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The adoption of chemical fallow rotations in Pacific Northwest dryland winter wheat production has caused a weed species composition shift in which scouringrush has established in production fields. Thus, there has been interest in identifying herbicides that effectively control scouringrush in winter wheat–chemical fallow cropping systems. Field experiments were established in growers’ fields near Reardan, WA, in 2014, and The Dalles, OR, in 2015. Ten herbicide treatments were applied to mowed and nonmowed plots during chemical fallow rotations. Scouringrush stem densities were quantified the following spring and after wheat harvest at both locations. Chlorsulfuron plus MCPA-ester resulted in nearly 100% control of scouringrush through wheat harvest. Before herbicide application, mowing had no effect on herbicide efficacy. We conclude chlorsulfuron plus MCPA-ester is a commercially acceptable treatment for smooth and intermediate scouringrush control in winter wheat–chemical fallow cropping systems; however, the lack of a positive yield response when scouringrushes were controlled should factor into management decisions.
Atomically resolved imaging of materials enabled by the advent of aberration-corrected scanning transmission electron microscopy (STEM) has become a mainstay of modern materials science. However, much of the wealth of quantitative information contained in the fine details of atomic structure or spectra remains largely unexplored. In this article, we discuss new opportunities enabled by physics-informed big data and machine learning technologies to extract physical information from static and dynamic STEM images, ranging from statistical thermodynamics of alloys to kinetics of solid-state reactions at a single defect level. The synergy of deep-learning image analytics and real-time feedback further allows harnessing beam-induced atomic and bond dynamics to enable direct atom-by-atom fabrication. Examples of direct atomic motion over mesoscopic distances, engineered doping at selected lattice sites, and assembly of multiatomic structures are reviewed. These advances position the scanning transmission electron microscope to transition from a mere imaging tool toward a complete nanoscale laboratory for exploring electronic, phonon, and quantum phenomena in atomically engineered structures.
Kochia is one of the most problematic weeds in the United States. Field studies were conducted in five states (Wyoming, Colorado, Kansas, Nebraska, and South Dakota) over 2 yr (2010 and 2011) to evaluate kochia control with selected herbicides registered in five common crop scenarios: winter wheat, fallow, corn, soybean, and sugar beet to provide insight for diversifying kochia management in crop rotations. Kochia control varied by experimental site such that more variation in kochia control and biomass production was explained by experimental site than herbicide choice within a crop. Kochia control with herbicides currently labeled for use in sugar beet averaged 32% across locations. Kochia control was greatest and most consistent from corn herbicide programs (99%), followed by soybean (96%) and fallow (97%) herbicide programs. Kochia control from wheat herbicide programs was 93%. With respect to the availability of effective herbicide options, glyphosate-resistant kochia control was easiest in corn, soybean, and fallow, followed by wheat; and difficult to manage with herbicides in sugar beet.
Compound heterozygotes occur when different variants at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of variants at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 Genomes Project participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or infantile spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 Genomes Project data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 Genomes Project participants using minor allele frequency (MAF) cutoffs of 0.5 and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous variants in six genes, including three involved in neuronal growth and development – PRTG (p = 0.00086, 1% MAF, combined ancestries), TNC (p = 0.022, 1% MAF, combined ancestries) and MACF1 (p = 0.0245, 0.5% MAF, EU ancestry). Due to the total number of transcripts considered in these analyses, the enrichment detected was not significant after correction for multiple testing and higher powered or prospective studies are necessary to validate the candidacy of these genes. However, PRTG, TNC and MACF1 are potential novel recessive epilepsy genes and our results highlight that compound heterozygous variants should be considered in sporadic epilepsy.
Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case–control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2–16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015–2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3–54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3–63.6) and 28.8% (95% CI −31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015–2016 and continues to support the rollout of the LAIV childhood programme.
The objective of this work was to describe treatment-emergent sexual dysfunction (TESD) and tolerability following a switch from selective serotonin reuptake inhibitor (SSRI: citalopram, paroxetine, or sertraline) monotherapy to vortioxetine or escitalopram monotherapy in adults with well-treated major depressive disorder (MDD) and SSRI-induced sexual dysfunction.
Data were analyzed from the primary study, an 8-week, randomized, double-blind, head-to-head study in which participants with well-treated depressive symptoms but experiencing TESD with SSRIs were directly switched to flexible doses (10/20 mg) of vortioxetine or escitalopram. Sexual functioning was assessed by the Changes in Sexual Functioning Questionnaire-14 (CSFQ-14), efficacy by the Montgomery–Åsberg Depression Rating Scale scores (MADRS) and Clinicians Global Impression of Severity/Improvement (CGI-S/CGI-I), and tolerability by adverse events. Efficacy and tolerability were assessed by pre-switch SSRI therapy where possible, and by participant characteristics.
