Rare Pelvic Malignant Tumors in Adults: Treatment Features and Clinical Outcome in Nonmetastatic Disease (Single Institution Experience)

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Novel KIAA1109 variants affecting splicing in a Russian family with ALKURAYA‐KUČINSKAS syndrome

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A Comparative Effectiveness Trial to Reduce Burnout and Improve Quality of Care

Abstract

Clinician burnout is presumed to negatively impact healthcare quality; yet scant research has rigorously addressed this hypothesis. Using a mixed-methods, randomized, comparative effectiveness design, we tested two competing approaches to improve care—one addressing clinician burnout and the other addressing how clinicians interact with consumers—with 192 clinicians and 469 consumers at two community mental health centers. Although qualitative reports were promising, we found no comparative effectiveness for either intervention on burnout, patient-centered processes, or other outcomes. Discussion includes identifying ways to strengthen approaches to clinician burnout.

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Acetaminophen pharmacokinetics in severely obese adolescents and young adults

Abstract

Background

Intravenous acetaminophen is commonly administered as an adjunctive to opioids during major surgical procedures, but neither the correct pharmacokinetic size descriptor nor the dose is certain in severely obese adolescents undergoing bariatric surgery.

Methods

Adolescents, 14‐20 years of age, with a body mass index (BMI) ≥95th percentile for age and sex or BMI ≥40 kg·m⁻², presenting for laparoscopic or robotic assisted or vertical sleeve gastrectomy were administered intravenous acetaminophen (1000 mg) following completion of the surgical procedure. Venous blood was drawn for acetaminophen assay at eight time points, starting 15 minutes after completion of the infusion and up to 12 hours afterward. Time‐concentration data profiles were analyzed using nonlinear mixed effects models. Parameter estimates were scaled to a 70‐kg person using allometry. Normal fat mass was used to assess the impact of obesity on pharmacokinetic parameters.

Results

The study cohort comprised 11 female patients, age 17 SD 2 years with a weight of 125 SD 19 kg and a mean BMI of 46 SD 5 kg·m⁻². The plasma acetaminophen serum concentration was 17 (SD 4) μg·mL⁻¹ at 10‐20 minutes after completion of the infusion and 5 (SD 6) μg·mL⁻¹ at 80‐100 minutes. A two‐compartment model, used to investigate pharmacokinetics, estimated clearance 10.6 (CV 72%) L·h·70 kg⁻¹, intercompartment clearance 37.3 (CV 63%) L·h·70 kg⁻¹, central volume of distribution 20.4 (CV 46%) L·70 kg⁻¹, and peripheral volume of distribution 16.8 (CV 42%) L·70 kg⁻¹. Clearance was best described using total body weight. Normal fat mass with a parameter that accounts for fat mass contribution (Ffat) of 0.88 best described volumes.

Conclusion

Current recommendations of acetaminophen to a maximum dose of 1000 mg resulted in serum concentrations below detection limits in all patients within 2 hours after administration. Dose is better predicted using total body mass with allometric scaling.

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WDR74 functions as a novel coactivator in TGF-β signaling

Publication date: Available online 27 November 2018

Source: Journal of Genetics and Genomics

Author(s): Jinquan Liu, Meiling Zhao, Bo Yuan, Shuchen Gu, Mingjie Zheng, Jian Zhou, Jianping Jin, Ting Liu, Xin-Hua Feng

Abstract

Smads are critical intracellular signal transducers for transforming growth factor-β (TGF-β) in mammalian cells. In this study, we have identified WD repeat-containing protein 74 (WDR74) as a novel transcriptional coactivator for Smads in the canonical TGF-β signaling pathway. Through direct interactions with Smad proteins, WDR74 enhances TGF-β-mediated phosphorylation and nuclear accumulation of Smad2 and Smad3. Consequently, WDR74 enables stronger transcriptional responses and more robust TGF-β-induced physiological responses. Our findings have elucidated a critical role of WDR74 in regulating TGF-β signaling.

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Rapid Assessment Procedure Informed Clinical Ethnography (RAPICE) in Pragmatic Clinical Trials of Mental Health Services Implementation: Methods and Applied Case Study

Abstract

Pragmatic clinical trials of mental health services are increasingly being developed to establish comparative effectiveness, influence sustainable implementation, and address real world policy decisions. However, use of time and resource intensive qualitative methods in pragmatic trials may be inconsistent with the aims of efficiency and cost minimization. This paper introduces a qualitative method known as Rapid Assessment Procedure-Informed Clinical Ethnography (RAPICE) that combines the techniques of Rapid Assessment Procedures with clinical ethnography. A case study is presented to illustrate how RAPICE can be used to efficiently understand pragmatic trial implementation processes and associated real world policy implications.

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OCMA: Fast, Memory-Efficient Factorization of Prohibitively Large Relationship Matrices

Matrices representing genetic relatedness among individuals (i.e., Genomic Relationship Matrices, GRMs) play a central role in genetic analysis. The eigen-decomposition of GRMs (or its alternative that generates fewer top singular values using genotype matrices) is a necessary step for many analyses including estimation of SNP-heritability, Principal Component Analysis (PCA), and genomic prediction. However, the GRMs and genotype matrices provided by modern biobanks are too large to be stored in active memory. To accommodate the current and future "bigger-data", we develop a disk-based tool, Out-of-Core Matrices Analyzer (OCMA), using state-of-the-art computational techniques that can nimbly perform eigen and Singular Value Decomposition (SVD) analyses. By integrating memory mapping (mmap) and the latest matrix factorization libraries, our tool is fast and memory-efficient. To demonstrate the impressive performance of OCMA, we test it on a personal computer. For full eigen-decomposition, it solves an ordinary GRM (N=10,000) in 55 seconds. For SVD, a commonly used faster alternative of full eigen-decomposition in genomic analyses, OCMA solves the top 200 singular values (SVs) in half an hour, top 2,000 SVs in 0.95 hour, and all 5,000 SVs in 1.77 hours based on a very large genotype matrix (N=1,000,000, M=5,000) on the same personal computer. OCMA also supports multi-threading when running in a desktop or HPC cluster. Our OCMA tool can thus alleviate the computing bottleneck of classical analyses on large genomic matrices, and make it possible to scale up current and emerging analytical methods to big genomics data using lightweight computing resources.

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