1,564 research outputs found
Internet technologies relevant to private investigators’ working practices
No full textMuch has been written and discussed especially in the various US media and in legislative organs, about how the Internet is used illegally (hacking, stalking for instance), but hardly if any research has been done as to how the investigative industry employs the new medium to its benefit. The author described in this thesis how private investigators (PIs) execute their profession these days using the facilities the Internet avail them in contrast to the time before the dawn of the Internet. This contrast is also investigated in an international context, an important part of the thesis, drawn from the author's 32 years of international business experience and that of PIs worldwide. The availability of the various online facilities in different countries are compared. To better understand the new medium, and its facilities a short outline of the Internet’s history, it’s set up in general and for the use of PIs in particular is supplied. PIs also face limitations in their daily work, limitations originating from online, legal, educational, financial and international causes. The new medium not only helps PIs in their investigative, but also in their office work. Finally PIs' wishes for new tools to facilitate their daily investigative work and their outlook as to where the new medium will head are also discussed
DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
No full textSingle Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be
associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose
polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p,0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03– 1.16), p = 2.761023) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03–1.21,
p = 4.861023). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/ 2 mutation carriers and should be more comprehensively studied
Hepatitis B-core antibody positive donors in Liver Trasplantation and their impact on graft survival:Evidence from the Liver Match cohort study
No full textBackground 82 Aims:The appropriate allocation of grafts from HBcAb positive donors in liver transplantation is crucial,yet a consensus is still lacking
A Systems Thinking Perspective on the Transportation and Regional Growth Study
No full textThis report integrates the findings of several individual reports from the Transportation and Regional Growth Study (TRGS) into a comprehensive "systems thinking perspective" on the Twin Cities' transportation and land use system. The document explores the findings and rationale in TRGS reports by principal investigators John Adams, Gary Barnes, Gary Davis, David Anderson, Gerard McCullough, Barry Ryan, Thomas F. Stinson, Lance Neckar, Barbara Lukermann, and Thomas Scott. The purpose of this report is to generate new insights that are valuable to policy makers and to surface the systemic assumptions underlying the research of the principal investigators. The results of the principal investigators' reports are summarized in three pages of nuggets, while the author of this document suggests several of his own key findings, principally the recommendation that all of the key variables in the Twin Cities land use and transportation system should be measured, monitored, and routinely communicated to the public and governmental policy makers. This integration report shows what those key variables are and presents a rich hypothesis on how they are causally related to each other.Ward, Edward. (2003). A Systems Thinking Perspective on the Transportation and Regional Growth Study. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/866
Real-world study in severe eosinophilic asthma patients refractory to anti-IL5 biological agents treated with benralizumab in Spain (ORBE study)
No full textPublisher Copyright: © 2021, The Author(s).Background: Benralizumab, a monoclonal antibody targeting the human interleukin-5 (IL-5) receptor (IL-5R), was used before marketing authorisation in Spain in a real world setting as part of an early-access programme (EAP) to treat patients with severe eosinophilic asthma with prior insufficient response or intolerance to anti-IL5 treatment (mepolizumab or reslizumab). The objective of this study is to describe the patient profile candidate for treatment and to assess benralizumab effectiveness. Methods: This is an observational, retrospective, multicentre study in severe eosinophilic asthma patients refractory to other biological agents targeting the IL-5 pathway. Baseline characteristics included closest data, from the previous 12 months, to benralizumab treatment onset (index date). Patients were followed until the last treatment dosage while EAP was active (March to December 2018). Effectiveness was evaluated versus baseline, in patients who received at least three doses, with asthma control test (ACT), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), annual severe exacerbation rate, oral corticosteroids treatment (OCS) and asthma-related healthcare resources utilization. Results: Twenty-seven patients treated with benralizumab were included in the analysis. Effectiveness was assessed in 19 patients. Both questionnaires showed clinically meaningful differences, i.e. ACT score ≥ 3 and MiniAQLQ score ≥ 0.5, compared with baseline [mean (SD), 3.3 (6.8) and 1.2 (1.9), respectively]. Patients treated with OCS decreased during follow-up from 88.9% (n = 24/27) at baseline to 78.9% (n = 15/19) and 31.6% (n = 6/19) had an OCS dose reduction ≥ 50%. The difference in annual severe exacerbation rate during follow-up showed a significant reduction vs. baseline (2.12 per patient-year, 95% CI 0.99–3.24, p = 0.002). The differences in annual rate of non-scheduled primary care and specialist visits during follow-up indicated a significant decrease [2.28 per patient-year (95% CI 1.55–3.01; p < 0.001) and 1.47 per patient-year (95% CI 0.65–2.30; p = 0.004), respectively], as well as the difference in annual rate of number of emergency department visits [1.18 per patient-year (95% CI 0.51–1.85; p = 0.007)]. Conclusions: These results suggest that severe eosinophilic asthma patients receiving benralizumab, presented clinically meaningful improvement in asthma control and asthma-related QoL as well as OCS dose reduction. Results also aim to significant reductions in annual severe exacerbation rates, non-scheduled primary care and specialist visits, and emergency department visits rates.Peer reviewe
Thrombolysis is associated with consistent functional improvement across baseline stroke severity: a comparison of outcomes in patients from the Virtual International Stroke Trials Archive (VISTA)
