Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022.

BACKGROUND: Treatment options for human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases (BCBMs) remain limited. We previously reported central nervous system (CNS) activity for neratinib and neratinib-capecitabine. Preclinical data suggest that neratinib may overcome resistance to ado-trastuzumab emtansine (T-DM1) when given in combination. In Translational Breast Cancer Research Consortium (TBCRC) 022's cohort 4, we examined the efficacy of neratinib plus T-DM1 in patients with HER2-positive BCBM. PATIENTS AND METHODS: In this multicenter, phase II study, patients with measurable HER2-positive BCBM received neratinib 160 mg daily plus T-DM1 3.6 mg/kg intravenously every 21 days in three parallel-enrolling cohorts [cohort 4A-previously untreated BCBM, cohorts 4B and 4C-BCBM progressing after local CNS-directed therapy without (4B) and with (4C) prior exposure to T-DM1]. Cycle 1 diarrheal prophylaxis was required. The primary endpoint was the Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) by cohort. The overall survival (OS) and toxicity were also assessed. RESULTS: Between 2018 and 2021, 6, 17, and 21 patients enrolled in cohorts 4A, 4B, and 4C. Enrollment was stopped prematurely for slow accrual. The CNS objective response rate in cohorts 4A, 4B, and 4C was 33.3% [95% confidence interval (CI) 4.3% to 77.7%], 35.3% (95% CI 14.2% to 61.7%), and 28.6% (95% CI 11.3% to 52.2%), respectively; 38.1%-50% experienced stable disease for ≥6 months or response. Diarrhea was the most common grade 3 toxicity (22.7%). The median OS was 30.2 [cohort 4A; 95% CI 21.9-not reached (NR)], 23.3 (cohort 4B; 95% CI 17.6-NR), and 20.9 (cohort 4C; 95% CI 14.9-NR) months. CONCLUSIONS: We observed intracranial activity for neratinib plus T-DM1, including those with prior T-DM1 exposure, suggesting synergistic effects with neratinib. Our data provide additional evidence for neratinib-based combinations in patients with HER2-positive BCBM, even those who are heavily pretreated.

The golden tickets: impact of preference signaling on obstetrics and gynecology residency applicants.

BACKGROUND: With the residency selection process becoming more competitive and programs receiving unprecedented numbers of applications, some specialties have introduced preference signaling in an attempt to help applicants target programs of interest. In the 2022-2023 application cycle, obstetrics and gynecology also introduced a 2-tiered system with a limited number of gold signals (n=3) and silver signals (n=15). OBJECTIVE: Given the novelty of preference signaling in the obstetrics and gynecology residency application process, this study aimed to (1) assess the effect of signals on interview offers and match and (2) discuss applicant attitudes toward this preference signaling system. STUDY DESIGN: This was a voluntary cross-sectional survey study conducted in April 2023 that was open to all fourth-year medical students who applied to an obstetrics and gynecology residency in the United States. Self-reported demographics, signaling, interview, and match data were collected. In addition, students were asked about attitudes toward signaling on a 5-point Likert scale. RESULTS: Of the 1507 applicants who entered an obstetrics and gynecology residency via match or Supplemental Offer and Acceptance Program process, 969 (64.3%) completed the survey. Moreover, an additional 22 applicants who did not match responded to the survey. More respondents used all 3 gold tokens (98.3%) and all 15 silver tokens (94.3%). The mean number of applications sent was 74.3±35.1, and the mean number of interviews received per applicant was 12.8±6.6. The interviews or token yields were 64.0%±31.5% for gold tokens, 43.8%±23.1% for silver tokens, and 9.8%±10.0% for no token. Of the survey respondents, 340/951 (35.8%) matched to a gold token program, 338/951 (35.5%) matched to a silver token program, and 244/951 (25.7%) matched to a nontoken program. Furthermore, 499/951 applicants (52.5%) reported feeling slightly positive or very positive about signaling. CONCLUSION: Most obstetrics and gynecology applicants in this survey participated in preference signaling. Gold and silver tokens were associated with high ratios of interview invitations compared with no token. However, the overall number of applications did not decrease in the 2022-2023 cycle, and only half of survey respondents reported feeling positive about the signaling process. These results can inform program directors and students about application number and strategy in upcoming cycles.

