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The Wisconsin Twin Project comprises multiple longitudinal studies that span infancy to early adulthood. We summarize recent papers that show how twin designs with deep phenotyping, including biological measures, can inform questions about phenotypic structure, etiology, comorbidity, heterogeneity, and gene–environment interplay of temperamental constructs and mental and physical health conditions of children and adolescents. The general framework for investigations begins with rich characterization of early temperament and follows with study of experiences and exposures across childhood and adolescence. Many studies incorporate neuroimaging and hormone assays.
The efficient and effective movement of research into practice is acknowledged as crucial to improving population health and assuring return on investment in healthcare research. The National Center for Advancing Translational Science which sponsors Clinical and Translational Science Awards (CTSA) recognizes that dissemination and implementation (D&I) sciences have matured over the last 15 years and are central to its goals to shift academic health institutions to better align with this reality. In 2016, the CTSA Collaboration and Engagement Domain Task Force chartered a D&I Science Workgroup to explore the role of D&I sciences across the translational research spectrum. This special communication discusses the conceptual distinctions and purposes of dissemination, implementation, and translational sciences. We propose an integrated framework and provide real-world examples for articulating the role of D&I sciences within and across all of the translational research spectrum. The framework’s major proposition is that it situates D&I sciences as targeted “sub-sciences” of translational science to be used by CTSAs, and others, to identify and investigate coherent strategies for more routinely and proactively accelerating research translation. The framework highlights the importance of D&I thought leaders in extending D&I principles to all research stages.
Methamphetamine (MA) dependence contributes to neurotoxicity and neurocognitive deficits. Although combined alcohol and MA misuse is common, how alcohol consumption relates to neurocognitive performance among MA users remains unclear. We hypothesized that alcohol and MA use would synergistically diminish neurocognitive functioning, such that greater reported alcohol consumption would exert larger negative effects on neurocognition among MA-dependent individuals compared to MA-nonusing persons.
Eighty-seven MA-dependent (MA+) and 114 MA-nonusing (MA−) adults underwent neuropsychological and substance use assessments. Linear and logistic regressions examined the interaction between MA status and lifetime average drinks per drinking day on demographically corrected global neurocognitive T scores and impairment rates, controlling for recent alcohol use, lifetime cannabis use, WRAT reading performance, and lifetime depression.
MA+ displayed moderately higher rates of impairment and lower T scores compared to MA−. Lifetime alcohol use significantly interacted with MA status to predict global impairment (ORR = 0.70, p = .003) such that greater lifetime alcohol use increased likelihood of impairment in MA−, but decreased likelihood of impairment in MA+. Greater lifetime alcohol use predicted poorer global T scores among MA− (b = −0.44, p = .030) but not MA+ (b = 0.08, p = .586).
Contrary to expectations, greater lifetime alcohol use related to reduced risk of neurocognitive impairment among MA users. Findings are supported by prior research identifying neurobiological mechanisms by which alcohol may attenuate stimulant-driven vasoconstriction and brain thermotoxicity. Replication and examination of neurophysiologic mechanisms underlying alcohol use in the context of MA dependence are warranted to elucidate whether alcohol confers a degree of neuroprotection.
