The lifelong orgasm gap: exploring age's impact on orgasm rates.

Background: Research demonstrates significant gender- and sexual orientation-based differences in orgasm rates from sexual intercourse; however, this "orgasm gap" has not been studied with respect to age. Aim: The study sought to examine age-related disparities in orgasm rates from sexual intercourse by gender and sexual orientation. Methods: A survey sample of 24 752 adults from the United States, ranging in age from 18 to 100 years. Data were collected across 8 cross-sectional surveys between 2015 and 2023. Outcomes: Participants reported their average rate of orgasm during sexual intercourse, from 0% to 100%. Results: Orgasm rate was associated with age but with minimal effect size. In all age groups, men reported higher rates of orgasm than did women. Men's orgasm rates ranged from 70% to 85%, while women's ranged from 46% to 58%. Men reported orgasm rates between 22% and 30% higher than women's rates. Sexual orientation impacted orgasm rates by gender but not uniformly across age groups. Clinical Translation: The persistence of the orgasm gap across ages necessitates a tailored approach in clinical practice and education, focusing on inclusive sexual health discussions, addressing the unique challenges of sexual minorities and aging, and emphasizing mutual satisfaction to promote sexual well-being for all. Strengths and Limitations: This study is the first to examine the orgasm gap with respect to age, and does so in a large, diverse sample. Findings are limited by methodology, including single-item assessments of orgasm and a sample of single adults. Conclusion: This study revealed enduring disparities in orgasm rates from sexual intercourse, likely resulting from many factors, including sociocultural norms and inadequate sex education.

Camsites as a Context for Sexual Consent Education: User Experiences.

Understanding sexual consent is essential for the promotion of healthy sexual relationships and the prevention of sexual violence. Emerging sexual technologies can provide opportunities for users to learn about and potentially practice navigating sexual consent with partners, but this field of research is still nascent. In this study, we surveyed 5,828 erotic camsite users to determine whether they learned something new about sexual consent from their use of the site. Participants mostly identified as heterosexual white men, aged 18 to 99. Our results showed that 12% (n = 699) reported learning something new about sexual consent from their camsite use. Those who reported learning something new were prompted to provide a qualitative report of what they had learned; 36% (n = 252) did so. Users reported learning about the importance of respecting boundaries; how consent can change or differ based on the person, context, or time; the implicit and explicit forms of sexual consent, and the need to explicitly communicate about sexual consent; and how consent norms apply to commercial sexual contexts. Our findings show that people are learning about sexual consent from camsites, but the obtained knowledge is complex and sometimes negative. This study sheds light on the potential of emerging sexual technologies as sources for sexual education, and highlights the need for further research exploring the ways in which understandings of digital sexual consent translate to broader contexts.

Exploring patterns in mental health treatment and interests of single adults in the United States: a secondary data analysis.

Objective: The objective of this study is to examine mental health treatment utilization and interest among the large and growing demographic of single adults in the United States, who face unique societal stressors and pressures that may contribute to their heightened need for mental healthcare. Method: We analyzed data from 3,453 single adults, focusing on those with possible mental health treatment needs by excluding those with positive self-assessments. We assessed prevalence and sociodemographic correlates of mental health treatment, including psychotherapy and psychiatric medication use, and interest in attending psychotherapy among participants who had never attended. Results: 26% were in mental health treatment; 17% were attending psychotherapy, 16% were taking psychiatric medications, and 7% were doing both. Further, 64% had never attended psychotherapy, of which 35% expressed interest in future attendance. There were differences in current psychotherapy attendance and psychiatric medication use by gender and sexual orientation, with women and gay/lesbian individuals more likely to engage in both forms of mental health treatment. Additionally, interest in future psychotherapy among those who had never attended varied significantly by age, gender, and race. Younger individuals, women, and Black/African-American participants showed higher likelihoods of interest in psychotherapy. Conclusion: Our research highlights a critical gap in mental health treatment utilization among single adults who may be experiencing a need for those services. Despite a seemingly higher likelihood of engagement in mental health treatment compared to the general population, only a minority of single adults in our sample were utilizing mental health treatment. This underutilization and the observed demographic disparities in mental health treatment underscore the need for targeted outreach, personalized treatment plans, enhanced provider training, and policy advocacy to ensure equitable access to mental healthcare for single adults across sociodemographic backgrounds.

