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The three-item occupational violence (OV) risk assessment tool was developed and validated for use in emergency departments (EDs). It prompts review of each patient's aggression history, behaviours, and clinical presentation. However, confidence around representativeness and generalisability are needed before widescale adoption; hence we measured the inter-rater reliability of the tool among a large group of emergency nurses.A cross-sectional study was conducted between Sep 2021 and Jan 2022. Nurses were directed to a website that hosted an e-learning module about the tool. They were asked to apply the tool to two video scenarios of typical patient presentations. Demographic data, including years of emergency experience, were collected to contextualise their responses. Gwet's Agreement Coefficients (AC1) were calculated to determine inter-rater reliability.There were 135 participants: typically female, under the age of 40 years, with more than 3 years of emergency nursing experience. Overall, there was excellent inter-rater agreement (AC1 =0.752, p = 0.001). This was consistent when years of ED experience was stratified: 0-2 years, AC1 = 0.764, p = 0.002; 3-5 years, AC1 = 0.826, p = 0.001; 6-10 years, AC1 = 0.751, p 0.001; 11-15 years, AC1 = 0.659, p = 0.004; ≥ 16 years, AC1 = 0.799, p 0.001.The three-item OV risk assessment tool has excellent inter-rater reliability across a large sample of emergency nurses.

Non-ischemic diabetic heart disease (NiDHD) is characterized by diastolic dysfunction and decreased or preserved systolic function, eventually resulting in heart failure. Accelerated apoptotic cell death because of alteration of molecular signaling pathways due to dysregulation in microRNAs (miRNAs) plays a significant role in the development of NiDHD. Here, we aimed to determine the pathological role of cardiomyocyte-enriched pro-apoptotic miR-320 in the development of NiDHD. We identified a marked upregulation of miR-320 that was associated with downregulation of its target protein insulin growth factor-1 (IGF-1) in human right atrial appendage tissue in the late stages of cardiomyopathy in type 2 diabetic db/db mice and high-glucose-cultured human ventricular cardiomyocytes (AC-16 cells).

Marginalized communities have been disproportionally impacted by SARS-CoV-2. How the associations between social determinants of health and the risk of SARS-CoV-2 infection shifted across time is unknown. In this evaluation, we examine individual-level social determinants of health as social risk factors for SARS-CoV-2 infection across the first 12 months of the pandemic among US Veterans.We conducted a retrospective cohort analysis of 946,358 Veterans who sought testing or treatment for SARS-CoV-2 infection in U.S. Department of Veterans Affairs medical facilities. We estimated risk ratios for testing positive by social risk factors, adjusting for demographics, comorbidities, and time. Adjusted models were stratified by pandemic phase to assess temporal fluctuations in social risks.Approximately 19% of Veterans tested positive for SARS-CoV-2. Larger household size was a persistent risk factor and this association increased over time. Early in the pandemic, lower county-level population density was associated with lower SARS-CoV-2 infection risk, but between June 1 and August 31, 2020, this trend reversed.Temporal fluctuations in social risks associated with Veterans' SARS-CoV-2 infection suggest the need for ongoing, real-time tracking as the social and medical environment continues to evolve.

Objective Although depression and anxiety often have distinct etiologies, they frequently co-occur in adolescence. Recent initiatives have underscored the importance of developing new ways of classifying mental illness based on underlying neural dimensions that cut across traditional diagnostic boundaries. Accordingly, the aim of the study was to clarify reward-related neural circuitry that may characterize depressed–anxious youth. Method The Boston Adolescent Neuroimaging of Depression and Anxiety Human Connectome Project tested group differences regarding subcortical volume and nucleus accumbens activation during an incentive processing task among 14- to 17-year-old adolescents presenting with a primary depressive and/or anxiety disorder (n = 129) or no lifetime history of mental disorders (n = 64). In addition, multimodal modeling examined predictors of depression and anxiety symptom change over a 6-month follow-up period. Results Our findings highlighted considerable convergence. Relative to healthy youth, depressed–anxious adolescents exhibited reduced nucleus accumbens volume and activation following reward receipt. These findings remained when removing all medicated participants (∼59% of depressed–anxious youth). Subgroup analyses comparing anxious-only, depressed–anxious, and healthy youth also were largely consistent. Multimodal modeling showed that only structural alterations predicted depressive symptoms over time. Conclusion Multimodal findings highlight alterations within nucleus accumbens structure and function that characterize depressed–anxious adolescents. In the current hypothesis-driven analyses, however, only reduced nucleus accumbens volume predicted depressive symptoms over time. An important next step will be to clarify why structural alterations have an impact on reward-related processes and associated symptoms.

