Improving Reachability and Navigability in Recommender Systems

In this paper, we investigate recommender systems from a network perspective and investigate recommendation networks, where nodes are items (e.g., movies) and edges are constructed from top-N recommendations (e.g., related movies). In particular, we focus on evaluating the reachability and navigability of recommendation networks and investigate the following questions: (i) How well do recommendation networks support navigation and exploratory search? (ii) What is the influence of parameters, in particular different recommendation algorithms and the number of recommendations shown, on reachability and navigability? and (iii) How can reachability and navigability be improved in these networks? We tackle these questions by first evaluating the reachability of recommendation networks by investigating their structural properties. Second, we evaluate navigability by simulating three different models of information seeking scenarios. We find that with standard algorithms, recommender systems are not well suited to navigation and exploration and propose methods to modify recommendations to improve this. Our work extends from one-click-based evaluations of recommender systems towards multi-click analysis (i.e., sequences of dependent clicks) and presents a general, comprehensive approach to evaluating navigability of arbitrary recommendation networks

Elevated Systemic IL-10 Levels Indicate Immunodepression Leading to Nosocomial Infections after Aneurysmal Subarachnoid Hemorrhage (SAH) in Patients

Background: Aneurysmal subarachnoid hemorrhage (SAH) is a highly complex disease with very high mortality and morbidity. About one-third of SAH patients suffer from systemic infections, predominantly pneumonia, that can contribute to excess mortality after SAH. Immunodepression is probably the most important mechanism leading to infections. Interleukin-10 (IL-10) is a master regulator of immunodepression, but it is still not clear if systemic IL-10 levels contribute to immunodepression, occurrence of infections and clinical outcome after SAH. Methods: This explorative study included 76 patients with SAH admitted to our neurointensive care unit within 24 h after ictus. A group of 24 patients without any known intracranial pathology were included as controls. Peripheral venous blood was withdrawn on day 1 and day 7 after SAH. Serum was isolated by centrifugation and stored at −80 °C until analysis. Serum IL-10 levels were determined by enzyme-linked immunoassay (ELISA). Patient characteristics, post-SAH complications and clinical outcome at discharge were retrieved from patients’ record files. Results: Serum IL-10 levels were significantly higher on day 1 and day 7 in SAH patients compared to controls. Serum IL-10 levels were significantly higher on day 7 in patients who developed any kind of infection, cerebral vasospasm (CVS) or chronic hydrocephalus. Serum IL-10 levels were significantly higher in SAH patients discharged with poor clinical outcome (modified Rankin Scale (mRS) 3–6 or Glasgow Outcome Scale (GOS) 1–3). Conclusion: Serum IL-10 might be an additional useful parameter along with other biomarkers to predict post-SAH infections

Protocol of a phase II trial

Background Current studies on salvage radiotherapy (sRT) investigate timing, dose-escalation and anti-hormonal treatment (ADT) for recurrent prostate cancer. These approaches could either be limited by radiation-related susceptibility of the anastomosis or by suspected side-effects of long-term ADT. A phase II protocol was developed to investigate the benefit and tolerability of regional hyperthermia with moderately dose-escalated radiotherapy. Methods The study hypothesis is that radio-thermotherapy is a safe and feasible salvage treatment modality. The primary endpoint is safety measured by frequency of grade 3+ genitourinary (GU) and gastrointestinal (GI) adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Feasibility is defined by number of hyperthermia treatments (n ≥ 7) and feasibility of radiotherapy according to protocol. Target volume delineation is performed according to the EORTC guidelines. Radiation treatment is administered with single doses of 2 Gy 5×/week to a total dose of 70 Gy. Regional hyperthermia is given 2×/week to a total of 10 treatments. Results European centres participate in the phase II trial using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The initiating centres were participants of the SAKK 09/10 study, where the same patient criteria and target volume definition (mandatory successful performed dummy run) were applied insuring a high standardisation of the study procedures. Conclusions The introduced phase II study implements highly precise image-guided radiotherapy and regional hyperthermia. If the phase II study is found to be safe and feasible, a multicenter phase III study is planned to test whether the addition of regional hyperthermia to dose-intensified sRT improves biochemical control

A mutational hot spot in keratin 10 (KRT 10) in patients with epidermolytic hyperkeratosis

