test results. Patients felt that communication with clinicians is key in the treatment support of patients with hypertension., Conclusion: Clinicians need to consider the reasons for nonadherence and the different responses of patients to the chemical adherence test results in their support to optimize treatment for patients with hypertension., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Fungal infections are serious complications after solid organ transplantation, with high mortality and morbidity. Given the importance of the local epidemiological data, and also extensive prophylactic regimens in solid organ transplant (SOT) recipients, this study aimed to investigate the clinical characteristics and resistance patterns of yeast isolates in SOT recipients at a main referral transplant center in Iran. Of the 275 recipients enrolled, 22 (8%) had at least one positive yeast culture at a median of 5 days after transplantation. Bacterial infection and reoperation were significantly associated with colonization or infection caused by yeast species (P:0.001). Moreover, mortality and length of ICU/hospital stay were significantly higher in patients with positive yeast cultures (P < 0.05). The most frequent species isolated was Candida albicans (50%), followed by C. glabrata (22.7%). Of species with definite breakpoints, the fluconazole- resistant rate was 23%. Caspofungin and amphotericin B showed potent activity against all isolates. Regarding the high risk of fungal infections, awareness of local epidemiological trends and resistance patterns can help improve outcomes in SOT recipients., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Youth with type 1 diabetes (T1D) are tasked with integrating their illness into their identity, a process conceptualized as illness identity. To date, longitudinal person-centered studies are lacking that substantiate qualitative research capturing illness identity as a process., Purpose: First, the current study examined patterns of stability and change among illness identity profiles in youth with T1D. Second, the study investigated how these profiles and patterns are related to background and medical characteristics, psychological, and contextual variables., Methods: This 4-wave longitudinal study (covering 3 years) included 558 adolescents and emerging adults with T1D at baseline recruited from the Belgian Diabetes Registry (age range = 14-26 years, 54% female). Latent transition analysis was used to examine (1) illness identity profiles and (2) patterns of stability and change among these profiles. Multinomial logistic regression models examined the profiles' and patterns' associations with the background and medical characteristics, psychological, and contextual variables., Results: Three illness identity profiles emerged: the more-integrated profile, the less-integrated profile, and the least-integrated profile. Although most individuals remained within their profile across 3 years, several meaningful transitions occurred as well. Age, self-esteem, diabetes distress, and psychological control were related to profile membership, whereas only illness duration was related to transitional patterns., Conclusion: The present study informed both theory and clinical practice on how illness identity is experienced by youth with T1D from a person-centered perspective. In addition, the results provided insight into which aspects are meaningfully related to illness identity integration, supporting tailored interventions for youth with T1D., (© Society of Behavioral Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Study Objectives: Alpha and theta oscillations characterize the waking human electroencephalogram (EEG) and can be modulated by closed-loop auditory stimulation (CLAS). These oscillations also occur during rapid eye movement (REM) sleep, but their function here remains elusive. CLAS represents a promising tool to pinpoint how these brain oscillations contribute to brain function in humans. Here we investigate whether CLAS can modulate alpha and theta oscillations during REM sleep in a phase-dependent manner., Methods: We recorded high-density EEG during an extended overnight sleep period in 18 healthy young adults. Auditory stimulation was delivered during both phasic and tonic REM sleep in alternating 6-second ON and 6-second OFF windows. During the ON windows, stimuli were phase-locked to four orthogonal phases of ongoing alpha or theta oscillations detected in a frontal electrode., Results: The phases of ongoing alpha and theta oscillations were targeted with high accuracy during REM sleep. Alpha