BACKGROUND: Noninvasive transcranial electrical stimulation (tES) research has been plagued with inconsistent effects. Recent work has suggested neuroanatomical and neurophysiological variability may alter tES efficacy. However, direct evidence is limited. OBJECTIVE: We have previously replicated effects of transcranial alternating current stimulation (tACS) on improving multitasking ability in young adults. Here, we attempt to assess whether these stimulation parameters have comparable effects in older adults (aged 60–80 years), which is a population known to have greater variability in neuroanatomy and neurophysiology. It is hypothesized that this variability in neuroanatomy and neurophysiology will be predictive of tACS efficacy. METHODS: We conducted a pre-registered study where tACS was applied above the prefrontal cortex (between electrodes F3-F4) while participants were engaged in multitasking. Participants were randomized to receive either 6-Hz (theta) tACS for 26.67 minutes daily for three days (80 minutes total; Long Exposure Theta group), 6-Hz tACS for 5.33 minutes daily (16-minutes total; Short Exposure Theta group), or 1-Hz tACS for 26.67 minutes (80 minutes total; Control group). To account for neuroanatomy, magnetic resonance imaging data was used to form individualized models of the tACS-induced electric field (EF) within the brain. To account for neurophysiology, electroencephalography data was used to identify individual peak theta frequency. RESULTS: Results indicated that only in the Long Theta group, performance change was correlated with modeled EF and peak theta frequency. Together, modeled EF and peak theta frequency accounted for 54% – 65% of the variance in tACS-related performance improvements, which sustained for a month. CONCLUSION: These results demonstrate the importance of individual differences in neuroanatomy and neurophysiology in tACS research and help account for inconsistent effects across studies.

Objective Surgical trainees are subject to pressure from variety of stakeholders to secure board certification from the American Board of Surgery (ABS). To meet these expectations, trainees must pass a written qualifying exam (QE) and an oral certifying exam (CE) within 7 years of completing general surgery residency. Board certification outcomes for candidates who fail either the QE or CE examination are not well characterized, but this information could help candidates, policymakers, and other stakeholders make informed decisions about how to respond to examination failure. Methods We retrospectively examined ABS records for all surgeons who completed general surgery residency from 2000 to 2013 and attempted general surgery board certification. Results Among 14,483 surgeons who attempted general surgery certification, 13,566 (94%) passed both the QE and CE within the 7-year certification window. Of those who did ultimately obtain certification, 97% passed the QE within 2 attempts and 97% passed the CE within 2 attempts. For those who failed either the QE or the CE twice, 67% ultimately obtained certification. Conclusions Most surgeons who obtained ABS general surgery board certification did so within 2 attempts at each board examination. Candidates who fail either examination twice are less likely to achieve board certification.

The limitations of central nervous system (CNS) drug delivery conferred by the blood-brain barrier (BBB) have been a significant obstacle in the development of large molecule therapeutics for CNS disease. Though significantly safer than direct CNS administration via intrathecal (IT) or intracerebroventricular (ICV) injection, the topical intranasal delivery of CNS therapeutics has failed to become clinically useful due to a variety of practical and physiologic drawbacks leading to high dose variability and poor bioavailability. This study describes the minimally invasive nasal depot (MIND) technique, a novel method of direct trans-nasal CNS drug delivery which overcomes the dosing variability and efficiency challenges of traditional topical trans-nasal, trans-olfactory strategies by delivering the entire therapeutic dose directly to the olfactory submucosal space. We found that the implantation of a depot containing an AntagoNAT (AT) capable of de-repressing brain derived neurotrophic factor (BDNF) expression enabled CNS distribution of ATs with significant and sustained upregulation of BDNF with efficiencies approaching 40% of ICV delivery. As the MIND technique is derived from common outpatient rhinological procedures routinely performed in Ear, Nose and Throat (ENT) clinics, our findings support the significant translational potential of this novel minimally invasive strategy as a reliable therapeutic delivery approach for the treatment of CNS diseases.

Editor's Note: This article is a reprint of a previously published article. For citation purposes, please use the original publication details: Marks JS, Hogelin GC, Gentry EM, et al. The Behavioral Risk Factor Surveys: I. State-specific prevalence estimates of behavioral risk factors. Am J Prev Med. 1985;1(6):1-8. The prevalence of most behavioral risk factors varies substantially among states. The prevalence of current cigarette smoking ranges from 22 percent to 38 percent. Estimates of alcohol use show geographic clustering, with lower rates in the southeastern states. The prevalence of sedentary lifestyle, uncontrolled hypertension, overweight, and seatbelt use differs markedly among states. These findings represent an initial step toward the analysis of state-specific baseline risk-factor data for use in developing state programs aimed at reducing the leading causes of death in the United States.