Greater improvements in TESD were seen in the vortioxetine compared with escitalopram groups based on: participant demographics (≤45 years, women; P = 0.045), prior SSRI treatment (P = 0.044), number of prior major depressive episodes (MDEs) (1–3; P = 0.001), and duration of prior SSRI therapy (>1 year; P = 0.001). Prior SSRI treatment did not appear to influence the incidence or severity of TEAEs, except for nausea. Regardless of prior SSRI, both treatments maintained antidepressant efficacy after 8 weeks.
Results suggest that vortioxetine is a safe and effective switch therapy for treating SSRI-induced sexual dysfunction in adults with well-treated MDD. Also, improvement in sexual dysfunction with vortioxetine or escitalopram may be influenced by prior SSRI usage, sex, age, and history of MDEs.
Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.
To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.
Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.
Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.
Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.
Depression is a common, serious, but under-recognised problem in multiple sclerosis (MS). The primary objective of this study was to assess whether a rapid visual analogue screening tool for depression could operate as a quick and reliable screening method for depression, in patients with MS.
Patients attending a regional MS outpatient clinic completed the Emotional Thermometer 7 tool (ET7), the Hospital Anxiety and Depression Scale – Depression Subscale (HADS-D) and the Major Depression Inventory (MDI) to establish a Diagnostic and Statistical Manual, 4th edition (DSM-IV) diagnosis of Major Depression. Full ET7, briefer subset ET4 version and depression and distress thermometers alone were compared with HADS-D and MDI. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and receiver operating characteristic (ROC) curve were calculated to compare the performance of all the screening tools.
In total, 190 patients were included. ET4 performed well as a ‘rule-out’ screening step (sensitivity 0.91, specificity 0.72, NPV 0.98, PPV 0.32). ET4 performance was comparable to HADS-D (sensitivity 0.96, specificity 0.77, NPV 0.99, PPV 0.37) without need for clinician scoring. The briefer ET4 performed as well as the full ET7.
ET are quick, sensitive and useful screening tools for depression in this MS population, to be complemented by further questioning or more detailed psychiatric assessment where indicated. Given that ET4 and ET7 perform equally well, we recommend the use of ET4 as it is briefer. It has the potential to be widely implemented across busy neurology clinics to assist in depression screening in this under diagnosed group.
This pilot randomised controlled study evaluated the effects of a nutrient-supported intermittent energy restriction nutrition programme to prevent weight gain in healthy overweight adults during the 6-week winter holiday period between Thanksgiving and New Year. For 52 d, twenty-two overweight adults (mean age 41·0 years, BMI 27·3 kg/m2) were assigned to either the nutrition programme (n 10; two fasting days of 730 kcal/d (3050 kJ/d) of balanced shake and dietary supplements to support weight management efforts, followed by 5 d of habitual diet) or a control group (n 12; habitual diet). A significant weight loss from baseline (pre-holiday 10 d before Thanksgiving) to day 52 (post-holiday 3 January) was observed in the nutrition programme (75·0 (sd 9·8) v. 76·3 (sd 9·8) kg; P < 0·05). Body weight did not significantly change in the control group and there was no between-group difference. Increases from baseline in fasting insulin (42·9 %; P = 0·0256), updated homoeostasis model assessment (HOMA2) (43 %; P = 0·025), LDL-cholesterol (8·4 %; P = 0·0426) and total cholesterol (7·1 %; P = 0·0154) levels were also reported in the control group. In the nutrition programme group, baseline HDL-cholesterol and TAG levels measured after two fasting days increased (13 %; P = 0·0245) and decreased (22·8 %; P = 0·0416), respectively. There was no significant change in HOMA2. Between-group differences in changes in insulin levels (P = 0·0227), total cholesterol:HDL-cholesterol ratio (P = 0·0419) and HOMA2 (P = 0·0210) were significant. Overall compliance rate was 98 % and no severe adverse events were reported. These preliminary findings suggest that this intermittent energy restriction intervention might support weight management efforts and help promote metabolic health during the winter holiday season.
Young women aged 16–24 are at high risk of common mental disorders (CMDs), but the risk during pregnancy is unclear.
To compare the population prevalence of CMDs in pregnant women aged 16–24 with pregnant women ≥25 years in a representative cohort, hypothesising that younger women are at higher risk of CMDs (depression, anxiety disorders, post-traumatic stress disorder, obsessive–compulsive disorder), and that this is associated with low social support, higher rates of lifetime abuse and unemployment.
Analysis of cross-sectional baseline data from a cohort of 545 women (of whom 57 were aged 16–24 years), attending a South London maternity service, with recruitment stratified by endorsement of questions on low mood, interviewed with the Structured Clinical Interview DSM-IV-TR.