No full text<p><b>Background and Purpose:</b> Baseline stroke severity predicts outcomes among thrombolysed patients. The baseline National Institutes of Health Stroke Scale (NIHSS) thresholds are sometimes used to select patients for thrombolysis, clinical trial enrollment, or both. Using data lodged with Virtual International Stroke Trials Archive, we compared adjusted outcomes between thrombolysed and nonthrombolysed patients enrolled in neuroprotection trials (1998-2007) to assess the influence of various levels of baseline NIHSS.</p>
<p><b>Method:</b> We assessed the association of treatment with outcome, measured across the modified Rankin scale score distribution, in patients categorized by baseline NIHSS in increments of 4. We used an age and baseline NIHSS adjusted Cochran-Mantel-Haenszel test followed by proportional odds logistic regression analysis. We report the Cochran-Mantel-Haenszel P values and estimated odds ratios (OR) for improved modified Rankin scale score distribution with treatment for patients within each baseline NIHSS category.</p>
<p><b>Results:</b> Data were available for 5817 patients (1585 thrombolysed and 4232 nonthrombolysed). Baseline severity was greater among thrombolysed than nonthrombolysed (median baseline NIHSS, 14 vs 13; P<0.05). An association of treatment with outcome was seen independently and was of similar magnitude within each of the baseline NIHSS categories 5 to 8 (P=0.04; OR, 1.25; 95% confidence interval [CI], 1.0-1.6; N=278/934 thrombolysed/nonthrombolysed), 9 to 12 (P=0.01; OR, 1.3; 95% CI, 1.1-1.6; N=404/942), 13 to 16 (P<0.05; OR, 1.6; 95% CI, 1.3-2.1; N=342/814), 17 to 20 (P<0.05; OR, 1.7; 95% CI, 1.3-2.1; N=311/736), and 21 to 24 (P<0.05; OR, 1.6; 95% CI, 1.1-2.1; N=178/466). No association was observed within baseline NIHSS categories 1 to 4 (P=0.8; OR, 1.1; 95% CI, 0.3-4.4; N=8/161) or >= 25 (P=0.08; OR, 1.1; 95% CI, 0.7-1.9; N=64/179).</p>
<p><b>Conclusions:</b> In this nonrandomized comparison, outcomes after thrombolysis were significantly better than in untreated comparators across baseline NIHSS 5 to 24. The significant association was lost only at extremes of baseline NIHSS when sample sizes were small and confidence limits were wide.</p>
Supporting forensic investigators on exploring web forums through Interactive Topic Modeling
No full textForums on the Web have become a highly popular platform for malicious activities as recent technologies allow to preserve anonymity. Forensic investigators are more and more interested to use these forums on the so-called Dark Web as their source of intelligence. Exploring the forums one by one is too time-consuming and it requires much effort of the investigator to create an overview. Topic Modeling (TM) has shown to be able to give insights on discussions on forums, this way improving the exploration of this unknown data, as an alternative to a traditional search engine. Interactive Topic Modeling (ITM) moreover has been introduced as a technique to incorporate the domain knowledge of the user into the generated topic model. As the investigators have much domain knowledge, incorporating their knowledge into the topic models should increase the quality of the model and align it the goal of the investigator. In lab studies in related work, ITM has shown to outscore both TM and traditional search. In this thesis, we evaluate the effectiveness, efficiency and preference of using ITM in a more realistic setup with stakeholders (forensic investigators) in a domain of their expertise (the Dark Web) in a user study setup. For this, based on stakeholder interviews and earlier research, we designed and built an ITM framework to explore forums on the Dark Web. We found that TM was more effective than ITM for forensic investigators to complete their tasks. Furthermore, traditional search was found most efficient and preferred. It was observed that participants incorrectly interacted with the topic model. Additionally, we found that the difficulty of a task influenced the use of ITM versus search. Users were found to fall back on using traditional search to complete their task more often for tasks with a low or high difficulty. We state that as ITM is introduced as a promising technique in lab studies; more effort is needed in explaining its use to the end user.Electrical Engineering, Mathematics and Computer ScienceSoftware TechnologyWeb Information System
Tucatinib and trastuzumab emtansine for patients with previously treated HER2-positive locally advanced and metastatic breast cancer: primary analysis of the randomized phase III trial HER2CLIMB-02
No full textTrastuzumab emtansine (T-DM1) is a standard treatment option in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) locally advanced or metastatic breast cancer (LA/MBC). Here, we report the efficacy and safety of tucatinib in combination with T-DM1 compared with T-DM1 alone from the phase III HER2CLIMB-02 study (NCT03975647).
Eligible patients had HER2+ LA/MBC that had been previously treated with trastuzumab and a taxane in any setting; these included patients with brain metastases (BMs). Patients were randomly assigned 1:1 to receive T-DM1 (3.6 mg/kg intravenously every 21 days) combined with either tucatinib (300 mg orally twice daily) in the tucatinib arm or placebo (orally twice daily) in the control arm.
In total, 463 patients were randomly assigned. After a median follow-up duration of 24.4 months, the median progression-free survival (PFS) was 9.5 months in the tucatinib arm and 7.4 months in the control arm (hazard ratio [HR]=0.76; 95% CI, 0.61-0.95; P=0.0163). A PFS benefit was observed across all prespecified subgroups, including in patients with BMs. Interim overall survival analysis results were immature. The median OS was not reached in the tucatinib arm and was 38.0 months in the control arm (HR=1.23; 95% CI, 0.87-1.74). The incidences of treatment-emergent adverse events (TEAEs) associated with any treatment discontinuation and of grade ≥3 TEAEs were higher in the tucatinib arm than in the control arm (22.1% versus 11.6% and 68.8% versus 41.2%, respectively). The most common grade ≥3 TEAEs in the tucatinib arm were elevated alanine aminotransferase (16.5%) and aspartate aminotransferase levels (16.5%) (versus 2.6% for both in the control arm).
The addition of tucatinib to T-DM1 improved PFS in patients with previously treated HER2+ LA/MBC, including patients with BMs, and exhibited a manageable safety profile.
Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved
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