Objective The proprietary cyanoacrylate closure (CAC) system vs radiofrequency ablation (RFA) trial (VenaSeal Sapheon Closure System Pivotal Study [VeClose]) showed that CAC, a nontumescent, nonthermal, nonsclerosant ablation technique, was effective and noninferior to RFA in vein closure with good 36-month outcomes. Conducted under a separate protocol, the aim of this extended follow-up was to assess the long-term safety and effectiveness of CAC and RFA for the treatment of incompetent great saphenous veins (GSV) at 5 years (60 months) of follow-up. Methods This 60-month extension study was conducted for all patients who completed the randomized VeClose study and who were willing to participate. The pivotal VeClose study included patients with symptomatic moderate to severe varicosities (Clinical, Etiology, Anatomy, and Pathophysiology [CEAP] class C2-C4b) and symptomatic GSV incompetence who were randomly assigned (1:1) to either CAC or RFA. The primary outcome measure of this 60-month extension study was complete closure of the target vein, with planned exploratory analysis of noninferiority. Secondary outcomes included CEAP class; completion of the Venous Clinical Severity Score, EuroQol-Five Dimension survey, and Aberdeen Varicose Vein Questionnaire; patient satisfaction with treatment; adverse events (AEs) related to target GSV; and details of adjunctive procedures. Results A total of 89 patients completed the 60-month visit, which included 47 from the CAC group, 33 from the RFA group, and 9 CAC roll-in patients. No new recanalization events have been observed in the groups between 36 and 60 months of follow-up. At 60 months, Kaplan-Meier estimates for freedom from recanalization in the randomized CAC and RFA groups were 91.4% and 85.2%, respectively, demonstrating noninferiority of CAC compared with RFA. Both groups demonstrated sustained improvements in EuroQol-Five Dimension and quality of life measures through 60 months. Whereas patients assigned to C0 or C1 clinical class were excluded from the original study, more than half of all returning patients (64% [57/89]) were now assigned to C0 or C1, suggesting an improved clinical class from baseline. Furthermore, 41.1% of returning CAC patients and 39.4% of returning RFA patients are presently at least two CEAP clinical classes lower than at baseline. No long-term device- or procedure-related serious AEs occurred in either group between 36- and 60-month follow-up. Conclusions CAC and RFA were effective in achieving complete target vein closure of the GSV at long-term follow-up, with CAC demonstrating continued noninferiority to RFA. CAC was also associated with sustained improvements in symptoms and quality of life, lower CEAP class, and high level of patient satisfaction without serious AEs between 36 and 60 months.

In plants, pluripotent cells in meristems divide to provide cells for the formation of postembryonic tissues. The cambium is the meristem from which the vascular tissue is derived and is the main driver for secondary (radial) growth in dicots. Xylem and phloem are specified on opposing sides of the cambium, and tightly regulated cell divisions ensure their spatial separation. Peptide ligands, phytohormones, and their receptors are central to maintaining this patterning and regulating proliferation. Here, we describe recent advances in our understanding of how these signals are integrated to control vascular development and secondary growth.

Objective Past studies have suggested a potential “J shaped” relationship between infrarenal aortic diameter and both cardiovascular disease (CVD) prevalence and all cause mortality. However, screening programmes have focused primarily on large (aneurysmal) aortas. In addition, aortic diameter is rarely adjusted for body size, which is particularly important for women. This study aimed to investigate specifically the relationship between body size adjusted infrarenal aortic diameter and baseline prevalence of CVD. Methods A retrospective analysis was performed on a total of 4882 elderly (>50 years) participants (mean age 69.4 ± 8.9 years) for whom duplex ultrasound to assess infrarenal abdominal aortic diameters had been performed. History of CVDs, including ischaemic heart disease (IHD), and associated risk factors were collected at the time of assessment. A derivation cohort of 1668 participants was used to select cut offs at the lower and upper 12.5% tails of the aortic size distributions (aortic size index of 1.2, respectively), which was then tested in a separate cohort. Results A significantly elevated prevalence of CVD, and specifically IHD, was observed in participants with both small and large aortas. These associations remained significant following adjustment for age, sex, diabetes, hypertension, dyslipidaemia, obesity (body mass index), and smoking. Conclusion The largest and smallest infrarenal aortic sizes were both associated with prevalence of IHD. In addition to identifying those with aneurysmal disease, it is hypothesised that screening programmes examining infrarenal aortic size may also have the potential to improve global CVD risk prediction by identifying those with small aortas.

