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Does the genetic aptitude for educational attainment (GAEA) moderate the genetic risk for alcohol use disorder (AUD) and drug use disorder (DUD)?
In the native Swedish population, born 1960–1980 and followed through 2017 (n = 1 862 435), the family genetic risk score (FGRS) for AUD and DUD and GAEA were calculated from, respectively, the educational attainment and risk for AUD and DUD, of 1st through 5th degree relatives from Swedish national registers. Analyses utilized Aalen's linear hazards models.
Risk for AUD was robustly predicted by the main effects of FGRSAUD [b = 6.32 (95% CI 6.21–6.43), z = 64.9, p < 0.001) and GAEA [b = −2.90 (2.83–2.97), z = 44.1, p < 0.001] and their interaction [b = −1.93 (1.83–2.03), z = 32.9, p < 0.001]. Results were similar for the prediction of DUD by the main effects of FGRSDUD [b = 4.65 (CI 4.56–4.74), z = 59.4, p < 0.001] and GAEA [−2.08 (2.03–2.13), z = 46.4, p < 0.001] and their interaction [b = −1.58 (1.50–1.66)), z = 30.2, p < 0.001]. The magnitude of the interactions between GAEA and FGRSAUD and FGRSDUD in the prediction of, respectively, AUD and DUD was attenuated only slightly by the addition of educational attainment to the model.
Conclusions and relevance
The genetic propensity to high educational attainment robustly moderates the genetic risk for both AUD and DUD such that the impact of the genetic liability to AUD and DUD on the risk of illness is substantially attenuated in those with high v. low GAEA. This effect is not appreciably mediated by the actual level of educational attainment. These naturalistic findings could form the basis of prevention efforts in high-risk youth.
Sabellidites cambriensis is a tubular non-mineralized metazoan that appears as compressed ribbon-shaped imprints with transverse wrinkling, thick walls and an even tube diameter of up to 3 mm. The distribution of Sabellidites is investigated in three Ediacaran–Cambrian sections on the Digermulen Peninsula in Arctic Norway, spanning the Manndrapselva Member of the Stáhpogieddi Formation and the lower member of the Breidvika Formation. Here, the Ediacaran–Cambrian boundary is located in the lower part of the upper parasequence (third cycle) of the Manndrapselva Member. Specimens of Sabellidites are rare but consistently present close to the lowest level of Treptichnus pedum and upsection, whereas the taxon is common and abundant in the lower part of the lower member of the Breidvika Formation, with an upper record at c. 55 m above the base. The range is comparable with that of the GSSP section in Newfoundland, Canada, establishing Sabellidites as an index fossil for the lowermost Cambrian. In the Manndrapselva Member, Sabellidites co-occurs with the acritarch Granomarginata, indicative of the lowermost Cambrian Granomarginata Zone, whereas in the Breidvika Formation it co-occurs with Asteridium. Sabellidites is widely distributed in Baltica, through the Rovnian and Lontovan regional stages but confined to the Fortunian global stage. In its lower range, Sabellidites is associated with a Treptichnus pedum trace fossil association and a depauperate leiosphaerid acritarch assemblage, followed by a Granomarginata assemblage. In its upper range, Sabellidites co-occurs with acritarchs of the Asteridium–Comasphaeridium Zone and the tubular foraminiferan Platysolenites. In Baltica, Sabellidites is a useful index fossil.
Characterize and compare SARS-CoV-2–specific immune responses in plasma and gingival crevicular fluid (GCF) from nursing home residents during and after natural infection
SARS-CoV-2–infected nursing home residents
A convenience sample of 14 SARS-CoV-2–infected nursing home residents, enrolled 4–13 days after real-time reverse transcription polymerase chain reaction diagnosis, were followed for 42 days. Post diagnosis, plasma SARS-CoV-2–specific pan-Immunoglobulin (Ig), IgG, IgA, IgM, and neutralizing antibodies were measured at 5 timepoints and GCF SARS-CoV-2–specific IgG and IgA were measured at 4 timepoints.
