Antibiotic Class and Outcome in Post-stroke Infections: An Individual Participant Data Pooled Analysis of VISTA-Acute

Antibiotics; Post-stroke infections; Post-stroke pneumoniaAntibiòtics; Infeccions posteriors a un accident cerebrovascular; Pneumònia posterior a un accident cerebrovascularAntibióticos; Infecciones posteriores a un accidente cerebrovascular; Neumonía posterior a un accidente cerebrovascularIntroduction: Antibiotics used to treat post-stroke infections have differing antimicrobial and anti-inflammatory effects. Our aim was to investigate whether antibiotic class was associated with outcome after post-stroke infection. Methods: We analyzed pooled individual participant data from the Virtual International Stroke Trials Archive (VISTA)-Acute. Patients with ischemic stroke and with an infection treated with systemic antibiotic therapy during the first 2 weeks after stroke onset were eligible. Antibiotics were grouped into eight classes, according to antimicrobial mechanism and prevalence. The primary analysis investigated whether antibiotic class for any infection, or for pneumonia, was independently associated with a shift in 90 day modified Rankin Scale (mRS) using ordinal logistic regression. Results: 2,708 patients were eligible (median age [IQR] = 74 [65 to 80] y; 51% female; median [IQR] NIHSS score = 15 [11 to 19]). Pneumonia occurred in 35%. Treatment with macrolides (5% of any infections; 9% of pneumonias) was independently associated with more favorable mRS distribution for any infection [OR (95% CI) = 0.59 (0.42 to 0.83), p = 0.004] and for pneumonia [OR (95% CI) = 0.46 (0.29 to 0.73), p = 0.001]. Unfavorable mRS distribution was independently associated with treatment of any infection either with carbapenems, cephalosporins or monobactams [OR (95% CI) = 1.62 (1.33 to 1.97), p < 0.001], penicillin plus β-lactamase inhibitors [OR (95% CI) = 1.26 (1.03 to 1.54), p = 0.025] or with aminoglycosides [OR (95% CI) = 1.73 (1.22 to 2.46), p = 0.002]. Conclusion: This retrospective study has several limitations including effect modification and confounding by indication. Macrolides may have favorable immune-modulatory effects in stroke-associated infections. Prospective evaluation of the impact of antibiotic class on treatment of post-stroke infections is warranted.The Open Access Publication Fund of Charité—Universitätsmedizin Berlin and Professor Meisel as corresponding author will provide funding to cover the open access publication/article processing fe

Thirty Years After Michael E. Porter: What Do We Know About Business Exit?

Although a business exit is an important corporate change initiative, the buyer’s side seems to be more appealing to management researchers than the seller’s because acquisitions imply growth, i.e., success. Yet from an optimistic viewpoint, business exit can effectively create value for the selling company. In this paper we attempt to bring the relevance of the seller’s side back into our consciousness by asking: What do we know about business exit? We start our exploration with Porter (1976), focusing on literature that investigates the antecedents of, barriers to, and outcomes of business exit. We also include studies from related fields such as finance and economics.1 Through this research we determine three clusters of findings: factors promoting business exit, exit barriers, and exit outcomes. Overall, it is the intention of this paper to highlight the importance of business exit for research and practice. Knowing what we know about business exits and their high financial value we should bear in mind that exit need not mean failure but a new beginning for a corporation