Project Sandman: A Quasi-Experimental Evaluation of a Group-Based Brief Sleep Intervention in Air Force Technical Training.

OBJECTIVES: Approximately 70% of the military personnel experience chronic sleep insufficiency, which negatively impacts military readiness and health. Military sleep health does not appear to be improving despite targeted programs to optimize sleep. The present quasi-experimental study aims to evaluate a single-session sleep intervention in United States Air Force (USAF) Technical Training. METHOD: A group-based Brief Sleep Intervention (BSI) was developed for the target population. Participants included 321 technical school students (Mean age = 21; 82% male; 67% White) who were assigned to the BSI (n = 203) or a control group (n = 118). Propensity-score-weighted multivariable logistic regression was employed to compare outcomes. RESULTS: At the 2-week follow-up, students in the BSI were significantly more likely to report sleeping 6 or more hours on weekdays (OR = 1.49, p < .001) and "Good/Very Good" sleep quality (OR = 1.50, p = .032) than those in the control group. In addition, 69.2% of the students in BSI reported having engaged in the self-selected "Action Step" chosen during the intervention. CONCLUSIONS: To our knowledge, this is the first study to test a preventative sleep intervention in USAF Technical Training. Results suggest that a single-session group intervention can promote behavioral changes and improve sleep health.

A social-ecological examination of sleep among Airmen in technical training.

Inadequate sleep is an on-going risk to the health and mission readiness of U.S. Armed Forces, with estimates of sleep problems high above U.S. civilian populations. Intervening early in the career of active duty Air Force personnel (or "Airmen") with education and the establishment of healthy behaviors may prevent short and long term-detriments of sleep problems. This paper describes the results of a qualitative study seeking to understand the facilitators and barriers to achieving good sleep in a technical training school during the first year of entry into the United States Air Force. Using the social ecological framework and content analysis, three focus groups with Airmen were conducted to explore themes at the individual, social, environmental, and organizational/policy level. Overall, results indicated a cohort motivated to achieve good sleep, and also struggling with a number of barriers across each level. This paper highlights opportunities for population health interventions during technical training aimed at supporting Airmen in developing healthy sleep behaviors early in the course of their career.

Intramedullary, periosteal, and extraskeletal Ewing sarcomas: retrospective study of a series of 126 cases in a reference center.

OBJECTIVE: To evaluate the proportion of extraskeletal, periosteal, and intramedullary Ewing sarcomas among musculoskeletal Ewing sarcomas. MATERIAL AND METHOD: Our single-center retrospective study included patients with musculoskeletal Ewing sarcoma diagnosed between 2005 and 2019 in our pathology center (cases from our adult bone tumor referral center and adult and pediatric cases referred for review). Recurrences, metastases, and visceral Ewing sarcomas were excluded. Intramedullary Ewing sarcomas were defined by involvement of the medullary cavity. Periosteal cases were defined by involvement of the subperiosteal area without extension to the medullary cavity. Extraskeletal cases were defined by the absence of involvement of the bone tissue and the subperiosteal area. RESULTS: Our series included 126 patients with musculoskeletal Ewing sarcoma, including 118 skeletal Ewing sarcomas (93.7%) and 8 extraskeletal Ewing sarcomas (6.3%). Of the 118 skeletal Ewing sarcomas 112 were intramedullary (88.9%) and 6 were periosteal (4.8%). Extraskeletal Ewing sarcomas were more common in women and in patients older than 40 (p < 0.05). DISCUSSION: The 6.3% proportion of extraskeletal Ewing sarcoma is lower than the median of 30% estimated from the literature. This difference could be explained by an overestimation of extraskeletal Ewing sarcomas of the chest wall (Askin tumors), an underestimation of periosteal cases confused with extraskeletal cases, and the presence of "Ewing-like" soft tissue sarcomas in previous series. Because of its prognostic and therapeutic impact, the distinction of morphologic subtypes requires the cooperation of experienced radiologists and pathologists.

