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Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments.
We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994–1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences.
Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06–1.33), depression PRS (OR = 1.20, 95% CI = 1.08–1.34), family history (OR = 1.25, 95% CI = 1.11–1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07–1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk.
Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.
Subjective cognitive difficulties are common in mental illness and have a negative impact on role functioning. Little is understood about subjective cognition and the longitudinal relationship with depression and anxiety symptoms in young people.
To examine the relationship between changes in levels of depression and anxiety and changes in subjective cognitive functioning over 3 months in help-seeking youth.
This was a cohort study of 656 youth aged 12–25 years attending Australian headspace primary mental health services. Subjective changes in cognitive functioning (rated as better, same, worse) reported after 3 months of treatment was assessed using the Neuropsychological Symptom Self-Report. Multivariate multinomial logistic regression analysis was conducted to evaluate the impact of baseline levels of and changes in depression (nine-item Patient Health Questionnaire; PHQ9) and anxiety symptoms (seven-item Generalised Anxiety Disorder scale; GAD7) on changes in subjective cognitive function at follow-up while controlling for covariates.
With a one-point reduction in PHQ9 at follow-up, there was an estimated 11–18% increase in ratings of better subjective cognitive functioning at follow-up, relative to stable cognitive functioning. A one-point increase in PHQ9 from baseline to follow-up was associated with 7–14% increase in ratings of worse subjective cognitive functioning over 3 months, relative to stable cognitive functioning. A similar attenuated pattern of findings was observed for the GAD7.
A clear association exists between subjective cognitive functioning outcomes and changes in self-reported severity of affective symptoms in young people over the first 3 months of treatment. Understanding the timing and mechanisms of these associations is needed to tailor treatment.
This chapter is about the emotion of interest as it may be experienced in the workplace. Interest has been described as “positive, focused, directed arousal, which prompts approach and engagement with the task” (Ainley, 2007, p. 153). Izard (1991, p. 100) describes the subjective experience of interest as “the feeling of being engaged, caught up, fascinated, or curious … wanting to investigate, become involved, or expand the self by incorporating new information and having new experiences with the person or object that has stimulated the interest. In intense interest or excitement, the person feels animated and enlivened.”
In recent years, there has been increased use of dicamba due to the introduction of dicamba-resistant cotton and soybean in the United States. Therefore, there is a potential increase in off-target movement of dicamba and injury to sensitive crops. Flue-cured tobacco is extremely sensitive to auxin herbicides, particularly dicamba. In addition to yield loss, residue from drift or equipment contamination can have severe repercussions for the marketability of the crop. Studies were conducted in 2016, 2017, and 2018 in North Carolina to evaluate spray-tank cleanout efficiency of dicamba using various cleaning procedures. No difference in dicamba recovery was observed regardless of dicamba formulation and cleaning agent. Dicamba residue decreased with the number of rinses. There was no difference in dicamba residue recovered from the third rinse compared with residue from the tank after being refilled for subsequent tank use. Recovery ranged from 2% to 19% of the original concentration rate among the three rinses. Field studies were also conducted in 2018 to evaluate flue-cured tobacco response to reduced rates of dicamba ranging, from 1/5 to 1/10,000 of a labeled rate. Injury and yield reductions varied by environment and application timing. When exposed to 1/500 of a labeled rate at 7 and 11 wk after transplanting, tobacco injury ranged from 39% to 53% and 10% to 16% 24 days after application, respectively. The maximum yield reduction was 62%, with a 55% reduction in value when exposed to 112 g ha−1 of dicamba. Correlations showed significant relationships between crop injury assessment and yield and value reductions, with Pearson values ranging from 0.24 to 0.63. These data can provide guidance to growers and stakeholders and emphasize the need for diligent stewardship when using dicamba technology.
Currently, there are seven herbicides labeled for U.S. tobacco production; however, additional modes of action are greatly needed in order to reduce the risk of herbicide resistance. Field experiments were conducted at five locations during the 2017 and 2018 growing seasons to evaluate flue-cured tobacco tolerance to S-metolachlor applied pretransplanting incorporated (PTI) and pretransplanting (PRETR) at 1.07 (1×) and 2.14 (2×) kg ai ha−1. Severe injury was observed 6 wk after transplanting at the Whiteville environment in 2017 when S-metolachlor was applied PTI. End-of-season plant heights from PTI treatments at Whiteville were likewise reduced by 9% to 29% compared with nontreated controls, although cured leaf yield and value were reduced only when S-metolachlor was applied PTI at the 2× rate. Severe growth reduction was also observed at the Kinston location in 2018 where S-metolachlor was applied at the 2× rate. End-of-season plant heights were reduced 11% (PTI, 2×) and 20% (PRETR, 2×) compared with nontreated control plants. Cured leaf yield was reduced in Kinston when S-metolachlor was applied PRETR at the 2× rate; however, treatments did not impact cured leaf quality or value. Visual injury and reductions in stalk height, yield, quality, and value were not observed at the other three locations. Ultimately, it appears that injury potential from S-metolachlor is promoted by coarse soil texture and high early-season precipitation close to transplanting, both of which were documented at the Whiteville and Kinston locations. To reduce plant injury and the negative impacts to leaf yield and value, application rates lower than 1.07 kg ha−1 may be required in these scenarios.
This study investigated the relationship between severe childhood abuse and cognitive functions in first-episode psychosis patients and geographically-matched controls. Reports of any abuse were associated with lower scores in the executive function domain in the control group. However, in contrast with our hypothesis, no relationships were found amongst cases.
