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There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.
We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.
We used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.
Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).
These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.
Declaration of interest
W.v.d.B received fees in the past 3 years from Indivior, C&A Pharma, Opiant and Angelini. G.M.G. is a National Institute for Health Research (NIHR) Emeritus Senior Investigator, holds shares in P1vital and has served as consultant, advisor or CME speaker in the past 3 years for Allergan, Angelini, Compass Pathways, MSD, Lundbeck (/Otsuka and /Takeda), Medscape, Minervra, P1Vital, Pfizer, Sage, Servier, Shire and Sun Pharma.
We analyzed antibiotic use data from 29 southeastern US hospitals over a 5-year period to determine changes in antibiotic use after the fluoroquinolone US Food and Drug Administration (FDA) advisory update in 2016. Fluoroquinolone use declined both before and after the FDA announcement, and the use of select, alternative antibiotics increased after the announcement.
Fluoroquinolones are among the 4 most commonly prescribed antibiotic classes.1,2 Postmarketing reports of serious adverse events linked to fluoroquinolones include tendonitis, neuropathy, hypoglycemia, psychiatric side effects, and possible aortic vessel rupture, leading to safety label changes in July 2008 and August 2013.3 In July 2016, the US Food and Drug Administration (FDA) strengthened the “black box” warning following an initial safety announcement in May 2016, recommending avoidance of fluoroquinolones for uncomplicated infections such as acute exacerbation of chronic bronchitis, uncomplicated urinary tract infections, and acute bacterial sinusitis.4 Concerns over safety and the association with Clostridiodes difficile infection have led inpatient antimicrobial stewardship programs (ASPs) to develop initiatives to promote avoidance of quinolones. The objective of this study was to quantify the effect of the 2016 FDA “black box” update on inpatient antibiotic use among a cohort of southeastern US hospitals.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1.Explore the current molecular landscape of pediatric high grade gliomas
2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3.Discuss the current status of NTRK inhibitor clinical trials
The sternocleidomastoid can be used as a pedicled flap in head and neck reconstruction. It has previously been associated with high complication rates, likely due in part to the variable nature of its blood supply.
To provide clinicians with an up-to-date review of clinical outcomes of sternocleidomastoid flap surgery in head and neck reconstruction, integrated with a review of vascular anatomical studies of the sternocleidomastoid.
A literature search of the Medline and Web of Science databases was conducted. Complications were analysed for each study. The trend in success rates was analysed by date of the study.
Reported complication rates have improved over time. The preservation of two vascular pedicles rather than one may have contributed to improved outcomes.
The sternocleidomastoid flap is a versatile option for patients where prolonged free flap surgery is inappropriate. Modern vascular imaging techniques could optimise pre-operative planning.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350
m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200
m images will also have a factor
30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
To describe and compare caffeinated energy drink adverse event (AE) report/exposure call data from the US Food and Drug Administration Center for Food Safety and Applied Nutrition’s Adverse Event Reporting System (CAERS) and the American Association of Poison Control Centers’ National Poison Data System (NPDS).
Data were evaluated from US-based CAERS reports and NPDS exposure calls, including report/exposure call year, age, sex, location, single v. multiple product consumption, outcome, symptom, intentionality (NPDS only), report type, product name (CAERS only).
The analysis defined participants (cases) by the number of caffeinated energy drink products indicated in each AE report or exposure call. Single product cases included 357 from CAERS and 12 822 from NPDS; multiple product cases included 153 from CAERS and 931 from NPDS.
CAERS v. NPDS single product cases were older and more frequently indicated serious symptoms. Multiple v. single product consumers were older in both. In CAERS, unlike NPDS, most multiple product consumers were female. CAERS single v. multiple product reports cited higher proportions of life-threatening events, but less often indicated hospitalization and serious events. NPDS multiple v. single product cases involved fewer ≤5-year-olds and were more often intentional.
Despite limitations, both data sources contribute to post-market surveillance and improve understanding of public health concerns.
To examine the association between parenting styles and overall child dietary quality within households that are low-income and food-insecure.
Child dietary intake was measured via a 24 h dietary recall. Dietary quality was assessed using the Healthy Eating Index-2005 (HEI-2005). Parenting styles were measured and scored using the Parenting Styles and Dimensions Questionnaire. Linear regressions were used to test main and interaction associations between HEI-2005 scores and parenting styles.
Non-probability sample of low-income and food-insecure households in South Carolina, USA.
Parent–child dyads (n 171). Parents were ≥18 years old and children were 9–15 years old.
