An investigation of the use of standardised leaving certificate performance as a method of estimating pre-morbid intelligence.

BACKGROUND: In cases of brain pathology, current levels of cognition can only be interpreted reliably relative to accurate estimations of pre-morbid functioning. Estimating levels of pre-morbid intelligence is, therefore, a crucial part of neuropsychological evaluation. However, current methods of estimation have proven problematic. OBJECTIVE: To evaluate if standardised leaving certificate (LC) performance can predict intellectual functioning in a healthy cohort. The LC is the senior school examination in the Republic of Ireland, taken by almost 50 000 students annually, with total performance distilled into Central Applications Office points. METHODS: A convenience sample of university students was recruited (n = 51), to provide their LC results and basic demographic information. Participants completed two cognitive tasks assessing current functioning (Vocabulary and Matrix Reasoning (MR) subtests - Wechsler Abbreviated Scale of Intelligence, Second Edition) and a test of pre-morbid intelligence (Spot-the-Word test from the Speed and Capacity of Language Processing). Separately, LC results were standardised relative to the population of test-takers, using a computer application designed specifically for this project. RESULTS: Hierarchical regression analysis revealed that standardised LC performance [F(2,48) = 3.90, p = 0.03] and Spot-the-Word [F(2,47) = 5.88, p = 0.005] significantly predicted current intellect. Crawford & Allen's demographic-based regression formula did not. Furthermore, after controlling for gender, English [F(1,49) = 11.27, p = 0.002] and Irish [F(1,46) = 4.06, p = 0.049) results significantly predicted Vocabulary performance, while Mathematics results significantly predicted MR [F(1,49) = 8.80, p = 0.005]. CONCLUSIONS: These results suggest that standardised LC performance may represent a useful resource for clinicians when estimating pre-morbid intelligence.

Long-term Outcomes of Childhood Family Income Supplements on Adult Functioning.

Importance: During an ongoing longitudinal cohort study, a casino opening created a natural cash transfer experiment. Some participating families received income supplements, and others did not. The children in this study are now adults. Objective: To assess the long-term outcomes of family income supplements received in childhood. Design, Setting, and Participants: This community-representative longitudinal cohort study set in western North Carolina assessed 1266 participants aged 9, 11, and 13 years at intake up to 11 times up to age 30 years from January 1993 to December 2015. Data were analyzed from January to December 2021. Exposures: In 1996, a southeastern American Indian tribe implemented a cash transfer program of approximately $5000 annually per person for tribal members. Participants were compared on whether their family ever received the cash transfers (American Indian vs non-American Indian), the duration of the transfers, and annual amount based on the number of parents. Main Outcomes and Measures: Participants were followed up at ages 25 and 30 years to assess mental health symptoms, substance use symptoms, and functional outcomes (physical health, risky or illegal behaviors, and financial and social functioning). Results: Of 1266 included participants, 320 (25.3%) were American Indian and 581 (49.7%) were female. Participants whose families received cash transfers during childhood reported fewer anxiety symptoms (relative risk [RR], 0.33; 95% CI, 0.25-0.44), depressive symptoms (RR, 0.51; 95% CI, 0.42-0.62), and cannabis symptoms (RR, 0.47; 95% CI, 0.27-0.82). They also reported improved physical health (RR, 0.66; 95% CI, 0.55-0.80) and financial functioning (RR, 0.78; 95% CI, 0.67-0.89) and fewer risky or illegal behaviors (RR, 0.57; 95% CI, 0.46-0.72) compared with those who did not receive the cash transfer. This pattern was supported by a series of heterogeneity analyses in which children whose families received the transfers for the longest duration and whose families received the largest transfer (due to having multiple American Indian parents) had the lowest levels of symptoms and the highest levels of functioning. Conclusions and Relevance: In this natural experiment, a family cash transfer in childhood was associated with positive adult functioning 20 years later. The findings support programs like the child tax credit or universal basic income that provide cash directly to families with children.

The Effects of Terrain Properties Upon the Small Crater Population Distribution at Giordano Bruno: Implications for Lunar Chronology.

