Measuring distance through dense weighted networks: The case of hospital-associated pathogens

Hospital networks, formed by patients visiting multiple hospitals, affect the spread of hospital-associated infections, resulting in differences in risks for hospitals depending on their network position. These networks are increasingly used to inform strategies to prevent and control the spread of hospital-associated pathogens. However, many studies only consider patients that are received directly from the initial hospital, without considering the effect of indirect trajectories through the network. We determine the optimal way to measure the distance between hospitals within the network, by reconstructing the English hospital network based on shared patients in 2014–2015, and simulating the spread of a hospital-associated pathogen between hospitals, taking into consideration that each intermediate hospital conveys a delay in the further spread of the pathogen. While the risk of transferring a hospital-associated pathogen between directly neighbouring hospitals is a direct reflection of the number of shared patients, the distance between two hospitals far-away in the network is determined largely by the number of intermediate hospitals in the network. Because the network is dense, most long distance transmission chains in fact involve only few intermediate steps, spreading along the many weak links. The dense connectivity of hospital networks, together with a strong regional structure, causes hospital-associated pathogens to spread from the initial outbreak in a two-step process: first, the directly surrounding hospitals are affected through the strong connections, second all other hospitals receive introductions through the multitude of weaker links. Although the strong connections matter for local spread, weak links in the network can offer ideal routes for hospital-associated pathogens to travel further faster. This hold important implications for infection prevention and control efforts: if a local outbreak is not controlled in time, colonised patients will appear in other regions, irrespective of the distance to the initial outbreak, making import screening ever more difficult

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Development, implementation and pilot evaluation of a Web-based Virtual Patient Case Simulation environment – Web-SP

BACKGROUND: The Web-based Simulation of Patients (Web-SP) project was initiated in order to facilitate the use of realistic and interactive virtual patients (VP) in medicine and healthcare education. Web-SP focuses on moving beyond the technology savvy teachers, when integrating simulation-based education into health sciences curricula, by making the creation and use of virtual patients easier. The project strives to provide a common generic platform for design/creation, management, evaluation and sharing of web-based virtual patients. The aim of this study was to evaluate if it was possible to develop a web-based virtual patient case simulation environment where the entire case authoring process might be handled by teachers and which would be flexible enough to be used in different healthcare disciplines. RESULTS: The Web-SP system was constructed to support easy authoring, management and presentation of virtual patient cases. The case authoring environment was found to facilitate for teachers to create full-fledged patient cases without the assistance of computer specialists. Web-SP was successfully implemented at several universities by taking into account key factors such as cost, access, security, scalability and flexibility. Pilot evaluations in medical, dentistry and pharmacy courses shows that students regarded Web-SP as easy to use, engaging and to be of educational value. Cases adapted for all three disciplines were judged to be of significant educational value by the course leaders. CONCLUSION: The Web-SP system seems to fulfil the aim of providing a common generic platform for creation, management and evaluation of web-based virtual patient cases. The responses regarding the authoring environment indicated that the system might be user-friendly enough to appeal to a majority of the academic staff. In terms of implementation strengths, Web-SP seems to fulfil most needs from course directors and teachers from various educational institutions and disciplines. The system is currently in use or under implementation in several healthcare disciplines at more than ten universities worldwide. Future aims include structuring the exchange of cases between teachers and academic institutions by building a VP library function. We intend to follow up the positive results presented in this paper with other studies looking at the learning outcomes, critical thinking and patient management. Studying the potential of Web-SP as an assessment tool will also be performed. More information about Web-SP

A novel role for RIP1 kinase in mediating TNFα production

Receptor-interacting protein 1 (RIP1) is a Ser/Thr kinase with both kinase-dependent and kinase-independent roles in death receptor signaling. The kinase activity of RIP1 is required for necroptosis, a caspase-independent pathway of programmed cell death. In some cell types, the inhibition of caspases leads to autocrine production of TNFα, which then activates necroptosis. Here, we describe a novel role for RIP1 kinase in regulating TNFα production after caspase inhibition. Caspase inhibitors activate RIP1 kinase and another protein, EDD, to mediate JNK signaling, which stimulates Sp1-dependent transcription of TNFα. This pathway is independent of nuclear factor κB and also occurs after Smac mimetic/IAP antagonist treatment or the loss of TNF receptor-associated factor 2 (Traf2). These findings implicate cIAP1/2 and Traf2 as negative regulators of this RIP1 kinase-dependent TNFα production pathway and suggest a novel role for RIP1 kinase in mediating TNFα production under certain conditions

Jean-Baptiste Bélanger, hydraulic engineer, researcher and academic

Jean-Baptiste BÉLANGER (1790-1874) worked as a hydraulic engineer at the beginning of his career. He developed the backwater equation to calculate gradually-varied open channel flow properties for steady flow conditions. Later, as an academic at the leading French engineering schools (Ecole Centrale des Arts et Manufactures, Ecole des Ponts et Chaussées, and Ecole Polytechnique), he developed a new university curriculum in mechanics and several textbooks including a seminal text in hydraulic engineering. His influence on his contemporaries was considerable, and his name is written on the border of one of the four facades of the Eiffel Tower. BÉLANGER's leading role demonstrated the dynamism of practicing engineers at the time, and his contributions paved the way to many significant works in hydraulics