Associations of adolescent lifestyle behaviors with body mass index within a nationally representative sample of US adolescents: a quantile regression analysis.

OBJECTIVES: The purpose of this study was to examine the associations between lifestyle behavior variables such as physical activity, television watching, computer use, and school night sleep duration with body mass index percentile (BMI%) using quantile regression within a representative sample of adolescents who completed the 2017 US National Youth Risk Behavior Survey. STUDY DESIGN: The study design was a cross-sectional study. METHODS: A multistage cluster sampling procedure obtained a representative sample of US adolescents. The number of sampled adolescents submitting questionnaires with BMI% data was 13,146. To examine the associations between lifestyle behaviors and BMI%, simultaneous quantile regression was used. RESULTS: When relationships were modeled at every 10th percentile, more precise parameter estimates were observed at higher percentiles. Across the interquartile range, physical activity associated with lower BMI% at the 50th and 75th percentiles (brange = -2.27% to -5.24%, P < 0.05), television watching associated with higher BMI% at the 25th to 75th percentiles (brange = 2.29%-4.16%, P < 0.05), sleep durations less than 8 h per school night associated with higher BMI% at the 25th and 50th percentile (brange = 2.81%-8.26%, P < 0.05), and 10 or more hours of school night sleep associated with higher BMI% at the 50th and 75th percentile (brange = 3.43%-7.53%, P < 0.05). CONCLUSIONS: Higher levels of physical activity associated with lower BMI% and longer time watching television, school night sleep durations less than 8 h, and school night sleep durations of 10 h or more at higher quantiles associated with higher BMI% in adolescents. Estimates of association were more precise within higher quantiles.

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

The impact of childhood parental quality on mental health outcomes in older adults.

OBJECTIVE: Parental bonding is cited as a determinant of mental health outcomes in childhood, adolescence and early-mid adulthood. Examination of the long-term impact for older adults is limited. We therefore examine the long-term risk of perceived poor parental bonding on mental health across the lifespan and into early-old age. METHODS: Participants (N = 1255) were aged 60-64 years of age and drawn from the Australian Life Histories and Health study. Quality of parental bonding was assessed with the Parental Bonding Instrument (PBI). Self-reported history of doctors' mental health diagnoses and current treatment for each participant was recorded. Current depression was assessed with the Centre for Epidemiologic Studies Depression-8 (CESD-8). Due to known gender differences in mental health rates across the lifespan, analyses were stratified by sex. RESULTS: A bi-factor analysis of the PBI in a structural equation framework indicated perceived Poor Parental Quality as a risk for both ever and current depression for both sexes. For males, Over-Protective Fathers were a risk for ever and current depression, whilst overall Poor Parental Quality was a risk for reporting current depression treatment. Whilst a number of the risks associated with current depression and treatment were attenuated when controlling for current mood, parental quality remained a significant risk for having reported a lifetime diagnosis for depression and anxiety for men. CONCLUSION: Our results extend the existing literature base and demonstrate that mental health risk attributed to poor perceived parental quality continues across the life-course and into early-old age.

Depression and risk of type 2 diabetes: the potential role of metabolic factors.

