Comparing Clinician Consensus Recommendations to Patient-reported Opioid Use Across Multiple Hospital Systems.

OBJECTIVE: We compare consensus recommendations for 5 surgical procedures to prospectively collected patient consumption data. To address local variation, we combined data from multiple hospitals across the country. SUMMARY OF BACKGROUND DATA: One approach to address the opioid epidemic has been to create prescribing consensus reports for common surgical procedures. However, it is unclear how these guidelines compare to patient-reported data from multiple hospital systems. METHODS: Prospective observational studies of surgery patients were completed between 3/2017 and 12/2018. Data were collected utilizing post-discharge surveys and chart reviews from 5 hospitals (representing 3 hospital systems) in 5 states across the USA. Prescribing recommendations for 5 common surgical procedures identified in 2 recent consensus reports were compared to the prospectively collected aggregated data. Surgeries included: laparoscopic cholecystectomy, open inguinal hernia repair, laparoscopic inguinal hernia repair, partial mastectomy without sentinel lymph node biopsy, and partial mastectomy with sentinel lymph node biopsy. RESULTS: Eight hundred forty-seven opioid-naïve patients who underwent 1 of the 5 studied procedures reported counts of unused opioid pills after discharge. Forty-one percent did not take any opioid medications, and across all surgeries, the median consumption was 3 5 mg oxycodone pills or less. Generally, consensus reports recommended opioid quantities that were greater than the 75th percentile of consumption, and for 2 procedures, recommendations exceeded the 90th percentile of consumption. CONCLUSIONS: Although consensus recommendations were an important first step to address opioid prescribing, our data suggests that following these recommendations would result in 47%-56% of pills prescribed remaining unused. Future multi-institutional efforts should be directed toward refining and personalizing prescribing recommendations.

Neuroendocrine correlates of juvenile amphibian behaviors across a latitudinal cline.

We assessed the macrogeographic and neuroendocrine correlates of behavioral variation exhibited by juveniles, an important life stage for dispersal, across the expansive range of the wood frog. By rearing animals from eggs in a common garden then using a novel environment test, we uniquely demonstrated differential expression of juvenile behaviors among 16 populations spanning 8° latitude. On the individual level, cluster analysis indicated three major behavior profiles and principal component analysis resolved four unique axes of behavior, including escape, foraging, food intake, feeding efficiency. We found that increased escape behavior was associated with lower adrenocorticotropic hormone (ACTH)-induced circulating corticosterone (CORT) levels, however, foraging and food intake behaviors were not associated with either resting or ACTH-induced CORT. At the population level, the expression of foraging behaviors increased with latitude while food intake behaviors declined with latitude, which raised several hypotheses of eco-evolutionary processes likely driving this variation. Given that these behaviors covary along the same ecological gradient as locally adapted developmental traits, genomic studies in this species could provide deep insights into how HPA/I activity is associated with the eco-evolutionary processes that structure intraspecific variation in morphology and behavior.

Ecological adaptation drives wood frog population divergence in life history traits.

Phenotypic variation among populations is thought to be generated from spatial heterogeneity in environments that exert selection pressures that overcome the effects of gene flow and genetic drift. Here, we tested for evidence of isolation by distance or by ecology (i.e., ecological adaptation) to generate variation in early life history traits and phenotypic plasticity among 13 wood frog populations spanning 1200 km and 7° latitude. We conducted a common garden experiment and related trait variation to an ecological gradient derived from an ecological niche model (ENM) validated to account for population density variation. Shorter larval periods, smaller body weight, and relative leg lengths were exhibited by populations with colder mean annual temperatures, greater precipitation, and less seasonality in precipitation and higher population density (high-suitability ENM values). After accounting for neutral genetic variation, the QST-FST analysis supported ecological selection as the key process generating population divergence. Further, the relationship between ecology and traits was dependent upon larval density. Specifically, high-suitability/high-density populations in the northern part of the range were better at coping with greater conspecific competition, evidenced by greater postmetamorphic survival and no difference in body weight when reared under stressful conditions of high larval density. Our results support that both climate and competition selection pressures drive clinal variation in larval and metamorphic traits in this species. Range-wide studies like this one are essential for accurate predictions of population's responses to ongoing ecological change.

Public Perceptions of Transoral Endocrine Surgery and their Influence on Choice of Operative Approach.

