bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward an optimal degree of openness in IT innovation projects
Authors: Bürger Olga , Moser Florian 
Published: September 2017

In spite of substantial interest in open innovation (OI), both research and practice lack methods that support companies in managing their IT innovation projects (ITIPs) relative to OI. We contribute to the closure of this gap by providing an approach for anex antefinancial evaluation of OI application, which involves developing a theoretical model that determines the optimal degree of openness in ITIPs. Based on our model, we examine relevant causal relationships by analyzing the influence of a company's ability to manage OI and the probability of success in OI application on the theoretical optimum. We find that the optimal openness level is linked with the company's ability to manage OI, which can incorporate organizational, cultural, and technological maturity. To increase the value contribution of OI, companies should focus on a steady improvement in managing OI. The results provide both an indicator for practical decision‐making and a starting point for future research.
Sustained sympathetic activity in altitude acclimatizing lowlanders and high‐altitude natives
Authors: Lundby C. , Calbet J. , van Hall G. , Saltin B. , Sander M. 
Published: September 2017

Combined results from different independent studies suggest that acclimatization to high altitude induces a slowly developing sympathetic activation, even at levels of hypoxia that cause no acute chemoreflex‐mediated sympathoexcitation. We here provide direct neurophysiological evidence for this phenomenon. In eight Danish lowlanders, we quantified mean arterial blood pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA), twice at sea level (normoxia and with acute hypoxic exposure to 12.6% O2) and twice at high altitude (after 10 and 50 days of exposure to 4100 m). Measurements were also obtained in eight Bolivian highlanders on one occasion at high altitude. Acute hypoxic exposure caused no increase in MSNA (15 ± 2 vs 16 ± 2 bursts per min, respectively, and also MAP and HR remained stable). In contrast, from sea level to 10 and 50 days in high‐altitude increases were observed in MAP: 72 ± 2 vs 78 ± 2 and 75 ± 2 mm Hg; HR: 54 ± 3 vs 67 ± 3 and 65 ± 3 beats per min; MSNA: 15 ± 2 vs 42 ± 5 and 42 ± 5 bursts per min, all P < .05. Bolivian subjects had high levels of MSNA: 34 ± 4 bursts per min. The simultaneous increase in MAP, HR, and MSNA suggests high altitude‐induced sympathetic activity, which is sustained in well‐acclimatized lowlanders. The high MSNA levels in the Bolivian highlanders suggest lifelong sympathetic activation at high altitude.
Constrained displacement boundary condition in embedment testing of dowel‐type fasteners in LVL
Authors: Schweigler Michael , Bader Thomas K. , Vessby Johan , Eberhardsteiner Josef 
Published: September 2017

AbstractThe influence of the loading orientation with respect to the grain direction of wood and the influence of the lateral dowel displacement boundary condition on the embedment behaviour of steel dowels in laminated veneer lumber (with parallel‐laminated veneers) are investigated in this study. For limit states of the lateral boundary condition, the load‐displacement behaviour was experimentally studied by means of full‐hole embedment tests on screw‐reinforced laminated veneer lumber, for two dowel diameters and up to large dowel displacements. A novel biaxial test set‐up is proposed for embedment tests with constrained lateral dowel displacement boundary condition, in order to quantify laterally evoked reaction forces. Corresponding forces were found to change orientation with increasing dowel displacement and amounted to about 20% and 40% of the vertical reaction force for dowel displacements of 5 mm and twice the dowel diameter, respectively. The influence of the lateral displacement boundary condition was highlighted by comparison of the test data with a previously established data set for unconstrained embedment testing. Constrained loading showed a stiffer response and higher nominal embedment stresses, as well as a more pronounced displacement hardening, compared to unconstrained loading.
Vitamin D deficiency accelerates ageing and age‐related diseases: a novel hypothesis
Authors: Berridge Michael J. 
Published: September 2017