The aim of the present study was to evaluate the interaction between depressive symptoms and metabolic dysregulations as risk factors for type 2 diabetes. The sample comprised of 2525 adults who participated in a baseline and a follow-up assessment over a 4.5-year period in the Emotional Health and Wellbeing Study (EMHS) in Quebec, Canada. A two-way stratified sampling design was used, on the basis of the presence of depressive symptoms and metabolic dysregulation (obesity, elevated blood sugar, high blood pressure, high levels of triglycerides and decreased high-density lipoprotein). A total of 87 (3.5%) individuals developed diabetes. Participants with both depressive symptoms and metabolic dysregulation had the highest risk of diabetes (adjusted odds ratio=6.61, 95% confidence interval (CI): 4.86-9.01), compared with those without depressive symptoms and metabolic dysregulation (reference group). The risk of diabetes in individuals with depressive symptoms and without metabolic dysregulation did not differ from the reference group (adjusted odds ratio=1.28, 95% CI: 0.81-2.03), whereas the adjusted odds ratio for those with metabolic dysregulation and without depressive symptoms was 4.40 (95% CI: 3.42-5.67). The Synergy Index (SI=1.52; 95% CI: 1.07-2.17) suggested that the combined effect of depressive symptoms and metabolic dysregulation was greater than the sum of individual effects. An interaction between depression and metabolic dysregulation was also suggested by a structural equation model. Our study highlights the interaction between depressive symptoms and metabolic dysregulation as a risk factor for type 2 diabetes. Early identification, monitoring and a comprehensive management approach of both conditions might be an important diabetes prevention strategy.

Depressive symptoms and glycated hemoglobin A1c: a reciprocal relationship in a prospective cohort study.

BACKGROUND: The aim of this study was to evaluate the dynamic association between depressive symptoms and glycated hemoglobin A1c (HbA1c) levels using data from the English Longitudinal Study of Ageing (ELSA). METHOD: The sample was comprised of 2886 participants aged ⩾50 years who participated in three clinical assessments over an 8-year period (21% with prediabetes and 7% with diabetes at baseline). Structural equation models were used to address reciprocal associations between depressive symptoms and HbA1c levels and to evaluate the mediating effects of lifestyle-related behaviors and cardiometabolic factors. RESULTS: We found a reciprocal association between depressive symptoms and HbA1c levels: depressive symptoms at one assessment point predicted HbA1c levels at the next assessment point (standardized ß = 0.052) which in turn predicted depressive symptoms at the following assessment point (standardized ß = 0.051). Mediation analysis suggested that both lifestyle-related behaviors and cardiometabolic factors might mediate the association between depressive symptoms and HbA1c levels: depressive symptoms at baseline predicted lifestyle-related behaviors and cardiometabolic factors at the next assessment, which in turn predicted HbA1c levels 4 years later. A similar association was observed for the other direction: HbA1c levels at baseline predicted lifestyle-related behaviors and cardiometabolic factors at the next assessment, which in turn predicted depressive symptoms 4 years later. CONCLUSIONS: Our results suggest a dynamic relationship between depressive symptoms and HbA1c which might be mediated by both lifestyle and cardiometabolic factors. This has important implications for investigating the pathways which could link depressive symptoms and increased risk of diabetes.

Contralateral breast cancer: incidence according to ductal or lobular phenotype of the primary.

AIM: To identify differences in the incidence of contralateral breast cancer between patients with a primary tumour diagnosis of invasive ductal carcinoma (IDC) and those with a diagnosis of invasive lobular carcinoma (ILC). MATERIALS AND METHODS: Data from two large cancer registries (registry A & B) the Northern and Yorkshire Cancer Registry Information Service (NYCRIS) and the West Midlands Cancer Intelligence Unit (WMCIU) from 1998-2003 for all cases of invasive breast cancer of either pure ductal or pure lobular reported histology were obtained. The invasive status of the contralateral tumour diagnosis and tumour morphology was collected. Chi-square tests were undertaken to examine the differences in contralateral rates for both registries and univariate analysis to ascertain which predictors affected contralateral breast cancer risk for registry A the WMCIU cases. RESULTS: A total of 38,132 patients were studied, 32,735 patients with IDC and 5397 (14.2%) patients with ILC over the 6-year period. There was no significant difference between the occurrence and time to occurrence of contralateral breast cancer according to original cancer histology, 901 (2.8%) patients with IDC versus 166 (3.1%) patients with ILC (p=0.169). The analysis of registry A cases showed no association between original histology (ductal versus lobular), age at diagnosis, tumour grade, use of radiotherapy for the primary cancer or use of systemic therapy (chemotherapy and/or endocrine therapy), and development of a contralateral breast cancer. CONCLUSION: There is no apparent increase in risk of developing a contralateral breast cancer according to the primary cancer histology either IDC or ILC. Standard mammographic follow-up does not need to take account of original tumour pathology. Increased intervention or post-treatment surveillance for the contralateral breast is not indicated in the context of ILC. The role of MRI should be restricted to those patients with ILC who are planning breast-conservation surgery, but not for assessing the contralateral breast.