We found a significant interaction between authoritative and authoritarian parenting style scores. For those with a mean authoritarian score, each unit increase in authoritative score was associated with a higher HEI-2005 score (b = 3·36, P < 0.05). For those with an authoritarian score that was 1 sd above the mean authoritarian score, each unit increase in authoritative score was associated with a higher HEI-2005 score (b = 8.42, P < 0.01). For those with an authoritarian score that was −1 sd below the mean authoritarian score, each unit increase in authoritative score was associated with a lower HEI-2005 score; however, this was not significant (b = −1·69, P > 0·05). Permissive parenting style scores were negatively associated with child dietary quality (b = −2·79, P < 0·05).
Parenting styles should be considered an important variable that is associated with overall dietary quality in children living within low-income and food-insecure households.
Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.
Young people with 22q11.2 deletion syndrome (22q11.2DS) are at high risk for neurodevelopmental disorders. Sleep problems may play a role in this risk but their prevalence, nature and links to psychopathology and cognitive function remain undescribed in this population.
Sleep problems, psychopathology, developmental coordination and cognitive function were assessed in 140 young people with 22q11.2DS (mean age = 10.1, s.d. = 2.46) and 65 unaffected sibling controls (mean age = 10.8, s.d.SD = 2.26). Primary carers completed questionnaires screening for the children's developmental coordination and autism spectrum disorder.
Sleep problems were identified in 60% of young people with 22q11.2DS compared to 23% of sibling controls (OR 5.00, p < 0.001). Two patterns best-described sleep problems in 22q11.2DS: restless sleep and insomnia. Restless sleep was linked to increased ADHD symptoms (OR 1.16, p < 0.001) and impaired executive function (OR 0.975, p = 0.013). Both patterns were associated with elevated symptoms of anxiety disorder (restless sleep: OR 1.10, p = 0.006 and insomnia: OR 1.07, p = 0.045) and developmental coordination disorder (OR 0.968, p = 0.0023, and OR 0.955, p = 0.009). The insomnia pattern was also linked to elevated conduct disorder symptoms (OR 1.53, p = 0.020).
Clinicians and carers should be aware that sleep problems are common in 22q11.2DS and index psychiatric risk, cognitive deficits and motor coordination problems. Future studies should explore the physiology of sleep and the links with the neurodevelopment in these young people.
Children with congenital heart disease are at high risk for malnutrition. Standardisation of feeding protocols has shown promise in decreasing some of this risk. With little standardisation between institutions’ feeding protocols and no understanding of protocol adherence, it is important to analyse the efficacy of individual aspects of the protocols.
Adherence to and deviation from a feeding protocol in high-risk congenital heart disease patients between December 2015 and March 2017 were analysed. Associations between adherence to and deviation from the protocol and clinical outcomes were also assessed. The primary outcome was change in weight-for-age z score between time intervals.
Increased adherence to and decreased deviation from individual instructions of a feeding protocol improves patients change in weight-for-age z score between birth and hospital discharge (p = 0.031). Secondary outcomes such as markers of clinical severity and nutritional delivery were not statistically different between groups with high or low adherence or deviation rates.
High-risk feeding protocol adherence and fewer deviations are associated with weight gain independent of their influence on nutritional delivery and caloric intake. Future studies assessing the efficacy of feeding protocols should include the measures of adherence and deviations that are not merely limited to caloric delivery and illness severity.
Ultrasound applications are widespread, and their utility in resource-limited environments are numerous. In disasters, the use of ultrasound can help reallocate resources by guiding decisions on management and transportation priorities. These interventions can occur on-scene, at triage collection points, during transport, and at the receiving medical facility. Literature related to this specific topic is limited. However, literature regarding prehospital use of ultrasound, ultrasound in combat situations, and some articles specific to disaster medicine allude to the potential growth of ultrasound utilization in disaster response.
To evaluate the utility of point-of-care ultrasound in a disaster response based on studies involving ultrasonography in resource-limited environments.
A narrative review of MEDLINE, MEDLINE InProcess, EPub, and Embase found 20 articles for inclusion.
Experiences from past disasters, prehospital care, and combat experiences have demonstrated the value of ultrasound both as a diagnostic and interventional modality.
Current literature supports the use of ultrasound in disaster response as a real-time, portable, safe, reliable, repeatable, easy-to-use, and accurate tool. While both false positives and false negatives were reported in prehospital studies, these values correlate to accepted false positive and negative rates of standard in-hospital point-of-care ultrasound exams. Studies involving austere environments demonstrate the ability to apply ultrasound in extreme conditions and to obtain high-quality images with only modest training and real-time remote guidance. The potential for point-of-care ultrasound in triage and management of mass casualty incidents is there. However, as these studies are heterogeneous and observational in nature, further research is needed as to how to integrate ultrasound into the response and recovery phases.