AbstractAgeing can occur at different rates, but what controls this variable rate is unknown. Here I have developed a hypothesis that vitamin D may act to control the rate of ageing. The basis of this hypothesis emerged from studyng the various cellular processes that control ageing. These processes such as autophagy, mitochondrial dysfunction, inflammation, oxidative stress, epigenetic changes, DNA disorders and alterations in Ca2+ and reactive oxygen species (ROS) signalling are all known to be regulated by vitamin D. The activity of these processes will be enhanced in individuals that are deficient in vitamin D. Not only will this increase the rate of ageing, but it will also increase the probability of developing age‐related diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and cardiovascular disease. In individual with normal vitamin D levels, these ageing‐related processes will occur at lower rates resulting in a reduced rate of ageing and enhanced protection against these age‐related diseases.
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Effect of Hepatic Impairment on the Pharmacokinetics of Grazoprevir, a Hepatitis C Virus Protease Inhibitor
Authors: Caro Luzelena , Wenning Larissa , Guo Zifang , Fraser Iain P. , Fandozzi Christine , Talaty Jennifer , Panebianco Deborah , Ho Maureen , Uemura Naoto , Reitmann Christina , Angus Peter , Gane Edward , Marbury Thomas , Smith William B. , Iwamoto Marian , Butterton Joan R. , Yeh Wendy W. 
Published: September 2017

ABSTRACT

Grazoprevir (GZR) plus elbasvir is an approved treatment for chronic infection with hepatitis C virus (HCV) genotype 1 or 4. HCV infection complications include liver cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The objective of this study was to evaluate the pharmacokinetics and safety of multiple-dose GZR (200, 100, or 50 mg) in non-HCV participants with mild, moderate, or severe hepatic impairment (HI), respectively, and in healthy matched controls (protocol MK-5172_p013; Merck & Co., Inc., Kenilworth, NJ). Participants with mild, moderate, or severe HI and controls (aged 18 to 65 years) matched for race, age, sex, and body mass index were enrolled in a 3-part, open-label, sequential-panel pharmacokinetic study. Participants received oral doses of GZR 200 mg (two 100-mg tablets), 100 mg (one 100-mg tablet), or 50 mg (two 25-mg tablets) once daily for 10 days. A total of 50 participants were enrolled: 8 with mild HI, 9 with moderate HI, 8 with severe HI, and a corresponding number of healthy matched controls for each hepatic cohort. Participants with HI demonstrated higher GZR exposure than healthy matched controls and showed an increase in exposure with increasing HI severity. The steady-state GZR AUC
0–24
(area under the concentration-time curve from 0 to 24 h) for participants with mild, moderate, or severe HI was ≈2-, ≈5-, or ≈12-fold higher, respectively, than that for healthy matched controls. GZR was generally well tolerated in participants with HI. No dose adjustment is required for GZR in people with HCV with mild HI. GZR is contraindicated for those with moderate or severe HI (Child-Pugh class B or C), since they may have significantly increased GZR exposures that may lead to an increased risk of transaminase elevation.
Pharmacokinetics-Pharmacodynamics of Tazobactam in Combination with Cefepime in an
In Vitro
Infection Model
Authors: VanScoy Brian D. , Tenero David , Turner Simon , Livermore David M. , McCauley Jennifer , Conde Haley , Bhavnani Sujata M. , Rubino Christopher M. , Ambrose Paul G. 
Published: September 2017

ABSTRACT

We previously demonstrated that for tazobactam administered in combination with ceftolozane, the pharmacokinetic-pharmacodynamic (PK-PD) index that best described tazobactam efficacy was the percentage of the dosing interval that tazobactam concentrations were above a threshold (%
T
>threshold). Using data from studies of
Enterobacteriaceae
producing extended-spectrum β-lactamases (ESBLs), a relationship between tazobactam %
T
>threshold and reduction in log
10
CFU/ml from baseline, for which the tazobactam threshold concentration was the product of the isolate's ceftolozane-tazobactam MIC value and 0.5, was identified. However, since the kinetics of cephalosporin hydrolysis vary among ESBLs and compounds, it is likely that the translational relationship used to derive the tazobactam threshold concentration varies among enzymes and compounds. Using a one-compartment
in vitro
infection model, the PK-PD of tazobactam administered in combination with cefepime was characterized, and a translational relationship across ESBL-producing
Enterobacteriaceae
was developed. Four clinical isolates, two
Escherichia coli
and two
Klebsiella pneumoniae
isolates, known to produce CTX-M-15 β-lactamase enzymes and displaying cefepime MIC values of 2 to 4 mg/liter in the presence of 4 mg/liter tazobactam, were evaluated. Tazobactam threshold concentrations from 0.0625× to 1× the tazobactam-potentiated cefepime MIC value were considered. The threshold that best described the relationship between tazobactam %
T
>threshold and change in log
10
CFU/ml from the baseline at 24 h was the product of 0.125 and the cefepime-tazobactam MIC (
R
2
= 0.813). The magnitudes of %
T
>threshold associated with net bacterial stasis and a 1-log
10
CFU/ml reduction from baseline at 24 h were 21.9% and 52.8%, respectively. These data will be useful in supporting the identification of tazobactam dosing regimens in combination with cefepime for evaluation in future clinical studies.
Killing of Pseudomonas aeruginosa by Chicken Cathelicidin-2 Is Immunogenically Silent, Preventing Lung Inflammation
In Vivo
Authors: Coorens Maarten , Banaschewski Brandon J. H. , Baer Brandon J. , Yamashita Cory , van Dijk Albert , Haagsman Henk P. , Veldhuizen Ruud A. W. , Veldhuizen Edwin J. A. 
Published: September 2017

