We provide evidence that arsenic trioxide (As2O3) targets the BCR-ABL oncoprotein via a novel mechanism involving p62/SQSTM1-mediated localization of the oncoprotein to the autolysosomes and ...subsequent degradation mediated by the protease cathepsin B. Our studies demonstrate that inhibitors of autophagy or cathepsin B activity and/or molecular targeting of p62/SQSTM1, Atg7, or cathepsin B result in partial reversal of the suppressive effects of AS2O3 on BCR-ABL expressing leukemic progenitors, including primitive leukemic precursors from chronic myelogenous leukemia (CML) patients. Altogether, these findings indicate that autophagic degradation of BCR-ABL is critical for the induction of the antileukemic effects of As2O3 and raise the potential for future therapeutic approaches to target BCR-ABL expressing cells by modulating elements of the autophagic machinery to promote BCR-ABL degradation.
The field of psychology has established high professional standards which have become a cornerstone of the practice of psychology. However, powerful boards tasked with administering these standards ...can operate with little oversight, making it difficult to monitor whether these institutions are operating in a fair and impartial way. In particular, early-career psychologists who have less experience and power in their initial years of independent practice may be singularly vulnerable as they have relatively little experience to navigate the profession, including fielding complaints that may be made against them to a licensing board. While it is essential to ensure early-career psychologists are upholding their commitments to the practice, there are risks in policing their activities without orienting toward growth, learning, and professional development. Even the smallest disciplinary action may never be expunged from a psychologist’s record, resulting in long-term implications for insurance coverage, reputation and future professional viability in the field. Overly-punitive approaches can be distressing or even traumatizing. In this paper, we examine disciplinary actions of the Kentucky Board of Examiners of Psychology (KBEP) from the years 2000 to 2020 (
N
= 65) to determine the methodology by which the Board administers its oversight function. We analyze the nature of the discipline received (fines, suspensions, continuing education, supervision) revealing a two-tiered system of punishments, and provide context regarding the nature of the disciplinary process and its impacts. We report on qualitative interviews of early career psychologists subject to disciplinary actions by the Board, and psychologists who supervised early career psychologists investigated by the Board. We compare legislation governing KBEP and make comparisons to the workings of licensing boards in three other states. Using these findings, we make recommendations for revisions to the applicable legislation and administrative processes of the Board to establish an improved balance between public safety, the well-being of new psychologists, equity considerations such as race, and the development of the practice of psychology in Kentucky. This work brings to light previously unexamined injustices that can knowingly or unknowingly be perpetuated by licensing Boards, and can be used to inform the creation of more just, balanced and inclusive professional Boards.
SOAP3 is the first short read alignment tool that leverages the multi-processors in a graphic processing unit (GPU) to achieve a drastic improvement in speed. We adapted the compressed full-text ...index (BWT) used by SOAP2 in view of the advantages and disadvantages of GPU. When tested with millions of Illumina Hiseq 2000 length-100 bp reads, SOAP3 takes < 30 s to align a million read pairs onto the human reference genome and is at least 7.5 and 20 times faster than BWA and Bowtie, respectively. For aligning reads with up to four mismatches, SOAP3 aligns slightly more reads than BWA and Bowtie; this is because SOAP3, unlike BWA and Bowtie, is not heuristic-based and always reports all answers.
Multivariate statistics have been applied to evaluate the water quality data collected at six monitoring stations in the Feitsui Reservoir watershed of Taipei, Taiwan. The objective is to evaluate ...the mutual correlations among the various water quality parameters to reveal the primary factors that affect reservoir water quality, and the differences among the various water quality parameters in the watershed. In this study, using water quality samples collected over a period of two and a half years will effectively raise the efficacy and reliability of the factor analysis results. This will be a valuable reference for managing water pollution in the watershed. Additionally, results obtained using the proposed theory and method to analyze and interpret statistical data must be examined to verify their similarity to field data collected on the stream geographical and geological characteristics, the physical and chemical phenomena of stream self-purification, and the stream hydrological phenomena. In this research, the water quality data has been collected over two and a half years so that sufficient sets of water quality data are available to increase the stability, effectiveness, and reliability of the final factor analysis results. These data sets can be valuable references for managing, regulating, and remediating water pollution in a reservoir watershed.