BACKGROUND: Transoral Endocrine Surgery (TES) represents an alternative to the open approach with no visible scar. Studies have shown TES has a safety profile similar to the open approach, but adoption has been limited. Public perception and preference for TES are factors associated with adoption that have not been explored. Here we aim to understand the perception of TES by the public and factors which influence decision making. MATERIALS AND METHODS: A 38-question survey was designed to assess factors which influence willingness to pursue TES. The survey was distributed utilizing Amazon Mechanical Turk (MTurk), a crowdsourcing marketplace in which individuals perform tasks virtually based on interest. Descriptive analyses, Pearson chi-squared tests, Student's t-tests, and multivariate logistic regression were performed to evaluate theoretical decision to pursue TES. RESULTS: Respondents (n = 795) were 47% female, 78% white, 70% held a college degree or higher, and had a mean age of 37. The majority (69%) preferred a mouth incision over a neck incision. Respondents were willing to pursue TES for a theoretical cancer despite increased cost (52%) and longer operative time (70%). Respondents top two most important surgical factors were safety and experience. CONCLUSIONS: Our data suggest the general public is willing to pursue TES and factors thought to be barriers to choosing TES may not deter the public. An informed discussion with appropriately-selected patients should be had between the patient and surgeon regarding specific surgical and postoperative differences including risks, safety, and experience.

Patient-Reported Financial Burden in Thyroid Cancer.

BACKGROUND: The incidence of thyroid cancer is increasing at a rapid rate. Prior studies have demonstrated financial burden and decreased quality of life in patients with thyroid cancer. Here, we characterize patient-reported financial burden in patients with thyroid cancer over a 28y period. MATERIALS AND METHODS: Patients who underwent thyroidectomy for thyroid cancer from 1990-2018 completed a phone survey assessing financial burden and its related psychological financial hardship. Descriptive statistics were performed to characterize these outcomes and correlation with sociodemographic data was assessed. RESULTS: Respondents (N = 147) were 73% female, 75% white, and had a median follow up of 7 y. The majority had a full-time job (59%) and private insurance (81%) at the time of diagnosis. Overall, 16% of respondents reported financial burden and 50% reported psychological financial hardship. Those reporting financial burden were disproportionately impacted by psychological financial hardship (87% versus 43%, P < 0.001). One in four (25%) respondents reported not being adequately informed about costs. CONCLUSIONS: Financial burdens are important outcomes of thyroid cancer which occur even among patients with protective financial factors, suggesting an even greater impact on the general population of patients with thyroid cancer. Further research is needed to explore the intersection of financial burden, cost, and quality of life.

'Water dripping on a stone': a feasibility study of a healthy weight management conversation approach in routine general practice consultations.

BACKGROUND: Primary health care has an important role to play in the management of weight and yet discussions of healthy weight management do not occur optimally, indicating a need for simple tools and training in brief weight counselling. The 'FABS' approach (focusing on four topic areas: Food, Activity, Behaviour and Support) was developed to address this. OBJECTIVES: To explore the feasibility of the 'FABS' approach within routine general practice consultations and its effectiveness in facilitating healthy weight conversations. METHOD: The FABS approach was run for a trial period in five New Zealand general practices. The approach entailed staff training, the addition to the practice patient management system of a template outlining potential topics for discussion and a patient handout. GPs were asked to use the approach with any adult patient with a body mass index of over 28 kg/m2. A descriptive analysis of anonymized quantitative practice data was conducted, with limited qualitative data from an online clinician questionnaire and interviews with GPs and patients. RESULTS: Over 4 months, the template was opened 862 times by 27 clinicians in 830 patient consultations. All FABS topics were raised at least once. Physical activity was raised most frequently, followed by two food-related topics. There was variation between practices and between GPs. GPs tended to raise more topics within a single consultation than the training recommended. The limited clinician survey results and patient interviews also indicated positive responses to the approach. CONCLUSIONS: It is possible to provide an infrastructure for healthy weight conversation approaches within general practice so that patients receive supportive and consistent messages on a regular basis. General practice is an appropriate setting for this due to the ongoing relationships with patients and team-based approach, but there is a need for effective training and education to ensure appropriate and effectively delivery.

Evaluation of Screening Tests for Cognitive Impairment in Patients Receiving Maintenance Hemodialysis.