ABSTRACT

The development of antibiotic resistance by
Pseudomonas aeruginosa
is a major concern in the treatment of bacterial pneumonia. In the search for novel anti-infective therapies, the chicken-derived peptide cathelicidin-2 (CATH-2) has emerged as a potential candidate, with strong broad-spectrum antimicrobial activity and the ability to limit inflammation by inhibiting Toll-like receptor 2 (TLR2) and TLR4 activation. However, as it is unknown how CATH-2 affects inflammation
in vivo
, we investigated how CATH-2-mediated killing of
P. aeruginosa
affects lung inflammation in a murine model. First, murine macrophages were used to determine whether CATH-2-mediated killing of
P. aeruginosa
reduced proinflammatory cytokine production
in vitro
. Next, a murine lung model was used to analyze how CATH-2-mediated killing of
P. aeruginosa
affects neutrophil and macrophage recruitment as well as cytokine/chemokine production in the lung. Our results show that CATH-2 kills
P. aeruginosa
in an immunogenically silent manner both
in vitro
and
in vivo
. Treatment with CATH-2-killed
P. aeruginosa
showed reduced neutrophil recruitment to the lung as well as inhibition of cytokine and chemokine production, compared to treatment with heat- or gentamicin-killed bacteria. Together, these results show the potential for CATH-2 as a dual-activity antibiotic in bacterial pneumonia, which can both kill
P. aeruginosa
and prevent excessive inflammation.
A Small Periplasmic Protein with a Hydrophobic C-Terminal Residue Enhances DegP Proteolysis as a Suicide Activator
Authors: Kim Sungjae , Song Inseok , Eom Gaeul , Kim Seokhee 
Published: September 2017

ABSTRACT

DegP is a highly conserved protease that performs regulated proteolysis to selectively remove misfolded proteins in the periplasm of
Escherichia coli
. Binding of misfolded proteins is known to be the main mechanism of DegP activation, but it is unknown whether any native proteins can alter DegP activity. Here, we show that a small periplasmic protein, YjfN, which is highly upregulated by the Cpx envelope stress response, functions as a “suicide activator” for DegP and promotes efficient degradation of misfolded proteins. YjfN readily binds to and is degraded by DegP, for which a hydrophobic C-terminal residue and transient unfolding of YjfN are critical. YjfN also activates DegP in
trans
while it is being degraded and accelerates degradation of a denatured outer membrane protein, OmpA, that is not easily recognized by DegP. Although YjfN also prevents OmpA aggregation, the
trans
-activation effect is mainly responsible for efficient OmpA degradation. Overexpression of YjfN enhances the viability of cells in misfolded protein stress that is induced by the presence of a less-active variant of DegP at high temperature. Collectively, we suggest that YjfN can enhance DegP proteolysis for relieving envelope stresses that may generate toxic misfolded proteins.

IMPORTANCE
Proper degradation of toxic misfolded proteins is essential for bacterial survival. This function is mainly performed by a highly conserved protease, DegP, in the periplasm of
Escherichia coli
. It is known that binding of misfolded proteins is the main mechanism for activating the DegP protease. Here, we find that a small periplasmic protein, YjfN, can be a substrate and an activator of DegP. It is the first example of a native protein showing an ability to directly alter DegP activity. The YjfN-mediated
trans
activation of DegP promotes efficient degradation of misfolded proteins. Our results suggest that YjfN is a novel “suicide activator” for DegP that enhances DegP proteolysis under misfolded protein stress.
An unexpected complication following uterine artery embolisation
Authors: Peters Sarah , Wise Michelle , Buckley Brendan 
Published: September 2017