Concordant B and T Cell Heterogeneity Inferred from the Multiomic Landscape of Peripheral Blood Mononuclear Cells in a Crohn's Disease Cohort.

BACKGROUND AND AIMS: Crohn's disease is characterized by inflammation in the gastrointestinal tract due to a combination of genetic, immune, and environmental factors. Transcriptomic and epigenomic profiling of intestinal tissue of Crohn's disease patients have revealed valuable insights into pathology, however have not been conducted jointly on less invasive peripheral blood mononuclear cells (PBMCs). Furthermore, the heterogeneous responses to treatments among individuals with Crohn's disease imply hidden diversity of pathological mechanisms. METHODS: We employed single nucleus multiomic analysis, integrating both snRNA-seq and snATAC-seq of PBMCs with a variety of open source bioinformatics applications. RESULTS: Our findings reveal a diverse range of transcriptional signatures among individuals, highlighting the heterogeneity in PBMC profiles. Nevertheless, striking concordance between three heterogeneous groups was observed across B cells and T cells. Differential gene regulatory mechanisms partially explain these profiles, notably including a signature involving TGFß signaling in two individuals with Crohn's disease. A mutation mapped to a transcription factor binding site within a differentially accessible peak associated with the expression of this pathway, with implications for a personalized approach to understanding disease pathology. CONCLUSIONS: This study highlights how multiomic analysis can reveal common regulatory mechanisms that underlie heterogeneity of PBMC profiles, one of which may be specific to inflammatory disease.

"They didn't think we'd do it!": Community gardening as an act of resistance for people with dementia.

People living with dementia commonly report negative experiences such as disempowerment, stigma, and oppression. Community gardening has demonstrated its potential as a forum for the practice of resistance against the oppressions experienced by other marginalised groups; however, this element of the experience of community gardening has yet to be explored in the context of dementia. A collaboratively-designed community gardening project took place over six weeks, involving six people with dementia. The participants selected all activities undertaken in the garden. Data were collected through semi-structured group interviews with the gardeners and researcher observations. Context-setting semi-structured individual interviews were conducted with four day centre staff members, and three key informants who had experienced working with people with dementia in the garden. The garden acted as a platform for the articulation of both verbal and embodied expressions of resistance against the disempowerment and loss of agency experienced by many people with dementia. The participatory design of the gardening sessions enabled the gardeners to assert their autonomy and independence, and defy the negative stereotypes associated with dementia, which some of the group members appeared to have internalised. Community gardening activities may offer a forum for expressions of resistance against the structures oppressing individuals with dementia. However, in order for this potential to be unlocked, such initiatives must be collaboratively designed, following an approach which recognises the strengths and enduring abilities of people living with dementia. Additionally, the empowering impact of community gardening should not be diluted by positioning the activity as a substitute for adequate statutory health and social care provision, thereby individualising responsibility for the wellbeing of people with dementia.

Women Who Experience More Affectionate Touch Report Better Body Satisfaction and Relationship Outcomes.

Affectionate touch (e.g. hugging, handholding) is an essential component of many intimate relationships and is a primary contributor to overall relationship satisfaction as well as sexual satisfaction. Affectionate touch is understood to be a form of non-verbal communication in which the giver is expressing positive feelings toward the receiver. Here, we propose that affectionate touch also positively impacts receivers' body satisfaction, because affectionate touch is a positive message communicated toward the receiver's body. In a cross-sectional sample of romantically partnered women (N = 1,156), we assessed the association between affectionate touch frequency and body satisfaction. We also investigated whether affectionate touch is associated with relationship/sexual satisfaction in part because touch helps to improve women's evaluations of their own bodies. Our results showed that body satisfaction was a significant, partial mediator and a valid path through which affectionate touch shapes relationship quality. Receiving affectionate touch could bolster relationship satisfaction and self-perceptions among women. Given the prevalence of body dissatisfaction amongst women, these results suggest that the underexplored associations between affectionate touch and body satisfaction may have significant impacts on a wide array of future empirical and applied research trajectories.