This study assesses the concentrations of the 54 ozone precursors (all being volatile organic compounds (VOCs)) detected at the four photochemical assessment monitoring stations that are part of the ...air quality monitoring network in the Kaohsiung-Pingtung area in Taiwan. Factor and cluster analyses of the multivariate statistical analysis are performed to explore the interrelationship among the 10 VOCs of relatively higher concentrations selected from the 54 ozone precursors to identify significant factors affecting ozone pollution levels in the study area. Moreover, the multivariate statistical analysis can faithfully reflect why the study area has been affected by photochemical pollution. First, results of the factor analysis suggest that the factors affecting how photochemical reactions occur in the study area can be divided into the following: “pollution from mobile sources”, “pollution from stationary sources”, and “pollution from energy sources”. Among them, mobile sources have the greatest impact on photochemical pollution levels. Second, the impacts of photochemical pollution on air quality in the study area can be classified into four clusters via cluster analysis. Each cluster represents how the 10 VOCs affect air quality, with different characteristics, and how they contribute to photochemical pollution in the study area. If there are more types and samples of photochemical pollutants when performing a multivariate statistical analysis, the analysis results will be more stable. This study adopts data on VOC monitoring over a period of nearly two years, which can effectively improve the validity and reliability of the factor analysis results, while helping environmental agencies review the effectiveness of air quality management in the future and serving as reference for the effectiveness of reducing photochemical pollution in the atmosphere.
Recent evidence demonstrated similar outcomes between nonsurgical and surgical management of displaced proximal humerus fractures. We analyzed treatment trends and performed a cost-minimization ...analysis comparing nonsurgical treatment, open reduction and internal fixation, reverse total shoulder arthroplasty, and hemiarthroplasty. We hypothesized that rates of surgical treatment have increased and that the costs associated with surgery are greater compared with nonsurgical management of proximal humerus fractures.
We used a US private-payer claims database of 22 million patient records from 2007 to 2016 to compare (1) cost for the episode of care from the payer perspective between each surgical group and nonsurgical treatment of proximal humerus fractures, and (2) annual trends and complication rates of each group. Cost data, including facility fees, physician fees, physical therapy, and clinic visits, were used to complete a cost-minimization analysis.
Nonsurgical treatment was associated with lower average total costs compared with surgical intervention. Facility and physician fees accounted for most of this difference. Physical therapy costs and number of physical therapy visits were higher in each surgical group compared with nonsurgical treatment. Surgical treatment was associated with higher complications, revision rates, and length of stay. There was a small but statistically significant decrease in nonsurgical management of proximal humerus fractures between 2007 and 2016. No change was observed in rates of open reduction and internal fixation, whereas rates of reverse total shoulder arthroplasty increased and rates of hemiarthroplasty decreased.
Nonsurgical management of proximal humerus fractures decreased during the study period. In the setting of treatment equipoise, cost-minimization analysis favors nonsurgical management of proximal humerus fractures. Surgical management is associated with higher complication rates, revision rates, and length of stay.
Economic Decision Analysis IV.
The subject of this study was the dust collected from an electric arc furnace at an unidentified-waste treatment site in southern Taiwan. The dust underwent an in situ vitrification (ISV) process and ...was tested using the toxicity characteristic leaching procedure (TCLP), at the end of which the final product was analyzed for its stability and weather resistance. This study then examined the above results to determine whether the ISV process helps to enhance the efficiency and economic benefits of said waste-treatment site. A TCLP test conducted on the dust that had been treated with ISV revealed that concentrations of various heavy metals were not only far below those of the unprocessed sample dust but also fell below the limit stipulated in the TCLP regulation of Taiwan’s Environmental Protection Administration. The results show that after undergoing ISV treatment, heavy metals in the dust were either encapsulated or bound in silicon lattices and thus barely leached from the dust. Analyses using scanning electron microscopy (SEM) and an energy dispersive spectrometry (EDS) indicate that the surface of the dust appeared more compacted after going through the ISV process. In addition, the highly contaminated dust that underwent ISV treatment saw a pronounced decrease in or elimination of wave crests. Another analysis applying X-ray diffraction (XRD) showed that the SiO2 crests disappeared in the processed dust, suggesting that the crystal structure was replaced with quasi-vitreous products after ISV treatment. In the event that pollutants were extant, they were usually characterized by smaller size, high stability, excellent weather resistance, an innocuous nature, and recyclability.