All participants demonstrated immune responses to SARS-CoV-2 infection. Among 12 phlebotomized participants, plasma was positive for pan-Ig and IgG in all 12, neutralizing antibodies in 11, IgM in 10, and IgA in 9. Among 14 participants with GCF specimens, GCF was positive for IgG in 13 and IgA in 12. Immunoglobulin responses in plasma and GCF had similar kinetics; median times to peak antibody response was similar across specimen types (4 weeks for IgG; 3 weeks for IgA). Participants with pan-Ig, IgG, and IgA detected in plasma and GCF IgG remained positive through this evaluation’s end 46–55 days post-diagnosis. All participants were viral culture negative by the first detection of antibodies.
Nursing home residents had detectable SARS-CoV-2 antibodies in plasma and GCF after infection. Kinetics of antibodies detected in GCF mirrored those from plasma. Non-invasive GCF may be useful for detecting and monitoring immunologic responses in populations unable or unwilling to be phlebotomized.
– Comorbidity between psychiatric disorders is extensive but, from a genetic perspective, still poorly understood. Modern molecular genetic approaches to this problem are limited by a reliance on case–control designs.
– In 5 828 760 individuals born in Sweden from 1932–1995 with a mean (s.d.) age at follow-up of 54.4 (18.1), we examined family genetic risk score (FGRS) profiles including internalizing, psychotic, substance use and developmental disorders in 10 pairs of psychiatric and substance use disorders diagnosed from population registries. We examined these profiles in three groups of patients: disorder A only, disorder B only and comorbid cases with both disorders.
– The most common pattern of findings, seen in five pairings, was simple and quantitative. Comorbid cases had higher FGRS than both non-comorbid cases for all (or nearly all) disorders. However, the pattern was more complex in the remaining five pairings and included qualitative changes where the comorbid cases showed no increases in FGRS for certain disorders and in a few cases significant decreases. Several comparisons showed an asymmetric pattern of findings with increases, in comorbidity compared to single disorder cases, of the FGRS for only one of the two disorders.
– The examination of FGRS profiles in general population samples where all disorders are assessed in all subjects provides a fruitful line of inquiry to understand the origins of psychiatric comorbidity. Further work will be needed, with an expansion of analytic approaches, to gain deeper insights into the complex mechanisms likely involved.
Self-rated health (SRH) is associated with higher risk of death. Since low plasma levels of fat-soluble vitamins are related to mortality, we aimed to assess whether plasma concentrations of vitamins A, D and E were associated with SRH in the MARK-AGE study. We included 3158 participants (52 % female) aged between 35 and 75 years. Cross-sectional data were collected via questionnaires. An enzyme immunoassay quantified 25-hydroxyvitamin D and HPLC determined α-tocopherol and retinol plasma concentrations. The median 25-hydroxyvitamin D and retinol concentrations differed significantly (P < 0·001) between SRH categories and were lower in the combined fair/poor category v. the excellent, very good and good categories (25-hydroxvitamin D: 40·8 v. 51·9, 49·3, 46·7 nmol/l, respectively; retinol: 1·67 v. 1·75, 1·74, 1·70 µmol/l, respectively). Both vitamin D and retinol status were independently associated with fair/poor SRH in multiple regression analyses: adjusted OR (95 % CI) for the vitamin D insufficiency, deficiency and severe deficiency categories were 1·33 (1·06–1·68), 1·50 (1·17–1·93) and 1·83 (1·34–2·50), respectively; P = 0·015, P = 0·001 and P < 0·001, and for the second/third/fourth retinol quartiles: 1·44 (1·18–1·75), 1·57 (1·28–1·93) and 1·49 (1·20–1·84); all P < 0·001. No significant associations were reported for α-tocopherol quartiles. Lower vitamin A and D status emerged as independent markers for fair/poor SRH. Further insights into the long-term implications of these modifiable nutrients on health status are warranted.
