How do learning orientation and strategy yield innovativeness and superior firm performance?

This paper attempts to shed light on the role of learning orientations of firms and their adoption of Porter’s generic strategies on four dependent variables: Behavioral innovativeness, product innovativeness, technological innovativeness and, ultimately, firm performance. Hierarchical regressions were run with data from a random sample of 121 firms operating in Turkey. Findings indicate that internally-focused learning, market-focused learning and differentiation strategy have significant effects on the three innovativeness dimensions. When firm performance is included as the eventual outcome variable into the analysis, internally-focused learning, focus strategy and product innovativeness emerge as its main predictors. In fast-paced, highly unpredictable market environments, managers can make use of these findings to their benefit in terms of elevating their firms’ innovativeness and performance levels

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: A systematic review and recommendations for future practice

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Ball et al.; licensee BioMed Central Ltd.Background: Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment. Methods: A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures. Results: Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years. Conclusions: There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes

The influence of sea ice cover and Atlantic water advection on annual particle export north of Svalbard

The Arctic Ocean north of Svalbard has recently experienced large sea ice losses and the increasing prominence of Atlantic water (AW) advection. To investigate the impact of these ongoing changes on annual particle export, two moorings with sequential sediment traps were deployed in ice‐free and seasonally ice‐covered waters on the shelf north (NSv) and east (ESv) of Svalbard, collecting sinking particles nearly continuously from October 2017 to October 2018. Vertical export of particulate organic carbon (POC), total particulate matter (TPM), planktonic protists, chlorophyll a, and zooplankton fecal pellets were measured, and swimmers were quantified and identified. Combined with sensor data from the moorings, these time‐series measurements provided a first assessment of the factors influencing particle export in this region of the Arctic Ocean. Higher annual TPM and POC fluxes at the ice‐free NSv site were primarily driven by the advection of AW, higher grazing by large copepods, and a wind‐induced mixing event during winter. Higher diatom fluxes were observed during spring in the presence of sea ice at the ESv site. Along with sea ice cover, regional differences in AW advection and the seasonal presence of grazers played a prominent role in the biological carbon pump along the continental shelf off Svalbard

The IKKâ related kinase TBK1 activates mTORC1 directly in response to growth factors and innate immune agonists

The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogeneâ induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through siteâ specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGFâ receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i.e., TLR3; TLR4), revealing a stimulusâ selective role for TBK1 in mTORC1 regulation. By studying cultured macrophages and those isolated from genome edited mTOR S2159A knockâ in mice, we show that mTOR S2159 phosphorylation promotes mTORC1 signaling, IRF3 nuclear translocation, and IFNâ β production. These data demonstrate a direct mechanistic link between TBK1 and mTORC1 function as well as physiologic significance of the TBK1â mTORC1 axis in control of innate immune function. These data unveil TBK1 as a direct mTORC1 activator and suggest unanticipated roles for mTORC1 downstream of TBK1 in control of innate immunity, tumorigenesis, and disorders linked to chronic inflammation.SynopsisTBK1, an IKKâ related kinase that drives interferon production as well cancer cell proliferation and survival, phosphorylates mTOR to activate mTORC1 in response to EGF and innate immune agonists, suggesting unanticipated roles for mTORC1 downstream of TBK1 in control of innate immunity and tumorigenesis.TBK1 interacts with mTORC1 and phosphorylates mTOR on S2159 to increase its catalytic activity.Cells lacking TBK1 or expressing a mTOR S2159A allele exhibit reduced mTORC1 signaling in response to EGFâ receptor and TLR3/4 activation.Primary macrophages derived from genome edited mTOR S2159A mice exhibit reduced mTORC1 signaling in response to TLR3/4 activation.Primary macrophages treated with rapamycin as well as those derived from mTORS2159A mice produce reduced levels of IFNâ β due to impaired nuclear translocation of the transcription factor IRF3.Innate immune kinase TBK1â dependent activation of mTORC1 occurs in response to pathogen recognition and EGF receptor activation and drives interferon production, thus highlighting the role of mTOR for innate immunity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/1/embj201696164.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/2/embj201696164.reviewer_comments.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/3/embj201696164_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/4/embj201696164-sup-0001-EVFigs.pd

Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande

We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Crimean-Congo hemorrhagic fever: epidemiological trends and controversies in treatment

Crimean-Congo hemorrhagic fever (CCHF) virus has the widest geographic range of all tick-borne viruses and is endemic in more than 30 countries in Eurasia and Africa. Over the past decade, new foci have emerged or re-emerged in the Balkans and neighboring areas. Here we discuss the factors influencing CCHF incidence and focus on the main issue of the use of ribavirin for treating this infection. Given the dynamics of CCHF emergence in the past decade, development of new anti-viral drugs and a vaccine is urgently needed to treat and prevent this acute, life-threatening disease