BACKGROUND: Neurocognitive testing shows that cognitive impairment is common among patients receiving maintenance hemodialysis. Identification of a well performing screening test for cognitive impairment might allow for broader assessment in dialysis facilities and thus optimal delivery of education and medical management. METHODS: From 2015 to 2018, in a cohort of 150 patients on hemodialysis, we performed a set of comprehensive neurocognitive tests that included the cognitive domains of memory, attention, and executive function to classify whether participants had normal cognitive function versus mild, moderate, or severe cognitive impairment. Using area-under-the-curve (AUC) analysis, we then examined the predictive ability of the Mini Mental State Examination, the Modified Mini Mental State Examination, the Montreal Cognitive Assessment, the Trail Making Test Part B, the Mini-Cog test, and the Digit Symbol Substitution Test, determining each test's performance for identifying severe cognitive impairment. RESULTS: Mean age was 64 years; 61% were men, 39% were black, and 94% had at least a high-school education. Of the 150 participants, 21% had normal cognitive function, 17% had mild cognitive impairment, 33% had moderate impairment, and 29% had severe impairment. The Montreal Cognitive Assessment had the highest overall predictive ability for severe cognitive impairment (AUC, 0.81); a score of ≤21 had a sensitivity of 86% and specificity of 55% for severe impairment, with a negative predictive value of 91%. The Trails B and Digit Symbol tests also performed reasonably well (AUCs, 0.73 and 0.78, respectively). The other tests had lower predictive performances. CONCLUSIONS: The Montreal Cognitive Assessment, a widely available and brief cognitive screening tool, showed high sensitivity and moderate specificity in detecting severe cognitive impairment in patients on maintenance hemodialysis.

Opioid Consumption After Gender-Affirming Mastectomy and Two Other Breast Surgeries.

BACKGROUND: There are few studies that evaluate patient-reported opioid consumption after discharge from surgery. In addition, there has been a call for "special care in prescribing opioids" for lesbian, gay, bisexual, transgender, questioning patients. Here, we evaluate if patients undergoing gender-affirming mastectomy (GAM) require different amounts of opioids for pain management after discharge compared alongside two surgeries with similar surgical exposure. MATERIALS AND METHODS: From October 2017 to July 2018, patients undergoing oncologic mastectomy without reconstruction, mammoplasty reduction, or gender-affirming mastectomy at a single institution were enrolled in a phone survey study to quantify opioids consumed after discharge from surgery. Patient information was captured from the medical record. A total of 170 patients were called between 14 and 30 d after discharge and were asked to count unused pills from their opioid prescription. RESULTS: A total of 99 patients participated and provided pill counts. There were differences between prescribed and consumed opioids within each surgery. Patients who underwent oncologic mastectomy were prescribed and consumed the lowest amounts of opioids. There were significantly more opioids prescribed to patients with GAM than mammoplasty reduction, but consumption was not statistically different. Patients with oncologic mastectomy, mammoplasty reduction, and GAM consumed a median of 0, 10, and 15 five mg oxycodone equivalent tablets, respectively. CONCLUSIONS: Despite similar approaches, surgeries had different opioid prescribing and use profiles. Generally, all patients were overprescribed opioids. Overprescribing may be especially problematic in patients with known higher risk of misuse and substance abuse. Granular data on patient consumption, demographics, and preoperative risk factors for opioid misuse may improve prescribing practices.

Urbanization and Population Genetic Structure of the Panama City crayfish (Procambarus econfinae).

For species with geographically restricted distributions, the impacts of habitat loss and fragmentation on long-term persistence may be particularly pronounced. We examined the genetic structure of Panama City crayfish (PCC), Procambarus econfinae, whose historical distribution is limited to an area approximately 145 km2, largely within the limits of Panama City and eastern Bay County, FL. Currently, PCC occupy approximately 28% of its historical range, with suitable habitat composed of fragmented patches in the highly urbanized western portion of the range and managed plantations in the more contiguous eastern portion of the range. We used 1640 anonymous single-nucleotide polymorphisms to evaluate the effects of anthropogenic habitat modification on the genetic diversity and population structure of 161 PCC sampled from across its known distribution. First, we examined urban habitat patches in the west compared with less-developed habitat patches in the east. Second, we used approximate Bayesian computation to model inferences on the demographic history of eastern and western populations. We found anthropogenic habitat modifications explain the genetic structure of PCC range-wide. Clustering analyses revealed significant genetic structure between and within eastern and western regions. Estimates of divergence between east and west were consistent with urban growth in the mid-20th century. PCC have low genetic diversity and high levels of inbreeding and relatedness, indicating populations are small and isolated. Our results suggest that PCC have been strongly affected by habitat loss and fragmentation and management strategies, including legal protection, translocations, or reintroductions, may be necessary to ensure long-term persistence.