Previous studies have demonstrated substantial associations between substance use disorders (SUD) and suicidal behavior. The current study empirically assesses the extent to which shared genetic and/or environmental factors contribute to associations between alcohol use disorders (AUD) or drug use disorders (DUD) and suicidal behavior, including attempts and death.
The authors used Swedish national registry data, including medical, pharmacy, criminal, and death registrations, for a large cohort of twins, full siblings, and half siblings (N = 1 314 990) born 1960–1980 and followed through 2017. They conducted twin-sibling modeling of suicide attempt (SA) or suicide death (SD) with AUD and DUD to estimate genetic and environmental correlations between outcomes. Analyses were stratified by sex.
Genetic correlations between SA and SUD ranged from rA = 0.60–0.88; corresponding shared environmental correlations were rC = 0.42–0.89 but accounted for little overall variance; and unique environmental correlations were rE = 0.42–0.57. When replacing attempt with SD, genetic and shared environmental correlations with AUD and DUD were comparable (rA = 0.48–0.72, rC = 0.92–1.00), but were attenuated for unique environmental factors (rE = −0.01 to 0.31).
These findings indicate that shared genetic and unique environmental factors contribute to comorbidity of suicidal behavior and SUD, in conjunction with previously reported causal associations. Thus, each outcome should be considered an indicator of risk for the others. Opportunities for joint prevention and intervention, while limited by the polygenic nature of these outcomes, may be feasible considering moderate environmental correlations between SA and SUD.
Alcohol use disorder (AUD) is clinically heterogeneous. We examine its potential genetic heterogeneity as a function of sex, age, clinical features and mode of ascertainment.
In the Swedish population born 1932–1995 (n = 5 829 952), we examined the genetic risk profiles for AUD, major depression (MD), anxiety disorders, bipolar disorder, drug use disorder (DUD), attention deficit-hyperactivity disorder (ADHD) and criminal behavior (CB) in 361 124 cases of AUD subdivided by sex, age at onset (AAO), recurrence, mode of ascertainment and medical complications. Family genetic risk scores (FGRS), calculated from 1st to 5th-degree relatives controlling of cohabitation, assesses genetic risk from phenotypes in the family, not from DNA variants.
FGRS profiles differed modestly across sex with all scores higher in females. Differences were more pronounced for AAO and recurrence with the FGRS for AUD, DUD, ADHD and CB substantially higher in cases with early AAO or high recurrence rates. Genetic profiles differed considerably by mode of ascertainment, with higher FGRS for AUD and most other disorders in patients seen in hospital v. primary care settings. Cases of AUD with medical complications had higher FGRS for AUD. AUD cases comorbid with MD and DUD had higher FGRS risk for AUD, but this genetic may be less specific given increases in FGRS for multiple other disorders.
From a genetic perspective, AUD differs substantially as a function of AAO, recurrence, mode of ascertainment and patterns of comorbidity, suggesting caution in cross-sample comparisons of AUD cohorts that differ in these features.
How does genetic liability to suicide attempt (SA), suicide death (SD), major depression (MD), bipolar disorder (BD), schizophrenia (SZ), alcohol use disorder (AUD), and drug use disorder (DUD) impact on risk for SA and SD?
In the Swedish general population born 1932–1995 and followed through 2017 (n = 7 661 519), we calculate family genetic risk scores (FGRS) for SA, SD, MD, BD, SZ, AUD, and DUD. Registration for SA and SD was assessed from Swedish national registers.
In univariate and multivariate models predicting SA, FGRS were highest for SA, AUD, DUD, and MD. In univariate models predicting SD, the strongest FGRS were AUD, DUD, SA, and SD. In multivariate models, the FGRS for SA and AUD were higher in predicting SA while the FGRS for SD, BD, and SZ were higher in predicting SD. Higher FGRS for all disorders significantly predicted both younger age at first SA and frequency of attempts. For SD, higher FGRS for MD, AUD, and SD predicted later age at SD. Mediation of FGRS effects on SA and SD was more pronounced for SD than SA, strongest for AUD, DUD, and SZ FGRS and weakest for MD.