The Bank of England publishes a quarterly Inflation Report that provides numerical forecasts and a text discussion of its assessment of the UK economy. Previous research has evaluated the quantitative forecasts that are included in these reports, but we focus on the qualitative discussion of output growth, by using an in-sample textual analysis procedure to convert these qualitative assessments into a score for each report over the period 2005–2014. We also construct out-of-sample scores for reports before and after this period. We then compare the scores both to real-time output growth data and to the corresponding quantitative projections published by the bank. We find that overall developments in the UK economy were represented accurately in the text of the Inflation Report. Furthermore, efficiency regressions suggest that there is information in the text that could improve the Bank of England’s quantitative nowcasts and one-quarter-ahead forecasts.

We examine the interaction between individual preferences for markets and state-level economic freedom as it relates to Satisfaction with Life (SWL). Fundamental tenets of economic freedom assert that societies free of excessive government involvement are wealthier and, ultimately, happier; individuals who are allowed to pursue self-interest are argued to be more motivated and more productive, and so society as a whole is better off. Though there is substantial empirical evidence that freer societies are wealthier, the evidence connecting economic freedom and happiness is less clear. We explore the relationship between economic freedom and SWL at the individual level. We examine differences between personal preferences for free markets and state policy and how this ‘preference-policy mismatch’ is related to SWL. We then briefly examine the relationship between preference-policy mismatches and individual self-reported voting behavior, including implications for Tiebout sorting. This study is the first to focus on individual economic ideology, i.e. individual level of support for free markets, and SWL in the United States. Combining individual and state level data we offer improvements to prior studies in a number of areas including an enhanced measure of life satisfaction, a richer basis for examining left-right differences than simple political identification, and an examination of the effect of preference-policy mismatches on satisfaction with life. We find significant relationships between SWL and individual support for markets, state-level economic freedom, and preference-policy mismatch. Further, preference-policy mismatch is positively associated with self-reported voting frequency. We find little support for Tiebout sorting.

Mucinous colorectal adenocarcinoma (CRC) is conventionally defined by extracellular mucin comprising >50% of the tumour area, while tumours with ≤50% mucin are designated as having a mucinous component. However, these definitions are largely arbitrary and comparisons of clinico-molecular features and outcomes by proportion of mucinous component are limited. A cohort of 1643 patients with stage II/III cancer was examined for tumour mucinous component, DNA mismatch repair (MMR) status, BRAF mutation and tumour infiltrating lymphocytes (TILs). Tumours with ≤50% mucinous component exhibited similar characteristics as mucinous tumours, including association with female gender, proximal location, high grade, TIL-high, defective MMR (dMMR) and BRAF mutation. Proportion of mucinous component did not stratify disease-free survival (DFS). In univariate analysis dMMR status, but not histological grade, stratified survival for mucinous and mucinous component tumours; however, in multivariate analysis dMMR status was not an independent predictor. BRAF mutation prognostic value depended on mucinous differentiation and MMR status, with poor prognosis limited to non-mucinous pMMR tumours (HR 2.61, 95% CI 1.69-4.03; p

TP53 mutations drive colorectal cancer development, with missense mutations frequently leading to accumulation of abnormal TP53 protein. TP53 alterations have been associated with poor prognosis and chemotherapy resistance, but data remain controversial. Here, we examined the predictive utility of TP53 overexpression in the context of current adjuvant treatment practice for patients with stage III colorectal cancer. A prospective cohort of 264 stage III patients was tested for association of TP53 expression with 5-year disease-free survival, grouped by adjuvant treatment. Findings were validated in an independent retrospective cohort of 274 stage III patients. Overexpression of TP53 protein (TP53+) was found in 53% and 52% of cases from the prospective and retrospective cohorts, respectively. Among patients receiving adjuvant chemotherapy, TP53+ status was associated with shorter disease-free survival (p ≤ 0.026 for both cohorts), while no difference in outcomes between TP53+ and TP53- cases was observed for patients treated with surgery alone. Considering patients with TP53- tumors, those receiving adjuvant treatment had better outcomes compared with those treated with surgery alone (p ≤ 0.018 for both cohorts), while no treatment benefit was apparent for patients with TP53+ tumors. Combined cohort-stratified analysis adjusted for clinicopathological variables and DNA mismatch repair status confirmed a significant interaction between TP53 expression and adjuvant treatment for disease-free survival (pinteraction = 0.030). For the combined cohort, the multivariate hazard ratio for TP53 overexpression among patients receiving adjuvant chemotherapy was 2.03 (95% confidence interval 1.41-2.95, p