Sumoylation of transcription factor Gcn4 facilitates its Srb10-mediated clearance from promoters in yeast.

The small ubiquitin-related modifier (SUMO) is a conserved factor that post-translationally regulates proteins involved in many cellular processes, including gene transcription. We previously demonstrated that promoter-bound factors become sumoylated during activation of inducible genes in yeast, but the identity of these factors, and the role of sumoylation in their function, was unknown. Here we show that the transcriptional activator Gcn4 is sumoylated on two specific lysine residues and in a manner that depends on its ability to bind DNA, indicating that sumoylation occurs after Gcn4 binding to target promoters. Importantly, this functions to facilitate the subsequent removal of the activator from these promoters after recruitment of RNA polymerase II, which can prevent inappropriate transcription of target genes. Furthermore, we show that clearance of sumoylated Gcn4 requires the protein kinase and Mediator complex subunit Srb10, linking activator removal with target gene transcription. Our study demonstrates an unexpected role for protein sumoylation in the process of transcriptional activation.

Blood Pressure and Cognitive Decline in Prevalent Hemodialysis Patients.

BACKGROUND: Hypertension is associated with cognitive decline in the general population. It is unclear what impact blood pressure (BP) has on cognitive decline in patients receiving maintenance hemodialysis (HD). METHODS: Using a longitudinal cohort of 314 prevalent HD patients without dementia at baseline, we examined the association of predialysis systolic BP (SBP) and diastolic BP (DBP), pulse pressure, and intradialytic SBP change (pre minus post), averaged for a month, with cognitive decline. Cognitive function was determined by a neurocognitive battery, administered yearly. Individual cognitive test results were reduced into 2 domain scores using principal components analysis (by definition mean of 0 and SD of 1), representing memory and executive function. Joint models, allowing for characterization of cognitive score slopes and including adjustment for potential confounders, were utilized to account for competing risks from death, dropout, or kidney transplantation. RESULTS: Mean age was 62 years; 54% were men, 23% were black, and 90% had at least a high school education. During median follow-up of 2.1 years (25th-75th: 1.0-4.5), 191 had at least one follow-up test, 148 died, and 43 received kidney transplants. Low predialysis DBP and high pulse pressure were both associated with steeper executive function decline (each 10 mm Hg lower DBP = -0.03 SD [-0.01 to -0.05] per year steeper decline) in executive function (each 10 mm Hg higher pulse pressure = -0.03 SD [-0.06 to -0.01] steeper decline) but not for memory function. SBP and intradialytic change were not associated with steeper decline for either memory or executive function. CONCLUSIONS: No relationship was seen between SBP or intradialytic change in BP with cognitive decline. In prevalent HD patients, lower predialysis DBP and wider predialysis pulse pressure are associated with steeper cognitive decline in executive function but not memory.

Trajectory of adherence behavior in pediatric and adolescent liver transplant recipients: The medication adherence in children who had a liver transplant cohort.

Knowledge of the longterm trajectory of nonadherence to immunosuppressants can inform decisions regarding organ allocation, adherence monitoring, and intervention efforts. The Medication Adherence in Children Who Had a Liver Transplant (MALT) prospective multisite study followed 400 pediatric and adolescent liver transplant recipients for 2 years, using the Medication Level Variability Index to monitor adherence. We hypothesized that adherence is an unstable (fluctuating) phenomenon: that patients who are adherent in year 1 may become nonadherent in year 2, and vice versa. However, we also hypothesized that a majority (more than 50%) of nonadherent patients remain nonadherent over time. We further hypothesized that the longer nonadherence lasts, the higher the likelihood of adverse events (rejection). Finally, we explored the effect of socioeconomic factors on the evolution of adherence over time. Most (59.7%) of the MALT patients who were nonadherent in year 1 remained so in year 2; 18.5% of patients who were adherent in year 1 became nonadherent in year 2. Only 4.4% of patients who were adherent in both year 1 and year 2 had a rejection, compared with 22.9% of patients who were nonadherent during 1 of the years, and 34.9% of those who were nonadherent in both years (P < 0.001), establishing a "dose-dependent" effect of adherence on transplant outcomes. Single-parent households were associated with worsening adherence. Our results suggest that good baseline adherence does not guarantee adherence later on, that nonadherence is likely to persist in the absence of interventions, and that monitoring of adherence and interventions to improve it should be expected to last for years if transplant outcomes are to be improved. Liver Transplantation 24 80-88 2018 AASLD.