Reading and language abilities are critical for educational achievement and success in adulthood. Variation in these traits is highly heritable, but the underlying genetic architecture is largely undiscovered. Genetic studies of reading and language skills traditionally focus on children with developmental disorders; however, much larger unselected adult samples are available, increasing power to identify associations with specific genetic variants of small effect size. We introduce an Australian adult population cohort (41.7–73.2 years of age, N = 1505) in which we obtained data using validated measures of several aspects of reading and language abilities. We performed genetic association analysis for a reading and spelling composite score, nonword reading (assessing phonological processing: a core component in learning to read), phonetic spelling, self-reported reading impairment and nonword repetition (a marker of language ability). Given the limited power in a sample of this size (~80% power to find a minimum effect size of 0.005), we focused on analyzing candidate genes that have been associated with dyslexia and developmental speech and language disorders in prior studies. In gene-based tests, FOXP2, a gene implicated in speech/language disorders, was associated with nonword repetition (p < .001), phonetic spelling (p = .002) and the reading and spelling composite score (p < .001). Gene-set analyses of candidate dyslexia and speech/language disorder genes were not significant. These findings contribute to the assessment of genetic associations in reading and language disorders, crucial for understanding their etiology and informing intervention strategies, and validate the approach of using unselected adult samples for gene discovery in language and reading.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Does President Trump face domestic costs for foreign policy inconsistency? Will co-partisans and opposition-partisans equally punish Donald Trump for issuing flippant international threats and backing down? While the president said he could “stand in the middle of Fifth Avenue and shoot somebody” without losing voters, the literature consistently shows that individuals, regardless of partisanship, disapprove of leaders who jeopardize the country’s reputation for credibility and resolve. Given the atypical nature of the Trump presidency, and the severe partisan polarization surrounding it, we investigate whether the logic of audience costs still applies in the Trump era. Using a unique experiment fielded during the 2016 presidential transition, we show that Republicans and Democrats impose equal audience costs on President Trump. And by varying the leader’s identity, between Donald Trump, Barack Obama, and “The President,” we demonstrate that the public adheres to a non-partisan logic in punishing leaders who renege on threats. Yet we also find Presidents Trump and Obama can reduce the magnitude of audience costs by justifying backing down as being “in America’s interest.” Even Democrats, despite their doubts of Donald Trump’s credibility, accept such justifications. Our findings encourage further exploration of partisan cues, leader-level attributes, and leader-level reputations.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
To explore the prevalence and drivers of hospital-level variability in antibiotic utilization among hematopoietic cell transplant (HCT) recipients to inform antimicrobial stewardship initiatives.
Retrospective cohort study using data merged from the Pediatric Health Information System and the Center for International Blood and Marrow Transplant Research.
The study included 27 transplant centers in freestanding children’s hospitals.
The primary outcome was days of broad-spectrum antibiotic use in the interval from day of HCT through neutrophil engraftment. Hospital antibiotic utilization rates were reported as days of therapy (DOTs) per 1,000 neutropenic days. Negative binomial regression was used to estimate hospital utilization rates, adjusting for patient covariates including demographics, transplant characteristics, and severity of illness. To better quantify the magnitude of hospital variation and to explore hospital-level drivers in addition to patient-level drivers of variation, mixed-effects negative binomial models were also constructed.
Adjusted hospital rates of antipseudomonal antibiotic use varied from 436 to 1121 DOTs per 1,000 neutropenic days, and rates of broad-spectrum, gram-positive antibiotic use varied from 153 to 728 DOTs per 1,000 neutropenic days. We detected variability by hospital in choice of antipseudomonal agent (ie, cephalosporins, penicillins, and carbapenems), but gram-positive coverage was primarily driven by vancomycin use. Considerable center-level variability remained even after controlling for additional hospital-level factors. Antibiotic use was not strongly associated with days of significant illness or mortality.
Among a homogenous population of children undergoing HCT for acute leukemia, both the quantity and spectrum of antibiotic exposure in the immediate posttransplant period varied widely. Antimicrobial stewardship initiatives can apply these data to optimize the use of antibiotics in transplant patients.
Highly anomalous platinum-group element (PGE) concentrations in the podiform chromitites at the Cliff and Harold's Grave localities in the Shetland ophiolite complex have been well documented previously. The focus of this study is alluvial platinum-group minerals (PGM) located in small streams that drain from the PGE-rich chromitites. The placer PGM assemblage at Cliff is dominated by Pt-arsenides (64%) and Pd-antimonides (17%), with less irarsite–hollingworthite (11%) and minor Pd-sulfides, Pt–Pd–Cu and Pt–Fe alloys and laurite. Gold also occurs with the PGM. Alluvial PGM have average sizes of 20 µm × 60 µm, with sperrylite the largest grain identified at 110 µm in diameter, matching the range reported for the primary PGM in the source rocks. The placer assemblage contains more Pt-bearing and less Pd-bearing PGM compared with the rocks. The more resistant sperrylite and irarsite–hollingworthite grains which are often euhedral become more rounded further downstream whereas the less resistant Pd-antimonides which are commonly subhedral may become striated and etched. Less stable phases such as Pt- and Pd-oxides and other Ni-Cu-bearing phases located in the rocks (i.e. Ru-pentlandite, PtCu, Pd–Cu alloy) are absent in the placer assemblage. Also the scarce PGM (PdHg, Rh- and Ir-Sb) and Os in the rocks are absent. At Harold's Grave only three alluvial PGM (laurite, Ir, Os) and Au were recovered reflecting the limited release of IPGM from chromite grains in the rocks. In this cold climate with high rainfall, where erosion dominates over weathering, the PGM appear to have been derived directly from the erosion of the adjacent PGE-rich source rocks and there is little evidence of in situ growth of any newly formed PGM. Only the presence of dendritic pure Au and Pd-, Cu-bearing Au covers on the surface of primary minerals may indicate some local reprecipitation of these metals in the surficial conditions.