Introduction: Low acuity patients have been controversially tagged as a source of emergency department (ED) misuse. Authorities for many Canadian health regions have set up policies so these patients preferably present to walk-in clinics (WIC). We compared the cost and quality of the care given to low acuity patients in an academic ED and a WIC of Québec City during fiscal year 2015-16. Methods: We conducted an ambidirectional (prospective and retrospective) cohort study using a time-driven activity-based costing method. This method uses duration of care processes (e.g., triage) to allocate to patient care all direct costs (e.g., personnel, consumables), overheads (e.g., building maintenance) and physician charges. We included consecutive adult patients, ambulatory at all time and discharged from the ED or WIC with a diagnosis of upper respiratory tract infection (URTI), urinary tract infection (UTI) or low back pain. Mean cost [95%CI] per patient per condition was compared between settings after risk-adjustment for age, sex, vital signs, number of regular medications and co-morbidities using generalized log-gamma regression models. Proportions [95%CI] of antibiotic prescription and chest X-Ray use in URTI, compliance with provincial guidelines on use of antibiotics in UTI, and column X-Ray use in low back pain were compared between settings using a Pearson Chi-Square test. Results: A total of 409 patients were included. ED and WIC groups were similar in terms of age, sex and vital signs on presentation, but ED patients had a greater burden of comorbidities. Adjusted mean cost (2016 CAN$) of care was significantly higher in the ED than in the WIC (p < 0.0001) for URTI (78.42[64.85-94.82] vs. 59.43[50.43-70.06]), UTI (78.88[69.53-89.48] vs. 53.29[43.68-65.03]), and low back pain (87.97[68.30-113.32] vs. 61.71[47.90-79.51]). For URTI, antibiotics were more frequently prescribed in the WIC (44.1%[34.3-54.3] vs. 5.8%[1.2-16.0]; p < 0.0001) and chest X-Rays, more frequently used in the ED (26.9%[15.6-41.0] vs. 13.7%[7.7-22.0]; p = 0.05). No significant differences were observed in the compliance with guidelines on use of antibiotics in UTI and in the use of column X-Ray in low back pain. Conclusion: Total cost of care for low acuity patients is lower in walk-in clinics than in EDs. However, our results suggest that quality-of-care issues should be considered in determining the best alternate setting for treating ambulatory emergency patients.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
Clarifying individual differences that predict resilience or vulnerability to emotional distress is crucial for identifying etiological factors contributing to affective disturbances, and to promoting emotional well-being. Despite recent progress identifying specific brain regions and personality traits, it remains unclear whether there are common factors underlying the structural aspects of the brain and the personality traits that, in turn, protect against symptoms of emotional distress. In the present study, an integrative structural equation model was developed to examine the associations among (1) a latent construct of Control, representing the volumes of a system of prefrontal cortical (PFC) regions including middle, inferior, and orbital frontal cortices; (2) a latent construct of Resilience personality traits including cognitive reappraisal, positive affectivity, and optimism; and (3) Anxiety and Depression symptoms, in a sample of 85 healthy young adults. Results showed that the latent construct of PFC volumes positively predicted the latent construct of Resilience, which in turn negatively predicted Anxiety. Mediation analysis confirmed that greater latent PFC volume is indirectly associated with lower Anxiety symptoms through greater latent trait Resilience. The model did not show a significant mediation for Depression. These results support the idea that there are common volumetric and personality factors that help protect against symptoms of emotional distress. These findings provide strong evidence that such brain-personality-symptom approaches can provide novel insights with valuable implications for understanding the interaction of these factors in healthy and clinically diagnosed individuals.
Sheep are an important part of the global agricultural economy. Growth and meat production traits are significant economic traits in sheep. The Texel breed is the most popular terminal sire breed in the UK, mainly selected for muscle growth and lean carcasses. This is a study based on a genome-wide association approach that investigates the links between some economically important traits, including computed tomography (CT) measurements, and molecular polymorphisms in UK Texel sheep. Our main aim was to identify single nucleotide polymorphisms (SNP) associated with growth, carcass, health and welfare traits of the Texel sheep breed. This study used data from 384 Texel rams. Data comprised ten traits, including two CT measured traits. The phenotypic data were placed in four categories: growth traits, carcass traits, health traits and welfare traits. De-regressed estimated breeding values (EBV) for these traits together with sire genotypes derived with the Ovine 50 K SNP array of Illumina were jointly analysed in a genome wide association analysis. Eight novel chromosome-wise significant associations were found for carcass, growth, health and welfare traits. Three significant markers were intronic variants and the remainder intergenic variants. This study is a first step to search for genomic regions controlling CT-based productivity traits related to body and carcass composition in a terminal sire sheep breed using a 50 K SNP genome-wide array. Results are important for the further development of strategies to identify causal variants associated with CT measures and other commercial traits in sheep. Independent studies are needed to confirm these results and identify candidate genes for the studied traits.
Objectives: Human immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos. Methods: Participants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry. Results: Compared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13–2.23; p<.01] after adjusting for significant covariates. Higher rates of global NCI were observed with Puerto Rican (n=60; 71%) versus Mexican (n=79, 44%) origin/descent; this disparity persisted in models adjusting for significant covariates (OR=2.40; CI=1.11–5.29; p=.03). Conclusions: HIV+ Latinos, especially of Puerto Rican (vs. Mexican) origin/descent had increased rates of NCI compared with Whites. Differences in rates of NCI were not completely explained by worse HIV-disease characteristics, neurocognitive comorbidities, or genetic ancestry. Future studies should explore culturally relevant psychosocial, biomedical, and genetic factors that might explain these disparities and inform the development of targeted interventions. (JINS, 2018, 24, 163–175)
We performed a spatial-temporal analysis to assess household risk factors for Ebola virus disease (Ebola) in a remote, severely-affected village. We defined a household as a family's shared living space and a case-household as a household with at least one resident who became a suspect, probable, or confirmed Ebola case from 1 August 2014 to 10 October 2014. We used Geographic Information System (GIS) software to calculate inter-household distances, performed space-time cluster analyses, and developed Generalized Estimating Equations (GEE). Village X consisted of 64 households; 42% of households became case-households over the observation period. Two significant space-time clusters occurred among households in the village; temporal effects outweighed spatial effects. GEE demonstrated that the odds of becoming a case-household increased by 4·0% for each additional person per household (P < 0·02) and 2·6% per day (P < 0·07). An increasing number of persons per household, and to a lesser extent, the passage of time after onset of the outbreak were risk factors for household Ebola acquisition, emphasizing the importance of prompt public health interventions that prioritize the most populated households. Using GIS with GEE can reveal complex spatial-temporal risk factors, which can inform prioritization of response activities in future outbreaks.
To determine the length and position of a thyroidectomy scar that is cosmetically most appealing to naïve raters.
Images of thyroidectomy scars were reproduced on male and female necks using digital imaging software. Surgical variables studied were scar position and length. Fifteen raters were presented with 56 scar pairings and asked to identify which was preferred cosmetically. Twenty duplicate pairings were included to assess rater reliability. Analysis of variance was used to determine preference.
Raters preferred low, short scars, followed by high, short scars, with long scars in either position being less desirable (p < 0.05). Twelve of 15 raters had acceptable intra-rater and inter-rater reliability.
Naïve raters preferred low, short scars over the alternatives. High, short scars were the next most favourably rated. If other factors influencing incision choice are considered equal, surgeons should consider these preferences in scar position and length when planning their thyroidectomy approach.
The Universe is permeated by hot, turbulent, magnetized plasmas. Turbulent plasma is a major constituent of active galactic nuclei, supernova remnants, the intergalactic and interstellar medium, the solar corona, the solar wind and the Earth’s magnetosphere, just to mention a few examples. Energy dissipation of turbulent fluctuations plays a key role in plasma heating and energization, yet we still do not understand the underlying physical mechanisms involved. THOR is a mission designed to answer the questions of how turbulent plasma is heated and particles accelerated, how the dissipated energy is partitioned and how dissipation operates in different regimes of turbulence. THOR is a single-spacecraft mission with an orbit tuned to maximize data return from regions in near-Earth space – magnetosheath, shock, foreshock and pristine solar wind – featuring different kinds of turbulence. Here we summarize the THOR proposal submitted on 15 January 2015 to the ‘Call for a Medium-size mission opportunity in ESAs Science Programme for a launch in 2025 (M4)’. THOR has been selected by European Space Agency (ESA) for the study phase.
The grounded ice in the Totten and Dalton glaciers is an essential component of the buttressing for the marine-based Aurora basin, and hence their stability is important to the future rate of mass loss from East Antarctica. Totten and Vanderford glaciers are joined by a deep east-west running subglacial trench between the continental ice sheet and Law Dome, while a shallower trench links the Totten and Dalton glaciers. All three glaciers flow into the ocean close to the Antarctic circle and experience ocean-driven ice shelf melt rates comparable with the Amundsen Sea Embayment. We investigate this combination of trenches and ice shelves with the BISICLES adaptive mesh ice-sheet model and ocean-forcing melt rates derived from two global climate models. We find that ice shelf ablation at a rate comparable with the present day is sufficient to cause widespread grounding line retreat in an east-west direction across Totten and Dalton glaciers, with projected future warming causing faster retreat. Meanwhile, southward retreat is limited by the shallower ocean facing slopes between the coast and the bulk of the Aurora sub-glacial trench. However the two climate models produce completely different future ice shelf basal melt rates in this region: HadCM3 drives increasing sub-ice shelf melting to ~2150, while ECHAM5 shows little or no increase in sub-ice shelf melting under the two greenhouse gas forcing scenarios.
We calibrated portions of the radiocarbon time scale with combined 230Th, 231Pa, 14C measurements of corals collected from Espiritu Santo, Vanuatu and the Huon Peninsula, Papua New Guinea. The new data map 14C variations ranging from the current limit of the tree-ring calibration [11,900 calendar years before present (cal BP), Kromer and Spurk 1998, now updated to 12,400 cal B P, see Kromer et al., this issue], to the 14C-dating limit of 50,000 cal BP, with detailed structure between 14 to 16 cal kyr BP and 19 to 24 cal kyr BP. Samples older than 25,000 cal BP were analyzed with high-precision 231Pa dating methods (Pickett et al. 1994; Edwards et al. 1997) as a rigorous second check on the accuracy of the 230Th ages. These are the first coral calibration data to receive this additional check, adding confidence to the age data forming the older portion of the calibration. Our results, in general, show that the offset between calibrated and 14C ages generally increases with age until about 28,000 cal BP, when the recorded 14C age is nearly 6800 yr too young. The gap between ages before this time is less; at 50,000 cal BP, the recorded 14C age is 4600 yr too young. Two major 14C-age plateaus result from a 130 drop in Δ14C between 14–15 cal kyr BP and a 700 drop in Δ14C between 22–25 cal kyr BP. In addition, a large atmospheric Δ14C excursion to values over 1000 occurs at 28 cal kyr BP. Between 20 and 10 cal kyr BP, a component of atmospheric Δ14C anti-correlates with Greenland ice δ18O, indicating that some portion of the variability in atmospheric Δ14C is related to climate change, most likely through climate-related changes in the carbon cycle. Furthermore, the 28-kyr excursion occurs at about the time of significant climate shifts. Taken as a whole, our data indicate that in addition to a terrestrial magnetic field, factors related to climate change have affected the history of atmospheric 14C.
The study of very early pregnancy loss is impractical in the general population, but possible amongst infertility patients receiving carefully monitored treatments. We examined the association between fetal loss and the risk of birth defects in the surviving co-twin in a retrospective cohort study of infertility patients within an infertility clinic in South Australia from January 1986 to December 2002, linked to population registries for births, terminations and birth defects. The study population consisted of a total of 5683 births. Births from singleton pregnancies without loss were compared with survivors from (1) pregnancies with an empty fetal sac at 6–8 weeks after embryo transfer, (2) fetal loss subsequent to 8-week ultrasound and (3) multiple pregnancy continuing to birth. Odds ratios (OR) for birth defects were calculated with adjustment for confounders. Amongst infertility patients, the prevalence of birth defects was 7.9% for all twin pregnancies without fetal loss compared with 14.6% in pregnancies in which there had been an empty sac at ultrasound, and 11.6% for pregnancies with fetal loss after 6–8 weeks. Compared with singleton pregnancies without loss, the presence of an empty sac was associated with an increased risk of any defect (OR=1.90, 95% confidence intervals (CI)=1.09–3.30) and with multiple defects (OR=2.87, 95% CI=1.31–6.28). Twin pregnancies continuing to birth without loss were not associated with an overall increased prevalence of defects. We conclude that the observed loss of a co-twin by 6–8 weeks of pregnancy is related to the risk of major birth defects in the survivor.
We have built an imaging polarimeter for use at mid-infrared wavelengths (i.e. N band or 8–13 μm). The detecting element is a 128 × 128 element Si:Ga Focal Plane Array, supplied by Amber Engineering, USA. The polarimeter itself provides diffraction limited images on a 4-m class telescope and has a field of view of about 32 arcsec of sky with 0·25 arcsec pixels. We describe the optical design, control electronics, observing modes and detector sensitivities. Also presented are some observational results to demonstrate the power of this new imaging polarimetric system.