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Hybrid whole genome sequencing was used to investigate if nosocomial Verona integron-encoded metallo-β-lactamase (VIM) carbapenemase transmission occurred between two patients without epidemiological links or common pathogens. Challenges in genomic methodology and appropriate analytical depth for mobile carbapenemase outbreaks are described including how inappropriate choices can mislead results and impact infection control practices.
It has not yet been determined if the commonly reported cannabis–psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders.
Methods
We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort.
Results
PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects.
Conclusions
These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis–psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.
The Quaternary Isotope Laboratory (QIL) at the University of Washington was launched in 1969 and directed by Minze Stuiver until his retirement in 1998. Here we review some of the scientific work undertaken in the QIL and the memories of some of Minze’s former students and colleagues.
ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.
Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.
Methods
Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).
Results
We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.
Conclusions
Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.
The systems ecology paradigm (SEP) emerged in the late 1960s at a time when societies throughout the world were beginning to recognize that our environment and natural resources were being threatened by their activities. Management practices in rangelands, forests, agricultural lands, wetlands, and waterways were inadequate to meet the challenges of deteriorating environments, many of which were caused by the practices themselves. Scientists recognized an immediate need was developing a knowledge base about how ecosystems function. That effort took nearly two decades (1980s) and concluded with the acceptance that humans were components of ecosystems, not just controllers and manipulators of lands and waters. While ecosystem science was being developed, management options based on ecosystem science were shifting dramatically toward practices supporting sustainability, resilience, ecosystem services, biodiversity, and local to global interconnections of ecosystems. Emerging from the new knowledge about how ecosystems function and the application of the systems ecology approach was the collaboration of scientists, managers, decision-makers, and stakeholders locally and globally. Today’s concepts of ecosystem management and related ideas, such as sustainable agriculture, ecosystem health and restoration, consequences of and adaptation to climate change, and many other important local to global challenges are a direct result of the SEP.
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.
Methods
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.
Results
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.
Conclusions
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.
The goal of this research was to identify, summarize, and evaluate pediatric disaster preparedness resources in the United States and to identify areas that need improvement or further development. Using standard literature, gray literature and website reviews, relevant resources were identified and the 50 most relevant resources were studied in depth. Each resource was given a grade of A, B, or C based on content, format, quality, and thoroughness. These resources were divided into 3 categories: (1) hospital resources, (2) school resources, and (3) training/education resources. Half of the 50 resources (25) were given a grade of A, indicating the highest level of quality and thoroughness, with pertinent information presented in a clear format. Sixteen of the resources were given a rating of B, while 9 of the resources were given a rating of C. Over 60% of the resources did not contain culturally sensitive information and more than 60% of the resources did not contain preparedness information for children with disabilities. Resources specific to hospitals and schools were limited in number and quality available, while training/education resources were widely available. In addition, 60% of resources were not specific to schools, children’s hospitals, or to certain occupations (ie, nurses, doctors, teachers, principals). Based on these results, gaps in cultural sensitivity were identified and limitations in resources for children with disabilities and for schools and hospitals currently exist. All these areas require further development in the field of pediatric disaster preparedness (Disaster Med Public Health Preparedness. 2019;13:330–337)
Eight million American children under the age of 5 attend daycare and more than another 50 million American children are in school or daycare settings. Emergency planning requirements for daycare licensing vary by state. Expert opinions were used to create a disaster preparedness video designed for daycare providers to cover a broad spectrum of scenarios.
Methods
Various stakeholders (17) devised the outline for an educational pre-disaster video for child daycare providers using the Delphi technique. Fleiss κ values were obtained for consensus data. A 20-minute video was created, addressing the physical, psychological, and legal needs of children during and after a disaster. Viewers completed an anonymous survey to evaluate topic comprehension.
Results
A consensus was attempted on all topics, ranging from elements for inclusion to presentation format. The Fleiss κ value of 0.07 was obtained. Fifty-seven of the total 168 video viewers completed the 10-question survey, with comprehension scores ranging from 72% to 100%.
Conclusion
Evaluation of caregivers that viewed our video supports understanding of video contents. Ultimately, the technique used to create and disseminate the resources may serve as a template for others providing pre-disaster planning education. (Disaster Med Public Health Preparedness. 2019;13:123–127)
Enumerations represented as bijections between the natural numbers and elements of some given type have recently garnered interest in property-based testing because of their efficiency and flexibility. There are, however, many ways of defining these bijections, some of which are better than others. This paper offers a new property of enumeration combinators called fairness that identifies enumeration combinators that are better suited to property-based testing. Intuitively, the result of a fair combinator indexes into its argument enumerations equally when constructing its result. For example, extracting the nth element from our enumeration of three-tuples indexes about $\sqrt[3]{n}$ elements into each of its components instead of, say, indexing $\sqrt[2]{n}$ into one and $\sqrt[4]{n}$ into the other two, as you would if a three-tuple were built out of nested pairs. Similarly, extracting the nth element from our enumeration of a three-way union returns an element that is $\frac{n}{3}$ into one of the argument enumerators. The paper presents a semantics of enumeration combinators, a theory of fairness, proofs establishing fairness of our new combinators and that some combinations of fair combinators are not fair. We also report on an evaluation of fairness for the purpose of finding bugs in programming-language models. We show that fair enumeration combinators have complementary strengths to an existing, well-tuned ad hoc random generator (better on short time scales and worse on long time scales) and that using unfair combinators is worse across the board.
