Association Between Blood Pressure and Adverse Renal Events in Type 1 Diabetes.

ObjectiveTo compare different blood pressure (BP) levels in their association with the risk of renal outcomes in type 1 diabetes and to determine whether an intensive glycemic control strategy modifies this association.Research design and methodsWe included 1,441 participants with type 1 diabetes between the ages of 13 and 39 years who had previously been randomized to receive intensive versus conventional glycemic control in the Diabetes Control and Complications Trial (DCCT). The exposures of interest were time-updated systolic BP (SBP) and diastolic BP (DBP) categories. Outcomes included macroalbuminuria (>300 mg/24 h) or stage III chronic kidney disease (CKD) (sustained estimated glomerular filtration rate <60 mL/min/1.73 m2).ResultsDuring a median follow-up time of 24 years, there were 84 cases of stage III CKD and 169 cases of macroalbuminuria. In adjusted models, SBP in the <120 mmHg range was associated with a 0.59 times higher risk of macroalbuminuria (95% CI 0.37-0.95) and a 0.32 times higher risk of stage III CKD (95% CI 0.14-0.75) compared with SBPs between 130 and 140 mmHg. DBP in the <70 mmHg range were associated with a 0.73 times higher risk of macroalbuminuria (95% CI 0.44-1.18) and a 0.47 times higher risk of stage III CKD (95% CI 0.21-1.05) compared with DBPs between 80 and 90 mmHg. No interaction was noted between BP and prior DCCT-assigned glycemic control strategy (all P > 0.05).ConclusionsA lower BP (<120/70 mmHg) was associated with a substantially lower risk of adverse renal outcomes, regardless of the prior assigned glycemic control strategy. Interventional trials may be useful to help determine whether the currently recommended BP target of 140/90 mmHg may be too high for optimal renal protection in type 1 diabetes

COVID‑Specific Coercive Control among Emerging Adults Attending College: A Brief Note

The COVID-19 pandemic represents a “perfect storm” with regards to risk for intimate partner violence (IPV). Abusive partners may engage in novel forms of coercive control, such as pressuring their partner to engage in activities associated with COVID-19 infection risk (e.g., attend a large gathering). However, no empirical research has focused on COVIDspecific coercive control. The current study sought to evaluate the prevalence of COVID-specific coercive control in a large sample of U.S. college students, as well as its association with other forms of IPV and depression and anxiety. A total of 2,289 undergraduate students attending eight U.S. universities who were currently in a sexual/dating/romantic relationship completed an online survey in Fall 2020 about COVID-specific coercive control, other forms of IPV (psychological, physical, sexual, coercive control) and depression and anxiety symptoms. Overall, 15.5% (n = 355) of students reported experiencing COVID-specific coercive control. Individuals who experienced COVID-specific coercive control were more likely to have experienced all other forms of IPV than those who did not experience COVID-specific coercive control. Further, individuals who experienced COVID-specific coercive control had significantly greater anxiety than individuals who did not experience any form of IPV. Individuals who experienced both COVID-specific coercive control and other forms of IPV had the highest levels of depression and anxiety. COVID-specific coercive control may serve to increase depression and anxiety, particularly if it co-occurs with other forms of IPV. Future work should evaluate the prevalence and long-term impact of coercive control during the COVID-19 pandemic

VESTIGE: Adjuvant Immunotherapy in Patients With Resected Esophageal, Gastroesophageal Junction and Gastric Cancer Following Preoperative Chemotherapy With High Risk for Recurrence (N+ and/or R1): An Open Label Randomized Controlled Phase-2-Study.

Background: Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma will be randomized to either adjuvant chemotherapy (as before surgery) or to immunotherapy with nivolumab and low dose ipilimumab (nivolumab 3 mg/kg IV Q2W plus Ipilimumab 1 mg/kg IV Q6W for 1 year). The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety and toxicity, and quality of life. This is an open label randomized controlled multi-center phase-2 superiority trial. Patients will be randomized in a 1:1 ratio to study arms. The trial will recruit 240 patients; recruitment commenced July 2019 and is anticipated to take 30 months. Detailed inclusion/exclusion criteria, toxicity management guidelines, and statistical plans for EORTC VESTIGE are described in the manuscript. Clinical Trial Registration: The trial is registered with www.ClinicalTrials.gov, identifier: NCT03443856

The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones

The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements. We demonstrate via a proteomic analysis that the muscle-specific signature is functional and conserved. Core chaperones are significantly more abundant across tissues and more important for cell survival than variable chaperones. Together with variable chaperones, they form tissue-specific functional networks. Analysis of human organ development and aging brain transcriptomes reveals that these functional networks are established in development and decline with age. In this work, we expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms

Performance of binary prediction models in high-correlation low-dimensional settings:a comparison of methods

