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The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
Adequate dietary intake is critical to prevent adverse pregnancy outcomes. India has a high burden of maternal and child morbidity and mortality, but there is a lack of adequate tools to assess dietary intake. We validate an FFQ, New Interactive Nutrition Assistant - Diet in India Study of Health (NINA-DISH), among pregnant women living with and without HIV in Pune, India. Women were selected from a cohort study investigating immune responses to HIV and latent tuberculosis during pregnancy. The FFQ was administered during the third trimester and validated against multiple 24-h dietary recalls (24-HDR) collected in second and third trimesters. Data for analysis were available from fifty-eight women out of seventy enrolled into this sub-study, after excluding those with incomplete data or implausible energy intake. The median (Q1, Q3) age of study participants was 23 (20, 25) years. Median (Q1, Q3) daily energy intakes were 10 552 (8000, 11 958) and 10 673 (8510, 13 962) kJ by 24-HDR and FFQ, respectively, with FFQ overestimating nutrient intake. Pearson correlations between log-transformed estimates from FFQ and 24-HDR for energy, protein, carbohydrate, fat, Fe and Zn were 0·47, 0·48, 0·45, 0·33, 0·4 and 0·54, respectively. Energy-adjusted and de-attenuated correlations ranged from 0·41 (saturated fat) to 0·73 (Na). The highest misclassification into extreme tertiles was observed for fat (22 %), saturated fat (21 %) and Na (21 %). Bias existed at higher intake levels as observed by Bland–Altman plots. In conclusion, NINA-DISH is a valid and feasible tool for estimating dietary intakes among urban pregnant women in Western India.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
OBJECTIVES/GOALS: In young women, there is significant symptomatic overlap among lower urinary tract conditions, including bladder and pelvic pain, leading to misdiagnosis and delayed care. The epidemiology of pelvic pain suggests a microbial involvement, but previous studies have not definitively identified specific bacteria associated with pain diagnoses. METHODS/STUDY POPULATION: We examined urinary bacterial associations with specific symptom clusters, not diagnoses. Catheterized urinary samples were obtained from 78 pre-menopausal controls and cases with bladder and pelvic pain. 16S next-generation sequencing (NGS) characterized urinary microbial populations; validated questionnaires quantified symptom type and severity. K means unsupervised clustering analysis of NGS data assigned subjects to urotypes based on the urinary bacterial community state types. Quantitative PCR (qPCR) confirmed the NGS results and provided objective concentrations for critical taxa. Linear regression analysis confirmed the associations of bacterial concentrations and specific symptoms. RESULTS/ANTICIPATED RESULTS: In a pilot study of 35 reproductive-age women with a variety of complaints NGS revealed four urotypes that correlated with symptomatology. Isolated urgency incontinence was rare; the majority of subjects with symptoms complained of genitourinary pain. Bladder-specific pain (worse with filling, relieved by voiding) was associated with Lactobacillus iners. Asymptomatic patients almost universally had a non-iners, Lactobacillus-predominant microbiota. Vaginal and urethral pain unrelated to voiding correlated with increasing Enterobacteriaceae, primarily Escherichia coli. Detection of these species by qPCR in a validation population (n = 43) was highly predictive of each phenotype (P < 0.00001). Pathologic bacteria were associated with the severity of specific pain symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results implicate a microbial role in genitourinary pain. We describe clinically-useful bacterial biomarkers for specific pelvic and bladder pain phenotypes. This objective, rapid, and inexpensive testing to classify bladder and pelvic pain would allow more accurate diagnosis and improve treatment. CONFLICT OF INTEREST DESCRIPTION: Dr. Anger is an expert witness for Boston Scientific. Dr. Eilber is an investigator and expert witness for Boston Scientific, an investigator for Aquinox, and a consultant for Boston Scientific and Allergan. Dr. Ackerman is an expert witness for Cynosure.
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.