Pediatric Liver Transplant Teams Coping With Patient Death.

OBJECTIVES: Coping with patient death among pediatric liver transplant teams has received little attention despite general recognition of the potentially negative emotional consequences associated with such loss. The purpose of this study was to investigate the ways in which members of pediatric liver transplant teams cope with the death of patients on the waitlist and post-transplant and the institutional resources available to facilitate this coping. METHODS: Participants included 120 physicians, nurses, and mental health professionals from multiple transplant centers across the United States. Participants completed an online questionnaire that assessed the availability of formal coping resources at their institutions, informal sources of support used to cope with patient death, and as indices of coping, bereavement, and emotional exhaustion symptoms experienced. RESULTS: Debriefing, the most commonly offered support, was available to about half (55.8%) of the sample; yet, nearly all respondents (98.3%) indicated that debriefing would be useful. On average, bereavement and emotional exhaustion levels were comparable to normative data, but patterns of coping varied based on participants' position within the transplant team. For participants who reported that debriefing was available at their institutions, emotional exhaustion was lower. CONCLUSIONS: Overall, formal supports were inconsistently offered to pediatric transplant team members. Team members expressed high acceptability for debriefing, which has been associated with benefits in other populations, and findings indicated better coping in the transplant setting when it was offered.

SUMO functions in constitutive transcription and during activation of inducible genes in yeast.

Transcription factors represent one of the largest groups of proteins regulated by SUMO (small ubiquitin-like modifier) modification, and their sumoylation is usually associated with transcriptional repression. To investigate whether sumoylation plays a general role in regulating transcription in yeast, we determined the occupancy of sumoylated proteins at a variety of genes by chromatin immunoprecipitation (ChIP) using an antibody that recognizes the yeast SUMO peptide. Surprisingly, we detected sumoylated proteins at all constitutively transcribed genes tested but not at repressed genes. Ubc9, the SUMO conjugation enzyme, was not present on these genes, but its inactivation reduced SUMO at the constitutive promoters and modestly decreased RNA polymerase II levels. In contrast, activation of the inducible GAL1, STL1, and ARG1 genes caused not only a striking accumulation of SUMO at all three promoter regions, but also recruitment of Ubc9, indicating that gene activation involves sumoylation of promoter-bound factors. However, Ubc9 inactivation, while reducing sumoylation at the induced promoters, paradoxically resulted in increased transcription. Providing an explanation for this, the reduced sumoylation impaired the cell's ability to appropriately shut off transcription of the induced ARG1 gene, indicating that SUMO can facilitate transcriptional silencing. Our findings thus establish unexpected roles for sumoylation in both constitutive and activated transcription, and provide a novel mechanism for regulating gene expression.

Cognitive Decline and Its Risk Factors in Prevalent Hemodialysis Patients.