Protocols for the field testing

The COMMON SENSE project has been designed and planned in order to meet the general and specific scientific and technical objectives mentioned in its Description of Work (page 77). In an overall strategy of the work plan, work packages (11) can be grouped into 3 key phases: (1) RD basis for cost-effective sensor development, (2) Sensor development, sensor web platform and integration, and (3) Field testing. In the first two phases WP1 and WP2 partners have provided a general understanding and integrated basis for a cost effective sensors development. Within the following WPs 4 to 8 the new sensors are created and integrated into different identified platforms. During the third phase 3, characterized by WP9, partners will deploy precompetitive prototypes at chosen platforms (e.g. research vessels, oil platforms, buoys and submerged moorings, ocean racing yachts, drifting buoys). Starting from August 2015 (month 22; task 9.2), these platforms will allow the partnership to test the adaptability and performance of the in-situ sensors and verify if the transmission of data is properly made, correcting deviations. In task 9.1 all stakeholders identified in WP2, and other relevant agents, have been contacted in order to close a coordinated agenda for the field testing phase for each of the platforms. Field testing procedures (WP2) and deployment specificities, defined during sensor development in WPs 4 to 8, are closely studied by all stakeholders involved in field testing activities in order for everyone to know their role, how to proceed and to provide themselves with the necessary material and equipment (e.g. transport of instruments). All this information will provide the basis for designing and coordinating field testing activities. Type and characteristics of the system (vessel or mooring, surface or deep, open sea or coastal area, duration, etc.), used for the field testing activities, are planned comprising the indicators included in the above-mentioned descriptors, taking into account that they must of interest for eutrophication, concentration of contaminants, marine litter and underwater noise. In order to obtain the necessary information, two tables were realized starting from the information acquired for D2.2 delivered in June 2014. One table was created for sensor developers and one for those partners that will test the sensors at sea. The six developers in COMMON SENSE have provided information on the seven sensors: CEFAS and IOPAN for underwater noise; IDRONAUT and LEITAT for microplastics; CSIC for an innovative piro and piezo resistive polymeric temperature and pressure and for heavy metal; DCU for the eutrophication sensor. This information is anyway incomplete because in most cases the novel sensors are still far to be ready and will be developed over the course of COMMON SENSE. So the sensors cannot be clearly designed yet and, consequently, technical characteristics cannot still be perfectly defined. This produces some lag in the acquired information and, consequently, in the planning of their testing on specific platforms that will be solved in the near future. In the table for Testers, partners have provided information on fifteen available platforms. Specific answers have been given on number and type of sensors on each platforms, their availability and technical characteristics, compatibility issues and, very important when new sensors are tested, comparative measurements to be implemented to verify them. Finally IOPAN has described two more platforms, a motorboat not listed in the DoW, but already introduced in D2.2, and their oceanographic buoy in the Gdansk Bay that was previously unavailable. The same availability now is present for the OBSEA Underwater observatory from CSIC, while their Aqualog undulating mooring is still not ready for use. In the following months, new information on sensors and platforms will be provided and the planning of testing activities will improve. Further updates of this report will be therefore necessary in order to individuate the most suitable platforms to test each kind of sensor. Objectives and rationale The objective of deliverable 9.1 is the definition of field testing procedures (WP2), the study of deployment specificities during sensor development work packages (from WP4 to WP8) and the preparation of protocols. This with the participation of all stakeholders involved in field testing activities in order for everyone to know their role, how to proceed and to provide themselves with the necessary material and equipment

Field testing, validation and optimization report

The COMMON SENSE project has been designed and planned in order to meet the general and specific scientific and technical objectives mentioned in its Description of Work (page 77). As the overall strategy, the 11 work packages (WPs) of the work plan were grouped into 3 key phases: (1) RD basis for cost-effective sensor development , (2) Sensor development, sensor web platform and integration, and (3) Field testing. In the first two phases, partners involved in WP1 and WP2 have provided a general understanding and integrated basis for a cost effective sensors development. Within the following WPs 4 to 8 the new sensors were created and integrated into different identified platforms. During the third phase of field testing (WP9), partners have deployed precompetitive prototypes at chosen platforms (e.g. research vessels, oil platforms, buoys and submerged moorings, ocean racing yachts, drifting buoys). Starting from August 2015 (month 22; task 9.2), these platforms have allowed the partnership to test the adaptability and performance of the in-situ sensors and verify if the transmission of data is properly made, correcting deviations. In task 9.1 all stakeholders identified in WP2 have been contacted in order to agree upon a coordinated agenda for the field testing phase for each of the platforms. Field testing procedures (WP2) and deployment specificities, defined during sensor development in WPs 4 to 8, have been closely studied by all stakeholders involved in field testing activities in order for everyone to know their role, how to proceed and to provide themselves with the necessary material and equipment (e.g. transport of instruments). All this information have provided the basis for designing and coordinating field testing activities. Subsequently, the available new sensors have been tested since August 2015 till mid-October of the current year (2016) as part of task 9.2, following the indications defined in D9.1, such as the intercomparison of the new sensors with commercial ones, when possible. The availability of new sensors was quite different in time starting with the first tests in September and October 2015 on noise, nutrient and heavy metals sensors and closing with pCO2 in late September 2016. Sensors are technically fully described in the deliverables of WPs 3 to 8 and are here just mentioned where necessary. For further details, please consider those reports. Objectives and rationale The protocols prepared in D9.1 have been verified during the field testing activities of the innovative sensors on platforms. These can be summarized into 3 categories: (1) Research vessels (regular cruises); (2) Fixed platforms; (3) Ocean racing yachts. An exhaustive analysis of the different data obtained during field testing activities has been carried on in order to set possible optimization actions for prototypes design and performances. The data from each platform have been analyzed to verify limits and optimal installations or possible improvements. Finally a set of possible optimization actions has been defined. Data and observations collected during the course of field testing have been used to iteratively optimize the design and performance of the precompetitive prototypes