UV Light Degradation of Polylactic Acid Kickstarts Enzymatic Hydrolysis.

Polylactic acid (PLA) and bioplastics alike have a designed degradability to avoid the environmental buildup that petroplastics have created. Yet, this designed biotic-degradation has typically been characterized in ideal conditions. This study seeks to relate the abiotic to the biotic degradation of PLA to accurately represent the degradation pathways bioplastics will encounter, supposing their improper disposal in the environment. Enzymatic hydrolysis was used to study the biodegradation of PLA with varying stages of photoaging. Utilizing a fluorescent tag to follow enzyme hydrolysis, it was determined that increasing the amount of irradiation yielded greater amounts of total enzymatic hydrolysis by proteinase K after 8 h of enzyme incubation. While photoaging of the polymers causes minimal changes in chemistry and increasing amounts of crystallinity, the trends in biotic degradation appear to primarily be driven by photoinduced reduction in molecular weight. The relationship between photoaging and enzyme hydrolysis appears to be independent of enzyme type, though commercial product degradation may be impacted by the presence of additives. Overall, this work reveals the importance of characterizing biodegradation with relevant samples that ultimately can inform optimization of production and disposal.

Medical Mistrust and Healthcare Seeking Among Women of Color with Chronic Vulvovaginal Pain.

BACKGROUND: Chronic vulvovaginal pain (CVVP), an umbrella term encompassing several gynecological pain conditions (e.g., vulvodynia, vaginismus), has a prevalence rate of 7-8% in the USA and is characterized by considerable diagnostic delay in patient experience research. Furthermore, current research in this area focuses largely on the experiences of white women, while the experiences of women of color are underrepresented. METHOD: In the present cross-sectional study (N = 488), we surveyed women of color (i.e., Asian, Black, and/or Hispanic/Latinx women) with CVVP about their perceptions and experiences with medical mistrust, healthcare seeking, and healthcare avoidance. RESULTS: Using the suspicion subscale of the Group-Based Medical Mistrust Scale, we found significant racial and ethnic differences in medical suspicion scores, with non-Black Hispanic/Latinx women reporting the highest suspicion scores and non-Hispanic/Latinx Black women reporting the lowest scores. Racial differences disappeared, however, after examining medical mistrust and perceived discrimination as predictors for various healthcare outcomes related to the journey to diagnosis and healthcare avoidance behaviors. We found that while suspicion was a reliable predictor of increased diagnostic delay and healthcare avoidance in many contexts, the results for perceived discrimination were more varied, suggesting considerable nuance in the relationship between medical mistrust, perceived discrimination, and healthcare seeking outcomes. CONCLUSION: These findings point to shared experiences of medical mistrust via suspicion that broadly characterize women of color's experiences in seeking CVVP-related care-future research is needed to examine nuances within racial and ethnic groups regarding their healthcare seeking experiences in the CVVP context.

Mutational impact of APOBEC3A and APOBEC3B in a human cell line and comparisons to breast cancer.

A prominent source of mutation in cancer is single-stranded DNA cytosine deamination by cellular APOBEC3 enzymes, which results in signature C-to-T and C-to-G mutations in TCA and TCT motifs. Although multiple enzymes have been implicated, reports conflict and it is unclear which protein(s) are responsible. Here we report the development of a selectable system to quantify genome mutation and demonstrate its utility by comparing the mutagenic activities of three leading candidates-APOBEC3A, APOBEC3B, and APOBEC3H. The human cell line, HAP1, is engineered to express the thymidine kinase (TK) gene of HSV-1, which confers sensitivity to ganciclovir. Expression of APOBEC3A and APOBEC3B, but not catalytic mutant controls or APOBEC3H, triggers increased frequencies of TK mutation and similar TC-biased cytosine mutation profiles in the selectable TK reporter gene. Whole genome sequences from independent clones enabled an analysis of thousands of single base substitution mutations and extraction of local sequence preferences with APOBEC3A preferring YTCW motifs 70% of the time and APOBEC3B 50% of the time (Y = C/T; W = A/T). Signature comparisons with breast tumor whole genome sequences indicate that most malignancies manifest intermediate percentages of APOBEC3 signature mutations in YTCW motifs, mostly between 50 and 70%, suggesting that both enzymes contribute in a combinatorial manner to the overall mutation landscape. Although the vast majority of APOBEC3A- and APOBEC3B-induced single base substitution mutations occur outside of predicted chromosomal DNA hairpin structures, whole genome sequence analyses and supporting biochemical studies also indicate that both enzymes are capable of deaminating the single-stranded loop regions of DNA hairpins at elevated rates. These studies combine to help resolve a long-standing etiologic debate on the source of APOBEC3 signature mutations in cancer and indicate that future diagnostic and therapeutic efforts should focus on both APOBEC3A and APOBEC3B.