BACKGROUND Primary thumb carpometacarpal (CMC) osteoarthritis is one of the most common conditions encountered by hand surgeons. Of the vast number of operations that have been proposed, none have ...demonstrated results significantly superior to trapeziectomy alone. AIM The purpose of our study was to determine why surgeons opt for their technique in treating CMC arthritis. METHODS A cross-sectional survey of active members of the American Society for Surgery of the Hand was conducted to evaluate the reasons behind their preferred technique in the treatment of isolated thumb CMC arthritis. Surgeons were contacted by e-mail once and provided with a link to a de-identified survey consisting of 5 treatment questions and 5 demographic questions. RESULTS Of 950 responses were received. 40.5% of surgeons preferred trapeziectomy + ligament reconstruction tendon interposition (LRTI), followed by trapeziectomy + suspensionplasty (28.2%), suture button suspension (5.9 %), trapeziectomy alone (4.6%), prosthetic arthroplasty (3.2%), arthrodesis (1.1%), and other (6.6%). Proponents of trapeziectomy + LRTI cited familiarity (73.2%), exposure during fellowship (48.8%) and less proximal migration (60%) to be the main reasons affecting their decision. Surgeons who preferred trapeziectomy + suspensionplasty most reported simplicity (74.9%), fewer complications (45.3%), less proximal migration (43.8%), and avoidance of autogenous tissue harvest (42.7%). Advocates of suture button suspension cited avoidance of autogenous tissue harvest (80.4%), shorter immobilization (76.8%), and quicker recovery (73.2%) with their technique. Advocates of trapeziectomy alone cited simplicity (97.7%), fewer complications (86.4%), and avoidance of autogenous tissue harvest (59.1%). In their comments, 45% of surgeons choosing trapeziectomy alone cited evidence as an additional rationale. Advocates of prosthetic arthroplasty cited improved pinch strength (83.3%) and improved range of motion (63.3%), while those preferring arthrodesis cited better pinch strength (90%) and frequently in their comments, durability. Of the surgeons who preferred a technique other than LRTI, 41.8% reported they had tried LRTI in the past, citing complexity of the procedure, flexor carpi radialis harvest, and longer operative time as reasons for moving on. CONCLUSION Our study provides an update on current treatment trends and offers new insight into the reasons behind surgeons' decision making in the management of thumb carpometacarpal osteoarthritis. Despite strong Level 1 evidence supporting the use of trapeziectomy alone, our findings demonstrate that most surgeons continue to supplement trapeziectomy with other techniques such as LRTI or suspensionplasty. Several factors including familiarity, personal experience (Level 4 evidence), and comfort may be more influential than Level 1 evidence in determining the techniques in a surgeon's armamentarium. Further prospective studies are needed to determine the optimal technique for surgical management of Eaton stages II-IV CMC arthritis and how these studies will affect surgeons’ choice.
To tackle the exponentially increasing throughput of Next-Generation Sequencing (NGS), most of the existing short-read aligners can be configured to favor speed in trade of accuracy and sensitivity. ...SOAP3-dp, through leveraging the computational power of both CPU and GPU with optimized algorithms, delivers high speed and sensitivity simultaneously. Compared with widely adopted aligners including BWA, Bowtie2, SeqAlto, CUSHAW2, GEM and GPU-based aligners BarraCUDA and CUSHAW, SOAP3-dp was found to be two to tens of times faster, while maintaining the highest sensitivity and lowest false discovery rate (FDR) on Illumina reads with different lengths. Transcending its predecessor SOAP3, which does not allow gapped alignment, SOAP3-dp by default tolerates alignment similarity as low as 60%. Real data evaluation using human genome demonstrates SOAP3-dp's power to enable more authentic variants and longer Indels to be discovered. Fosmid sequencing shows a 9.1% FDR on newly discovered deletions. SOAP3-dp natively supports BAM file format and provides the same scoring scheme as BWA, which enables it to be integrated into existing analysis pipelines. SOAP3-dp has been deployed on Amazon-EC2, NIH-Biowulf and Tianhe-1A.
Abstract
Background
Primary care providers face challenges in recognizing and controlling hypertension in patients with chronic kidney disease (CKD). Clinical decision support (CDS) has the potential ...to aid clinicians in identifying patients who could benefit from medication changes. This study designed an alert to control hypertension in CKD patients using an iterative human-centered design process.
Methods
In this study, we present a human-centered design process employing multiple methods for gathering user requirements and feedback on design and usability. Initially, we conducted contextual inquiry sessions to gather user requirements for the CDS. This was followed by group design sessions and one-on-one formative think-aloud sessions to validate requirements, obtain feedback on the design and layout, uncover usability issues, and validate changes.
Results
This study included 20 participants. The contextual inquiry produced 10 user requirements which influenced the initial alert design. The group design sessions revealed issues related to several themes, including recommendations and clinical content that did not match providers' expectations and extraneous information on the alerts that did not provide value. Findings from the individual think-aloud sessions revealed that participants disagreed with some recommended clinical actions, requested additional information, and had concerns about the placement in their workflow. Following each step, iterative changes were made to the alert content and design.
Discussion
This study showed that participation from users throughout the design process can lead to a better understanding of user requirements and optimal design, even within the constraints of an EHR alerting system. While raising awareness of design needs, it also revealed concerns related to workflow, understandability, and relevance.
Conclusion
The human-centered design framework using multiple methods for CDS development informed the creation of an alert to assist in the treatment and recognition of hypertension in patients with CKD.
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