The distribution of impact craters on the ejecta of Giordano Bruno, a recent (<10 Ma) 22-km diameter crater within the lunar highlands, exhibits substantial variations. We surveyed craters D ≥ 10 m across a 1,323 km2 area of Giordano Bruno's ejecta and compared the distribution of craters with variations in thermophysical properties derived from the Lunar Reconnaissance Orbiter Diviner instrument. We used Diviner-derived rock abundance and nighttime regolith temperatures along with thermal model-predicted surface temperatures for a diversity of terrains to identify and isolate areas of the ejecta based on thermophysical properties such as bulk density and thermal conductivity. We found that thermophysical properties of the ejecta vary considerably both laterally and vertically, and consistently differ from typical regolith, indicating the presence of higher thermal inertia materials. Crater-size frequencies are significantly lower in areas with terrain properties exhibiting higher: rock abundance, nighttime temperatures, and/or modeled thermal inertia. This discrepancy in crater distribution increases for craters smaller than ∼25 m. These thermophysical variations indicate changes in the mechanical properties of the target materials. We suggest that these variations-specifically, terrain-dependent crater scaling variations and impactor-scale heterogeneities in material properties such as the presence or absence of large boulders-may influence crater diameters or inhibit crater production altogether in Giordano Bruno's ejecta; furthermore, these factors are size-dependent.

The Radiation Environment of Ceres and Implications for Surface Sampling.

Ceres is a large water-rich dwarf planet located within the asteroid belt. Its surface displays evidence of material sourced from a deep subsurface liquid brine layer within recent geologic time, making it a candidate ocean world with possible present-day activity. However, Ceres lacks a substantial atmosphere and likely does not possess a global magnetic field. Therefore, any material emplaced or exposed on the surface will be subject to weathering by charged particles of solar and galactic origin. We have evaluated the effect of charged particle radiation on material within the near-surface of Ceres and find that the timescale for radiation-induced modification and destruction of organics and endogenic material is ∼100 Myr to 1 Gyr within the top 10-20 cm of the surface. Furthermore, we find that the timescale for sterilization of any putative living organisms contained within material at these depths is <500 kyr. Future missions to the surface may therefore consider targeting regions with geologic ages that fall between these two timescales to avoid the risk of backward contamination while ensuring that sampled material is not heavily radiation processed.

Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study.

BACKGROUND AND AIMS: The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection). METHODS: Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders. RESULTS: Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33-2.16). The ORs were 4.84 (95% CI 2.96-7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79-1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15-2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87-1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13-2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62-1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14-2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88-1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity. CONCLUSION: Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.

Associations of Despair With Suicidality and Substance Misuse Among Young Adults.

Importance: Deaths of despair is a term that has recently been used to describe the increases in premature mortality from suicides, drug overdoses (particularly from opiates), and alcohol-related liver disease among US adults. Despite the use of the term despair, its role in these causes of premature death has not been empirically tested. Objective: To test whether despair among young adults is associated with suicidal thoughts and behavior, alcohol misuse, and drug misuse. Design, Setting, and Participants: The Great Smoky Mountains Study is a Southeastern, mixed urban-rural population-based cohort study conducted from November 10, 1992, to September 22, 2015. A total of 1420 participants originally 9, 11, and 13 years of age were followed up 11 times to 30 years of age (11 230 person-observations). A total of 1154 of 1400 living participants (82.4%) were assessed at 30 years of age. Statistical analysis was performed from May 7, 2019, to April 10, 2020. Exposures: Participants were assessed with structured interviews for indicators of despair (eg, hopelessness, helplessness, low self-worth, and feeling unloved). Despair was assessed with items from structured interviews: the Child and Adolescent Psychiatric Assessment and the Young Adult Psychiatric Assessment. Main Outcomes and Measures: Structured interviews were used to assess suicidal thoughts and behavior, substance use, and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) alcohol use disorder and drug use disorder (including opioids) in young adulthood (2424 observations of 1266 individuals between 25 and 30 years of age). Results: This study included 1420 individuals (790 male individuals). During young adulthood (25 and 30 years of age), the 3-month weighted prevalence of any despair was 19.5% (476 of 2424 observations) with 7.6% of participants (201 of 2424 observations) reporting 2 or more despair items. In longitudinal, lagged models, despair scores (range, 0-3) were associated with more suicidal thoughts and behaviors (odds ratio [OR], 1.5; 95% CI, 1.1-2.0), illicit drug use (OR, 1.7; 95% CI, 1.2-2.5), and opioid use (OR, 1.9; 95% CI, 1.1-3.3) but not alcohol use disorder (OR, 0.8; 95% CI, 0.6-1.2). These associations persisted after accounting for sociodemographic factors (eg, poverty and educational level), lagged outcome status, and lagged depression status. The associations between despair and study outcomes were stronger in models accounting for long-term measures of despair extending back to childhood. There was no consistent pattern of moderation by sociodemographic factors. Conclusions and Relevance: This study's findings suggest an empirical basis for longitudinal associations between despair and several, but not all, precursors of "deaths of despair" in rural Appalachia. Individual despair should be studied as a potential factor associated with morbidity and impairment in young adulthood.