Changing the phospholipid composition of lipid droplets alters localization of select lipid droplet proteins.

Our experiments aim to determine if decreasing the amount of phosphatidylcholine (PC) relative to phosphatidylethanolamine (PE) at the lipid droplet surface changes the localization of specific lipid droplet proteins. We manipulate lipid droplet phospholipids in both a cultured mouse hepatocyte (AML12) cell line and on synthetic lipid droplets. Decreasing the PC:PE ratio increases perilipin 2, decreases DGAT2, and does not change rab18 or lanosterol synthase levels on lipid droplets. These differences may be explained by the distinct structural motifs that mediate the protein-lipid droplet interactions.

Mental Health Impacts of Climate Change Among Vulnerable Populations Globally: An Integrative Review.

Background: Climate change has been shown to be directly linked to multiple physiological sequelae and to impact health consequences. However, the impact of climate change on mental health globally, particularly among vulnerable populations, is less well understood. Objective: To explore the mental health impacts of climate change in vulnerable populations globally. Methods: We performed an integrative literature review to identify published articles that addressed the research question: What are the mental health impacts of climate change among vulnerable populations globally? The Vulnerable Populations Conceptual Model served as a theoretical model during the review process and data synthesis. Findings/Results: One hundred and four articles were selected for inclusion in this review after a comprehensive review of 1828 manuscripts. Articles were diverse in scope and populations addressed. Land-vulnerable persons (either due to occupation or geographic location), Indigenous persons, children, older adults, and climate migrants were among the vulnerable populations whose mental health was most impacted by climate change. The most prevalent mental health responses to climate change included solastalgia, suicidality, depression, anxiety/eco-anxiety, PTSD, substance use, insomnia, and behavioral disturbance. Conclusions: Mental health professionals including physicians, nurses, physician assistants and other healthcare providers have the opportunity to mitigate the mental health impacts of climate change among vulnerable populations through assessment, preventative education and care. An inclusive and trauma-informed response to climate-related disasters, use of validated measures of mental health, and a long-term therapeutic relationship that extends beyond the immediate consequences of climate change-related events are approaches to successful mental health care in a climate-changing world.

APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer.

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions, as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts genes overexpressed in tumors and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW motifs consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B regulates R-loops and contributes to R-loop mutagenesis in cancer.

An analysis of suicides among first responders ─ Findings from the National Violent Death Reporting System, 2015-2017.

INTRODUCTION: First responders, including law enforcement officers (LEOs), firefighters, emergency medical services (EMS) clinicians, and public safety telecommunicators, face unique occupational stressors and may be at elevated risk for suicide. This study characterized suicides among first responders and identifies potential opportunities for additional data collection. METHODS: Using suicides identified from the three most recent years of National Violent Death Reporting System data with industry and occupation codes from the NIOSH Industry and Occupation Computerized Coding System (2015-2017), decedents were categorized as first responders or non-first responders based on usual occupation. Chi-square tests were used to evaluate differences in sociodemographic and suicide circumstances between first and non-first responders. RESULTS: First responder decedents made up 1% of all suicides. Over half of first responders (58%) were LEOs, 21% were firefighters, 18% were EMS clinicians, and 2% were public safety telecommunicators. Compared to non-first responder decedents, more first responders served in the military (23% vs. 11%) and used a firearm as the method of injury (69% vs. 44%). Among first responder decedents for whom circumstances were known, intimate partner problems, job problems, and physical health problems were most frequent. Some common risk factors for suicide (history of suicidal thoughts, previous suicide attempt, alcohol/substance abuse problem) were significantly lower among first responders. Selected sociodemographics and characteristics were compared across first responder occupations. Compared to firefighters and EMS clinicians, LEO decedents had slightly lower percentages of depressed mood, mental health problems, history of suicidal thoughts, and history of suicide attempts. CONCLUSIONS: While this analysis provides a small glimpse into some of these stressors, more detailed research may help inform future suicide prevention efforts and interventions. PRACTICAL APPLICATION: Understanding stressors and their relation to suicide and suicidal behaviors can facilitate suicide prevention among this critical workforce.

