Direct and indirect effects of new business formation on regional employment

We investigate the impact of new business formation on regional employment. The main effects occur after a considerable time lag. Obviously, a large part of the effect is not due to job creation by the newcomers but rather is of indirect nature. This implies that a large part of the debate about job creation by new businesses so far has been misleading. -- Wir analysieren den Einfluss von Gründungen auf die regionale Beschäftigung. Die wesentlichen Effekte treten erst mit erheblicher zeitlicher Verzögerung auf. Offensichtlich ist ein großer Teil der Wirkungen nicht auf die Beschäftigungsentwicklung der Newcomer zurück zu führen, sondern mehr indirekter Natur. Dies impliziert, dass ein wesentlicher Teil der bisherigen Debatte über die Beschäftigungswirkungen von Neugründungen von falschen Voraussetzungen ausgeht.Regional growth,new businesses,entrepreneurship,time lags,start-up cohorts,Regionalentwicklung,Unternehmensgründungen,Entrepreneurship,Time Lags,Gründungskohorten

The versatility of counselling psychology in the field of substance misuse

The present study was part of a nationwide multisite trial of contingency management (CM) implemented by the National Treatment Agency for Substance Misuse (NTA). The research programme aimed to target drug using, health and attendance related behaviours to gain an understanding of the acceptability and feasibility of contingency management to the UK substance misuse population. The use of CM to incentivise abstinence from an illicit substance was recommended in the guidelines of the National Institute for Health and Clinical Excellence (NICE, 2007). This study examined whether CM reduced concurrent crack cocaine misuse among opiate maintenance clients at a community drug and alcohol service (NHS). The study employed a quasi experimental design in which twenty-one (n = 21) opiate maintenance clients voluntarily chose to participate in the CM group. The incentive consisted of monetary based vouchers in the CM group, contingent upon the submission of cocaine free urine samples. A natural unplanned comparison group (n = 21) developed from participants that initially agreed to participate in the CM intervention but did not attend any of the scheduled reinforcement sessions. These clients continued to receive standard treatment (ST), including opiate maintenance treatment and key working. The data analysis consisted of two parts of data analysis; the first part employed a between-group analysis to compare the frequency of self-reported crack cocaine misuse for the CM and ST groups at baseline, 1 week after the 12-week CM intervention concluded and at 6 months follow-up. The analysis showed that there was a significant difference in crack use at followup and that there was a decrease in crack use over time in the CM group but not in the ST group. The second part utilised a within-group analysis, investigating study results for evidence of clinically meaningful changes on an individual participant level in the CM group. Accordingly, 5 participants (24%) demonstrated statistical and clinical improvement. Additionally, a survival analysis revealed that the estimated median time to study dropout was 14 days. These results seemed to indicate onset of crack abstinence is likely to occur early in treatment or not at all. The results of the study provide a tentative overview of the feasibility and generalisability of a voucher based contingency management programme reducing crack use among clients in opiate maintenance treatment in the UK. The 29 implications of the study will be discussed in relation to clinical practice and future research. Finally, a brief discussion of the moral and ethical concerns about using incentives in health care will be provided. This information will be useful in expanding this evidence-based approach into community settings

A transdisciplinary account of water research

TK acknowledges funding by the German Excellence Initiative through IRI THESys. GC acknowledges funding from the Austrian Science Funds (FWF) as part of the Vienna Doctoral Programme on Water Resource Systems (DK-plus W1219-N22).Water research is introduced from the combined perspectives of natural and social science and cases of citizen and stakeholder coproduction of knowledge. Using the overarching notion of transdisciplinarity, we examine how interdisciplinary and participatory water research has taken place and could be developed further. It becomes apparent that water knowledge is produced widely within society, across certified disciplinary experts and noncertified expert stakeholders and citizens. However, understanding and management interventions may remain partial, or even conflicting, as much research across and between traditional disciplines has failed to integrate disciplinary paradigms due to philosophical, methodological, and communication barriers. We argue for more agonistic relationships that challenge both certified and noncertified knowledge productively. These should include examination of how water research itself embeds and is embedded in social context and performs political work. While case studies of the cultural and political economy of water knowledge exist, we need more empirical evidence on how exactly culture, politics, and economics have shaped this knowledge and how and at what junctures this could have turned out differently. We may thus channel the coproductionist critique productively to bring perspectives, alternative knowledges, and implications into water politics where they were not previously considered; in an attempt to counter potential lock‐in to particular water policies and technologies that may be inequitable, unsustainable, or unacceptable. While engaging explicitly with politics, transdisciplinary water research should remain attentive to closing down moments in the research process, such as framings, path‐dependencies, vested interests, researchers’ positionalities, power, and scale.Publisher PDFPeer reviewe