Psychosocial working conditions and the risk of depression and anxiety disorders in the Danish workforce

<p>Abstract</p> <p>Background</p> <p>To examine the risk of depressive and anxiety disorders according to psychosocial working conditions in a large population-based sample.</p> <p>Methods</p> <p>Job Exposure Matrix was applied to assess psychosocial working conditions in a population-based nested case-control study of 14,166 psychiatric patients, diagnosed with depressive or anxiety disorders during 1995–1998 selected from The Danish Psychiatric Central Research Register, compared with 58,060 controls drawn from Statistics Denmark's Integrated Database for Labour Market Research.</p> <p>Results</p> <p>Low job control was associated with an increased risk of anxiety disorders in men (IRR 1.40, 95% CI 1.24–1.58).</p> <p>In women an elevated risk of depression was related to high emotional demands (IRR 1.39, 95%CI 1.22–1.58) and to working with people (IRR 1.15, 95% CI 1.01–1.30). In both sexes high demands were associated with a decreased risk of anxiety disorders. There was a weak association between job strain and anxiety disorders in men (IRR 1.13, 95%, CI 1.02–1.25)</p> <p>Conclusion</p> <p>Psychosocial work exposures related to the risk of depressive and anxiety disorders differ as between the sexes. The pattern of risks is inconsistent. The results give rise to rethinking both study designs and possible causal links between work exposures and mental health.</p

Living well with dementia: a systematic review and correlational meta-analysis of factors associated with quality of life, well-being and life satisfaction in people with dementia - CORRIGENDUM

This is the final version. Available on open access from Cambridge University Press via the DOI in this recor

Wellbeing, mental health knowledge and caregiving experiences of siblings of people with psychosis, compared to their peers and parents: An exploratory study

Purpose The wellbeing and caregiving experiences of family carers supporting people with psychosis has garnered increasing interest. Evidence indicates that the burden of caregiving can adversely impact on parents’ wellbeing, few studies have investigated whether this is also the case for siblings, who often take on caregiving responsibilities. This exploratory study investigated the wellbeing, mental health knowledge, and appraisals of caregiving in siblings of individuals with psychosis. Method Using a cross-sectional design, 90 siblings completed three validated questionnaires: Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS), Mental Health Knowledge Schedule (MAKS), and Experience of Caregiving Inventory (ECI). Data obtained were compared to general population norms and parent-carers’ scores. Multi-variable regression analyses were conducted to examine relationships between questionnaire scores and demographic characteristics including age, sex, birth order, marital status, accommodation and educational level. Results Siblings, especially sisters, had significantly poorer mental wellbeing, compared to normative scores. Conversely, they had better mental health knowledge. Siblings and parent-carers had comparable high levels of negative appraisals of caregiving experiences, but siblings reported more satisfaction with personal experiences and relationships. Education level was a significant predictor for better mental health knowledge; there were no other relationships between siblings’ demographic factors and outcomes. Conclusion Study findings suggest that siblings have overlapping as well as distinct needs, compared to parent-carers. Further research is required to better understand siblings’ experiences so as to inform development of targeted interventions that enhance wellbeing and caregiving capacity

NGTS-13b: A hot 4.8 Jupiter-mass planet transiting a subgiant star

We report the discovery of the massive hot Jupiter NGTS-13b by the Next Generation Transit Survey (NGTS). The V = 12.7 host star is likely in the subgiant evolutionary phase with log g$_{*}$ = 4.04 $\pm$ 0.05, T$_{eff}$ = 5819 $\pm$ 73 K, M$_{*}$ = 1.30$^{+0.11}_{-0.18}$ M$_{\odot}$, and R$_{*}$ = 1.79 $\pm$ 0.06 R$_{\odot}$. NGTS detected a transiting planet with a period of P = 4.12 days around the star, which was later validated with the Transiting Exoplanet Survey Satellite (TESS; TIC 454069765). We confirm the planet using radial velocities from the CORALIE spectrograph. Using NGTS and TESS full-frame image photometry combined with CORALIE radial velocities we determine NGTS-13b to have a radius of R$_{P}$ = 1.142 $\pm$ 0.046 R$_{Jup}$, mass of M$_{P}$ = 4.84 $\pm$ 0.44 M$_{Jup}$ and eccentricity e = 0.086 $\pm$ 0.034. Some previous studies suggest that $\sim$4 M$_{Jup}$ may be a border between two separate formation scenarios (e.g., core accretion and disk instability) and that massive giant planets share similar formation mechanisms as lower-mass brown dwarfs. NGTS-13b is just above 4 M$_{Jup}$ making it an important addition to the statistical sample needed to understand the differences between various classes of substellar companions. The high metallicity, [Fe/H] = 0.25 $\pm$ 0.17, of NGTS-13 does not support previous suggestions that massive giants are found preferentially around lower metallicity host stars, but NGTS-13b does support findings that more massive and evolved hosts may have a higher occurrence of close-in massive planets than lower-mass unevolved stars