BACKGROUND: Cognitive impairment is common in patients treated with hemodialysis. The trajectory of cognitive function and risk factors for cognitive decline remain uncertain in this population. STUDY DESIGN: Longitudinal cohort. SETTING & PARTICIPANTS: 314 prevalent hemodialysis patients. PREDICTORS: Age, sex, race, education level, hemodialysis vintage, cause of end-stage renal disease, and baseline history of cardiovascular disease. OUTCOMES: Cognitive function as determined by a comprehensive neurocognitive battery, administered at baseline and yearly when possible. Individual cognitive test results were reduced into 2 domain scores using principal components analysis, representing memory and executive function, which were used as our coprimary outcomes and by definition have a mean of zero and SD of 1. RESULTS: Mean age was 63 years; 54% were men, 22% were black, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 0.9-4.2) years, 196 had at least 1 follow-up test, 156 died, and 43 received a kidney transplant. Linear mixed models and joint models, which accounted for competing risks from death, dropout, or kidney transplantation, showed nearly identical results. The joint model demonstrated a decline in executive function (-0.09 [95% CI, -0.13 to -0.05] SD per year), whereas memory improved slightly (0.05 [95% CI, 0.02 to 0.08] SD per year). A significant yearly decline was also seen in the Mini-Mental State Examination score (median change, -0.41; 95% CI, -0.57 to -0.25). Older age was the only significant risk factor for steeper executive function decline (-0.04 [95% CI, -0.06 to -0.02] SD steeper annual decline for each 10 years of age). LIMITATIONS: Prevalent hemodialysis patients only, limited follow-up testing due to high mortality rate, and exclusion of participants with severe cognitive deficits or dementia. CONCLUSIONS: Prevalent hemodialysis patients demonstrate significant cognitive decline, particularly within tests of executive function. Older age was the only statistically significant risk factor for steeper cognitive decline, which may have important clinical consequences for patient management and education. Future studies should evaluate strategies to maintain or improve cognitive function.

Measuring Maladaptive Cognitions in Complicated Grief: Introducing the Typical Beliefs Questionnaire.

OBJECTIVES: Maladaptive cognitions related to loss are thought to contribute to development of complicated grief and are crucial to address in treatment, but tools available to assess them are limited. This paper introduces the Typical Beliefs Questionnaire (TBQ), a 25-item self-report instrument to assess cognitions that interfere with adaptation to loss. DESIGN: Study participants completed an assessment battery during their initial evaluation and again after completing treatment at 20 weeks. Test-retest reliability was assessed on a subsample of the participants who did not show change in complicated grief severity after the first 4 weeks of treatment. To examine latent structure of the TBQ, an exploratory factor analysis (EFA) was performed. SETTING: Academic medical centers in Boston, New York, Pittsburgh, and San Diego from 2010-2014. PARTICIPANTS: 394 bereaved adults who met criteria for complicated grief. MEASUREMENTS: The TBQ along with assessments of complicated grief symptoms and related avoidance, depression symptoms, functional impairment, and perceived social support. RESULTS: The TBQ exhibited good internal consistency (α = 0.82) and test-retest reliability (N = 105; intraclass correlation coefficient = 0.74). EFA indicated a five-factor structure: "Protesting the Death," "Negative Thoughts About the World," "Needing the Person," "Less Grief is Wrong" and "Grieving Too Much." The total score and all factors showed sensitivity to change with treatment. CONCLUSIONS: This new tool allows a clinician to quickly and reliably ascertain presence of specific maladaptive cognitions related to complicated grief, and subsequently, to use the information to aid a diagnostic assessment, to structure the treatment, and to measure treatment outcomes.

White matter damage in maintenance hemodialysis patients: a diffusion tensor imaging study.

BACKGROUND: Patients treated with dialysis have high rates of brain infarcts, brain atrophy, and white matter disease. There are limited data regarding the presence of more subtle damage to brain white matter. METHODS: In the Cognition and Dialysis Study, we compared brain structure using diffusion tensor imaging in hemodialysis (HD) patients to individuals without known kidney disease, using tract based spatial statistics (TBSS) to compare Fractional Anisotropy (FA) and Mean Diffusivity (MD). Statistical comparison of each overlaid voxel was age controlled using a permutation based corrected p value of <0.05. RESULTS: Thirty-four HD patients and twenty six controls (52 vs 51 years for HD vs control) had adequate magnetic resonance imaging for analysis. The HD group had fewer women (38% vs 23%) and a higher prevalence of diabetes (29% vs 8%), heart failure (29% vs 0%) and clinical stroke (15% vs 0%). Hemodialysis patients had significantly lower FA across multiple white matter fiber tracts, with fronto-temporal connections, the genu of the corpus callosum and the fornix more significantly affected than posterior regions of the brain. Similarly, HD patients had significantly higher mean diffusivity in multiple anterior brain regions. Results remained similar when those with a prior history of stroke were excluded. CONCLUSIONS: In HD patients, there is more white matter disease in the anterior than posterior parts of the brain compared to controls without kidney disease. This pattern of injury is most similar to that seen in aging, suggesting that developing chronic kidney disease and ultimately kidney failure may result in a phenotype consistent with accelerated aging.

History matters more when explaining genetic diversity within the context of the core-periphery hypothesis.