Β-(I→3)-D-Glucan Modulates Dna Binding of Nuclear Factors κB, at and IL-6 Leading to an Anti-Inflammatory Shift of the IL-I β/IL-I Receptor Antagonist Ratio

Background: β-1→3-D-glucans represent a pathogen-associated molecular pattern and are able to modify biological responses. Employing a comprehensive methodological approach, the aim of our in vitro study was to elucidate novel molecular and cellular mechanisms of human peripheral blood immune cells mediated by a fungal β-1→3-D-glucan, i.e. glucan phosphate, in the presence of lipopolysaccharide (LPS) or toxic shock syndrome toxin 1 (TSST-1). Results: Despite an activation of nuclear factor (NF)κB, NFinterleukin(IL)-6 and NFAT similar to LPS or TSST-1, we observed no significant production of IL-1β, IL-6, tumor necrosis factor α or interferon γ induced by glucan phosphate. Glucan phosphate-treated leukocytes induced a substantial amount of IL-8 (peak at 18 h: 5000 pg/ ml), likely due to binding of NFκB to a consensus site in the IL-8 promoter. An increase in IL-1 receptor antagonist(RA) production (peak at 24 h: 12000 pg/ml) by glucan phosphate-treated cells positively correlated with IL-8 levels. Glucan phosphate induced significant binding to a known NFIL-6 site and a new NFAT site within the IL-1RA promoter, which was confirmed by inhibition experiments. When applied in combination with either LPS or TSST-1 at the same time points, we detected that glucan phosphate elevated the LPS- and the TSST-1-induced DNA binding of NFκB, NFIL-6 and NFAT, leading to a synergistic increase of IL-1RA. Further, glucan phosphate modulated the TSST-1-induced inflammatory response via reduction of IL-Iβ and IL-6. As a consequence, glucan phosphate shifted the TSST-1-induced IL-1β/IL-1RA ratio towards an anti-inflammatory phenotype. Subsequently, glucan phosphate decreased the TSST-1-induced, IL-1-dependent production of IL-2. Conclusion: Thus, β-1→3-D-glucans may induce beneficial effects in the presence of pro-inflammatory responses, downstream of receptor binding and signaling by switching a pro- to an anti-inflammatory IL-1RA-mediated reaction. Our results also offer new insights into the complex regulation of the IL-1RA gene, which can be modulated by a β-1→3-D-glucan

Effect of oral beta-blocker on short and long-term mortality in patients with acute respiratory failure: results from the BASEL-II-ICU study

Acute respiratory failure (ARF) is responsible for about one-third of intensive care unit (ICU) admissions and is associated with adverse outcomes. Predictors of short- and long-term outcomes in unselected ICU-patients with ARF are ill-defined. The purpose of this analysis was to determine predictors of in-hospital and one-year mortality and assess the effects of oral beta-blockers in unselected ICU patients with ARF included in the BASEL-II-ICU study. The BASEL II-ICU study was a prospective, multicenter, randomized, single-blinded, controlled trial of 314 (mean age 70 (62 to 79) years) ICU patients with ARF evaluating impact of a B-type natriuretic peptide- (BNP) guided management strategy on short-term outcomes. In-hospital mortality was 16% (51 patients) and one-year mortality 41% (128 patients). Multivariate analysis assessed that oral beta-blockers at admission were associated with a lower risk of both in-hospital (HR 0.33 (0.14 to 0.74) P = 0.007) and one-year mortality (HR 0.29 (0.16 to 0.51) P = 0.0003). Kaplan-Meier analysis confirmed the lower mortality in ARF patients when admitted with oral beta-blocker and further shows that the beneficial effect of oral beta-blockers at admission holds true in the two subgroups of patients with ARF related to cardiac or non-cardiac causes. Kaplan-Meier analysis also shows that administration of oral beta-blockers before hospital discharge gives striking additional beneficial effects on one-year mortality. Established beta-blocker therapy appears to be associated with a reduced mortality in ICU patients with acute respiratory failure. Cessation of established therapy appears to be hazardous. Initiation of therapy prior to discharge appears to confer benefit. This finding was seen regardless of the cardiac or non-cardiac etiology of respiratory failure. ClinicalTrials.gov Identifier: NCT00130559

β-(1→3)-D-glucan modulates DNA binding of nuclear factors κB, AT and IL-6 leading to an anti-inflammatory shift of the IL-1β/IL-1 receptor antagonist ratio