A 35-year-old nulliparous woman underwent uterine artery embolisation (UAE) for heavy menstrual bleeding and anaemia due to fibroids, refractive to medical and surgical treatment.Bilateral UAE was performed after cephazolin prophylaxis and analgesia. Postoperatively, pain and abdominal bloating were prominent. Symptoms were initially treated as postembolisation syndrome, and analgesia was escalated. By the third day, pain was worsening and the woman developed marked tachypnoea and tachycardia, with raised inflammatory markers and lactate. An abdominal X-ray and CT showed dilated colon. A colonoscopy demonstrated severe mucosal ulceration down to the muscular layer.A subtotal colectomy and end ileostomy formation was performed with intraoperative findings of toxic megacolon with near perforation. The cause of the toxic megacolon, in the absence of previous bowel pathology, was attributed to pseudomembranous colitis as a consequence of single dose prophylactic antibiotic.
Overview of the uptake and implementation of non-medical prescribing in Wales: a national survey
Authors: Courtenay Molly , Khanfer Riyad , Harries-Huntly Gail , Deslandes Rhain , Gillespie David , Hodson Karen , Morris Gary , Pritchard Anthony , Williams Elizabeth 
Published: September 2017

ObjectivesTo identify (1) the non-medical healthcare professionals in Wales qualified to prescribe medicines (including job title, employer, where the prescribing qualification is used, care setting and service provided); (2) the mode of prescribing used by these healthcare professionals, the frequency with which medicines are prescribed and the different ways in which the prescribing qualification is used; and (3) the safety and clinical governance systems within which these healthcare professionals practise.DesignNational questionnaire survey.SettingAll three National Health Service (NHS) Trusts and seven Health Boards (HB) in Wales.ParticipantsNon-medical prescribers.Results379 (63%) participants responded to the survey. Most of these prescribers (41.1%) were specialist nurses who work in a variety of healthcare settings (primarily in secondary care) within each HB/NHS Trust, and regularly use independent prescribing to prescribe for a broad range of conditions. Nearly a quarter of the sample (22%) reported that prior to undertaking the prescribing programme, they had completed master’s level specialist training and 65.5% had 5 years qualified experience. Over half (55.8%) reported that there were plans to increase non-medical prescriber numbers within the team in which they worked. Only 7.1% reported they did not prescribe and the median number of items prescribed per week was between 21 and 30. Nearly all (87.8%) of the sample reported that they perceived prescribing to have ensured better use of their skills and 91.5% indicated that they believed it had improved the quality of care they were able to provide.ConclusionNon-medical prescribing has been implemented across the whole of Wales; however, its uptake within HBs and NHS Trusts has been inconsistent, and it has not been considered across all services, particularly those in primary care. Opportunities therefore exist to share learning across organisations.
Risks associated with managing asthma without a preventer: urgent healthcare, poor asthma control and over-the-counter reliever use in a cross-sectional population survey
Authors: Reddel Helen K , Ampon Rosario D , Sawyer Susan M , Peters Matthew J 
Published: September 2017

ObjectivesOveruse of asthma relievers, particularly without anti-inflammatory preventers, increases asthma risks. This study aimed to identify how many reliever-only users have urgent healthcare, explore their attitudes and beliefs about asthma and its treatment, and investigate whether purchasing over-the-counter relievers was associated with worse asthma outcomes than by prescription.Design and settingCross-sectional population-based Internet survey in Australia.ParticipantsOf 2686 participants ≥16 years with current asthma randomly drawn from a web-based panel, 1038 (50.7% male) used only reliever medication.Main outcome measuresUrgent asthma-related healthcare; Asthma Control Test (ACT); patient attitudes about asthma and medications; reliever purchase (with/without prescription).ResultsOf 1038 reliever-only participants, 23.3% had required urgent healthcare for asthma in the previous year, and only 36.0% had a non-urgent asthma review. Those needing urgent healthcare were more likely than those without such events to be male (56.5% vs 49.0%, p=0.003) and current smokers (29.4% vs 23.3%, p=0.009). Only 30.6% had well-controlled asthma (ACT ≥20) compared with 71.0% of those with no urgent healthcare (p<0.0001), and 20.8% used relievers regularly to prevent asthma symptoms (vs 5.5% of those without urgent healthcare). Those with urgent healthcare were more frustrated by their asthma and less happy with how they managed it, and they were less confident about their ability to manage worsening asthma, but just as likely as those without urgent healthcare to manage worsening asthma themselves rather than visit a doctor. Reliever-only users purchasing over-the-counter relievers were no more likely than those purchasing relievers by prescription to have uncontrolled asthma (35.9% vs 40.6%, p=0.23) but were less likely to have had a non-urgent asthma review.ConclusionsOne-quarter of the reliever-only population had needed urgent asthma healthcare in the previous year, demonstrating the importance of identifying such patients. Their attitudes and beliefs suggest opportunities for targeting this population in the community.
The importance of maternal diet quality during pregnancy on cognitive and behavioural outcomes in children: a systematic review and meta-analysis
Authors: Borge Tiril Cecilie , Aase Heidi , Brantsæter Anne Lise , Biele Guido 
Published: September 2017