We argue that the CLASH model makes a number of questionable assumptions about the harshness and unpredictability of low-latitude environments, calling into question the life history strategy approach used, and that it is inconsistent with more nuanced global patterns of violence. We suggest an alternative account for less violence at high latitudes, based on a greater need for cooperation.
Dose-response experiments were conducted on a biotype of prickly lettuce collected from Whitman County, WA, to determine the level of resistance to 2,4-D. Initially, progeny of prickly lettuce that survived two applications of glyphosate and 2,4-D in mixture were collected to determine if antagonism of the 2,4-D or glyphosate was occurring. Prickly lettuce survival was determined to not be due to antagonism of 2,4-D or glyphosate when the two herbicides were applied in mixture. The doses required to reduce growth 50% (GR50) for resistant and susceptible field-collected prickly lettuce were 150 and 6 g ae/ha 2,4-D, respectively, indicating the resistant biotype was 25 times more resistant to 2,4-D than the susceptible biotype. The resistant biotype expressed injury but produced regrowth following application. A dose of 2,4-D at 220 g/ha was required to reduce regrowth frequency 50% (FR50) for resistant field-collected prickly lettuce. Regrowth was also observed with the susceptible biotype, although the FR50 was much lower (10 g/ha), resulting in an R/S ratio of 22 based on the respective FR50 values. A rate of 4,300 g/ha 2,4-D (10 times the maximum labeled rate in wheat) was required to reduce the regrowth frequency in the resistant biotype to zero.
Soilborne bacteria with novel metabolic abilities have been linked with enhanced atrazine degradation and complaints of reduced residual weed control in soils with an s-triazine use history. However, no field study has verified that enhanced degradation reduces atrazine's residual weed control. The objectives of this study were to (1) compare atrazine persistence and prickly sida density in s-triazine-adapted and nonadapted field sites at two planting dates; (2) utilize original and published data to construct a diagnostic test for identifying s-triazine-adapted soils; and (3) develop and validate an s-triazine persistence model based on data generated from the diagnostic test, i.e., mineralization of ring-labeled 14C-s-triazine. Atrazine half-life values in s-triazine-adapted soil were at least 1.4-fold lower than nonadapted soil and 5-fold lower than historic estimates (60 d). At both planting dates atrazine reduced prickly sida density in the nonadapted soils (P ≤ 0.0091). Conversely, in the s-triazine-adapted soil, prickly sida density was not different between no atrazine PRE and atrazine PRE at the March 15 planting date (P = 0.1397). A lack of significance in this contrast signifies that enhanced degradation can reduce atrazine's residual control of sensitive weed species. Analyses of published data indicate that cumulative mineralization in excess of 50% of C0 after 30 d of incubation is diagnostic for enhanced s-triazine degradation. An s-triazine persistence model was developed and validated; model predictions for atrazine persistence under field conditions were within the 95% confidence intervals of observed values. Results indicate that enhanced atrazine degradation can decrease the herbicide's persistence and residual activity; however, coupling the diagnostic test with the persistence model could enable weed scientists to identify s-triazine-adapted soils, predict herbicide persistence under field conditions, and implement alternative weed control strategies in affected areas if warranted.
Organic wheat and small grains are produced on relatively few acres in the inland Pacific Northwest. The objective of this study was to examine how the nitrogen (N) dynamics of cropping systems (CSs) produced during the transition phase impacted organic wheat yield and protein levels in the first 2 years of certified organic production. Certified organic spring wheat (SW) was produced in 2006 and winter wheat (WW) in 2007 following nine, 3-year transitional cereal, small grain and legume-intensive CSs. SW and WW following perennial alfalfa + oat/pea forage or 3 years of legume green manure tended to be more productive than wheat that followed systems that contained a small grain crop for at least 1 year during the transition. In addition to increasing soil N, well-established stands of forage and green manure provided adequate cover to reduce weed establishment prior to organic production. Effective weed control strategies were as important as increasing soil inorganic N levels for improving organic wheat production. Choice of crop type, cultivar and rotation is important in organic wheat systems and in this study, WW had better stand establishment, competition with weeds and higher overall yield than SW and would be a better-suited class of wheat for organic production in situations where spring weeds are the dominant problem. Regardless of CS or crop type, supplemental soil fertility (primarily N) during the organic production phase will be necessary to maintain high soil N levels and wheat yields in these dryland systems.