Income dividends and subjective survival in a Cherokee Indian cohort: a quasi-experiment.

Persons with high temporal discounting tend to value immediate gratification over future gains. Low self-reported lifespan (SRL)-an individual's assessment of a relatively short future lifespan-concentrates in low-income populations and may reflect high temporal discounting. We use casino-based cash dividends among the Eastern Band of Cherokee Indians (EBCI) as a quasi-experiment to test whether large income gains among EBCI members translate into increased SRL. We used SRL data for EBCI and White youth, aged 19 to 28, participating in two waves of the Life Time Trajectory of Youth (LTI-Y) survey from 2000 to 2010. We controlled for unobserved confounding across individuals, time, and region through a longitudinal design using a difference-in-difference analytic approach (N = 294). We conducted all analyses separately by gender and by quartile of socioeconomic status. Cash dividends correspond with a 15.23 year increase in SRL among EBCI men below the lowest socio-economic quartile at baseline relative to Whites (standard error = 5.39, p < .01). Results using other socio-economic cut-points support improved SRL among EBCI men (but not women). The large magnitude of this result among EBCI men indicates that a non-trivial cash dividend to a low-income population may confer long-term benefits on perceptions of future lifespan and, in turn, reduce temporal discounting.Abbreviations: EBCI: Eastern Band of Cherokee Indians; SES: Socioeconomic Status; LTI-Y: Life Trajectory Interview for Youth; GSMS: Great Smoky Mountains Study; SRL: Self-Reported Lifespan; SSS: Subjective Social Status.

Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium.

To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10-5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10-5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10-5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.

Association of Parental Incarceration With Psychiatric and Functional Outcomes of Young Adults.

Importance: In 2016, an estimated 8% of US children younger than 18 years had experienced the incarceration of a parent, and rates were substantially higher among children from racial and ethnic minority backgrounds and disadvantaged groups. Little is known about whether parental incarceration during childhood is associated with adult psychiatric problems and functional outcomes. Objective: To examine whether parental incarceration is associated with increased levels of psychiatric diagnosis and poor outcomes in health, legal, financial, and social domains in adulthood. Design, Setting, and Participants: This cohort study used data from the community-representative, prospective, longitudinal Great Smoky Mountains Study. Children and their parents were interviewed up to 8 times from January 1993 to December 2000 (ages 9-16 years; 6674 observations of 1420 participants) using the Child and Adolescent Psychiatric Assessment, which assessed parental incarceration, childhood psychiatric diagnoses, and other adversities. Young adults were followed up at ages 19, 21, 25, and 30 years from January 1999 to December 2015 (4556 observations of 1334 participants) to assess psychiatric diagnoses and functional outcomes indicative of a disrupted transition to adulthood. Data analysis was conducted from June 2018 to June 2019. Results: By age 16 years, 475 participants (weighted percentage, 23.9%) had a parental figure who had been incarcerated, including 259 young men (22.2%) and 216 young women (25.5%). Parental incarceration was associated with higher prevalence of childhood psychiatric diagnoses (eg, any depressive diagnosis: adjusted odds ratio [aOR], 2.5; 95% CI, 1.3-4.6; P = .006; attention-deficit/hyperactivity disorder: aOR, 2.3; 95% CI, 1.0-5.5; P = .06; and conduct disorder: aOR, 2.5; 95% CI, 1.4-4.3; P = .001). After accounting for childhood psychiatric diagnoses and adversity exposure, parental incarceration remained associated with increased odds of having an adult anxiety disorder (aOR, 1.7; 95% CI, 1.0-3.0; P = .04), having an illicit drug use disorder (aOR, 6.6; 95% CI, 2.6-17.0; P < .001), having a felony charge (aOR, 3.4; 95% CI, 1.8-6.5; P < .001), incarceration (aOR, 2.8; 95% CI, 1.4-5.4; P = .003), not completing high school (aOR, 4.4; 95% CI, 2.2-8.8; P < .001), early parenthood (aOR, 1.7; 95% CI, 1.0-3.0; P = .04), and being socially isolated (aOR, 2.2; 95% CI, 1.2-4.0; P = .009). Conclusions and Relevance: This study suggests that parental incarceration is associated with a broad range of psychiatric, legal, financial, and social outcomes during young adulthood. Parental incarceration is a common experience that may perpetuate disadvantage from generation to generation.

Does Despair Really Kill? A Roadmap for an Evidence-Based Answer.