ObjectivesThis systematic review and meta-analysis provides a quantitative summary of the literature exploring the relationship between maternal diet quality during pregnancy and child cognitive and affective outcomes. We investigate whether there are indications for robust associations and aim to identify methodological strengths and challenges of the current research to provide suggestions of improvement for future research.Design and participantsRelevant studies were identified through a systematic literature search in relevant databases. All studies investigating maternal diet quality during pregnancy in relation to child cognitive or affective functioning in children of elementary school age or younger were assessed for inclusion.Results18 relevant studies, comprising 63 861 participants were identified. The results indicated a small positive association between better maternal diet quality during pregnancy and child functioning. We observed publication bias and significant heterogeneity between studies, where type of diet classification, publication year and outcome domain together accounted for about 30% of this heterogeneity. Trim and fill analysis substantiated the presence of publication bias for studies in the affective domain and showed an adjusted effect size of Hedge’s g=0.088 (p=0.0018) (unadjusted g=0.093 (p=0.03)). We observed no publication bias in the cognitive domain, where results indicated a slightly larger effect size (g=0.14 (p<0.0001)) compared with that of the affective domain. The overall summary effect size was g=0.075 (p<0.0001) adjusted for publication bias (unadjusted g=0.112 (p=0.0001)). Child diet was not systematically controlled for in the majority of the studies.ConclusionThe results indicated that a better maternal diet quality during pregnancy has a small positive association with child neurodevelopment, with more reliable results seen for cognitive development. These results warrant further research on the association between maternal diet quality during pregnancy and cognitive and affective aspects of child neurodevelopment, whereby it is crucial that future studies account for child diet in the analysis.
Birth outcomes of immigrant women married to native men in the Republic of Korea: a population register-based study
Authors: Song In Gyu , Kim Min Sun , Shin Seung Han , Kim Ee-Kyung , Kim Han-suk , Choi Seulggie , Kwon Soonman , Park Sang Min 
Published: September 2017

ObjectivesThe Republic of Korea (Korea) has experienced a steady increase in the number of births from immigrant women over the last 20 years. However, little is known about the birth outcomes of immigrant women in Korea. This study compared Korean birth data from immigrant and native women who married native men, and explored the factors that affected birth outcomes among immigrant women.DesignObservational cross-sectional study.SettingNationwide registry-based study in Korea.ParticipantsA total of 70 258 records from immigrant women and 1700 976 records from native women were examined using the National Birth Registration Database, from 2010 to 2013.Independent variableNative Korean women and immigrant women who married native men.OutcomesProportion of preterm births, post-term births, low birth weights and macrosomia.ResultsAdjusted ORs (aOR) were calculated for the adverse birth outcomes, and subgroup analyses were performed according to parity and mothers from three Asian countries (China, Vietnam, the Philippines). Multivariate logistic regression analyses were also conducted to evaluate the association of these factors with birth outcomes among immigrant women. Immigrant women had higher OR of post-term births (aOR 1.62; 95% CI 1.44 to 1.83) and low birth weights (aOR 1.17; CI 1.12 to 1.22). Mothers from the Philippines had higher OR of preterm births (aOR 1.26; CI 1.12 to 1.52) and Chinese mothers had higher OR of macrosomia (aOR 1.55; CI 1.44 to 1.66). The OR of post-term births and low birth weights was significantly higher in the first pregnancies of immigrant women.ConclusionsThis study has demonstrated higher proportions of adverse birth outcomes among immigrant women who married Korean men, compared with native women in Korea. Policies reducing the gap in birth outcomes between native and immigrant women are needed.