and theta CLAS induced phase-dependent changes in power and frequency at the target location. Frequency-specific effects were observed for alpha trough (speeding up) and rising (slowing down) and theta trough (speeding up) conditions. CLAS-induced phase-dependent changes were observed during both REM sleep substages, even though auditory evoked potentials were very much reduced in phasic compared to tonic REM sleep., Conclusions: This study provides evidence that faster REM sleep rhythms can be modulated by CLAS in a phase-dependent manner. This offers a new approach to investigating how modulation of REM sleep oscillations affects the contribution of this vigilance state to brain function., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Study Objectives: The STOP-Bang questionnaire is a validated screening tool for obstructive sleep apnea (OSA). We conducted this study to validate it among patients hospitalized with acute symptomatic pulmonary embolism (PE)., Methods: This prospective cohort study enrolled consecutive stable patients with acute PE who underwent an overnight sleep study within 7 days after diagnosis. Our outcomes were: (1) the STOP-Bang questionnaire's utility for risk stratification, (2) the discrimination of the STOP-Bang questionnaire categories, (3) the false negative rate of STOP-Bang questionnaire prediction, and (4) the clinical utility of the STOP-Bang questionnaire to exclude OSA. We also calculated the test performance characteristics to predict OSA., Results: During the study period, 268 patients completed a sleep study. OSA was found in 47% of patients. OSA incidence in low-, moderate-, and high-risk STOP-Bang groups was 22.4%, 48.2%, and 61.5%, respectively (p < .001). The area under the receiver operating characteristics curve of the STOP-Bang questionnaire for risk of OSA was 0.65. The false negative rate of a low-risk STOP-Bang questionnaire result to rule out OSA was 22.4% and the clinical utility was 21.6%. The sensitivity was 89.8% (97.2% for men and 80.4% for women)., Conclusions: The STOP-Bang questionnaire showed poor discrimination for the risk of OSA in hospitalized patients with acute symptomatic PE. It had a high false negative rate and a low clinical utility. The STOP-Bang questionnaire had a good sensitivity in men, and might be used to rule out OSA in this population., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

To date, over 40 epigenetic and 300 epitranscriptomic modifications have been identified. However, current short-read sequencing-based experimental methods can detect <10% of these modifications. Integrating long-read sequencing technologies with advanced computational approaches, including statistical analysis and machine learning, offers a promising new frontier to address this challenge. While supervised machine learning methods have achieved some success, their usefulness is restricted to a limited number of well-characterized modifications. Here, we introduce Modena, an innovative unsupervised learning approach utilizing long-read nanopore sequencing capable of detecting a broad range of modifications. Modena outperformed other methods in five out of six benchmark datasets, in some cases by a wide margin, while being equally competitive with the second best method on one dataset. Uniquely, Modena also demonstrates consistent accuracy on a DNA dataset, distinguishing it from other approaches. A key feature of Modena is its use of 'dynamic thresholding', an approach based on 1D score-clustering. This methodology differs substantially from the traditional statistics-based 'hard-thresholds.' We show that this approach is not limited to Modena but has broader applicability. Specifically, when combined with two existing algorithms, 'dynamic thresholding' significantly enhances their performance, resulting in up to a threefold improvement in F1-scores., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objectives: The Ross procedure is currently receiving renewed interest. Its function and durability depend on preservation of pulmonary valve anatomy; limited data exists on normal pulmonary valve geometry. The objective was to compare aortic and pulmonary root and cusp dimensions in adults with normal tricuspid aortic and pulmonary valves., Methods: We reviewed 507 coronary computed tomography studies, selecting those with adequate visibility of both pulmonary and aortic roots for further analysis. Diastolic aortic and pulmonary root and cusp dimensions were measured. Root dimensions at different phases of the cardiac cycle were measured in three patients., Results: We analysed