Search

Progression-free survival (PFS) is a common primary endpoint in newly diagnosed multiple myeloma (NDMM). Patients with NDMM typically have longer PFS and are more likely to achieve minimal residual disease (MRD) or complete response (CR) compared to patients with relapsed or refractory multiple myeloma. Response-based surrogate endpoints may hold value given the longer follow-up time required to evaluate PFS in NDMM. In this work, systematic literature reviews of Medline, Embase, and Cochrane databases (2010-06/2020) and relevant congresses (2018-2020) were performed to identify randomized clinical trials (RCTs) and real-world studies in NDMM reporting median PFS and objective response. Associations between PFS and each response endpoint were evaluated using Pearson's product-moment correlation weighted by sample size in each RCT arm. Unadjusted and adjusted weighted linear regression models were applied to estimate the gain in median PFS associated with each response endpoint. Statistically significant correlations were identified for median PFS with overall response rate (ORR; Pearson r = 0.59), CR (r = 0.48), stringent CR (sCR; r = 0.68), and MRD (r = 0.69). The unadjusted models estimated 0.50 (95% CI: 0.36, 0.64; p

**Introduction:** This systematic literature review analyzed published evidence on IgA nephropathy (IgAN), focusing on US epidemiology, health-related quality of life (HRQoL), and economic burden of illness. **Methods:** Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Embase®, MEDLINE®, Cochrane, and Econlit (January 2010 to June 2020) were searched, along with relevant congresses (2017-2020). **Results:** Of 123 epidemiologic studies selected for data extraction, 24 reported IgAN diagnosis rates ranging from 6.3% to 29.7% among adult and pediatric patients undergoing renal biopsy, with all reported US rates

BackgroundObstructive sleep apnea (OSA) patients are at increased risk of cardiovascular disease (CVD). Cell adhesion molecules (CAM) are increased in OSA and CAM are also implicated in the development of CVD.Research questionDo CAM (ICAM-1, VCAM-1 and E-selectin) have prognostic value in identifying risk of cardiovascular events in OSA?Study design and methodsPatients with suspected OSA referred for a polysomnogram provided a fasting blood sample. Plasma levels of ICAM-1, VCAM-1 and E-selectin were determined by multiplex Luminex Assay (Milliporesigma ON, Canada). Cardiovascular events were determined by deterministic linkage to provincial health databases.Results418 patients were included in the analysis. Mostly male (68.2%), mean age of 50.7 yrs, median AHI 16.5 events/hour, and mean BMI of 31.7 kg/m2. 36 cardiovascular events occurred in 8-yrs of follow up. Higher levels of ICAM-1 were associated with developing CVD (HR = 3.65 95% CI 1.40-9.53, 2nd and 3rd tertiles vs. 1st tertile), including in patients with OSA (HR = 3.1 95% CI 1.16-8.25). E-selectin was significantly associated with cardiovascular events in patients with moderate to severe OSA (HR = 3.31 95% CI 0.94-11.72, 2nd and 3rd tertiles vs. 1st tertile) but not in patients without moderate to severe OSA (HR = 0.67 95% CI 0.19-2.38), p-value for interaction = 0.07.InterpretationIn a suspected OSA cohort, patients with higher levels of ICAM-1 (>816 ng/ml) were significantly more likely to experience a cardiovascular event within 8 years after PSG. In moderate to severe OSA patients, a higher E-selectin (>36.4 ng/ml) was significantly associated with cardiovascular events.

Many modern jobs require long periods of sitting on a chair that may result in serious health complications. Dynamic chairs are proposed as alternatives to the traditional sitting chairs; however, previous studies have suggested that most users are not aware of their postures and do not take advantage of the increased range of motion offered by the dynamic chairs. Building a system that identifies users’ postures in real time, as well as forecasts the next few postures, can bring awareness to the sitting behavior of each user. In this study, machine learning algorithms have been implemented to automatically classify users’ postures and forecast their next motions. The random forest, gradient decision tree, and support vector machine algorithms were used to classify postures. The evaluation of the trained classifiers indicated that they could successfully identify users’ postures with an accuracy above 90%. The algorithm can provide users with an accurate report of their sitting habits. A 1D-convolutional-LSTM network has also been implemented to forecast users’ future postures based on their previous motions, the model can forecast a user’s motions with high accuracy (97%). The ability of the algorithm to forecast future postures could be used to suggest alternative postures as needed.

The low background incidence of tumors in rodents from subchronic toxicity studies makes it difficult to assess their relevance, especially when present only in treated animals. This report investigates the occurrence of renal tubule tumors (RTTs), specifically the amphophilic-vacuolar (AV) phenotypic variant, in young Sprague-Dawley (SD) rats from a survey of laboratories conducting subchronic toxicity studies spanning a period of 10 years (2002–2012). This survey establishes a general profile of tumor occurrence; it does not estimate overall incidence or prevalence. AV tumors are spontaneous, nontreatment-related tumors of familial origin, and morphologically distinct from conventional RTTs induced by exposure to renal carcinogens. They are composed of distinct lobules of large, round to polyhedral cells with vacuolated amphophilic to eosinophilic cytoplasm and prominent nucleoli. Data from five collaborating laboratories, representing 37 qualifying studies, are presented. In total, 58 renal tubule neoplasms were recorded in this data set. The AV tumor variant was reported more commonly than the conventional RTT (n = 45 and 13, respectively), and it was recorded in both experimental (n = 32) and control (n = 13) groups. AV tumors occurred more often in females (n = 34) than in males (n = 11); conventional RTTs were recorded more often in males (n = 9) than in females (n = 4). AV tumors often occurred in more than one rat within the same study (up to 7) and were documented to occur in rats as young as 7 to 10 weeks of age. Results from this survey indicate that AV tumors are being reported more commonly in recent years; the majority (n = 33) were reported in studies commencing since 2009. In conclusion, this study reaffirms that AV tumors are spontaneous, nontreatment-related lesions, and suggests that they may be more common than conventional RTTs in young SD rats. The authors propose that AV tumors be recorded separately from conventional RTTs in order to clearly distinguish these two renal tubule neoplasms from one another and allow for appropriate interpretation of a compound’s potential carcinogenic effect in the kidney. [ABSTRACT FROM AUTHOR]