Population prevalence estimates of CMDs were 45.1% (95% CI 23.5–68.7) in young women and 15.5% (95% CI 12.0–19.8) in women ≥25, and for ‘any mental disorder’ 67.2% (95% CI 41.7–85.4) and 21.2% (95% CI 17.0–26.1), respectively. Young women had greater odds of having a CMD (adjusted odds ratio (aOR) = 5.8, 95% CI 1.8–18.6) and CMDs were associated with living alone (aOR = 3.0, 95% CI 1.1–8.0) and abuse (aOR = 1.5, 95% CI 0.8–2.8).
Pregnant women between 16 and 24 years are at very high risk of mental disorders; services need to target resources for pregnant women under 25, including those in their early 20s. Interventions enhancing social networks, addressing abuse and providing adequate mental health treatment may minimise adverse outcomes for young women and their children.
OBJECTIVES/SPECIFIC AIMS: Preterm birth rates have been rising in the United States, and reducing preterm birth is a high-priority clinical and public health concern. There are no existing strategies to reduce preterm birth in nulliparous individuals. The present study aims to evaluate prenatal care as a protective factor for preterm birth in this population. METHODS/STUDY POPULATION: Missouri birth record data for child birth years 1993-2016 were used to create a sample of 325,088 singleton births to nulliparous women, themselves born in MO 1975-1985. Logistic regressions, stratified by maternal race (White, African-American, Asian, American Indian/Alaskan Native, Other), were used to predict preterm birth (< 37 weeks gestational age) as a function of 1) initiation of prenatal care of by end of first trimester and 2) Adequacy of Prenatal Care Utilization Index, with sociodemographic covariates of child birth year, maternal age, highest educational level, and marital status (four level variable, including married yes/no, and partner named on birth record, yes/no). Subsequent analyses will use this logistic regression to create a propensity score predicting smoking during pregnancy using birth record parental sociodemographic characteristics, stratified by maternal race. Primary analyses will focus on the role of prenatal care in predicting smoking during pregnancy and preterm birth risk within propensity score stratum. Secondary analyses will consider the role of other risk factors, including maternal pre-pregnancy BMI and maternal DUI history, on preterm birth risk. RESULTS/ANTICIPATED RESULTS: Preliminary logistic regressions predicting preterm birth were analyzed, stratified by maternal race. In White mothers, preterm birth prevalence was 8.2%, and risk was significantly increased by maternal age ≤ 15 and ≥ 31, being unmarried, and by receiving no prenatal care, yet unaffected by timing of prenatal care initiation. For African-American mothers, preterm birth prevalence was 11.9%, and risk was significantly increased by being unmarried and both by not initiating prenatal care by end of first trimester and receiving no prenatal care. Preliminary samples were too small for solid inferences for other races. Anticipated results are that after propensity score match, earlier initiation of prenatal care will show modest protective effect on preterm birth, but other characteristics such as maternal cigarette smoking during pregnancy and DUI status will show stronger effects on predicting preterm birth risk. DISCUSSION/SIGNIFICANCE OF IMPACT: By evaluating the role of prenatal care initiation and delivery on preterm birth, this work provides an evidence base for prenatal care schedules and for understanding the interplay of sociodemographics, healthcare delivery, and individual characteristics in the context of preterm birth risk and potentially reduce negative health outcomes.
OBJECTIVES/SPECIFIC AIMS: Our objective was to assess and compare the attitudes of patients with head and neck cancer and their clinicians regarding the commercialization of genetic research data. We explored whether such opinions changed when profits from such transactions were used to fund 1) cancer research, 2) academic research generally, or 3) if patients were given personalized genetic information in return. METHODS/STUDY POPULATION: This qualitative analysis was nested within a prospective precision oncology genomic sequencing study in an NCI-designated cancer center. We conducted paired, semi-structured interviews with enrolled participants with head & neck cancer and with their doctors (medical oncologists, surgical oncologists, and radiation oncologists). Interviews were recorded, transcribed, and coded for analysis. Codes were developed through an iterative process until saturation was reached, and all transcripts were double-coded (and discrepancies reconciled) to ensure reliability. RESULTS/ANTICIPATED RESULTS: We identified three main themes from the patients and clinicians: (1) Both clinicians and their patients were unclear about how the study protocol and informed consent form authorized patients’ genetic data to be used and commercialized in the future. (2) Patients with cancer were generally more comfortable than their clinician thought they were regarding the ongoing research use of their genetic data and commercialization thereof. (3) There is a strong interest among patients and clinicians in focusing academic medical center profits from commercialization back into the research program from which the data was acquired, rather than being invested into academic research more broadly. DISCUSSION/SIGNIFICANCE OF IMPACT: Given patients’ strong feelings about the commercialization of their data, our results highlight the need for greater transparency—both with patients and with their clinicians—about potential future use of research data. Clinicians appear inclined to be particularly cautious regarding access to and commercialization of patients’ data, however patients generally hope that their data may be used to help future cancer patients. Explicit discussions with patients about specific future uses of profits derived from commercialization of research data can ensure both transparency and participation in future primary and secondary precision health research programs.