Can Doctors Be Compelled to Prolong the Life of a Dying Patient? The Ongoing Medical, Legal and Social Issues.

The law does not require health professionals to provide medical treatment that is of no benefit to the patient. Despite this, medical staff who are caring for patients at the end of their lives frequently experience pressure from the patients' families to prolong their lives. This article considers the Australian law relating to the right to demand treatment when a loved one is dying, and whether an increasing emphasis on shared decision-making has introduced uncertainty. It discusses factors that affect the application of the law, including widespread ignorance of the law, the difficulty of deciding whether a treatment is futile and the need to ration scarce health care resources. It also introduces the perspectives of three senior medical practitioners on disputes with families of dying patients. The article concludes that community education is needed on legal and medical issues at the end of life, including conversations about advance care directives.

A systems science approach to identifying data gaps in national data sources on adolescent suicidal ideation and suicide attempt in the United States.

BACKGROUND: Suicide is currently the second leading cause of death among adolescents ages 10-14, and third leading cause of death among adolescents ages 15-19 in the United States (U.S). Although we have numerous U.S. based surveillance systems and survey data sources, the coverage offered by these data with regard to the complexity of youth suicide had yet to be examined. The recent release of a comprehensive systems map for adolescent suicide provides an opportunity to contrast the content of surveillance systems and surveys with the mechanisms listed in the map. OBJECTIVE: To inform existing data collection efforts and advance future research on the risk and protective factors relevant to adolescent suicide. METHODS: We examined data from U.S. based surveillance systems and nationally-representative surveys that included (1) observations for an adolescent population and (2) questions or indicators in the data that identified suicidal ideation or suicide attempt. Using thematic analysis, we evaluated the codebooks and data dictionaries for each source to match questions or indicators to suicide-related risk and protective factors identified through a recently published suicide systems map. We used descriptive analysis to summarize where data were available or missing and categorized data gaps by social-ecological level. RESULTS: Approximately 1-of-5 of the suicide-related risk and protective factors identified in the systems map had no supporting data, in any of the considered data sources. All sources cover less than half the factors, except the Adolescent Brain Cognitive Development Study (ABCD), which covers nearly 70% of factors. CONCLUSIONS: Examining gaps in suicide research can help focus future data collection efforts in suicide prevention. Our analysis precisely identified where data is missing and also revealed that missing data affects some aspects of suicide research (e.g., distal factors at the community and societal level) more than others (e.g., proximal factors about individual characteristics). In sum, our analysis highlights limitations in current suicide-related data availability and provides new opportunities to identify and expand current data collection efforts.

Single-cell analysis of human nasal mucosal IgE antibody secreting cells reveals a newly minted phenotype.

Immunoglobulin (Ig) E is central to the pathogenesis of allergic conditions, including allergic fungal rhinosinusitis. However, little is known about IgE antibody secreting cells (ASCs). We performed single-cell RNA sequencing from cluster of differentiation (CD)19+ and CD19- ASCs of nasal polyps from patients with allergic fungal rhinosinusitis (n = 3). Nasal polyps were highly enriched in CD19+ ASCs. Class-switched IgG and IgA ASCs were dominant (95.8%), whereas IgE ASCs were rare (2%) and found only in the CD19+ compartment. Through Ig gene repertoire analysis, IgE ASCs shared clones with IgD-CD27- "double-negative" B cells, IgD+CD27+ unswitched memory B cells, and IgD-CD27+ switched memory B cells, suggesting ontogeny from both IgD+ and memory B cells. Transcriptionally, mucosal IgE ASCs upregulate pathways related to antigen presentation, chemotaxis, B cell receptor stimulation, and survival compared with non-IgE ASCs. Additionally, IgE ASCs have a higher expression of genes encoding lysosomal-associated protein transmembrane 5 (LAPTM5) and CD23, as well as upregulation of CD74 (receptor for macrophage inhibitory factor), store-operated Calcium entry-associated regulatory factor (SARAF), and B cell activating factor receptor (BAFFR), which resemble an early minted ASC phenotype. Overall, these findings reinforce the paradigm that human ex vivo mucosal IgE ASCs have a more immature plasma cell phenotype than other class-switched mucosal ASCs and suggest unique functional roles for mucosal IgE ASCs in concert with Ig secretion.