Introduction: Elder abuse is infrequently detected in the emergency department (ED) and less than 2% are reported to proper law authorities by ED physicians. This study aims to examine the characteristics of community-dwelling older adults who screened positive for elder abuse during home care assessments and the epidemiology of ED visits by these patients relative to other home care patients. Methods: This study utilized a population-based retrospective cohort study of home care patients in Canada between April 1, 2007 and March 31, 2015. Standardized, comprehensive home care assessments were extracted from the Home Care Reporting System. A positive screen for elder abuse was defined as at least one these criteria: fearful of a caregiver; unusually poor hygiene; unexplained injuries; or neglected, abused, or mistreated. Home care assessments were linked to the National Ambulatory Care Reporting System in the regions and time periods in which population-based estimates could be obtained to identify all ED visits within 6 months of the home care assessment. Results: A total of 30,413 from the 2,401,492 patients (1.3%) screened positive for elder abuse during a home care assessment. They were more likely to be male (40.5% versus 35.3%, p < 0.001), to have a cognitive impairment (82.9% versus 65.3%, p < 0.001), a higher frailty index (0.27 versus 0.22, p < 0.001) and to exhibit more depressive symptoms (depression rating scale 1 or more: 68.7% versus 42.7%, p < 0.001). Patient who screened positive for elder abuse were less likely to be independent in activities of daily living (41.9% versus 52.7%, p < 0.001) and reported having fallen more frequently (44.2% versus 35.5%, p < 0.001). Caregiver expressing distress was associated with elder abuse (35.3% versus 18.3%, p < 0.001) but not a higher number of hours caring for the patient. Victims of elder abuse were more likely to attend the ED for low acuity conditions (Canadian triage and acuity scale (CTAS) 4 or 5). Diagnosis at discharge from ED were similar with the exception of acute intoxication that was more frequent in patients who are victims of abuse. Conclusion: Elder abuse is infrequently detected during home care assessments in community-dwelling older adults. Higher frailty index, cognitive impairment, depressive symptoms were associated with elder abuse during homecare assessments. Patients who are victims of elder abuse are attending EDs more frequently for low acuity conditions but ED diagnosis at discharge, except for acute intoxication, are similar.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
Although there are extensive data on clinical psychopathology in youth with suicidal ideation, data are lacking regarding their neurocognitive function.
To characterise the cognitive profile of youth with suicidal ideation in a community sample and evaluate gender differences and pubertal status effects.
Participants (N = 6151, age 11–21 years, 54.9% females) from the Philadelphia Neurodevelopmental Cohort, a non-help-seeking community sample, underwent detailed clinical evaluation. Cognitive phenotyping included executive functioning, episodic memory, complex reasoning and social cognitive functioning. We compared participants with suicidal ideation (N = 672) and without suicidal ideation (N = 5479). Regression models were employed to evaluate differences in cognitive performance and functional level, with gender and pubertal status as independent variables. Models controlled for lifetime depression or general psychopathology, and for covariates including age and socioeconomic status.
Youth with suicidal ideation showed greater psychopathology, poorer level of function but better overall neurocognitive performance. Greater functional impairment was observed in females with suicidal ideation (suicidal ideation × gender interaction, t = 3.091, P = 0.002). Greater neurocognition was associated with suicidal ideation post-puberty (suicidal ideation × puberty interaction, t = 3.057, P = 0.002). Exploratory analyses of specific neurocognitive domains showed that suicidal ideation-associated cognitive superiority was more prominent in post-pubertal males compared with females (Cohen's d = 0.32 and d = 0.11, respectively) across all cognitive domains.
Suicidal ideation was associated with poorer functioning yet better cognitive performance, especially in post-pubertal males, as measured by a comprehensive cognitive battery. Findings point to gender and pubertal-status specificity in the relationship between suicidal ideation, cognition and function in youth.
Declaration of interest
R.B. serves on the scientific board and reports stock ownership in ‘Taliaz Health’, with no conflict of interest relevant to this work. M.A.O. receives royalties for the commercial use of the Columbia-Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Her family owns stock in Bristol-Myers Squibb. All other authors declare no potential conflict of interest.
The analysis of cements and ores has been studied using the Applied Research Laboratories, Inc. Production Control X-ray Quantometer (PXQ), Elements included in the program were magnesium, aluminum, silicon, phosphorus, calcium and iron. The PXQ, utilizing the polychromator concept, allows the simultaneous determination of the listed elements.
Focusing ADP, EDT, quartz and LiF crystals were used with flow Geigers or Multitrons. Helium paths were used as required. The choice of crystals, detectors, and slit widths was determined to give optimum results for each element.
The effects of briquetting and ratioing to scattered background on accuracy were studied. Various instrumental factors such as helium flow rate, detector gas flow rate, short and long term stability were also investigated.