studies of 50 patients with the mean age of 54 years (SD : 16). In end-diastole, pulmonary root had a smaller sinutubular to basal ring ratio than the aortic root (0.82 (SD : 0.09) vs 1.14 (SD : 0.12), P < 0.001). Aortic and pulmonary cusps had similar dimensions; however, pulmonary cusp effective height was lower (5.9 mm (SD : 1.6) vs 8.4 mm (SD : 1.2), P < 0.001). Pulmonary basal ring perimeter was largest at end-diastole and smallest at end-systole, with the relative difference of 23.5% (SD : 2.7)., Conclusions: The pulmonary root has a similar cusp size compared to the aortic root, but a different shape, resulting in a lower pulmonary cusp effective height. The perimeter of the pulmonary basal ring changes during the cardiac cycle. These findings suggest that stabilising the autograft to normal aortic, rather than pulmonary, root dimensions should result in normal autograft cusp configuration. CTA could become a tool for personalized planning of the Ross procedure., Meeting Presentation: Presented at the 38th EACTS meeting in October 2024 in Lisbon., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Genome-wide association studies (GWAS) have increased our understanding of Parkinson's disease (PD) genetics by identifying common disease-associated variants. However, much of the heritability remains unaccounted for and we hypothesized that this could be partly explained by epistasis, the statistical interaction between two or more genetic variants. Here, we developed a genome-wide non-exhaustive epistasis screening pipeline called Variant-variant interaction through variable thresholds (VARI3) and applied it to diverse PD GWAS cohorts. We used 14 cohorts of European ancestry (14,671 cases and 17,667 controls) as a discovery stage, identifying 14 significant candidate variant-variant interactions. We then used four independent cohorts (13,377 cases and 413,789 controls) as replication stage, successfully replicating three epistasis signals located nearby SNCA and within MAPT and WNT3. Admixture analysis showed that the epistatic effect on PD of those variants at these loci was observed in both European ancestry and Native American ancestry individuals. We assessed the functional impact of the epistasis signals across a range of functional/-omics datasets identifying significant single-variant eQTLs across brain tissues, epistasis eQTL signals in whole-blood, PD-relevant pathways and ontologies, and chromatin interactions between the regions of the interacting SNPs. In conclusion, we identified and replicated novel epistatic signals associated with PD risk across multiple diverse genetic ancestry cohorts, highlighting their enrichment in pathways relevant to Parkinson's disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Among older adults with cancer receiving chemotherapy, frailty indices predict OS and toxicity. Given the increased use of immunotherapy and targeted therapy for advanced non-small cell lung cancer (aNSCLC), we evaluated frailty and Karnofsky Performance Status (KPS) among older adults with aNSCLC receiving chemotherapy, immunotherapy, and/or targeted therapy., Methods: Patients aged ≥ 65 with aNSCLC starting systemic therapy with non-curative intent underwent geriatric assessments over 6 months. We developed a deficit-accumulation frailty index to categorize patients as robust, pre-frail, or frail. To evaluate associations between frailty and KPS with OS, we used Cox proportional hazards models adjusted for race, insurance, and treatment. We used logistic regression to evaluate hospitalizations, functional decline, and severe toxicity., Results: Among 155 patients (median age 73), 45.8% were robust, 36.1% pre-frail, and 18.2% frail; 34.8% had a KPS ≥ 90, 32.9% had a KPS of 80, and 32.3% had a KPS ≤ 70. The median OS was 17.9 months. Pre-frail/frail patients had worse OS compared to robust patients (adjusted hazard ratio [HR] 2.09, 95% CI, 1.31-3.34) and were more likely to be hospitalized (adjusted odds ratio [OR] 2.21, 95% CI, 1.09-4.48), functionally decline (adjusted OR 2.29, 95% CI, 1.09-4.78), and experience grade ≥ 3 hematologic toxicity (adjusted OR 5.18, 95% CI, 1.02-26.03). KPS was only associated with OS., Conclusions: Our frailty index was associated with OS, hospitalization, functional decline, and hematologic AEs among older adults with aNSCLC receiving systemic therapies, while KPS was only associated with OS. Pretreatment frailty assessment may help identify older adults at risk for poor outcomes to optimize decision-making and supportive care., (© The Author(s) 2024. Published by Oxford University Press.)