FGRS for both SA and SD and for our five psychiatric disorders impact on risk for SA and SD in a complex manner. While some of the impact of genetic risk factors for psychiatric disorders on risk for SA and SD is mediated through developing the disorders, these risks also predispose directly to suicidal behaviors.
Knowledge on cheetah population densities across their current range is limited. Therefore, new and efficient assessment tools are needed to gain more knowledge on species distribution, ecology and behaviour. Scat detection dogs have emerged as an efficient and non-invasive method to monitor elusive and vulnerable animal species, like cheetahs, due to the dog’s superior olfactory system. However, the success of locating scat using detection dogs can be significantly improved under suitable weather conditions. We examined the impact of temperature, humidity and wind speed on detection rates of scat from cheetahs during a scat detection dog survey in Northern Kenya. We found that average wind speed positively influences the scat detection rate of detection dogs working on leash. Humidity showed no significant influence. Temperature showed a strong negative correlation with humidity and thus was excluded from our model analyses. While it is likely that wind speed is especially invalid for dogs working off leash, this study did not demonstrate this. Wind speed could thus influence the success of monitoring cheetahs or other target species. Our findings help to improve the survey and thus maximise the coverage of study area and the collection of target samples of elusive and rare species.
The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia.
Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects.
There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness.
Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.
Characteristic pseudohyphae or smaller budding yeast, both singly and in variably sized clusters in the smear as well as mixed directly with clusters of squamous cells, neutrophils, and necrotic material
Three species of the family Teloschistaceae (lichenized Ascomycota) are described as new to science from Southern and Eastern Siberia and the Far East. Corticolous Caloplaca saviczii belongs to the genus Caloplaca s. str.; it has C. cerina-like apothecia and green to grey-green, crateriform soralia with a white rim. Lendemeriella aureopruinosa is a saxicolous taxon with a thin grey thallus and small apothecia 0.3–0.6 mm in diameter, with a dark orange disc usually bearing epipsamma and often with a grey true exciple containing the pigment Cinereorufa-green. Orientophila infirma is a corticolous species with an endophloeodal thallus and small orange apothecia, 0.2–0.3 mm in diameter, usually with an inconspicuous thalline exciple. All new taxa presumably have a boreal north-eastern distribution in Asia.
We show local higher integrability of derivative of a suitable weak solution to the surface growth model, provided a scale-invariant quantity is locally bounded. If additionally our scale-invariant quantity is small, we prove local smoothness of solutions.
Population genetic studies often overlook the evidence for variability and change in past material culture. Here, the authors use a Mesolithic example to demonstrate the importance of integrating archaeological evidence into the interpretation of the Scandinavian hunter-gatherer genetic group. Genetic studies conclude that this group resulted from two single-event dispersals into Scandinavia before 7500 BC. Archaeological evidence, however, shows at least six immigration events pre-dating the earliest DNA, and that the first incoming groups arrived in Scandinavia before 9000 BC. The findings underline the importance of conducting careful archaeological analysis of prehistoric human dispersal in tandem with the study of ancient population genomics.
Predictors of new-onset bipolar disorder (BD) or psychotic disorder (PD) have been proposed on the basis of retrospective or prospective studies of ‘at-risk’ cohorts. Few studies have compared concurrently or longitudinally factors associated with the onset of BD or PDs in youth presenting to early intervention services. We aimed to identify clinical predictors of the onset of full-threshold (FT) BD or PD in this population.
Multi-state Markov modelling was used to assess the relationships between baseline characteristics and the likelihood of the onset of FT BD or PD in youth (aged 12–30) presenting to mental health services.