New regulations regarding Postgraduate Medical Training in Spain: perception of the tutor's role in the Murcia Region

<p>Abstract</p> <p>Background</p> <p>Recently introduced regulatory changes have expanded the Tutor role to include their primary responsibility for Postgraduate Medical Training (PMT). However, accreditation and recognition of that role has been devolved to the autonomic regions. The opinions of the RT may be relevant to future decisions;</p> <p>Methods</p> <p>A comprehensive questionnaire, including demographic characteristics, academic and research achievement and personal views about their role, was sent to 201 RTs in the Murcia Region of Spain. The responses are described using median and interquartile ranges (IQR);</p> <p>Results</p> <p>There were 147 replies (response rate 73%), 69% male, mean age 45 ± 7 yrs. RTs perception of the residents' initial knowledge and commitment throughout the program was 5 (IQR 4-6) and 7 (IQR 5-8), respectively. As regards their impact on the PMT program, RTs considered that their own contribution was similar to that of senior residents. RTs perception of how their role was recognised was 5 (IQR 3-6). Only 16% did not encounter difficulties in accessing specific RT training programs. Regarding the RTs view of their various duties, supervision of patient care was accorded the greatest importance (64%) while the satisfactory completion of the PMT program and supervision of day-to-day activities were also considered important (61% and 59% respectively). The main RT requirements were: a greater professional recognition (97%), protected time (95%), specific RT training programs (95%) and financial recognition (86%);</p> <p>Conclusions</p> <p>This comprehensive study, reflecting the feelings of our RTs, provides a useful insight into the reality of their work and the findings ought to be taken into consideration in the imminent definitive regulatory document on PMT.</p

The Distinct Conformational Dynamics of K-Ras and H-Ras A59G

Ras proteins regulate signaling cascades crucial for cell proliferation and differentiation by switching between GTP- and GDP-bound conformations. Distinct Ras isoforms have unique physiological functions with individual isoforms associated with different cancers and developmental diseases. Given the small structural differences among isoforms and mutants, it is currently unclear how these functional differences and aberrant properties arise. Here we investigate whether the subtle differences among isoforms and mutants are associated with detectable dynamical differences. Extensive molecular dynamics simulations reveal that wild-type K-Ras and mutant H-Ras A59G are intrinsically more dynamic than wild-type H-Ras. The crucial switch 1 and switch 2 regions along with loop 3, helix 3, and loop 7 contribute to this enhanced flexibility. Removing the gamma-phosphate of the bound GTP from the structure of A59G led to a spontaneous GTP-to-GDP conformational transition in a 20-ns unbiased simulation. The switch 1 and 2 regions exhibit enhanced flexibility and correlated motion when compared to non-transitioning wild-type H-Ras over a similar timeframe. Correlated motions between loop 3 and helix 5 of wild-type H-Ras are absent in the mutant A59G reflecting the enhanced dynamics of the loop 3 region. Taken together with earlier findings, these results suggest the existence of a lower energetic barrier between GTP and GDP states of the mutant. Molecular dynamics simulations combined with principal component analysis of available Ras crystallographic structures can be used to discriminate ligand- and sequence-based dynamic perturbations with potential functional implications. Furthermore, the identification of specific conformations associated with distinct Ras isoforms and mutants provides useful information for efforts that attempt to selectively interfere with the aberrant functions of these species

Making Self-Regulation More than Merely Symbolic: The Critical Role of the Legal Environment

Using data from a sample of U.S. industrial facilities subject to the federal Clean Air Act from 1993 to 2003, this article theorizes and tests the conditions under which organizations’ symbolic commitments to self-regulate are particularly likely to result in improved compliance practices and outcomes. We argue that the legal environment, particularly as it is constructed by the enforcement activities of regulators, significantly influences the likelihood that organizations will effectively implement the self-regulatory commitments they symbolically adopt. We investigate how different enforcement tools can foster or undermine organizations’ normative motivations to self-regulate. We find that organizations are more likely to follow through on their commitments to self-regulate when they (and their competitors) are subject to heavy regulatory surveillance and when they adopt self-regulation in the absence of an explicit threat of sanctions. We also find that historically poor compliers are significantly less likely to follow through on their commitments to self-regulate, suggesting a substantial limitation on the use of self-regulation as a strategy for reforming struggling organizations. Taken together, these findings suggest that self-regulation can be a useful tool for leveraging the normative motivations of regulated organizations but that it cannot replace traditional deterrence-based enforcement