Two seemingly associated demographic trends have generated considerable interest: income stagnation and rising premature mortality from suicides, drug poisoning, and alcoholic liver disease among US non-Hispanic Whites with low education. Economists interpret these population-level trends to indicate that despair induced by financial stressors is a shared pathway to these causes of death. Although we now have the catchy term "deaths of despair," we have yet to study its central empirical claim: that conceptually defined and empirically assessed "despair" is indeed a common pathway to several causes of death. At the level of the person, despair consists of cognitive, emotional, behavioral, and biological domains. Despair can also permeate social relationships, networks, institutions, and communities. Extant longitudinal data sets feature repeated measures of despair-before, during, and after the Great Recession-offering resources to test the role that despair induced by economic decline plays in premature morbidity and mortality. Such tests must also focus on protective factors that could shield individuals. Deaths of despair is more than a phrase; it constitutes a hypothesis that deserves conceptual mapping and empirical study with longitudinal, multilevel data.

Early Pubertal Timing and Testosterone Associated With Higher Levels of Adolescent Depression in Girls.

OBJECTIVE: The prevalence of depression increases dramatically during puberty in girls. Earlier work in this sample reported that the sex steroids estradiol and testosterone were associated with increased depression in girls. Using three additional data waves (983 new observations), we retest the relative contributions of pubertal timing, pubertal status, and sex hormones on the increases in female depression. METHOD: Eight waves of data from the prospective, representative Great Smoky Mountains Study were used covering female participants in the community who were 9 to 16 years of age (3,005 assessments of 630 girls; 1993-2000). Structured interviews assessed depressive disorders. Youth rated their pubertal status using Tanner stage drawings, and sex steroids were assayed from dried blood spots. RESULTS: Risk for depression during puberty was associated with both age and Tanner stage in univariate models. In adjusted models accounting for pubertal timing and sex steroids, the apparent effects of age and Tanner stage were attenuated both in terms of statistical significance and effect size. The only significant predictors of change in depression status during puberty were early pubertal timing (odds ratio = 5.8, 95% CI = 1.9-17.9, p = .002 after age 12 years) and higher testosterone levels (odds ratio = 2.0, 95% CI = 1.1-3.8, p = .03 for quartile-split variable). CONCLUSION: The added observations have modified the original conclusions, implicating the following: testosterone only, but not estradiol; and early pubertal timing, but not age or pubertal status per se. These findings argue for multiple pubertal determinants of depression risk, including factors that are socially and biologically mediated.

Identification of Cystic Lesions by Secondary Screening of Familial Pancreatic Cancer (FPC) Kindreds Is Not Associated with the Stratified Risk of Cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.

Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.

How Does Household Income Affect Child Personality Traits and Behaviors?

We examine the effects of a quasi-experimental unconditional household income transfer on child emotional and behavioral health and personality traits. Using longitudinal data, we find that there are large beneficial effects on children's emotional and behavioral health and personality traits during adolescence. We find evidence that these effects are most pronounced for children who start out with the lowest initial endowments. The income intervention also results in improvements in parental relationships which we interpret as a potential mechanism behind our findings.

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy.

BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives.

Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

Association of Childhood Trauma Exposure With Adult Psychiatric Disorders and Functional Outcomes.

Importance: Being exposed to trauma is a common childhood experience associated with symptoms and impairments in childhood. Objective: To assess the association between cumulative childhood trauma exposure and adult psychiatric and functional outcomes. Design, Setting, and Participants: Prospective, population-based cohort study of 1420 participants. A community representative sample of participants was assessed with structured Child and Adolescent Psychiatric Assessment interviews up to 8 times in childhood (ages 9-16 years; 6674 observations; 1993-2000) for lifetime trauma exposure as defined by the Diagnostic and Statistical Manual of Mental Disorders. Participants were followed up 4 times in adulthood (ages 19, 21, 25, and 30 years; 4556 observations of 1336 participants; 1999-2015) with the structured Young Adult Psychiatric Assessment Interview for psychiatric outcomes, functional outcomes, and evidence of a disrupted transition to adulthood. Analysis was completed in 2018. Exposure: Participants were assessed with the structured Child and Adolescent Psychiatric Assessment interview (parent and self-report) up to 8 times in childhood for lifetime trauma exposure (ages 9-16 years; 6674 observations; 1993-2000). Main Outcomes and Measures: Participants were assessed up to 4 times with the structured Young Adult Psychiatric Assessment interview (self-report) in adulthood (ages 19, 21, 25, and 30 years; 4556 observations of 1336 participants; 1999-2015) for psychiatric outcomes, functional outcomes, and evidence of a disrupted transition to adulthood. Results: Among the 1420 study participants, 630 (49.0%) were female and 983 (89.4%) were white. By age 16 years, 30.9% of children (n = 451) were exposed to 1 traumatic event, 22.5% (n = 289) were exposed to 2 such events, and 14.8% (n = 267) were exposed to 3 or more. Cumulative childhood trauma exposure to age 16 years was associated with higher rates of adult psychiatric disorders (odds ratio for any disorder, 1.2; 95% CI, 1.0-1.4) and poorer functional outcomes, including key outcomes that indicate a significantly disrupted transition to adulthood (eg, failure to hold a job and social isolation). Childhood trauma exposure continued to be associated with higher rates of adult psychiatric and functional outcomes after adjusting for a broad range of childhood risk factors, including psychiatric functioning and family adversities and hardships (adjusted odds ratio for any disorder, 1.3; 95% CI, 1.0-1.5). Conclusions and Relevance: Cumulative childhood trauma exposure was associated with poor adult outcomes even after accounting for many of the childhood and family factors associated with both trauma exposure and poor adult outcomes. Childhood trauma exposures are common, but often preventable, thus providing a clear target for child-focused public health efforts to ameliorate long-term morbidity.