Raman spectroscopy (RS) was used to identify and quantify different nitrogen species in fertilizers. This is a fast and inexpensive method that requires no extensive sample preparation. Urea and nitrate were determined at 1000 and 1045 cm

The onset of the COVID-19 (coronavirus disease 2019) pandemic mandated postponement of the in-person Vascular Surgery Board 2020 certifying examination (CE). Vascular surgery virtual CEs (VVCEs) were developed for the scheduled 2020 CEs (rescheduled to January 2021) and 2021 CEs (rescheduled to July 2021) to avoid postponing the certification testing. In the present study, we have reported the development, implementation, and outcomes of the first two VVCEs.The VVCE was similar to the in-person format (three 30-minutes sessions, two examiners, four questions) but required a proctor and a host. In contrast to the general surgery VCEs, the VVCE also incorporated images. The candidates and examiners were instructed on the format, and technology checks were performed before the VVCE. The candidates were given the opportunity to invalidate their examination for technology-related reasons immediately after the examination. Postexamination surveys were administered to all the participants.The VVCEs were completed by 356 of 357 candidates (99.7%). The pass rates for the January 2021 and July 2021 examinations were 97.6% (first time, 99.4%; retake, 70%) and 94.7% (first time, 94.6%; retake, 100%), respectively. The pass rates were not significantly different from the 2019 in-person CE (χThe two Vascular Surgery Board VCEs were shown to be psychometrically sound and were overwhelmingly successful, demonstrating that image-based virtual examinations are feasible and could become the standard for the future.

High concentrations of mercury, possibly connected with widespread volcanism of the Siberian Traps, have previously been associated with the Smithian/Spathian (Early Triassic) boundary (SSB) in the Sverdrup Basin, Tethyan sections in India and China, as well as with a shallow-water record in western Spitsbergen. We confirm this Hg/TOC anomaly in the deeper water record at Wallenbergfjellet, central Spitsbergen. However, both paleontological age control and carbon isotopes indicate that the Hg anomaly occurred mainly within strata of middle Smithian age. Therefore, this Hg anomaly is unlikely to be directly and causally related to mechanisms contributing to the late Smithian global extinction of nektonic faunas. The TOC and trace element data suggest generally more oxygenated conditions during the Smithian compared to the Spathian, which is at odds with the hypothesis that oxygen depletion may have been a global kill mechanism for the SSB extinction. Further work is needed to assess if precise timing and paleogeographic distribution of anoxia shows any consistent pattern or not during the Smithian and Spathian. The very abrupt lower limb of the positive carbon isotope excursion (CIE) and the coarser grain size immediately below the boundary between the Lusitaniadalen Member and the Vendomdalen Member indicate a substantial stratigraphic gap of latest Smithian age, a previously neglected signal shared with many other boreal SSB sections. Ammonoid age control also indicates that the onset of the late Smithian gap in the high latitudes was earlier than in the Tropics. The gradual end of the positive CIE contrasts with the frequent spike shape observed in tropical shelf records and is definitively earliest Spathian in age. The middle Smithian Hg anomaly in the Boreal record is only visible in the Hg/TOC values, and is associated with a possible shift in organic matter type from terrestrial to marine in the case of Spitsbergen. This suggests that the middle Smithian Hg/TOC anomaly in Spitsbergen may not unequivocally originate from volcanism, and calls for additional caution before interpreting Hg spikes as a volcanic proxy.

Microwave-induced plasma optical emission spectrometry (MIP OES) has increasingly become a major resource for multi-elemental analysis. One of the greatest breakthroughs in the field has been the development of a commercial instrument based on a Hammer cavity, which runs on N2 gas obtained from an air compressor and a N2 generator. Here, we describe the most recent advances in MIP OES instrumentation, as well as related developments in sample preparation and alternative sample introduction systems, strategies to reduce the effects of background emission and analytical signal fluctuations on accuracy, and new calibration and plasma diagnostics methods. Recently published studies have contributed to minimize matrix effects and improve robustness of MIP OES analysis, which allowed for applications involving a broad range of analytes and sample types. Together, the array of recent developments in MIP OES contributes to its acceptance and increasing adoption as a cost-effective alternative in trace element analysis.

