The labor market regimes of Denmark and Norway – one Nordic model?

The literature on the Danish and Norwegian labor market systems emphasizes the commonalities of the two systems. We challenge this perception by investigating how employers in multinational companies in Denmark and Norway communicate with employees on staffing changes. We argue that the development of ‘flexicurity’ in Denmark grants Danish employers considerably greater latitude in engaging in staffing changes than its Nordic counterpart, Norway. Institutional theory leads us to suppose that large firms located in the Danish setting will be less likely to engage in employer–employee communication on staffing plans than their Norwegian counterparts. In addition, we argue that in the Danish context indigenous firms will have a better insight into the normative and cognitive aspects to flexicurity than foreign-owned firms, meaning that they are more likely to engage in institutional entrepreneurialism than their foreign owned counterparts. We supplement institutional theory with an actor perspective in order to take into account the role of labor unions. Our analysis is based on a survey of 203 firms in Norway and Denmark which are either indigenous multinational companies or the subsidiaries of foreign multinational companies. The differences we observe cause us to conclude that the notion of a common Nordic model is problematic

Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: findings from the LIBERATE study

Background Apremilast, an oral phosphodiesterase‐4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis. Objective To evaluate long‐term efficacy and safety of apremilast in biologic‐naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial. Methods Two hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and Severity Index (PASI; 0–72), Scalp Physician Global Assessment (ScPGA; 0–5) and Nail Psoriasis Severity Index (NAPSI; 0–8); patient‐reported outcomes (PROs) were assessed using the Dermatology Life Quality Index (DLQI; 0–32) and pruritus visual analog scale (VAS; 0–100 mm). Results The apremilast‐extension phase (Weeks 16–104) included 226 patients in the placebo/apremilast (n = 73), apremilast/apremilast (n = 74) and etanercept/apremilast (n = 79) groups, and at Week 104, 50.7%, 45.9% and 51.9% of these patients, respectively, maintained ≥75% reduction from baseline in PASI score (based on last‐observation‐carried‐forward analysis). Across treatment groups, ScPGA 0 (clear) or 1 (minimal) was achieved by 50.0%–59.2% of patients; NAPSI mean change from baseline was −48.1% to −51.1%; DLQI score ≤5 was achieved by 66.0%–72.5% of patients; and pruritus VAS mean change from baseline was −24.4 to −32.3. AEs in ≥5% of patients (diarrhoea, nausea, nasopharyngitis, upper respiratory tract infection and headache) did not increase with prolonged apremilast exposure. Conclusions Apremilast demonstrated significant and sustained improvements in skin, scalp, nails and PROs (pruritus and quality of life) over 104 weeks in patients with moderate to severe plaque psoriasis. Safety was consistent with the known safety profile of apremilast

The Burden of Brain Hypoxia and Optimal Mean Arterial Pressure in Patients With Hypoxic Ischemic Brain Injury After Cardiac Arrest.

OBJECTIVES: In patients at risk of hypoxic ischemic brain injury following cardiac arrest, we sought to: 1) characterize brain oxygenation and determine the prevalence of brain hypoxia, 2) characterize autoregulation using the pressure reactivity index and identify the optimal mean arterial pressure, and 3) assess the relationship between optimal mean arterial pressure and brain tissue oxygenation. DESIGN: Prospective interventional study. SETTING: Quaternary ICU. PATIENTS: Adult patients with return of spontaneous circulation greater than 10 minutes and a postresuscitation Glasgow Coma Scale score under 9 within 72 hours of cardiac arrest. INTERVENTIONS: All patients underwent multimodal neuromonitoring which included: 1) brain tissue oxygenation, 2) intracranial pressure, 3) jugular venous continuous oximetry, 4) regional saturation of oxygen using near-infrared spectroscopy, and 5) pressure reactivity index-based determination of optimal mean arterial pressure, lower and upper limit of autoregulation. We additionally collected mean arterial pressure, end-tidal CO2, and temperature. All data were captured at 300 Hz using ICM+ (Cambridge Enterprise, Cambridge, United Kingdom) brain monitoring software. MEASUREMENTS AND MAIN RESULTS: Ten patients (7 males) were included with a median age 47 (range 20-71) and return to spontaneous circulation 22 minutes (12-36 min). The median duration of monitoring was 47 hours (15-88 hr), and median duration from cardiac arrest to inclusion was 15 hours (6-44 hr). The mean brain tissue oxygenation was 23 mm Hg (SD 8 mm Hg), and the mean percentage of time with a brain tissue oxygenation below 20 mm Hg was 38% (6-100%). The mean pressure reactivity index was 0.23 (0.27), and the percentage of time with a pressure reactivity index greater than 0.3 was 50% (12-91%). The mean optimal mean arterial pressure, lower and upper of autoregulation were 89 mm Hg (11), 82 mm Hg (8), and 96 mm Hg (9), respectively. There was marked between-patient variability in the relationship between mean arterial pressure and indices of brain oxygenation. As the patients' actual mean arterial pressure approached optimal mean arterial pressure, brain tissue oxygenation increased (p < 0.001). This positive relationship did not persist when the actual mean arterial pressure was above optimal mean arterial pressure. CONCLUSIONS: Episodes of brain hypoxia in hypoxic ischemic brain injury are frequent, and perfusion within proximity of optimal mean arterial pressure is associated with increased brain tissue oxygenation. Pressure reactivity index can yield optimal mean arterial pressure, lower and upper limit of autoregulation in patients following cardiac arrest

Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate‐to‐severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2)

SummaryBackground Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 4·4%, respectively; P < 0·001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0·001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks

Experimental Bariatric Surgery in Rats Generates a Cytotoxic Chemical Environment in the Gut Contents

Bariatric surgery, also known as metabolic surgery, is an effective treatment for morbid obesity, which also offers pronounced metabolic effects including the resolution of type 2 diabetes and a decrease in cardiovascular disease and long-term cancer risk. However, the mechanisms of surgical weight loss and the long-term consequences of bariatric surgery remain unclear. Bariatric surgery has been demonstrated to alter the composition of both the microbiome and the metabolic phenotype. We observed a marked shift toward Gammaproteobacteria, particularly Enterobacter hormaechei, following Roux-en-Y gastric bypass (RYGB) surgery in a rat model compared with sham-operated controls. Fecal water from RYGB surgery rats was highly cytotoxic to rodent cells (mouse lymphoma cell line). In contrast, fecal water from sham-operated animals showed no/very low cytotoxicity. This shift in the gross structure of the microbiome correlated with greatly increased cytotoxicity. Urinary phenylacetylglycine and indoxyl sulfate and fecal gamma-aminobutyric acid, putrescine, tyramine, and uracil were found to be inversely correlated with cell survival rate. This profound co-dependent response of mammalian and microbial metabolism to RYGB surgery and the impact on the cytotoxicity of the gut luminal environment suggests that RYGB exerts local and global metabolic effects which may have an influence on long-term cancer risk and cytotoxic load

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that ncRNA expression profiling data requires careful evaluation to determine the utility of specific ncRNAs as biomarkers. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify possibly suitable ncRNAs and areas of toxicology where ncRNA expression profiling could address prevailing scientific deficiencies. (2) Develop consensus on how to conduct ncRNA expression profiling in a toxicological context. (3) Conduct experimental projects, including, e.g., rat (90-day) oral toxicity studies, to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. Thereby, physiological ncRNA expression profiles should be established, including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be dose-dependently linked with substance-induced apical effects. Applying a holistic approach, knowledge on ncRNAs, 'omics and epigenetics technologies should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context

Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

National and firm-level drivers of the devolution of HRM decision making to line managers

Multinational companies must understand the influences on responsibility for managing people so that they can manage talent consistently thus ensuring that it is transferable across locations. We examine the impact of firm and national level characteristics on the devolution of HRM decision making to line managers. Our analysis draws on data from 2335 indigenous organizations in 21 countries. At the firm level, we found that where the HR function has higher power, devolution is less likely. At the national level, devolution of decision making to line management is more likely in societies with more stringent employment laws and lower power distance

The effects of market economy and foreign MNE subsidiaries on the convergence and divergence of HRM

This study explores patterns of human resource management (HRM) practices across market economies, and between indigenous firms and foreign MNE subsidiary operations, offering a novel perspective on convergence and divergence. Applying institutional theorizing to improve our understanding of convergence/ divergence as a process and an outcome, data collected from nine countries at three points in time over a decade confirm that convergence and divergence occur to different extents in a non-linear fashion, and vary depending on the area of HRM practice observed. Patterns of adoption and convergence/ divergence are explained through the effect of institutional constraints, which vary between liberal and coordinated market economies, and between indigenous firms and foreign MNE subsidiaries. The study contributes a more graded conceptualization of convergence/ divergence, which reflects the complex dynamic reality of international business