Of 2330 individuals assessed longitudinally, 4.3% (n = 100) met criteria for new-onset FT BD and 2.2% (n = 51) met criteria for a new-onset FT PD. The emergence of FT BD was associated with older age, lower social and occupational functioning, mania-like experiences (MLE), suicide attempts, reduced incidence of physical illness, childhood-onset depression, and childhood-onset anxiety. The emergence of a PD was associated with older age, male sex, psychosis-like experiences (PLE), suicide attempts, stimulant use, and childhood-onset depression.
Identifying risk factors for the onset of either BD or PDs in young people presenting to early intervention services is assisted not only by the increased focus on MLE and PLE, but also by recognising the predictive significance of poorer social function, childhood-onset anxiety and mood disorders, and suicide attempts prior to the time of entry to services. Secondary prevention may be enhanced by greater attention to those risk factors that are modifiable or shared by both illness trajectories.
Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association.
We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide.
In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73–2.78 after 1 month of use, and 1.25–1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period.
Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.
Opioid use disorder is a major public health crisis, and evidence suggests ways of better serving patients who live with opioid use disorder in the emergency department (ED). A multi-disciplinary team developed a quality improvement project to implement this evidence.
The intervention was developed by an expert working group consisting of specialists and stakeholders. The group set goals of increasing prescribing of buprenorphine/naloxone and providing next day walk-in referrals to opioid use disorder treatment clinics. From May to September 2018, three Alberta ED sites and three opioid use disorder treatment clinics worked together to trial the intervention. We used administrative data to track the number of ED visits where patients were given buprenorphine/naloxone. Monthly ED prescribing rates before and after the intervention were considered and compared with eight nonintervention sites. We considered whether patients continued to fill opioid agonist treatment prescriptions at 30, 60, and 90 days after their index ED visit to measure continuity in treatment.
The intervention sites increased their prescribing of buprenorphine/naloxone during the intervention period and prescribed more buprenorphine/naloxone than the controls. Thirty-five of 47 patients (74.4%) discharged from the ED with buprenorphine/naloxone continued to fill opioid agonist treatment prescriptions 30 days and 60 days after their index ED visit. Thirty-four patients (72.3%) filled prescriptions at 90 days.
Emergency clinicians can effectively initiate patients on buprenorphine/naloxone when supports for this standardized evidence-based care are in place within their practice setting and timely follow-up in community is available.
Accurate and timely data are essential for identifying populations at risk for undernutrition due to poor-quality diets, for implementing appropriate interventions and for evaluating change. Life-logging wearable cameras (LLWC) have been used to prospectively capture food/beverage consumed by adults in high-income countries. This study aimed to evaluate the concurrent criterion validity, for assessing maternal and child dietary diversity scores (DDS), of a LLWC-based image-assisted recall (IAR) and 24-h recall (24HR). Direct observation was the criterion method. Food/beverage consumption of rural Eastern Ugandan mothers and their 12–23-month-old child (n 211) was assessed, for the same day for each method, and the IAR and 24HR DDS were compared with the weighed food record DDS using the Bland–Altman limits of agreement (LOA) method of analysis and Cohen’s κ. The relative bias was low for the 24HR (–0·1801 for mothers; –0·1358 for children) and the IAR (0·1227 for mothers; 0·1104 for children), but the LOA were wide (–1·6615 to 1·3012 and –1·6883 to 1·4167 for mothers and children via 24HR, respectively; –2·1322 to 1·8868 and –1·7130 to 1·4921 for mothers and children via IAR, respectively). Cohen’s κ, for DDS via 24HR and IAR, was 0·68 and 0·59, respectively, for mothers, and 0·60 and 0·59, respectively, for children. Both the 24HR and IAR provide an accurate estimate of median dietary diversity, for mothers and their young child, but non-differential measurement error would attenuate associations between DDS and outcomes, thereby under-estimating the true associations between DDS – where estimated via 24HR or IAR – and outcomes measured.