An unsupervised data-driven methodology is used to quantify matrix effects caused by carbon and easily ionizable elements (EIEs) in inductively coupled plasma optical emission spectrometry (ICP OES). Background signals from nine plasma naturally-occurring species of Ar, H and O are used with principal component analysis (PCA) and affinity propagation (AP) clustering to evaluate the effects of complex matrices on ionic emission lines of Cd, Co, Cr and Pb. Matrix effect severity is then quantified based on Euclidean distance in principal component space from an average calibration curve point. The method has been applied to spiked solutions of Mediterranean Sea and Dead Sea water samples, and a significant correlation (- 0.997) was found between Euclidean distance and analyte recoveries. For sea water analysis, accurate results are found using external standard calibration (EC) when Euclidean distance 1 for a given sample, and/or when that sample point groups with the calibration curve after affinity propagation clustering. Thus, by applying the PCA-AP strategy, one needs to perform no addition/recovery experiment to evaluate EC applicability. In addition, it can be carried out on the fly, as the background species used to monitor plasma changes are simultaneously recorded with the analytical signals, and a specific algorithm can be added to the instrument control software to flag instances in which EC may be ineffective. This is a proof-of-concept study, and additional work is required to evaluate the method's applicability to a larger number of analytes and sample matrices. However, the PCA-AP method described here for ICP OES can be used to quantify matrix effects, allowing for informed decisions regarding calibration. It requires no additional sample preparation and can be easily implemented in routine analyses of such complex-matrix samples as sea water.

Background When oral examinations are administered, examiner subjectivity may possibly affect ratings, particularly when examiner severity is influenced by examinee characteristics (e.g., gender) that are independent of examinee ability. This study explored whether the ratings of the general surgery oral certifying examination (CE) of the American Board of Surgery and likelihood of passing the CE were influenced by the gender of examinees or examiners. Materials and methods Data collected from examinees who attempted the general surgery CE in the 2016-2017 academic year were analyzed. There were 1341 examinees (61% male) and 216 examiners (82% male). Factorial analysis of variance and logistic regression analyses were used to evaluate the effect of examinee and examiner gender on CE ratings and likelihood of passing the CE. Results Examinees received similar ratings and had similar likelihood of passing the CE regardless of examinee or examiner genders and different combinations of examiner gender pairs (all P values > 0.05). Conclusions These results indicate that CE ratings of examinees are not influenced by examinee or examiner gender. There was no evidence of examiner bias due to gender on the CE.

Introduction This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate. Methods Venous and arterial TEEs within ±365 days of diagnosis of ROS1+, ALK+, EGFR+, or KRAS+ advanced NSCLC at five academic centers in the United States and China were captured (October 2002–April 2018). The primary endpoint was incidence of TEE in ROS1+ compared to anaplastic lymphoma kinase (ALK)+, EGFR+, and KRAS+ NSCLC within ±90 days of diagnosis. Logistic regression was used to assess if the odds of TEE differed among oncogene drivers. Results Eligible data from 95 ROS1+, 193 ALK+, 300 EGFR+, and 152 KRAS+ NSCLC patients were analyzed. The incidence rate of TEE was 34.7% (n = 33), 22.3% (n = 43), 13.7% (n = 41), and 18.4% (n = 28), respectively. In univariate analysis, the odds of a TEE in ROS1+ NSCLC were higher than ALK+, EGFR+, and KRAS+ cohorts. In multivariable analysis, the odds of a TEE were significantly higher for ROS1+ compared to EGFR+ and KRAS+ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31–4.57 (p = 0.005), and OR: 2.62, with a 95% confidence interval of 1.26–5.46 (p = 0.01), respectively. Although numerically superior, the odds for a TEE with ROS1+ compared to ALK+ was not statistically significant (OR: 1.45, p = 0.229). Overall survival was not significantly different in patients with or without TEE within ±90 days of diagnosis in the overall study cohort or within each molecular group. Conclusions The risk of peridiagnostic TEEs is significantly elevated in patients with advanced ROS+ NSCLC compared to EGFR+ and KRAS+ cases. TEE risk may be similarly elevated in ALK+ NSCLC.

PURPOSE: We retrospectively assessed the incidence of cataracts in patients with retinoblastoma (Rb) treated with either lens-sparing radiation therapy (LSRT) or whole-eye radiation therapy (WERT). A secondary aim of this study was to model the dose-response risk of cataract. METHODS AND MATERIALS: We reviewed 65 patients with Rb treated with radiation therapy (RT) at Children’s Hospital, Los Angeles from 1997 to 2015. Eyes that were enucleated before RT or lacked follow-up eye examinations were excluded. All patients underwent computed tomography simulation, and mean lens dose data were collected. Follow-up ophthalmologic examinations and intraocular lens implant history were reviewed for cataracts. The primary event-free survival (EFS) outcome was cataract development. Eyes without cataracts were censored on the last date of eye examination or post-RT enucleation, if applicable. Kaplan-Meier estimates were used to compare EFS outcomes, and dose response was projected with Cox regression and logistic regression models. RESULTS: Sixty-one patients (94 eyes) were analyzed with a median follow-up of 51.8 months. For eyes treated with WERT, cataracts developed in 71.7% versus 35.3% for LSRT. Median EFS for WERT and LSRT were 20.8 and 67.9 months, respectively. Compared with WERT, a significant EFS benefit was demonstrated for LSRT (P

Intensification of agriculture has led to major losses of hedgerows and field margins worldwide. Soil sample extraction, in situ time series of soil moisture, temperature and soil water quality analyses, annual earthworm sampling and arbuscular mycorrhizal (AM) fungi sampling enabled comparison of soil functions between typical hedgerows, grass field margins, pasture and arable (mainly winter wheat) fields in a temperate, lowland setting. Mean bulk density (upper 50 cm), surface compaction and soil moisture content were significantly lower while organic matter content and porewater dissolved organic carbon concentrations were significantly greater in hedgerow soils, than margins or fields. Mean nitrate and phosphate concentrations were three and ten times larger, respectively, in soil solutions under hedgerows than arable fields while ammonium concentrations were least in arable fields. Saturated hydraulic conductivity was significantly greater under hedgerows (median = 102 mm hr−1) where it took an average of one hour longer for soils to reach maximum moisture content following rainfall, than adjacent arable (median = 3 mm hr−1) or pasture fields and margins (median = 27 mm hr−1). Hedgerow soils had a greater proportion of flow through micropores and less macropore flow than other soils. The pasture and margin soils had the largest proportion of macropore flow (>85%) and more (and larger) anecic earthworm species, such as Lumbricus terrestris which produce vertical burrows. Earthworm density, biomass and diversity were greater in pasture and margin soils, followed by hedgerow soils, and tended to be lowest in arable soils. For both total and AM fungi, hedgerow soils hosted a distinct and heterogeneous soil community, margin and pasture communities were diverse but clustered together, and arable communities formed a distinct cluster, with low inter-sample variation and significantly lowest AM fungal richness. The findings demonstrate that soils under hedgerows, which should be conserved, can provide important functions on farmland including storing organic carbon, promoting infiltration and storing runoff, increasing earthworm diversity and hosting distinct AM communities.

Polysorbates are complex mixtures of over a thousand components with a wide range of hydrophobicity. This paper describes a methodology for characterization of heterogeneity and stability of polysorbates in therapeutic protein formulation. The method utilizes on-line coupling of a hydrophobic interaction chromatography (HIC) column with reverse phase liquid chromatography (RPLC) and charged aerosol detection (CAD)/mass spectrometer (MS). The addition of a low concentration of formic acid and organic solvent (e.g. 0.05% formic acid and 3% acetonitrile) in the mobile phase enables the use of the HIC column to separate small molecule excipients (including major components of polysorbates) and the large protein molecules by a mixed mechanism of size exclusion chromatography (SEC) and RPLC. The protein and the charged excipients, which elute early from the HIC column, are directed by a switching valve to waste. The polysorbates and other neutral excipients, which elute later from the HIC column, are directed to the RPLC column for further separation. The separated polysorbate components are detected by CAD, and characterized by MS. This method has been used to characterize the degradation of polysorbate 80 (PS80) in placebo and protein formulations. Our studies have revealed different degradation behavior of PS80 in placebo vs. protein formulation.

Objective Recently, the prevalence of abdominal aortic aneurysm (AAA) using screening strategies based on elevated cardiovascular disease (CVD) risk was reported. AAA was defined as a diameter ≥30 mm, with prevalence of 6.1% and 1.8% in men and women respectively, consistent with the widely reported AAA predominant prevalence in males. Given the obvious differences in body size between sexes this study aimed to re-evaluate the expanded CVD risk based AAA screening dataset to determine the effect of body size on sex specific AAA prevalence. Methods Absolute (26 and 30 mm) and relative (aortic size index [ASI] equals the maximum infrarenal aorta diameter (cm) divided by body surface area (m2), ASI ≥ 1.5) thresholds were used to assess targeted AAA screening groups (n = 4115) and compared with a self reported healthy elderly control group (n = 800). Results Male AAA prevalence was the same using either the 30 mm or ASI ≥1.5 aneurysm definitions (5.7%). In females, AAA prevalence was significantly different between the 30 mm (2.4%) and ASI ≥ 1.5 (4.5%) or the 26 mm (4.4%) thresholds. Conclusion The results suggest the purported male predominance in AAA prevalence is primarily an artefact of body size differences. When aortic size is adjusted for body surface area there is only a modest sex difference in AAA prevalence. This observation has potential implications in the context of the ongoing discussion regarding AAA screening in women.

Mafic sills of the Central Atlantic Magmatic Province (CAMP) in Brazil are temporally linked to the end-Triassic extinction (ETE), one of the largest mass extinctions of the Phanerozoic. The sills were emplaced into the volatile-rich sedimentary rocks of the Amazonas and Solimoes basins in northern Brazil. Here we present a new geochemical study of 26 dolerite samples from 6 deep boreholes in the Brazilian basins, including whole-rock major and trace elements, whole-rock Sr–Nd isotopes and detailed biotite mineral chemistry. The bulk of the dolerites are characterized by phenocrysts of clinopyroxene and plagioclase in subophitic to intergranular textures, Fe–Ti oxides, and rare olivine and orthopyroxene. A different mineralogical assemblage (microphenocrysts of alkali-feldspar, quartz, biotite and apatite) is found in small independent domains, localized within the framework of coarser plagioclase and clinopyroxene laths. These fine-grained evolved domains crystallized in late-stage, evolved melt pockets in the interstitial spaces between earlier crystallized coarser grained crystals. The majority of the studied dolerites are generally evolved tholeiitic basalts and basaltic andesites with low TiO2 concentrations ( 2.0 wt.%), and are found in the eastern part of the Amazonas Basin. Whole-rock major and trace element and Sr–Nd isotope geochemistry of both low- and high-Ti sills is similar to that of previously published CAMP rocks from the two magma types. Low-Ti sills show enriched isotopic signatures (143Nd/144Nd201Ma 0.51215 to 0.51244; 87Sr/86Sr201Ma 0.70568 to 0.70756), coupled with crustal-like characteristics in the incompatible element patters (e.g. depletion in Nb and Ta). Unaltered high-Ti samples show more depleted isotopic signatures (143Nd/144Nd201Ma 0.51260 to 0.51262; 87Sr/86Sr201Ma 0.70363 to 0.70398). Low-Ti dolerites from both the Amazonas and Solimoes basins contain biotite with extremely high Cl concentrations (up to 4.7 wt.%). We show that there is a strong correlation between host-rock lithology and Cl concentrations in biotite from the dolerites, and interpret this to reflect large-scale crustal contamination of the low-Ti magmas by halite-rich evaporites. Our findings support the hypothesis that sill-evaporite interactions increased volatile release during the emplacement of CAMP. This strengthens the case for active involvement of this LIP in the end-Triassic crisis, and suggests that the sub-volcanic part of a LIP can be of major importance in driving climate change and mass extinctions.

The use of videoconferencing technologies (VCT) is on the rise given its potential to close the gap between mental health care need and availability. Yet, little is known about the effectiveness of these services compared to those delivered in-person. A series of meta-analyses were conducted using 57 empirical studies (43 examining intervention outcomes; 14 examining assessment reliability) published over the past two decades that included a variety of populations and clinical settings. Using conventional and HLM3 meta-analytical approaches, VCT consistently produced treatment effects that were largely equivalent to in-person delivered interventions across 281 individual outcomes and 4336 clients, with female clients and those treated in medical facilities tending to respond more favorably to VCT than in-person. Results of an HLM3 model suggested assessments conducted using VCT did not appear to lead to differential decisions compared to those conducted in-person across 83 individual outcomes and 332 clients/examinees. Although aggregate findings support the use of VCT as a viable alternative to in-person service delivery of mental healthcare, several limitations in the current literature base were revealed. Most concerning was the relatively limited number of randomized controlled trials and the inconsistent (and often incomplete) reporting of methodological features and results. Recommendations for reporting the findings of telemental health research are provided.

Frontotemporal dementia (FTD) therapy development is hamstrung by a lack of susceptibility, diagnostic, and prognostic biomarkers. Blood neurofilament light (NfL) shows promise as a biomarker, but studies have largely focused only on core FTD syndromes, often grouping patients with different diagnoses. To expedite the clinical translation of NfL, we avail ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources and conduct a comprehensive investigation of plasma NfL across FTD syndromes and in presymptomatic FTD mutation carriers. We find plasma NfL is elevated in all studied syndromes, including mild cases; increases in presymptomatic mutation carriers prior to phenoconversion; and associates with indicators of disease severity. By facilitating the identification of individuals at risk of phenoconversion, and the early diagnosis of FTD, plasma NfL can aid in participant selection for prevention or early treatment trials. Moreover, its prognostic utility would improve patient care, clinical trial efficiency, and treatment outcome estimations.