LEARNING OBJECTIVES
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
Introduction: Elevated intracranial pressure (ICP) is a devastating complication of brain injury, such as traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, and other conditions. Delay to diagnosis and treatment are associated with increased morbidity and mortality. For Emergency Department (ED) physicians, invasive ICP measurement is typically not available. We sought to summarize and compare the accuracy of physical examination, imaging, and ultrasonography of the optic nerve sheath diameter (ONSD) for diagnosis of elevated ICP. Methods: We searched Medline, EMBASE and 4 other databases from inception through August 2018. We included only English studies (randomized controlled trials, cohort and case-control studies). Gold standard was ICP≥20 mmHg on invasive ICP monitoring. Two reviewers independently screened studies and extracted data. We assessed risk of bias using Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Hierarchical Summary Receiver Operating Characteristic model generated summary diagnostic accuracy estimates. Results: We included 37 studies (n = 4,768, kappa = 0.96). Of exam signs, pooled sensitivity and specificity for increased ICP were: mydriasis (28.2% [95% CI: 16.0-44.8], 85.9.0% [95% CI: 74.9-92.5]), motor posturing (54.3% [95% CI: 36.6-71.0], 63.6% [95% CI: 46.5-77.8]) and Glasgow Coma Scale (GCS) ≤8 (75.8% [95% CI: 62.4-85.5], 39.9% [95% CI: 26.9-54.5]). Computed tomography findings: compression of basal cisterns had 85.9% [95% CI: 58.0-96.4] sensitivity and 61.0% [95% CI: 29.1-85.6] specificity; any midline shift had 80.9% [95% CI: 64.3-90.9] sensitivity and 42.7% [95% CI: 24.0-63.7] specificity; midline shift≥1cm had 20.7% [95% CI: 13.0-31.3] sensitivity and 89.2% {95% CI: 77.5-95.2] specificity. Finally, pooled area under the ROC curve describing accuracy for ONSD sonography for ICP was 0.94 (95% CI: 0.91-0.96). Conclusion: The absence of any one physical exam feature (e.g. mydriasis, posturing, or decreased GCS) is not sufficient to rule-out elevated ICP. Significant midline shift is highly suggestive of elevated ICP, but absence of shift does not rule it out. ONSD sonography may be useful in diagnosing elevated ICP. High suspicion of elevated ICP may necessitate treatment and transfer to a centre capable of invasive ICP monitoring.
Our objective was to identify predictors of severe acute respiratory infection in hospitalised patients and understand the impact of vaccination and neuraminidase inhibitor administration on severe influenza. We analysed data from a study evaluating influenza vaccine effectiveness in two Michigan hospitals during the 2014–2015 and 2015–2016 influenza seasons. Adults admitted to the hospital with an acute respiratory infection were eligible. Through patient interview and medical record review, we evaluated potential risk factors for severe disease, defined as ICU admission, 30-day readmission, and hospital length of stay (LOS). Two hundred sixteen of 1119 participants had PCR-confirmed influenza. Frailty score, Charlson score and tertile of prior-year healthcare visits were associated with LOS. Charlson score >2 (OR 1.5 (1.0–2.3)) was associated with ICU admission. Highest tertile of prior-year visits (OR 0.3 (0.2–0.7)) was associated with decreased ICU admission. Increasing tertile of visits (OR 1.5 (1.2–1.8)) was associated with 30-day readmission. Frailty and prior-year healthcare visits were associated with 30-day readmission among influenza-positive participants. Neuraminidase inhibitors were associated with decreased LOS among vaccinated participants with influenza A (HR 1.6 (1.0–2.4)). Overall, frailty and lack of prior-year healthcare visits were predictors of disease severity. Neuraminidase inhibitors were associated with reduced severity among vaccine recipients.