BACKGROUND: Clinical prediction models are developed widely across medical disciplines. When predictors in such models are highly collinear, unexpected or spurious predictor-outcome associations may occur, thereby potentially reducing face-validity of the prediction model. Collinearity can be dealt with by exclusion of collinear predictors, but when there is no a priori motivation (besides collinearity) to include or exclude specific predictors, such an approach is arbitrary and possibly inappropriate. METHODS: We compare different methods to address collinearity, including shrinkage, dimensionality reduction, and constrained optimization. The effectiveness of these methods is illustrated via simulations. RESULTS: In the conducted simulations, no effect of collinearity was observed on predictive outcomes (AUC, R(2), Intercept, Slope) across methods. However, a negative effect of collinearity on the stability of predictor selection was found, affecting all compared methods, but in particular methods that perform strong predictor selection (e.g., Lasso). Methods for which the included set of predictors remained most stable under increased collinearity were Ridge, PCLR, LAELR, and Dropout. CONCLUSIONS: Based on the results, we would recommend refraining from data-driven predictor selection approaches in the presence of high collinearity, because of the increased instability of predictor selection, even in relatively high events-per-variable settings. The selection of certain predictors over others may disproportionally give the impression that included predictors have a stronger association with the outcome than excluded predictors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41512-021-00115-5

High-risk human papillomavirus (HPV) screening and detection in normal, healthy patient saliva samples: a pilot cluster randomized study

Background: The human papillomaviruses (HPV) are a large family of non-enveloped DNA viruses, mainly associated with cervical cancers. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers. Evidence now suggests HPV may modulate the malignancy process in some tobacco- and alcohol-induced oropharynx tumors, but might also be the primary oncogenic factor for inducing carcinogenesis among some non-smokers. More evidence, however, is needed regarding oral HPV prevalence among healthy adults to estimate risk. The goal of this study was to perform an HPV screening of normal healthy adults to assess oral HPV prevalence. Methods: Healthy adult patients at a US dental school were selected to participate in this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains HPV16 and HPV18 and further processed using qPCR for quantification and to confirm analytical sensitivity and specificity. Results: Chi-square analysis revealed the patient sample was representative of the general clinic population with respect to gender, race and age (p \u3c 0.05). Four patient samples were found to harbor HPV16 DNA, representing 2.6% of the total (n = 151). Three of the four HPV16-positive samples were from patients under 65 years of age and all four were female and Hispanic (non-White). No samples tested positive for HPV18. Conclusions: The successful recruitment and screening of healthy adult patients revealed HPV16, but not HPV18, was present in a small subset. These results provide new information about oral HPV status, which may help to contextualize results from other studies that demonstrate oral cancer rates have risen in the US among both females and minorities and in some geographic areas that are not solely explained by rates of tobacco and alcohol use. The results of this study may be of significant value to further our understanding of oral health and disease risk, as well as to help design future studies exploring the role of other factors that influence oral HPV exposure, as well as the short- and long-term consequences of oral HPV infection

Ultrasonic Sensors to Measure Internal Temperature Distribution

The in-process measurement of the internal temperature distribution is an important step toward improved processing of steels. A promising approach is the measurement of ultrasonic velocity, combined with a priori information on heat flow. Reference data on ultrasonic velocity versus temperature have been obtained for austenitic 304 stainless steel and for ferritic AISI 1018 steel. For stainless steel the longitudinal-wave velocity is nearly linear with temperature, with a proportionality constant of about -0.7 meters per second per degree Kelvin. In this paper we review the technical approach being used to ultrasonically determine internal temperature distribution. For this we (1) map the average velocity (hence average temperature) within hot steel samples (using a pulsed-laser driver and an electromagnetic acoustic transducer (EMAT) receiver) and (2) apply a reconstruction model that is based on ultrasonic tomography and utilizes the equations of heat flow

Simultaneous in-field boost for patients with 1 to 4 brain metastasis/es treated with volumetric modulated arc therapy: a prospective study on quality-of-life

<p>Abstract</p> <p>Purpose</p> <p>To assess treatment toxicity and patients' survival/quality of life (QoL) after volumetric modulated arc therapy (VMAT) with simultaneous in-field boost (SIB) for cancer patients with 1 - 4 brain metastases (BM) treated with or without surgery.</p> <p>Methods and Materials</p> <p>Between March and December 2010, 29 BM patients (total volume BM, < 40 cm³) aged < 80 years, KPS ≥ 70, RPA < III were included in this prospective trial. Whole brain VMAT (30 Gy) and a SIB to the BM (40 Gy) was delivered in 10 fraction. Mean age was 62.1 ± 8.5 years. Fifteen (51.7%) underwent surgery. KPS and MMSE were prospectively assessed. A self-assessed questionnaire was used to assess the QoL (EORTC QLQ-C30 with -BN20 module).</p> <p>Results</p> <p>As of April 2011 and after a mean FU of 5.4 ± 2.8 months, 14 (48.3%) patients died. The 6-month overall survival was 55.1%. Alopecia was only observed in 9 (31%) patients. In 3-month survivors, KPS was significantly (<it>p </it>= 0.01) decreased. MMSE score remained however stable (<it>p </it>= 0.33). Overall, QoL did decrease after VMAT. The mean QLQ-C30 global health status (<it>p </it>= 0.72) and emotional functional (<it>p </it>= 0.91) scores were decreased (low QoL). Physical (<it>p </it>= 0.05) and role functioning score (<it>p </it>= 0.01) were significantly worse and rapidly decreased during treatment. The majority of BN20 domains and single items worsened 3 months after VMAT except headaches (<it>p </it>= 0.046) and bladder control (<it>p </it>= 0.26) which improved.</p> <p>Conclusions</p> <p>The delivery of 40 Gy in 10 fractions to 1 - 4 BM using VMAT was achieved with no significant toxicity. QoL, performance status, but not MMSE, was however compromised 3 months after treatment in this selected cohort of BM patients.</p