Early administration of oral oseltamivir increases the benefits of influenza treatment

Our objective was to evaluate the benefit of early treatment of influenza illness using oral oseltamivir. This open-label, multicentre international study investigated the relationship between the interval from illness onset to first dose (time-to-treatment) and illness duration in the intent-to-treat infected population using accelerated failure time (AFT) modelling. A total of 1426 patients (12-70 years) presenting within 48 h of the onset of influenza symptoms were treated with oseltamivir 75 mg twice a day for 5 days during the 1999-2000 influenza season; 958 (67%) had laboratory-confirmed influenza virus infection. Earlier intervention was associated with shorter illness duration (P < 0.0001). Initiation of therapy within the first 12 h after fever onset reduced the total median illness duration by 74.6 h (3.1 days; 41%) more than intervention at 48 h. Intermediate interventions reduced the illness proportionately compared with 48 h. In addition, the earlier administration of oseltamivir further reduced the duration of fever, severity of symptoms and the times to return to baseline activity and health scores. Oseltamivir was well tolerated. The most common adverse events were nausea and vomiting, which were transient and generally occurred only with first dosing. When oseltamivir was taken with food, the tolerability was enhanced. The overall discontinuation rate was low (1.8%). In conclusion, the IMPACT study demonstrated that earlier initiation of oral oseltamivir therapy increased its therapeutic effects, which were seen at every time point of intervention and were progressive. Thus, early presentation, diagnosis and treatment of patients with influenza maximized the benefits of oseltamivir therap

Interweaving temporal qualitative comparative analysis with necessary conditions analysis: an empirical application in the european monitoring systems context

There are very few empirical applications of Temporal Qualitative Comparative Analysis (TQCA). By interweaving TQCA with the necessary condition analysis stepwise procedure, I endeavour to compare instances of cheating and non-cheating practices within the European Social Fund context and unravel the multiple sequences of events leading to the outcome of interest. Implications for theory and practice are discussed by shedding a new light on the non-trivially necessary causes for both cheating and non-cheating activities

AEDGE: Atomic Experiment for Dark Matter and Gravity Exploration in Space

We propose in this White Paper a concept for a space experiment using cold atoms to search for ultra-light dark matter, and to detect gravitational waves in the frequency range between the most sensitive ranges of LISA and the terrestrial LIGO/Virgo/KAGRA/INDIGO experiments. This interdisciplinary experiment, called Atomic Experiment for Dark Matter and Gravity Exploration (AEDGE), will also complement other planned searches for dark matter, and exploit synergies with other gravitational wave detectors. We give examples of the extended range of sensitivity to ultra-light dark matter offered by AEDGE, and how its gravitational-wave measurements could explore the assembly of super-massive black holes, first-order phase transitions in the early universe and cosmic strings. AEDGE will be based upon technologies now being developed for terrestrial experiments using cold atoms, and will benefit from the space experience obtained with, e.g., LISA and cold atom experiments in microgravity. This paper is based on a submission (v1) in response to the Call for White Papers for the Voyage 2050 long-term plan in the ESA Science Programme. ESA limited the number of White Paper authors to 30. However, in this version (v2) we have welcomed as supporting authors participants in the Workshop on Atomic Experiments for Dark Matter and Gravity Exploration held at CERN: ({\tt https://indico.cern.ch/event/830432/}), as well as other interested scientists, and have incorporated additional material

Leveraging Big Data Analytics to Improve Quality of Care in Healthcare Organizations:A Configurational Perspective

Big data analytics (BDA) is beneficial for organizations, yet implementing BDA to leverage profitability is fundamental challenge confronting practitioners. Although prior research has explored the impact that BDA has on business growth, there is a lack of research that explains the full complexity of BDA implementations. Examination of how and under what conditions BDA achieves organizational performance from a holistic perspective is absent from the existing literature. Extending the theoretical perspective from the traditional views (e.g. resource-based theory) to configuration theory, the authors have developed a conceptual model of BDA success that aims to investigate how BDA capabilities interact with complementary organizational resources and organizational capabilities in multiple configuration solutions leading to higher quality of care in healthcare organizations. To test this model, the authors use fuzzy-set qualitative comparative analysis to analyse multi-source data acquired from a survey and databases maintained by the Centres for Medicare & Medicaid Services. The findings suggest that BDA, when given alone, is not sufficient in achieving the outcome, but is a synergy effect in which BDA capabilities and analytical personnel's skills together with organizational resources and capabilities as supportive role can improve average excess readmission rates and patient satisfaction in healthcare organizations

Magnetic Monopole Search with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions Interpreted in Photon-Fusion and Drell-Yan Production

MoEDAL is designed to identify new physics in the form of stable or pseudostable highly ionizing particles produced in high-energy Large Hadron Collider (LHC) collisions. Here we update our previous search for magnetic monopoles in Run 2 using the full trapping detector with almost four times more material and almost twice more integrated luminosity. For the first time at the LHC, the data were interpreted in terms of photon-fusion monopole direct production in addition to the Drell-Yan-like mechanism. The MoEDAL trapping detector, consisting of 794 kg of aluminum samples installed in the forward and lateral regions, was exposed to 4.0 fb(-1) of 13 TeV proton-proton collisions at the LHCb interaction point and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to or above the Dirac charge are excluded in all samples. Monopole spins 0, 1/2, and 1 are considered and both velocity-independent and-dependent couplings are assumed. This search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.Peer reviewe

What Every Business Student Needs to Know About Information Systems

Whether Information Systems should or should not be part of the core business school curriculum is a recurring discussion in many universities. In this article, a task force of 40 prominent information systems scholars address the issue. They conclude that information systems is absolutely an essential body of knowledge for business school students to acquire as well as a key element of the business school\u27s long-run strategic positioning within the university. Originally prepared in response to draft accreditation guidelines prepared by AACSB International, the article includes a compilation of the concepts that the authors believe to be the core information systems knowledge that all business school students should be familiar with

Evolutionary Conservation of the Functional Modularity of Primate and Murine LINE-1 Elements

LINE-1 (L1) retroelements emerged in mammalian genomes over 80 million years ago with a few dominant subfamilies amplifying over discrete time periods that led to distinct human and mouse L1 lineages. We evaluated the functional conservation of L1 sequences by comparing retrotransposition rates of chimeric human-rodent L1 constructs to their parental L1 counterparts. Although amino acid conservation varies from ∼35% to 63% for the L1 ORF1p and ORF2p, most human and mouse L1 sequences can be functionally exchanged. Replacing either ORF1 or ORF2 to create chimeric human-mouse L1 elements did not adversely affect retrotransposition. The mouse ORF2p retains retrotransposition-competency to support both Alu and L1 mobilization when any of the domain sequences we evaluated were substituted with human counterparts. However, the substitution of portions of the mouse cys-domain into the human ORF2p reduces both L1 retrotransposition and Alu trans-mobilization by 200–1000 fold. The observed loss of ORF2p function is independent of the endonuclease or reverse transcriptase activities of ORF2p and RNA interaction required for reverse transcription. In addition, the loss of function is physically separate from the cysteine-rich motif sequence previously shown to be required for RNP formation. Our data suggest an additional role of the less characterized carboxy-terminus of the L1 ORF2 protein by demonstrating that this domain, in addition to mediating RNP interaction(s), provides an independent and required function for the retroelement amplification process. Our experiments show a functional modularity of most of the LINE sequences. However, divergent evolution of interactions within L1 has led to non-reciprocal incompatibilities between human and mouse ORF2 cys-domain sequences

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially