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Tobacco smoking remains one of the leading causes of preventable illness and death and is heritable with complex underpinnings. Converging evidence suggests a contribution of the polygenic risk for smoking to the use of tobacco and other substances. Yet, the underlying brain mechanisms between the genetic risk and tobacco smoking remain poorly understood.
Genomic, neuroimaging, and self-report data were acquired from a large cohort of adolescents from the IMAGEN study (a European multicenter study). Polygenic risk scores (PGRS) for smoking were calculated based on a genome-wide association study meta-analysis conducted by the Tobacco and Genetics Consortium. We examined the interrelationships among the genetic risk for smoking initiation, brain structure, and the number of occasions of tobacco use.
A higher smoking PGRS was significantly associated with both an increased number of occasions of tobacco use and smaller cortical volume of the right orbitofrontal cortex (OFC). Furthermore, reduced cortical volume within this cluster correlated with greater tobacco use. A subsequent path analysis suggested that the cortical volume within this cluster partially mediated the association between the genetic risk for smoking and the number of occasions of tobacco use.
Our data provide the first evidence for the involvement of the OFC in the relationship between smoking PGRS and tobacco use. Future studies of the molecular mechanisms underlying tobacco smoking should consider the mediation effect of the related neural structure.
To evaluate the validity and reproducibility of a 152-item semi-quantitative FFQ (SFFQ) for estimating flavonoid intakes.
Over a 1-year period, participants completed two SFFQ and two weighed 7-d dietary records (7DDR). Flavonoid intakes from the SFFQ were estimated separately using Harvard (SFFQHarvard) and Phenol-Explorer (SFFQPE) food composition databases. 7DDR flavonoid intakes were derived using the Phenol-Explorer database (7DDRPE). Validity was assessed using Spearman’s rank correlation coefficients deattenuated for random measurement error (rs), and reproducibility was assessed using rank intraclass correlation coefficients.
This validation study included primarily participants from two large observational cohort studies.
Six hundred forty-one men and 724 women.
When compared with two 7DDRPE, the validity of total flavonoid intake assessed by SFFQPE was high for both men and women (rs = 0·77 and rs = 0·74, respectively). The rs for flavonoid subclasses ranged from 0·47 for flavones to 0·78 for anthocyanins in men and from 0·46 for flavonols to 0·77 for anthocyanins in women. We observed similarly moderate (0·4–0·7) to high (≥0·7) validity when using SFFQHarvard estimates, except for flavonesHarvard (rs = 0·25 for men and rs = 0·19 for women). The SFFQ demonstrated high reproducibility for total flavonoid and flavonoid subclass intake estimates when using either food composition database. The intraclass correlation coefficients ranged from 0·69 (flavonolsPE) to 0·80 (proanthocyanidinsPE) in men and from 0·67 (flavonolsPE) to 0·77 (flavan-3-ol monomersHarvard) in women.
SFFQ-derived intakes of total flavonoids and flavonoid subclasses (except for flavones) are valid and reproducible for both men and women.
To assess the time to achieve reliable reporting of electronic health record data compared with manual reporting during validation.
Secondary analysis of aggregate data for number of patients present, number of patients with a central venous catheter, and number of patients with an indwelling urinary catheter during validation of an electronic health record reporting tool.
Mayo Clinic Health System in Wisconsin.
Mayo Clinic infection prevention and control staff, unit champions, and all inpatients.
We simultaneously collected electronic and manual counts of device data and compared discrepancies to determine their source. If manual data entry was incorrect, manual counts were coded as inaccurate. If electronically abstracted data did not reflect an accurate count, errors were attributed to the system. Data were compared using standard statistical methods.
Within 30 days after beginning validation of electronic reporting for central venous catheter days and urinary catheter days, electronic counts were durably more reliable than manual counts.
Manual validation for capturing and reporting electronic data and reporting can be shorter than the 90 days currently mandated by National Healthcare Safety Network criteria. Compared with a longer validation period, a shorter validation period may yield substantial savings while achieving the same validity.
Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia.
To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort.
Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479).
In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16–34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58–14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28–19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9–86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0–100.0%) for the replication cohort.
These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders.
To compare the risk of mild cognitive impairment (MCI) among a wide range of ethnoracial groups in the US.
Non-probabilistic longitudinal clinical research.
Participants enrolling into the National Alzheimer’s Coordinating Center Unified Data Set recruited via multiple approaches including clinician referral, self-referral by patients or family members, or active recruitment through community organizations.
Cognitively normal individuals 55 and older at the initial visit, who reported race and ethnicity information, with at least two visits between September 2005 and November 2018.
Ethnoracial information was self-reported and grouped into non-Latino Whites, Asian Americans, Native Americans, African Americans (AAs), and individuals simultaneously identifying as AAs and another minority race (AA+), as well as Latinos of Caribbean, Mexican, and Central/South American origin. MCI was evaluated clinically following standard criteria. Four competing risk analysis models were used to calculate MCI risk adjusting for risk of death, including an unadjusted model, and models adjusting for non-modifiable and modifiable risk factors.
After controlling for sex and age at initial visit, subhazard ratios of MCI were statistically higher than non-Latino Whites among Native Americans (1.73), Caribbean Latinos (1.80), and Central/South American Latinos (1.55). Subhazard ratios were higher among AA+ compared to non-Latino Whites only in the model controlling for all risk factors (1.40).
Compared to non-Latino Whites, MCI risk was higher among Caribbean and South/Central American Latinos as well as Native Americans and AA+. The factors explaining the differential MCI risk among ethnoracial groups are not clear and warrant future research.
Wildlife is an essential component of all ecosystems. Most places in the globe do not have local, timely information on which species are present or how their populations are changing. With the arrival of new technologies, camera traps have become a popular way to collect wildlife data. However, data collection has increased at a much faster rate than the development of tools to manage, process and analyse these data. Without these tools, wildlife managers and other stakeholders have little information to effectively manage, understand and monitor wildlife populations. We identify four barriers that are hindering the widespread use of camera trap data for conservation. We propose specific solutions to remove these barriers integrated in a modern technology platform called Wildlife Insights. We present an architecture for this platform and describe its main components. We recognize and discuss the potential risks of publishing shared biodiversity data and a framework to mitigate those risks. Finally, we discuss a strategy to ensure platforms like Wildlife Insights are sustainable and have an enduring impact on the conservation of wildlife.
Patient assessment is a fundamental feature of community paramedicine, but the absence of a recognized standard for assessment practices contributes to uncertainty about what drives care planning and treatment decisions. Our objective was to summarize the content of assessment instruments and describe the state of current practice in community paramedicine home visit programs.
We performed an environmental scan of all community paramedicine programs in Ontario, Canada, and used content analysis to describe current assessment practices in home visit programs. The International Classification on Functioning, Disability, and Health (ICF) was used to categorize and compare assessments. Each item within each assessment form was classified according to the ICF taxonomy.
A total of 43 of 52 paramedic services in Ontario, Canada, participated in the environmental scan with 24 being eligible for further investigation through content analysis of intake assessment forms. Among the 24 services, 16 met inclusion criteria for content analysis. Assessment forms contained between 13 and 252 assessment items (median 116.5, IQR 134.5). Most assessments included some content from each of the domains outlined in the ICF. At the subdomain level, only assessment of impairments of the functions of the cardiovascular, hematological, immunological, and respiratory systems appeared in all assessments.
Although community paramedicine home visit programs may differ in design and aim, all complete multi-domain assessments as part of patient intake. If community paramedicine home visit programs share similar characteristics but assess patients differently, it is difficult to expect that the resulting referrals, care planning, treatments, or interventions will be similar.
The consumption of nitrate-rich vegetables can acutely lower blood pressure and improve mediators shown to optimise vascular health. However, we do not yet understand the impact of long-term habitual dietary nitrate intake and its association with CVD. Therefore, the aim of this investigation was to examine the relationship between habitual dietary nitrate intakes and risk of CHD in women from the Nurses’ Health Study. We prospectively followed 62 535 women who were free from diabetes, CVD and cancer at baseline in 1986. Information on diet was updated every 4 years with validated FFQ. The main outcome was CHD defined by the occurrence of non-fatal myocardial infarction or fatal CHD. Cox proportional hazard regression models were used to estimate the relative risks (RR) and 95 % CI. During 26 years of follow-up, 2257 cases of CHD were identified. When comparing the highest quintile of nitrate intake with the lowest quintile, in aged-adjusted analysis there was a protective association for CHD (RR=0·77, 95 % CI 0·68, 0·97; P=0·0002) which dissipated after further adjustment for smoking, physical activity, BMI and race (RR=0·91; 95 % CI 0·80, 1·04; P=0·27). This magnitude of association was further attenuated once we adjusted for the Alternative Healthy Eating Index excluding vegetable and fruit consumption (RR=1·04, 95 % CI 0·91, 1·20; P=0·34). Dietary nitrate intake was not related to the risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors in a large group of US women.
Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both.
In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age.
The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction.
These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.
Though not often discussed explicitly in literature, sample handling and preparation for advanced characterization techniques is a significant challenge for radiological materials. In this contribution, a detailed description is given of method development associated with characterization of highly radioactive and, in some cases, hygroscopic oxides of technetium. Details are given on developed protocols, fixtures, and tooling designed for x-ray and neutron diffraction, x-ray absorption, Raman spectroscopy, magic angle spinning nuclear magnetic resonance, and electron paramagnetic resonance. In some cases, multiple iterations of improved sample holder design are described. Lessons learned in handling Tc compounds for these and similar characterization methods are discussed.
Quantification of lean body mass and fat mass can provide important insight into epidemiological research. However, there is no consensus on generalisable anthropometric prediction equations to validly estimate body composition. We aimed to develop and validate practical anthropometric prediction equations for lean body mass, fat mass and percent fat in adults (men, n 7531; women, n 6534) from the National Health and Nutrition Examination Survey 1999–2006. Using a prediction sample, we predicted each of dual-energy X-ray absorptiometry (DXA)-measured lean body mass, fat mass and percent fat based on different combinations of anthropometric measures. The proposed equations were validated using a validation sample and obesity-related biomarkers. The practical equation including age, race, height, weight and waist circumference had high predictive ability for lean body mass (men: R2=0·91, standard error of estimate (SEE)=2·6 kg; women: R2=0·85, SEE=2·4 kg) and fat mass (men: R2=0·90, SEE=2·6 kg; women: R2=0·93, SEE=2·4 kg). Waist circumference was a strong predictor in men only. Addition of other circumference and skinfold measures slightly improved the prediction model. For percent fat, R2 were generally lower but the trend in variation explained was similar. Our validation tests showed robust and consistent results with no evidence of substantial bias. Additional validation using biomarkers demonstrated comparable abilities to predict obesity-related biomarkers between direct DXA measurements and predicted scores. Moreover, predicted fat mass and percent fat had significantly stronger associations with obesity-related biomarkers than BMI did. Our findings suggest the potential application of the proposed equations in various epidemiological settings.
Electrochemical sensing systems are advancing into a wide range of new applications, moving from the traditional lab environment into disposable devices and systems, enabling real-time continuous monitoring of complex media. This transition presents numerous challenges ranging from issues such as sensitivity and dynamic range, to autocalibration and antifouling, to enabling multiparameter analyte and biomarker detection from an array of nanosensors within a miniaturized form factor. New materials are required not only to address these challenges, but also to facilitate new manufacturing processes for integrated electrochemical systems. This paper examines the recent advances in the instrumentation, sensor architectures, and sensor materials in the context of developing the next generation of nanoenabled electrochemical sensors for life sciences applications, and identifies the most promising solutions based on selected well established application exemplars.
Attempts to discover new active ingredients and target sites within the aromatic pathway have resulted in the synthesis of potent enzyme inhibitors, but no herbicides. As an aid in identifying a new target for inhibitor design and screening, we have determined the mode of action of a compound (6-methyl anthranilate) that exhibits noncommercial levels of herbicidal activity. Our evidence suggests that 6-methyl anthranilate is converted in vivo, by traversing the tryptophan biosynthetic sequence, to 4-methyl tryptophan, which inhibits anthranilate synthase. Inhibitors synthesized by design and those found by target-based screening converged on analogs of tryptophan and anthranilate. None, however, was more herbicidal than 6-methyl anthranilate.
The local chemistry of technetium-99 (99Tc) in oxide glasses is important for understanding the incorporation and long-term release of Tc from nuclear waste glasses, both those for legacy defense wastes and fuel reprocessing wastes. Tc preferably forms Tc(VII), Tc(IV), or Tc(0) in glass, depending on the level of reduction of the melt. Tc(VII) in oxide glasses is normally assumed to be isolated pertechnetate TcO4- anions surrounded by alkali, but can occasionally precipitate as alkali pertechnetate salts such as KTcO4 and NaTcO4 when Tc concentration is high. In these cases, Tc(VII) is 4-coordinated by oxygen. A reinvestigation of the chemistry of alkali-technetium-oxides formed under oxidizing conditions and at temperatures used to prepare nuclear waste glasses showed that higher coordinated alkali Tc(VII) oxide species had been reported, including those with the TcO5- and TcO6- anions. The chemistry of alkali Tc(VII) and other alkali-Tc-oxides is reviewed, along with relevant synthesis conditions.
Additionally, we report attempts to make 5- and 6-coordinate pertechnetate compounds of K, Na, and Li, i.e. TcO5- and TcO6-. It was found that higher coordinated species are very sensitive to water, and easily decompose into their respective pertechnetates. It was difficult to obtain pure compounds, but mixtures of the pertechnetate and other phase(s) were frequently found, as evidenced by x-ray absorption spectroscopy (XAS), neutron diffraction (ND), and Raman spectroscopy. Low temperature electron paramagnetic resonance (EPR) measurements showed the possibility of Tc(IV) and Tc(VI) in Na3TcO5 and Na5TcO6 compounds.
It was hypothesized that the smaller counter cation would result in more stable pertechnetates. To confirm the synthesis method, LiReO4 and Li5ReO6 were prepared, and their Raman spectra match those in the literature. Subsequently, the Tc versions LiTcO4 and Li5TcO6 were synthesized and characterized by ND, Raman spectroscopy, XANES, and EXAFS. The Li5TcO6 was a marginally stable compound that appears to have the same structure as that known for Li5ReO6. Implications of the experimental work on stability of alkali technetate compounds and possible role in the volatilization of Tc are discussed.