The core-periphery hypothesis (CPH) predicts that populations located at the periphery of a species' range should have lower levels of genetic variation than those at the centre of the range. However, most of the research on the CPH focuses on geographic distance and not on ecological distance, or uses categorical definitions of core and periphery to explain the distribution of genetic diversity. We use current climate data and historical climate data from the last glacial maxima to develop quantitative estimates of contemporary and historical ecological suitability using ecological niche models. We analysed genetic diversity using 12 polymorphic microsatellites to estimate changes in heterozygosity, allelic richness and population differentiation in 31 populations of the wood frog (Lithobates sylvaticus) spanning the species' entire eastern clade (33(o) to 45(o) latitude) from Alabama, USA, to Nova Scotia, Canada. Our data support predictions based on the CPH. Populations showed significant differences in genetic diversity across the range, with lower levels of genetic variation at the geographic range edge and in areas with lower levels of historical and contemporary ecological suitability. However, history and geography (not current ecological suitability) best explain the patterns. This study highlights the importance of examining more than just geography when assessing the CPH, and the importance of historical ecological suitability in the maintenance of genetic diversity and population differentiation.

Evaluation of WHO screening algorithm for the presumptive treatment of asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya.

OBJECTIVES: The WHO recommends that men who have sex with men (MSM) reporting unprotected receptive anal intercourse (RAI) and either multiple partners or a partner with a sexually transmitted infection (STI) in the past 6 months should be presumptively treated for asymptomatic rectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections. We evaluated this recommendation in a cohort of 'high-risk' MSM in Coastal Kenya. METHODS: We assessed presence of genitourinary and rectal symptoms, and determined prevalence and 3-month incidence of rectal NG and CT infections. We performed nucleic acid amplification testing of urine and rectal swab samples collected from MSM followed prospectively, and assessed predictive values of the WHO algorithm at baseline screening. RESULTS: Of 244 MSM screened, 240 (98.4%) were asymptomatic, and 147 (61.3%) reported any RAI in the past 6 months. Among 85 (35.4%) asymptomatic MSM meeting criteria for the WHO presumptive treatment (PT) recommendation, we identified 20 with rectal infections (six NG, 12 CT and two NG-CT co-infections). Among 62 asymptomatic MSM who did not meet criteria, we identified seven who were infected. The sensitivity and specificity of the WHO algorithm were 74.1% (95% CI 53.7% to 88.9%) and 45.8% (95% CI 36.7% to 55.2%), respectively. The 3-month incidence of any rectal NG or CT infection in asymptomatic men reporting any RAI was 39.7 (95% CI 24.3 to 64.8) per 100 person-years. CONCLUSIONS: About one-third of asymptomatic MSM were eligible to receive PT for NG and CT infections. Among MSM who would qualify for PT of rectal STIs, the number needed to treat in order to treat one infection was four. Our results support the value of the WHO screening algorithm and recommended PT strategy in this population.

Psychosocial determinants of adolescents' attitudes toward disclosing dating violence.

This study combined a person-oriented approach with a psychosocial framework of help-seeking to examine factors associated with the intent to disclose dating violence among developing adolescents. Data came from adolescents in middle and high school in a rural area in the southeastern United States, who were surveyed annually for 4 years (Nwave 1 = 580; Mage = 13 years, SD = 1.48; 52.7% female; 49% Black, 39% White, 11% Hispanic, or other minorities). Results confirm expectations that intraindividual (adolescent views on violence and safety); interindividual (peer and family dynamics); positional (gender, having a supportive adult); and ideological factors are all significant predictors of patterns in help-seeking attitudes. However, predictive relevance of some factors varied across help-seeking groups and data collection periods, supporting the differential effects hypothesis. For example, while greater friend social support increased the odds of belonging to "friend confidants," it simultaneously decreased the odds of being a member of "parent confidants" and "moderate help-seekers" groups. Additionally, the influence of family functioning tended to decrease over time, eventually losing its explanatory value at Wave 4. The article concludes by discussing how integration of a person-centered methodological approach with a robust theoretical foundation advances our understanding of variability in adolescents' responses to dating violence. Consideration of diversity in adolescent intentions to react to interpersonal violence is discussed further in the context of policy and practice to enhance protective options and prevent or minimize harm. (PsycInfo Database Record (c) 2024 APA, all rights reserved).