115 research outputs found
Linux kernel compaction through cold code swapping
There is a growing trend to use general-purpose operating systems like Linux in embedded systems. Previous research focused on using compaction and specialization techniques to adapt a general-purpose OS to the memory-constrained environment, presented by most, embedded systems. However, there is still room for improvement: it has been shown that even after application of the aforementioned techniques more than 50% of the kernel code remains unexecuted under normal system operation. We introduce a new technique that reduces the Linux kernel code memory footprint, through on-demand code loading of infrequently executed code, for systems that support virtual memory. In this paper, we describe our general approach, and we study code placement algorithms to minimize the performance impact of the code loading. A code, size reduction of 68% is achieved, with a 2.2% execution speedup of the system-mode execution time, for a case study based on the MediaBench II benchmark suite
Scoping review and characteristics of publicly available checklists for assessing clinical trial feasibility
BACKGROUND: Whether there is sufficient capacity and capability for the successful conduct and delivery of a clinical trial should be assessed by several stakeholders according to transparent and evidence-based criteria during trial planning. For this openly shared, user-tested, and validated tools are necessary. Therefore, we systematically examined the public availability and content of checklists which assess the study-level feasibility in the planning phase of clinical trials. METHODS: In our scoping review we systematically searched Medline, EMBASE, and Google (last search, June 2021). We included all publicly available checklists or tools that assessed study level feasibility of clinical trials, examined their content, and checked whether they were user-tested or validated in any form. Data was analysed and synthesised using conventional content analysis. RESULTS: A total of 10 publicly available checklists from five countries were identified. The checklists included 48 distinct items that were classified according to the following seven different domains of clinical trial feasibility: regulation, review and oversight; participant recruitment; space, material and equipment; financial resources; trial team resources; trial management; and pilot or feasibility studies. None of the available checklists appeared to be user-tested or validated. CONCLUSIONS: Although a number of publicly available checklists to assess the feasibility of clinical trials exist, their reliability and usefulness remain unclear. Openly shared, user-tested, and validated feasibility assessment tools for a better planning of clinical trials are lacking
First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)—a systematic review and individual patient data meta-analysis
Evidence for prognosis and treatment of elderly patient with primary central nervous system is limited. High-dose methotrexate should be applied whenever possible, especially combination with oral alkylating agents is a promising approach. Further combinations with other intravenous drugs do not seem to improve outcome. More prospective trials designed for elderly PCNSL patients are warrante
Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.
BACKGROUND: Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees.
METHODS AND FINDINGS: We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements.
CONCLUSIONS: Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol
Prevalence, characteristics, and publication of discontinued randomized trials.
IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear.
OBJECTIVES: To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication.
DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013.
MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys.
RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001).
CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials
Dpr Acts as a Molecular Switch, Inhibiting Wnt Signaling when Unphosphorylated, but Promoting Wnt Signaling when Phosphorylated by Casein Kinase Iδ/ε
The Wnt pathway is a key regulator of development and tumorigenesis. Dpr (Dact/Frodo) influences Wnt signaling in part through the interaction of its PDZ-B domain with Dsh's PDZ domain. Studies have shown that XDpr1a and its close relative, Frodo, are involved in multiple steps of the Wnt pathway in either inhibitory or activating roles. We found that XDpr1a is phosphorylated by casein kinase Iδ/ε (CKIδ/ε), an activator of Wnt signaling, in the presence of XDsh. Abrogating XDpr1a's ability to bind XDsh through mutation of XDpr1a's PDZ-B domain blocks CK1δ/ε's phosphorylation of XDpr1a. Conversely, XDsh possessing a mutation in its PDZ domain that is unable to bind XDpr1a does not promote XDpr1a phosphorylation. Phosphorylation of XDpr1a and XDsh by CKIδ/ε decreases their interaction. Moreover, the phosphorylation of XDpr1a by CKIδ/ε not only abrogates XDpr1a's promotion of β-catenin degradation but blocks β-catenin degradation. Our data suggest that XDpr1a phosphorylation by CKIδ/ε is dependent on the interaction of XDpr1a's PDZ-B domain with XDsh's PDZ domain, and that the phosphorylation state of XDpr1a determines whether it inhibits or activates Wnt signaling
The Influence of Information Sources on Inter- and Intra-Firm Diffusion: Evidence from UK Farming
We study the effect of different information sources on diffusion between and within companies. Our model of economically optimising farmers replicates results from dual process persuasion theory, and predicts that inter-firm diffusion will be primarily affected by reliable, easily accessible information while intra-firm diffusion will be influenced by technical information. The results are tested on UK farming data. Consistent with our model, information from agents, suppliers, farmers, and agricultural magazines influences inter-firm adoption, from buyers influences intra-firm adoption, and from crop consultants, academics, government, and an industry body influences both
Psychological Aspects of Bariatric Surgery as a Treatment for Obesity
PURPOSE OF REVIEW: Little is known about the psychological effects on life after bariatric surgery despite the high prevalence of psychological disorders in candidates seeking this procedure. Our review discusses the literature around the psychological impact of bariatric surgery, exploring whether the procedure addresses underlying psychological conditions that can lead to morbid obesity and the effect on eating behaviour postoperatively.RECENT FINDINGS: Findings show that despite undisputed significant weight loss and improvements in comorbidities, current literature suggests some persisting disorder in psychological outcomes like depression and body image for patients at longer term follow-up, compared to control groups. Lack of postoperative psychological monitoring and theoretical mapping limits our understanding of reasons behind these findings. Reframing bariatric approaches to morbid obesity to incorporate psychological experience postoperatively would facilitate understanding of psychological aspects of bariatric surgery and how this surgical treatment maps onto the disease trajectory of obesity
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