Adult Associations of Childhood Suicidal Thoughts and Behaviors: A Prospective, Longitudinal Analysis.

OBJECTIVE: Suicidal thoughts and behavior (STBs) have their peak period of onset in adolescence, but little is known about how such behavior is associated with later functioning. The aim of this study is to test whether childhood STBs are related to adult psychiatric, suicidal, and functional outcomes. METHOD: This is a prospective, population-based community study of 1,420 participants assessed with structured interviews up to 7 times in childhood/adolescence (ages 9-16 years; 6,674 observations) for STBs including passive and active ideation, plans, and attempts. Participants were then assessed 4 times in young adulthood (ages 19, 21, 24, and 30 years; 4,556 observations of 1,273 participants) for psychiatric diagnoses, STBs, and functional outcomes. RESULTS: By age 16 years, 7.0% of participants had reported some type of STBs, with 3.9% reporting an attempt. Both ideation only and suicide attempts were associated with higher levels of anxiety disorders and STBs in adulthood, as well as poor functioning across financial, health, risky/illegal, and social domains. These observed effects generally were attenuated after adjusting for other psychiatric and psychosocial factors that predict childhood STBs (particularly maltreatment, depression, and disruptive behavior disorders). The exception was adult suicidal behavior, which was predicted by both childhood ideation and attempts, even in the fully adjusted model. Children and adolescents with STBs were more likely to have had a disrupted transition to adulthood. CONCLUSION: Childhood STBs are a marker for a multitude of poor psychiatric and functional outcomes in adulthood, but these effects are largely accounted for by other factors. In contrast, childhood STBs are a robust risk factor for adult suicidal thoughts and behavior.

Predicting Persistent, Limited, and Delayed Problematic Cannabis Use in Early Adulthood: Findings From a Longitudinal Study.

OBJECTIVE: To identify risk profiles associated with patterns of problematic cannabis use in early adulthood. METHOD: Data came from 1,229 participants in the Great Smoky Mountains Study, a prospective 20-year cohort study from 1993 to 2015 that is representative of western North Carolina with yearly assessments conducted from ages 9 and 16 years, and assessments at ages 19, 21, 26, and 30 years. Patterns of problematic cannabis use (i.e., DSM-5 cannabis use disorder or daily use) in early adulthood included the following: nonproblematic use in late adolescence (ages 19-21) and early adulthood (ages 26-30); limited problematic use in late adolescence only; persistent problematic use in late adolescence and early adulthood; and delayed problematic use in early adulthood only. Multinominal logistic regression models examined pairwise associations between these patterns and risk factors in childhood/early adolescence (ages 9-16) and late adolescence (ages 19-21). Risk factors included psychiatric disorders (e.g., anxiety, depressive), other substance use (smoking, alcohol, illicit drugs), and challenging social factors (e.g., low socioeconomic status, family functioning, peers). Sex and race/ethnicity (white, African American, American Indian) interactions were tested. RESULTS: The persistent pattern (6.7% of sample) was characterized by more anxiety disorders across development and more DSM-5 CUD symptoms during late adolescence compared to the limited pattern (13.3%), which, in turn, had more childhood family instability and dysfunction. The delayed pattern (3.7%) was characterized by more externalizing disorders, maltreatment, and peer bullying in childhood compared to those in nonproblematic users. There were no significant interactions of sex or race/ethnicity. CONCLUSION: Problematic cannabis use patterns during early adulthood have distinctive risk profiles, which may be useful in tailoring targeted interventions.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.