Iodine Status over Two Decades: Influence of Seaweed Exposure.

Iodine deficiency is known to result in deficits in neuropsychological development in children born to iodine deficient mothers. However, a remedy in terms of iodisation of table salt as is the norm in most countries, has not been embraced by Ireland. The borderline iodine status of the Irish population persists unchanged over the past 20 years with the annual median urinary iodine (UI) varying from 62.9 to 105 µg/L; overall median 72.4 µg/L (WHO recommended 100 µg/L). Exposure to a seaweed rich environment allowing for intake by respiration of seaweed derived gaseous iodine, rather than simple proximity to the sea, confers advantages in terms of iodine intake with 21/46 (45.6%) of schoolchildren in seaweed rich coastal areas having UI values > 150 µg/L compared to 1/28 (3.6 %) and 2/93 (2.2%) in low seaweed abundant coastal and inland areas respectively. The corresponding values for adult females were 31/72 (43%), 7/60 (11.6%) and 21/132 (16.0%). The findings support introduction of iodine prophylaxis through Universal Salt Iodisation (USI), to ensure that women of child bearing age have access to sufficient dietary iodine.

Cyclical relationship between depressive symptoms and diabetes distress in people with Type 2 diabetes mellitus: results from the Montreal Evaluation of Diabetes Treatment Cohort Study.

AIMS: To determine if longitudinal cyclical relationships exist between depressive symptoms and diabetes distress in people with Type 2 diabetes mellitus. METHODS: Data were obtained from the Montreal Evaluation of Diabetes Treatment study, a cohort study of 1691 people with Type 2 diabetes mellitus. Depressive symptoms and diabetes distress, measured with the Patient Health Questionnaire and Diabetes Distress Scale, respectively, were assessed at baseline, 1 year and 2 years. A cross-lagged path model analysis with all autoregressive associations was used. Paths and indirect associations were examined. RESULTS: All paths in the model were significant. Depressive symptoms were positively associated with diabetes distress across consecutive time points and diabetes distress was positively associated with depressive symptoms across consecutive time points. The association between depressive symptoms at baseline and depressive symptoms at 2 years was mediated by both depressive symptoms and diabetes distress at 1 year. The association between diabetes distress at baseline and diabetes distress at 2 years was also mediated by both depressive symptoms and diabetes distress. CONCLUSIONS: Depressive symptoms and diabetes distress are cyclically related; results suggest that depressive symptoms influence diabetes distress, which, in turn, influences depressive symptoms. Although many studies focus on the differences between depressive symptoms and diabetes distress, the present study is the first to provide longitudinal evidence that these constructs are cyclically related.

Examining the 16-year trajectories of mental health and wellbeing through the transition into widowhood.