Abstract The need to monitor change in sagebrush steppe is urgent due to the increasing impacts of climate change, shifting fire regimes, and management practices on ecosystem health. Remote sensing provides a cost‐effective and reliable method for monitoring change through time and attributing changes to drivers. We report an automated method of mapping rangeland fractional component cover over a large portion of the Northern Great Basin, USA, from 1986 to 2016 using a dense Landsat imagery time series. Our method improved upon the traditional change vector method by considering the legacy of change at each pixel. We evaluate cover trends stratified by climate bin and assess spatial and temporal relationships with climate variables. Finally, we statistically evaluate the minimum time density needed to accurately characterize temporal patterns and relationships with climate drivers. Over the 30‐yr period, shrub cover declined and bare ground increased. While few pixels had >10% cover change, a large majority had at least some change. All fractional components had significant spatial relationships with water year precipitation (WYPRCP), maximum temperature (WYTMAX), and minimum temperature (WYTMIN) in all years. Shrub and sagebrush cover in particular respond positively to warming WYTMIN, resulting from the largest increases in WYTMIN being in the coolest and wettest areas, and respond negatively to warming WYTMAX because the largest increases in WYTMAX are in the warmest and driest areas. The trade‐off of lowering temporal density against removing cloud‐contaminated years is justified as temporal density appears to have only a modest impact on trends and climate relationships until n ≤ 6, but multi‐year gaps are proportionally more influential. Gradual change analysis is likely to be less sensitive to n than abrupt change. These data can be used to answer critical questions regarding the influence of climate change and the suitability of management practices.

The advancement of an investigational new drug in humans is a significant developmental milestone. In first-in-human (FIH)-enabling toxicology studies, the highest dose without a test article–related adverse effect (no-observed-adverse-effect-level [NOAEL]) serves as the basis for deriving a safe FIH starting dose. For anticancer pharmaceuticals, the FIH dose may be calculated using the highest non-severely toxic dose (HNSTD) in nonrodent models or the dose severely toxic to 10% (STD10) in rodents. Given the practice of reporting the NOAEL, but the lack of regulatory requirements to do so for anticancer pharmaceuticals, we conducted an informal survey of 20 companies to answer the question "How is our industry reporting toxic/adverse dose levels in FIH-enabling toxicology studies for anticancer indications?" The data indicated 4 reporting approaches, each providing a path to regulatory acceptance. Within the integrated toxicology study report, 45% of respondents report the HNSTD/STD10, 25% report the NOAEL, 20% report both the HNSTD/STD10 and NOAEL, and 10% do not define either, reserving definitions for regulatory submissions. One reporting approach may be preferred over another for reasons including consistency across indications, repurposing pharmaceuticals, regulatory feedback, or simplicity. The reporting approach should be defined in advance of study initiation, and the pathologist should provide context to support the chosen approach. [ABSTRACT FROM AUTHOR]

Monitoring temporal dynamics of rangelands to detect and understand change in vegetation cover and composition provides a wealth of information to improve management and sustainability. Remote sensing allows the evaluation of both abrupt and gradual rangeland change at unprecedented spatial and temporal extents. Here, we describe the production of the National Land Cover Database (NLCD) Back in Time (BIT) dataset which quantified the percent cover of rangeland components (bare ground, herbaceous, annual herbaceous, litter, shrub, and sagebrush (Artemisia spp. Nutt.) across the western United States using Landsat imagery from 1985 to 2018. We evaluate the relationships of component trends with climate drivers at an ecoregion scale, describe the nature of landscape change, and demonstrate several case studies related to changes in grazing management, prescribed burns, and vegetation treatments. Our results showed the net cover of shrub, sagebrush, and litter significantly (p < 0.01) decreased, bare ground and herbaceous cover had no significant change, and annual herbaceous cover significantly (p < 0.05) increased. Change was ubiquitous, with a mean of 92% of pixels with some change and 38% of pixels with significant change (p < 0.10). However, most change was gradual, well over half of pixels have a range of less than 10%, and most change occurred outside of known disturbances. The BIT data facilitate a comprehensive assessment of rangeland condition, evaluation of past management actions, understanding of system variability, and opportunities for future planning.

In developed nations, monitoring for drug-induced liver injury through serial measurements of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] in at-risk individuals is the standard of care. Despite the need, monitoring for drug-related hepatotoxicity in resource-limited settings is often limited by expense and logistics, even for patients at highest risk. This article describes the development and clinical testing of a paper-based, multiplexed microfluidic assay designed for rapid, semiquantitative measurement of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained by venipuncture and 10 fingerstick specimens from healthy volunteers, we have shown that our assay can, in 15 min, provide visual measurements of AST and ALT in whole blood or serum, which allow the user to place those values into one of three readout “bins” [<3× upper limit of normal (ULN), 3 to 5× ULN, and >5× ULN, corresponding to tuberculosis/HIV treatment guidelines] with >90% accuracy. These data suggest that the ultimate point-of-care fingerstick device will have high impact on patient care in low-resource settings., Chemistry and Chemical Biology