A comparison of international treatment guidelines for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare and life-threatening mucocutaneous diseases that occur almost exclusively as a result of adverse drug reactions, although there are rare cases attributed to infection, immunization, or malignancy.1,2 Given the low incidence of these diseases as well as the high level of morbidity and mortality, randomized controlled clinical trials are difficult to perform, making it difficult to establish a "gold-standard" treatment. To date, there are only five published articles in the literature detailing evidence-based guidelines for the treatment of SJS and TEN, one of which is specifically tailored to pediatric and young adult patients.3-7 These guidelines have significant overlap in regards to the importance of prompt discontinuation of the offending drug and the need for supportive care, but there are differences in regards to the ideal supportive care measures. Additionally, there is still no clear consensus agreement on the pharmacological treatment of SJS and TEN.4-7 Herein, we aim to compare the international treatment guidelines for management of SJS and TEN as well as promote continued discussion and a multidisciplinary approach to establish consensus recommendations for these mucocutaneous emergencies.

Constructive communication patterns as related to relationship satisfaction, seizure severity, and patient activation among people with epilepsy.

PURPOSE: People with epilepsy (PWE) must manage their condition properly for both quality and longevity of life. Effective self-management is critical and can be monitored via levels of patient activation (i.e., a continuum of taking a passive vs active role in personal healthcare) and the presence/severity of seizures. One known influencer of self-management is the quality of one's intimate relationship, a documented area of major concern for PWE. Here we examined a critical facet of PWEs' intimate relationships-(un)constructive communication with their partner. METHODS: Using data from a web-based survey of 89 PWE, and regression-based mediation analyses, we examined associations with patient activation and seizure severity. We added further explanatory utility by examining relationship satisfaction as a mediator of those links. RESULTS: There were positive links between more constructive communication, more patient activation, and less severe seizures. The explanatory path of constructive communication to better relationship satisfaction to lower seizure severity emerged as a significant partial mediation (i.e., direct effect remained significant), while relationship satisfaction fully mediated (i.e., direct effect became non-significant) the link between constructive communication and greater patient activation. CONCLUSION: Our results provide insight into how relationship processes may impact the experience of epilepsy, including seizure severity and patient activation. Future research is needed.

Effect of all-but-one conditional analysis for eQTL isolation in peripheral blood.

Expression quantitative trait locus detection has become increasingly important for understanding how noncoding variants contribute to disease susceptibility and complex traits. The major challenges in expression quantitative trait locus fine-mapping and causal variant discovery relate to the impact of linkage disequilibrium on signals due to one or multiple functional variants that lie within a credible set. We perform expression quantitative trait locus fine-mapping using the all-but-one approach, conditioning each signal on all others detected in an interval, on the Consortium for the Architecture of Gene Expression cohorts of microarray-based peripheral blood gene expression in 2,138 European-ancestry human adults. We contrast these results with traditional forward stepwise conditional analysis and a Bayesian localization method. All-but-one conditioning significantly modifies effect-size estimates for 51% of 2,351 expression quantitative trait locus peaks, but only modestly affects credible set size and location. On the other hand, both conditioning approaches result in unexpectedly low overlap with Bayesian credible sets, with just 57% peak concordance and between 50% and 70% SNP sharing, leading us to caution against the assumption that any one localization method is superior to another. We also cross reference our results with ATAC-seq data, cell-type-specific expression quantitative trait locus, and activity-by-contact-enhancers, leading to the proposal of a 5-tier approach to further reduce credible set sizes and prioritize likely causal variants for all known inflammatory bowel disease risk loci active in immune cells.