OBJECTIVES/SPECIFIC AIMS: The DIAMOND project encourages study team workforce development through the creation of a digital learning space that brings together resources from across the CTSA consortium. This allows for widespread access to and dissemination of training and assessment materials. DIAMOND also includes access to an ePortfolio that encourages CRPs to define career goals and document professional skills and training. METHODS/STUDY POPULATION: Four CTSA institutions (the University of Michigan, the Ohio State University, University of Rochester, and Tufts CTSI) collaborated to develop and implement the DIAMOND portal. The platform is structured around eight competency domains, making it easy for users to search for research training and assessment materials. Contributors can upload links to (and meta-data about) training and assessment materials from their institutions, allowing resources to be widely disseminated through the DIAMOND platform. Detailed information about materials included in DIAMOND is collected through an easy to use submission form. DIAMOND also includes an ePortfolio designed for CRPs. This encourages workforce development by providing a tool for self-assessment of clinical research skills, allowing users to showcase evidence of experience, training and education, and fosters professional connections. RESULTS/ANTICIPATED RESULTS: To date, more than 100 items have been posted to DIAMOND from nine contributors. In the first 30 days there were 229 active users with more than 500 page views from across the U.S. as well as China and India. Training materials were viewed most often from four competency domains: 1) Scientific Concepts & Research Design, 2) Clinical Study Operations, 3) Ethical & Participant Safety, and 4) Leadership & Professionalism. Additionally, over 100 CRPs have created a DIAMOND ePortfolio account, using the platform to document skills, connect with each other, and search for internships and job opportunities. DISCUSSION/SIGNIFICANCE OF IMPACT: Lessons learned during development of the DIAMOND digital platform include defining relevant information to collect for the best user experience; selection of a standardized, user-friendly digital platform; and integration of the digital network and ePortfolio. Combined, the DIAMOND portal and ePortfolio provide a professional development platform for clinical research professionals to contribute, access, and benefit from training and assessment opportunities relevant to workforce development and their individual career development needs.
OBJECTIVES/SPECIFIC AIMS: The study investigated whether adults diagnosed with epilepsy or migraine (a neurological disorder with common features to epilepsy) are at increased risk for developing substance abuse disorders following diagnosis compared to (presumably healthy) adults with lower extremity fracture (LEF). METHODS/STUDY POPULATION: A retrospective cohort analysis was conducted using a subset of surveillance data of hospital admissions, emergency department visits and outpatient visits in South Carolina, USA from January 1, 2000 through December 31, 2011. Individuals aged 18 years or older were identified using the International Classification of Disease, 9th Revision Clinical modification (ICD-9) with a diagnosis of epilepsy (epilepsy-cohort 1; n = 78,547; 52.7% female, mean age [SD] 51.3 years [19.2]), migraine (migraine-cohort 2; n = 121,155; 81.5% female, mean age [SD] 40.0 years [14.5]), or LEF (control cohort; n = 73,911; 55.4% female, mean age [SD] 48.7 years [18.7]). Individuals with substance abuse or dependence diagnosis following epilepsy, migraine, or LEF were identified with ICD-9 codes. Cox proportional hazard regression analyses modelled the time to substance abuse diagnosis comparing epilepsy to LEF and comparing migraine to LEF. RESULTS/ANTICIPATED RESULTS: Adjusting for insurance payer, age and sex, adults with epilepsy are diagnosed with substance abuse disorders at 2.5 times the rate of those with LEF [HR 2.54 (2.43, 2.67)] and adults with migraine are diagnosed with substance abuse disorders at 1.10 times the rate of those with LEF [HR 1.10 (1.04, 1.16)]. An interaction between exposure and insurance payer was found with hazard ratios comparing epilepsy to LEF of 4.56, 3.60, and 1.94 within the commercial payer, uninsured and Medicaid strata, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Compared to adults with LEF, adults with epilepsy had a substantially higher hazard of subsequent substance abuse, while adults with migraine showed a small, but still significant, increased hazard of subsequent substance abuse.
Several grass and broadleaf weed species around the world have evolved multiple-herbicide resistance at alarmingly increasing rates. Research on the biochemical and molecular resistance mechanisms of multiple-resistant weed populations indicate a prevalence of herbicide metabolism catalyzed by enzyme systems such as cytochrome P450 monooxygenases and glutathione S-transferases and, to a lesser extent, by glucosyl transferases. A symposium was conducted to gain an understanding of the current state of research on metabolic resistance mechanisms in weed species that pose major management problems around the world. These topics, as well as future directions of investigations that were identified in the symposium, are summarized herein. In addition, the latest information on selected topics such as the role of safeners in inducing crop tolerance to herbicides, selectivity to clomazone, glyphosate metabolism in crops and weeds, and bioactivation of natural molecules is reviewed.