Epidermolytic hyperkeratosis (EHK), (bullous congenital ichthyosiform erythroderma), is an autosomal dominant human skin disorder. Recently, we and others have described mutations in keratins 1 and 10 (K1 and K10) in patients with this disease. Structure-function models predict that these mutations would impair normal filament assembly and function. We have extended our earlier studies to include 8 more incidences of EHK. In half of these families, we were unable to locate a mutation within the rod domains of either K1 or K10. However, polymorphic restriction site and sequence analysis of the other families revealed a mutational hot spot within the 1A alpha-helical segment of K10. These involve Arginine to Histidine, Arginine to Cysteine and Arginine to Leucine substitutions at residue 10 of the rod domain. Interestingly, mutations in the corresponding Arginine residue in keratin K14 have been identified in patients with epidermolysis bullosa simplex. The large number of mutations found at this position in both keratins K10 and K14 suggests that other epithelia cell disorders will be discovered that are caused by the corresponding mutation in related type I keratin gene

The Trade-Off between Phosphorus Recycling and Health Protection during the BSE Crisis in Switzerland. A “Disposal Dilemma”

Phosphorus (P) is an essential, finite resource whose geological, economic, and geopolitical accessibility may become critical in the future. Because P losses from agriculture, sewage and waste have serious environmental impacts such as eutrophication, it would be desirable to close P cycles. However, there may arise dilemmas due to trade-offs with other issues. For instance, recycling of animal bones – containing relatively high amounts of P – was prohibited in Switzerland after the BSE crisis (1989 to 2000) due to perceived health risks. Our analysis indicates that the great- est potentials for closing the P cycle in Switzerland are to reduce P losses in agriculture and to increase P recovery from sewage and waste. Whereas in agriculture significant improvements have been made, the disposal dilemma of animal bones led to diminishing amounts of P being recycled from waste. Based on their risk perception, the involved stakeholders prioritized preventing potential harm to (human) health over maximizing P recycling

The Impact of Exercise Training and Supplemental Oxygen on Peripheral Muscles in COPD: A Randomized Controlled Trial

Objective: Exercise training is a cornerstone of the treatment of COPD while the related inter-individual heterogeneity in skeletal muscle dysfunction and adaptations are not yet fully understood. We set out to investigate the effects of exercise training and supplemental oxygen on functional and structural peripheral muscle adaptation. Methods: In this prospective, randomized, controlled, double-blind study, 28 patients with non-hypoxemic COPD (FEV1 45.92 ± 9.06%) performed six-weeks of combined endurance and strength training, three times a week while breathing either supplemental oxygen or medical air. The impact on exercise capacity, muscle strength and quadriceps femoris muscle cross-sectional area (CSA), was assessed by maximal cardiopulmonary exercise testing, ten-repetition maximum strength test of knee extension, and magnetic resonance imaging, respectively. Results: After exercise training, patients demonstrated a significant increase of functional capacity, aerobic capacity, exercise tolerance, quadriceps muscle strength and bilateral CSA. Supplemental oxygen affected significantly the training impact on peak work rate when compared to medical air (+0.20 ± 0.03 vs +0.12 ± 0.03 Watt/kg, p = 0.047); a significant increase in CSA (+3.9 ± 1.3 cm2, p = 0.013) was only observed in the training group using oxygen. Supplemental oxygen and exercise induced peripheral desaturation were identified as significant opposing determinants of muscle gain during this exercise training intervention, which led to different adaptations of CSA between the respective subgroups. Conclusions: The heterogenous functional and structural muscle adaptations seem determined by supplemental oxygen and exercise induced hypoxia. Indeed, supplemental oxygen may facilitate muscular training adaptations, particularly in limb muscle dysfunction, thereby contributing to the enhanced training responses on maximal aerobic and functional capacity

Introducing the FAIR Principles for research software

Research software is a fundamental and vital part of research, yet significant challenges to discoverability, productivity, quality, reproducibility, and sustainability exist. Improving the practice of scholarship is a common goal of the open science, open source, and FAIR (Findable, Accessible, Interoperable and Reusable) communities and research software is now being understood as a type of digital object to which FAIR should be applied. This emergence reflects a maturation of the research community to better understand the crucial role of FAIR research software in maximising research value. The FAIR for Research Software (FAIR4RS) Working Group has adapted the FAIR Guiding Principles to create the FAIR Principles for Research Software (FAIR4RS Principles). The contents and context of the FAIR4RS Principles are summarised here to provide the basis for discussion of their adoption. Examples of implementation by organisations are provided to share information on how to maximise the value of research outputs, and to encourage others to amplify the importance and impact of this work

Regulation of E-cadherin and Β-catenin by Ca 2+ in colon carcinoma is dependent on calcium-sensing receptor expression and function