BACKGROUND: Becoming widowed is a significant event. There is considerable evidence that surviving partners report substantial changes in their wellbeing and mental health. Changes can occur prior to partner's death as an anticipatory effect and consequently during the period after partner's death. For most, declines in wellbeing and mental health dissipate over time. However, there is a limited long-term evidence to compare age-normative trajectories in mental health and wellbeing with the trajectories of those who transition into widowhood. METHODS: Participants (n = 652) were older adults (aged 65-94 years at baseline) from the 16-year Melbourne Longitudinal Studies on Healthy Ageing project who were either married or de facto (n = 577), or recently widowed (n = 75). Generalized Estimating Equations (GEE) examined the immediate and long-term impact of widowhood. GEE piecewise regression analyses examined the trajectories of wellbeing and mental health in those who transitioned into widowed with time centered at time of partner's death. Analyses were stratified by gender. RESULTS: For both men and women, becoming widowed was strongly related to a strong decline in positive affect post partner's death. Otherwise, no long-term impact of widowhood on negative affect or depressive symptomology was reported. CONCLUSIONS: The impact of widowhood reports differential impacts on different indicators of wellbeing and mental health, which were inconsistent between men and women.

The utility of estimating population-level trajectories of terminal wellbeing decline within a growth mixture modelling framework.

PURPOSE: Mortality-related decline has been identified across multiple domains of human functioning, including mental health and wellbeing. The current study utilised a growth mixture modelling framework to establish whether a single population-level trajectory best describes mortality-related changes in both wellbeing and mental health, or whether subpopulations report quite different mortality-related changes. METHODS: Participants were older-aged (M = 69.59 years; SD = 8.08 years) deceased females (N = 1,862) from the dynamic analyses to optimise ageing (DYNOPTA) project. Growth mixture models analysed participants' responses on measures of mental health and wellbeing for up to 16 years from death. RESULTS: Multi-level models confirmed overall terminal decline and terminal drop in both mental health and wellbeing. However, modelling data from the same participants within a latent class growth mixture framework indicated that most participants reported stability in mental health (90.3 %) and wellbeing (89.0 %) in the years preceding death. CONCLUSIONS: Whilst confirming other population-level analyses which support terminal decline and drop hypotheses in both mental health and wellbeing, we subsequently identified that most of this effect is driven by a small, but significant minority of the population. Instead, most individuals report stable levels of mental health and wellbeing in the years preceding death.

Proximal duodenal obstruction associated with compression from a replaced right hepatic artery.

Replaced right hepatic artery is a well-described normal anatomical variant, not previously associated with acute or chronic abdominal symptoms or long-term sequelae. We report a 15-year-old girl presenting with nearly a decade of symptoms secondary to external compression of the proximal duodenum by the ventral passage of a replaced right hepatic artery. Surgical bypass of the duodenal obstruction significantly improved her symptoms. Replaced right hepatic artery related duodenal compression should be considered in the differential diagnosis of proximal duodenal obstruction. The presence of the replaced right hepatic artery should be clearly communicated to allow optimal presurgical planning.

Ammonia and nitrous oxide emissions from a commercial broiler house.

Complex variation in gas emissions from animal facilities has been shown in recent research reports. Uncertainties in these emission estimates are driving research activities concerning different animal species across the globe. Greenhouse gas (NO and CO) and NH concentrations were measured in a modern, tunnel-ventilated, commercial broiler house in Mississippi during five flocks (spanning approximately 1 yr). These were flocks 9 through 13 on reused pine shavings litter, representing litter reuse beyond 2 yr. Gas concentrations obtained from a photoacoustic multigas analyzer were coupled with ventilation measurements of air flow through the house to develop NH and NO emission rates. Ammonia emission during a flock (43 d) averaged approximately 14.8 ± 9.8 kg d in the commercial house (equivalent to 23.5 g bird marketed or 0.54 g bird d). Nitrous oxide emission averaged 2.3 ± 1.7 kg d in the house (equivalent to 3.64 g bird marketed or 0.085 g bird d). Emission rates increased with time from Day 1 to Day 43 and reached average values on Day 23 and 24 for NH and NO. Even with extended litter reuse, estimates of NH emissions from the broiler house agree well with recently published research that reused litter in eight or fewer flocks. This is important information for farmers who may not be able to afford to replace the litter with fresh bedding material annually.

