629 research outputs found

    Secondary user relations in emerging mobile computing environments

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    Mobile technologies are enabling access to information in diverse environ.ments, and are exposing a wider group of individuals to said technology. Therefore, this paper proposes that a wider view of user relations than is usually considered in information systems research is required. Specifically, we examine the potential effects of emerging mobile technologies on end-­‐user relations with a focus on the ‘secondary user’, those who are not intended to interact directly with the technology but are intended consumers of the technology’s output. For illustration, we draw on a study of a U.K. regional Fire and Rescue Service and deconstruct mobile technology use at Fire Service incidents. Our findings provide insights, which suggest that, because of the nature of mobile technologies and their context of use, secondary user relations in such emerging mobile environments are important and need further exploration

    Real-time detection of TDP1 activity using a fluorophore-quencher coupled DNA-biosensor

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    Real-time detection of enzyme activities may present the easiest and most reliable way of obtaining quantitative analyses in biological samples. We present a new DNA-biosensor capable of detecting the activity of the potential anticancer drug target tyrosyl-DNA phosphodiesterase 1 (TDP1) in a very simple, high throughput, and real-time format. The biosensor is specific for Tdp1 even in complex biological samples, such as human cell extracts, and may consequently find future use in fundamental studies as well as a cancer predictive tool allowing fast analyses of diagnostic cell samples such as biopsies. TDP1 removes covalent 3'DNA adducts in DNA single-strand break repair. This enzymatic activity forms the basis of the design of the TDP1-biosensor, which consists of a short hairpin-forming oligonucleotide having a 5'fluorophore and a 3'quencher brought in close proximity by the secondary structure of the biosensor. The specific action of TDP1 removes the quencher, thereby enabling optical detection of the fluorophore. Since the enzymatic action of TDP1 is the only "signal amplification" the increase in fluorescence may easily be followed in real-time and allows quantitative analyses of TDP1 activity in pure enzyme fractions as well as in crude cell extracts. In the present study we demonstrate the specificity of the biosensor, its ability to quantitatively detect up- or down-regulated TDP1 activity, and that it may be used for measuring and for analyzing the mechanism of TDP1 inhibition

    Study protocol for OptimalTTF-2:enhancing Tumor Treating Fields with skull remodeling surgery for first recurrence glioblastoma: a phase 2, multi-center, randomized, prospective, interventional trial

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    Abstract Background OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional study aiming to test skull remodeling surgery in combination with Tumor Treating Fields therapy (TTFields) and best physicians choice medical oncological therapy for first recurrence in glioblastoma patients. OptimalTTF-2 is a phase 2 trial initiated in November 2020. Skull remodeling surgery consists of five burrholes, each 15 mm in diameter, directly over the tumor resection cavity. Preclinical research indicates that this procedure enhances the effect of Tumor Treating Fields considerably. We recently concluded a phase 1 safety/feasibility trial that indicated improved overall survival and no additional toxicity. This phase 2 trial aims to validate the efficacy of the proposed intervention. Methods The trial is designed as a comparative, 1:1 randomized, minimax two-stage phase 2 with an expected 70 patients to a maximum sample size of 84 patients. After 12-months follow-up of the first 52 patients, an interim futility analysis will be performed. The two trial arms will consist of either a) TTFields therapy combined with best physicians choice oncological treatment (control arm) or b) skull remodeling surgery, TTFields therapy and best practice oncology (interventional arm). Major eligibility criteria include age ≥ 18 years, 1st recurrence of supratentorial glioblastoma, Karnofsky performance score ≥ 70, focal tumor, and lack of significant co-morbidity. Study design aims to detect a 20% increase in overall survival after 12 months (OS12), assuming OS12 = 40% in the control group and OS12 = 60% in the intervention group. Secondary endpoints include hazard rate ratio of overall survival and progression-free survival, objective tumor response rate, quality of life, KPS, steroid dose, and toxicity. Toxicity, objective tumor response rate, and QoL will be assessed every 3rd month. Endpoint data will be collected at the end of the trial, including the occurrence of suspected unexpected serious adverse reactions (SUSARs), unacceptable serious adverse events (SAEs), withdrawal of consent, or loss-to-follow-up. Discussion New treatment modalities are highly needed for first recurrence glioblastoma. Our proposed treatment modality of skull remodeling surgery, Tumor Treating Fields, and best practice medical oncological therapy may increase overall survival significantly. Trial registration ClinicalTrials.gov Identifier: NCT0422399 , registered 13. January 2020

    Wandering behaviour prevents inter and intra oceanic speciation in a coastal pelagic fish

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    Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0.4%) are compatible with intra-specific divergence, showing evidence of both ancient and contemporary admixture between the Pacific and Atlantic populations, enhanced by high asymmetrical migration from the Pacific to the Atlantic. The estimated divergence between Atlantic and Pacific anchovies (0.67 [0.53-0.80] Ma) matches a severe drop of sea temperature during the Gunz glacial stage of the Pleistocene. Our results support an alternative evolutionary scenario for the OWA, suggesting a coastal migration along south Asia, Middle East and eastern Africa continental platforms, followed by the colonization of the Atlantic via the Cape of the Good Hope.Portuguese Foundation for Science & Technology (FCT) [SFRH/BD/36600/2007]; FCT [UID/MAR/04292/2013, SFRH/BPD/65830/2009]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

    Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease

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    BACKGROUND: Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma. OBJECTIVE: Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels. METHODS: This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-β (Aβ) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models. RESULTS: No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aβ42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOEɛ4 carriers. CONCLUSION: CSF iron levels are elevated with cerebral microbleeds in APOEɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients

    Any difference? Use of a CAM provider among cancer patients, coronary heart disease (CHD) patients and individuals with no cancer/CHD

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    <p>Abstract</p> <p>Background</p> <p>Although use of complementary and alternative medicine (CAM) among cancer patients has been described previously, prevalence of use has not commonly been compared to other disease groups in a true population sample where CAM use or cancer is not the main focus. The aims of the present study are to (1) examine how CAM use in cancer patients differs from people with a previous CHD diagnosis and people with no cancer or CHD diagnosis in an unselected general population and (2), investigate the use of a CAM provider among individuals with a previous cancer diagnosis.</p> <p>Methods</p> <p>A total of 8040 men and women aged 29 to 87 in the city of Tromsø, Norway filled in a questionnaire developed specifically for the Tromsø V study with questions on life style and health issues. Visits to a CAM provider within the last 12 months and information on cancer, heart attack and angina pectoris (heart cramp) were among the questions. 1449 respondents were excluded from the analyses.</p> <p>Results</p> <p>Among the 6591 analysed respondents 331 had a prior cancer diagnosis, of whom 7.9% reported to have seen a CAM provider within the last 12 months. This did not differ significantly from neither the CHD group (6.4%, p = 0.402) nor the no cancer/CHD group (9.5%, p = 0.325).</p> <p>Conclusion</p> <p>According to this study, the proportion of cancer patients seeing a CAM provider was not statistically significantly different from patients with CHD or individuals without cancer or CHD.</p

    Understanding sources of sea lice for salmon farms in Chile

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    The decline of fisheries over recent decades and a growing human population has coincided with an increase in aquaculture production. As farmed fish densities increase, so have their rates of infectious diseases, as predicted by the theory of density-dependent disease transmission. One of the pathogen that has increased with the growth of salmon farming is sea lice. Effective management of this pathogen requires an understanding of the spatial scale of transmission. We used a two-part multi-scale model to account for the zero-inflated data observed in weekly sea lice abundance levels on rainbow trout and Atlantic salmon farms in Chile, and to assess internal (farm) and external (regional) sources of sea lice infection. We observed that the level of juvenile sea lice was higher on farms that were closer to processing plants with fish holding facilities. Further, evidence for sea lice exposure from the surrounding area was supported by a strong positive correlation between the level of juvenile sea lice on a farm and the number of gravid females on neighboring farms within 30. km two weeks prior. The relationship between external sources of sea lice from neighboring farms and juvenile sea lice on a farm was one of the strongest detected in our multivariable model. Our findings suggest that the management of sea lice should be coordinated between farms and should include all farms and processing plants with holding facilities within a relatively large geographic area. Understanding the contribution of pathogens on a farm from different sources is an important step in developing effective control strategies

    Tool for predicting Caligus rogercresseyi abundance on salt water salmon farms in Chile

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    Caligus rogercresseyi is a host-dependent parasite that affects rainbow trout and Atlantic salmon in Chile. Numbers of sea lice on fish increase over time at relatively predictable rates when the environment is conducive to the parasite's survival and fish are not undergoing treatment. We developed a tool for the salmon industry in Chile that predicts the abundance of adult sea lice over time on farms that are relatively isolated. We used data on sea louse abundance collected through the SalmonChile INTESAL sea lice monitoring program to create series of weekly lice counts between lice treatment events on isolated farms. We defined isolated farms as those with no known neighbors within a 10 km seaway distance and no more than two neighbors within a 20 km seaway distance. We defined the time between sea lice treatments as starting the week immediately post treatment and ending the week before a subsequent treatment. Our final dataset of isolated farms consisted of 65 series from 32 farms, between 2009 and 2015. Given an observed abundance at time t = 0, we built a model that predicted 8 consecutive weekly sea louse abundance levels, based on the preceding week's lice prediction. We calibrated the parameters in our model on a randomly selected subset of training data, choosing the parameter combinations that minimized the absolute difference between the predicted and observed sea louse abundance values. We validated the parameters on the remaining, unseen, subset of data. We encoded our model and made it available as a Web-accessible applet for producers. We determined a threshold, based on the upper 97.5% predictive interval, as a guideline for producers using the tool. We hypothesize that if farms exceed this threshold, especially if the sea lice levels are above this threshold 2 and 4 weeks into the model predictions, the sea louse population on the farm is likely influenced by sources other than lice within the farm

    Molecular tracing of viral diseases in aquaculture

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    Molecular Tracing of Viral Diseases in Aquaculture = Traçage Moléculaire des Maladies Virales en Aquaculture : Colloque, Montpellier (FRA), 2015/01/27-29International audienc
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