Introduction: With the current opioid crisis in Canada, presentations of acute opioid withdrawal (AOW) to emergency departments (ED) are increasing. Undertreated symptoms may result in relapse, overdose and death. Buprenorphine/naloxone (bup/nal) is a partial opioid agonist/antagonist used to mitigate symptoms of AOW, approved by Health Canad in 2007 for opioid use disorder. It is superior to clonidine, and increases follow up with addiction treatment programs when initiated in the ED. Nevertheless, in our inner-city ED in 2014, bup/nal was rarely prescribed. We aimed to increase ED physician prescribing of bup/nal for AOW by 50% over a 26-month period. Methods: Commencing in 2014, an interprofessional team of ED physicians, nurses (RN), pharmacists and QI specialists collaborated to improve the care of patients with AOW. PDSA cycles included: (1) needs assessment of emergency physicians knowledge and practices in 2014; (2) Grand Rounds and a web based information sheet in 2015; (3) ED stocking of bup/nal; (4) convenience order set to standardize AOW management; (5) Grand Rounds in 2016 and (6) peer-coaching for RNs, including case-based discussions and pocket card cognitive aids. The outcome was the number of times bup/nal was prescribed per month by ED physicians between Sept, 2015 and Oct, 2017. Data included the prescriber and use of order set as the process measure. The balancing measure was the number of patients referred to the Addiction Medicine Team who subsequently received bup/nal. Results: Bup/nal was prescribed by ED physicians 70 times, and 14 times by the Addiction Medicine Team. With each PDSA cycle, there was an increase in prescribing, with no significant shifts or trends. By all physicians, the median number of prescriptions per month was 3, and increased from 2 to 4 prescriptions/month after nursing education. There was a smaller increase in the median from 2 to 3 prescriptions/month by ED physicians alone. The order set was used 97% of the time. Conclusion: Bup/nal is safe, effective, and increases follow up with addiction programs for comprehensive assessment and treatment planning. We met our goal of increasing bup/nal prescribing in the ED for AOW by 50%. Moreover, prescribing increased by 100% with the addition of patients who received bup/nal after a referral to the Addiction Medicine Team. The intervention with the greatest impact was RN education, demonstrating that peer-coaching and teaching by an interprofessional team is key to changing practice. Unfortunately, overall prescribing remains low, and ED physicians may still be hesitant to prescribe bup/nal and defer to the specialists. It is unclear if this is due to a low number of patients presenting with AOW, patients with contraindications to bup/nal, or ED physician factors. The next step is an audit of all patients with AOW to see what percentage of those eligible are treated with bup/nal. A follow up survey to determine ongoing barriers will inform further PDSA cycles.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
We present the first experimentally determined oscillator strengths for the Pb ii transitions at 1203.6 Å and 1433.9 Å, obtained from lifetime measurements made using beam-foil techniques. We also present new detections of these lines in the interstellar medium from an analysis of archival spectra acquired by the Space Telescope Imaging Spectrograph onboard the Hubble Space Telescope. Our observations of the Pb ii λ1203 line represent the first detection of this transition in interstellar gas. Our experimental f-values for the Pb ii λ1203 and λ1433 transitions are consistent with recent theoretical results, including our own relativistic calculations, but are significantly smaller than previous values based on older calculations. Our new f-value for Pb ii λ1433 (0.321 ± 0.034) yields an increase in the interstellar abundance of Pb of 0.43 dex over estimates based on the f-value listed by Morton. With our revised f-values, and with our new detections of Pb ii λ1203 and λ1433, we find that the depletion of Pb onto interstellar grains is not nearly as severe as previously thought, and is very similar to the depletions seen for elements such as Zn and Sn, which have similar condensation temperatures.
Demonstrating the equivalence of constructs is a key requirement for cross-cultural empirical research. The major purpose of this paper is to demonstrate how to assess measurement and functional equivalence or invariance using the 9-item, 3-factor Love of Money Scale (LOMS, a second-order factor model) and the 4-item, 1-factor Pay Level Satisfaction Scale (PLSS, a first-order factor model) across 29 samples in six continents (N = 5973). In step 1, we tested the configural, metric and scalar invariance of the LOMS and 17 samples achieved measurement invariance. In step 2, we applied the same procedures to the PLSS and nine samples achieved measurement invariance. Five samples (Brazil, China, South Africa, Spain and the USA) passed the measurement invariance criteria for both measures. In step 3, we found that for these two measures, common method variance was non-significant. In step 4, we tested the functional equivalence between the Love of Money Scale and Pay Level Satisfaction Scale. We achieved functional equivalence for these two scales in all five samples. The results of this study suggest the critical importance of evaluating and establishing measurement equivalence in cross-cultural studies. Suggestions for remedying measurement non-equivalence are offered.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from 14C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.
Silicon nanoparticles (Si NPs) were synthesized by plasma enhanced chemical vapor deposition (PECVD) using silane as a silicon source. Allylamine was used as passivation ligands to form water-soluble Si NPs. Finally, aqueous asymmetric flow field-flow fractionation was used to successfully separate the polydisperse Si NPs into monodisperse Si NP fractions.