An siRNA directed against the extracellular calcium-sensing receptor (CaSR) was used to down-regulate this protein in CBS colon carcinoma cells. In additional studies, we utilized a variant of the parental CBS line that demonstrates CaSR expression but does not upregulate this protein in response to extracellular Ca 2+ . In neither the siRNA-transfected cells nor the Ca 2+ -nonresponsive variant cells did inclusion of Ca 2+ in the culture medium inhibit proliferation or induce morphological alterations. Extracellular Ca 2+ also failed to induce E-cadherin production or a shift in Β-catenin from the cytoplasm to the cell membrane. In mock-transfected cells and in a Ca 2+ -responsive variant line derived from the same parental CBS cells, Ca 2+ treatment resulted in growth-reduction. This was accompanied by increased E-cadherin production and a shift in Β-catenin distribution from the cytoplasm to the cell membrane. Additionally, down-regulation of c-myc and cyclin D1 expression was observed in mock-transfected cells and in the Ca 2+ -responsive variant line (along with reduced T cell factor transcriptional activation). Neither c-myc nor cyclin D1 was significantly down-regulated in the siRNA-transfected cells or in the Ca 2+ -nonresponsive variant cells upon Ca 2+ stimulation. In histological sections of human colon carcinoma CaSR was significantly reduced as compared to the level in normal colonic crypt epithelial cells. Where CaSR expression was high, strong surface staining for E-cadherin and Β-catenin was observed. Where CaSR expression was reduced, Β-catenin surface expression was likewise reduced. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56113/1/22858_ftp.pd

Quantitative, Multi-institutional Evaluation of MR Thermometry Accuracy for Deep-Pelvic MR-Hyperthermia Systems Operating in Multi-vendor MR-systems Using a New Anthropomorphic Phantom

Clinical outcome of hyperthermia depends on the achieved target temperature, therefore target conformal heating is essential. Currently, invasive temperature probe measurements are the gold standard for temperature monitoring, however, they only provide limited sparse data. In contrast, magnetic resonance thermometry (MRT) provides unique capabilities to non-invasively measure the 3D-temperature. This study investigates MRT accuracy for MR-hyperthermia hybrid systems located at five European institutions while heating a centric or eccentric target in anthropomorphic phantoms with pelvic and spine structures. Scatter plots, root mean square error (RMSE) and Bland–Altman analysis were used to quantify accuracy of MRT compared to high resistance thermistor probe measurements. For all institutions, a linear relation between MRT and thermistor probes measurements was found with R2 (mean ± standard deviation) of 0.97 ± 0.03 and 0.97 ± 0.02, respectively for centric and eccentric heating targets. The RMSE was found to be 0.52 ± 0.31 °C and 0.30 ± 0.20 °C, respectively. The Bland-Altman evaluation showed a mean difference of 0.46 ± 0.20 °C and 0.13 ± 0.08 °C, respectively. This first multi-institutional evaluation of MR-hyperthermia hybrid systems indicates comparable device performance and good agreement between MRT and thermistor probes measurements. This forms the basis to standardize treatments in multi-institution studies of MR-guided hyperthermia and to elucidate thermal dose-effect relations

The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis

Purpose: We aimed to assess the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis. Methods: An international expert panel determined diagnoses and clinical management in patients with suspected large vessel vasculitis, with and without the results of 18F-FDG PET, respectively. The accuracy of the clinical diagnosis and the resulting clinical management with and without the 18F-FDG PET results were compared using logistic regression models. Results: The analysis included 30 patients referred to a tertiary care centre with large vessel vasculitis and 31 controls. 18F-FDG PET had an overall sensitivity of 73.3% [95% confidence interval (CI) 54.1-87.7%], a specificity of 83.9% (95% CI 66.3-94.5%), a positive predictive value of 81.5% (95% CI 61.9-93.7%) and a negative predictive value of 76.5% (95% CI 58.8-89.3%). The diagnostic accuracy of 18F-FDG PET was higher in patients not receiving immunosuppressive drugs (93.3 vs 64.5%, p = 0.006). Taken in context with other available diagnostic modalities, the addition of 18F-FDG PET increased the clinical diagnostic accuracy from 54.1 to 70.5% (p = 0.04). The addition of 18F-FDG PET increased the number of indicated biopsies from 22 of 61 patients (36.1%) to 25 of 61 patients (41.0%) and changed the treatment recommendation in 8 of 30 patients (26.7%) not receiving immunosuppressive medication and in 7 of 31 patients (22.6%) receiving immunosuppressive medication. Conclusion: 18F-FDG PET is a sensitive and specific imaging tool for large vessel vasculitis, especially when performed in patients not receiving immunosuppressive drugs. It increases the overall diagnostic accuracy and has an impact on the clinical management in a significant proportion of patient