Gender differences in the trajectories of late-life depressive symptomology and probable depression in the years prior to death.

BACKGROUND: Gender differences in depression are well established. Whether these differences persist into late life and in the years preceding death is less clear. There is a suggestion that there is no increased likelihood of depression in late life, but that there is an increase in depressive symptomology, particularly with proximity to death. We compared trajectories of probable depression and depressive symptomology between men and women over age and distance-to-death metrics to determine whether reports of depressive symptoms are more strongly related to age or mortality. METHODS: Participants (N = 2,852) from the Dynamic Analyses to Optimise Ageing (DYNOPTA) project had a mean age of 75 years (SD = 5.68 years) at baseline and were observed for up to 16 years prior to death. Multi-level regression models estimated change in depressive symptomology and probable depression over two time metrics, increasing age, and distance-to-death. RESULTS: Increases in depressive symptomology were reported over increasing age and in the years approaching death. Only male participants reported increased probable depression in the years preceding death. Models that utilized distance-to-death metrics better represented changes in late-life depression, although any changes in depression appear to be accounted for by co-varying physical health status. CONCLUSIONS: As death approaches, there are increases in the levels of depressive symptomology even after controlling for socio-demographic and health covariates. In line with increases in suicide rates in late life, male participants were at greater risk of reporting increases in depressive symptomology.

Tumoral calcinosis form of hydroxyapatite deposition disease in related red-bellied short-necked turtles, Emydura subglobosa.

Ten of 12 red-bellied short-necked turtles from a single clutch presented at 9 months of age with multiple white to tan nodules on their feet. Histologically, the nodules were composed of large periarticular deposits of mineralized crystalline material that extended into the joint spaces of interphalangeal joints and was surrounded by granulomatous inflammation and fibrosis. Crystallographic analysis determined the material to be apatite (calcium phosphate hydroxide) consistent with the tumoral calcinosis form of hydroxyapatite deposition disease (HADD). HADD has previously been described in aquatic turtles and rarely lizards and must be differentiated from gout in reptiles. A cause for the tumoral calcinosis lesions in these turtles could not be determined; however, based on previous reports in this species, a species-specific predilection, in conjunction with unknown environmental factors, is suspected. The use of the terms HADD, pseudogout (calcium pyrophosphate crystal deposition disease), and calcinosis circumscripta has been inconsistent, creating confusion in the literature.

Reconsidering Race Adjustment in Prenatal Alpha-Fetoprotein Screening.

OBJECTIVE: Black racial designation is the only race for which adjustment is recommended for maternal prenatal serum alpha-fetoprotein (AFP) screening. The objective of this study is to reevaluate the relationship between maternal race and maternal serum AFP values in prenatal analyte screening. METHODS: This was a single-center retrospective analysis of patients who underwent prenatal analyte screening between January 2007 and December 2020. Nomograms for raw maternal serum AFP values by gestational age were created and compared between patients identified as "Black" and "non-Black" on the laboratory requisition. Multivariable linear regression models were created to evaluate the relationship among gestational age, maternal weight, and maternal race on maternal serum AFP levels. The new models were compared with the laboratory-derived calculations, which used historically determined race adjustments. RESULTS: A total of 43,997 patients underwent analyte screening, and 27,710 patients had complete data for analysis. Of these, 6% were identified as Black. Black patients had laboratory blood draws at a mean gestational age of 123 days, compared with 120 days in non-Black patients ( P <.001), and had higher maternal weight (mean 170 vs 161 lbs, P <.001). Nomograms for raw maternal serum AFP values did not differ between Black and non-Black patients ( P =.065). When adjusted for gestational age and maternal weight, no difference in maternal serum AFP values was identified between Black and non-Black individuals ( P =.81). CONCLUSION: No difference in maternal serum AFP values was identified between Black and non-Black pregnant individuals when adjusted by maternal weight and gestational age at blood draw. These findings suggest that routine race-based adjustment of maternal serum AFP screening should be discontinued.