BACKGROUND: β-1→3-D-glucans represent a pathogen-associated molecular pattern and are able to modify biological responses. Employing a comprehensive methodological approach, the aim of our in vitro study was to elucidate novel molecular and cellular mechanisms of human peripheral blood immune cells mediated by a fungal β-1→3-D-glucan, i.e. glucan phosphate, in the presence of lipopolysaccharide (LPS) or toxic shock syndrome toxin 1 (TSST-1). RESULTS: Despite an activation of nuclear factor (NF)κB, NFinterleukin(IL)-6 and NFAT similar to LPS or TSST-1, we observed no significant production of IL-1β, IL-6, tumor necrosis factor α or interferon γ induced by glucan phosphate. Glucan phosphate-treated leukocytes induced a substantial amount of IL-8 (peak at 18 h: 5000 pg/ml), likely due to binding of NFκB to a consensus site in the IL-8 promoter. An increase in IL-1receptor antagonist(RA) production (peak at 24 h: 12000 pg/ml) by glucan phosphate-treated cells positively correlated with IL-8 levels. Glucan phosphate induced significant binding to a known NFIL-6 site and a new NFAT site within the IL-1RA promoter, which was confirmed by inhibition experiments. When applied in combination with either LPS or TSST-1 at the same time points, we detected that glucan phosphate elevated the LPS- and the TSST-1-induced DNA binding of NFκB, NFIL-6 and NFAT, leading to a synergistic increase of IL-1RA. Further, glucan phosphate modulated the TSST-1-induced inflammatory response via reduction of IL-1β and IL-6. As a consequence, glucan phosphate shifted the TSST-1-induced IL-1β/IL-1RA ratio towards an anti-inflammatory phenotype. Subsequently, glucan phosphate decreased the TSST-1-induced, IL-1-dependent production of IL-2. CONCLUSION: Thus, β-1→3-D-glucans may induce beneficial effects in the presence of pro-inflammatory responses, downstream of receptor binding and signaling by switching a pro- to an anti-inflammatory IL-1RA-mediated reaction. Our results also offer new insights into the complex regulation of the IL-1RA gene, which can be modulated by a β-1→3-D-glucan

Genetic Selection for Enhanced Folding In Vivo Targets the Cys14-Cys38 Disulfide Bond in Bovine Pancreatic Trypsin Inhibitor

The periplasm provides a strongly oxidizing environment; however, periplasmic expression of proteins with disulfide bonds is often inefficient. Here, we used two different tripartite fusion systems to perform in vivo selections for mutants of the model protein bovine pancreatic trypsin inhibitor (BPTI) with the aim of enhancing its expression in Escherichia coli. This trypsin inhibitor contains three disulfides that contribute to its extreme stability and protease resistance. The mutants we isolated for increased expression appear to act by eliminating or destabilizing the Cys14-Cys38 disulfide in BPTI. In doing so, they are expected to reduce or eliminate kinetic traps that exist within the well characterized in vitro folding pathway of BPTI. These results suggest that elimination or destabilization of a disulfide bond whose formation is problematic in vitro can enhance in vivo protein folding. The use of these in vivo selections may prove a valuable way to identify and eliminate disulfides and other rate-limiting steps in the folding of proteins, including those proteins whose in vitro folding pathways are unknown. Antioxid. Redox Signal. 14, 973-984.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90494/1/ars-2E2010-2E3712.pd

Increased Reward-Related Activation in the Ventral Striatum During Stress Exposure Associated With Positive Affect in the Daily Life of Young Adults With a Family History of Depression. Preliminary Findings

Background: Being the offspring of a parent with major depression disorder (MDD) is a strong predictor for developing MDD. Blunted striatal responses to reward were identified in individuals with MDD and in asymptomatic individuals with family history of depression (FHD). Stress is a major etiological factor for MDD and was also reported to reduce the striatal responses to reward. The stress-reward interactions in FHD individuals has not been explored yet. Extending neuroimaging results into daily-life experience, self-reported ambulatory measures of positive affect (PA) were shown to be associated with striatal activation during reward processing. A reduction of self-reported PA in daily life is consistently reported in individuals with current MDD. Here, we aimed to test (1) whether increased family risk of depression is associated with blunted neural and self-reported reward responses. (2) the stress-reward interactions at the neural level. We expected a stronger reduction of reward-related striatal activation under stress in FHD individuals compared to HC. (3) the associations between fMRI and daily life self-reported data on reward and stress experiences, with a specific interest in the striatum as a crucial region for reward processing. Method: Participants were 16 asymptomatic young adults with FHD and 16 controls (HC). They performed the Fribourg Reward Task with and without stress induction, using event-related fMRI. We conducted whole-brain analyses comparing the two groups for the main effect of reward (rewarded > not-rewarded) during reward feedback in control (no-stress) and stress conditions. Beta weights extracted from significant activation in this contrast were correlated with self-reported PA and negative affect (NA) assessed over 1 week. Results: Under stress induction, the reward-related activation in the ventral striatum (VS) was higher in the FHD group than in the HC group. Unexpectedly, we did not find significant group differences in the self-reported daily life PA measures. During stress induction, VS reward-related activation correlated positively with PA in both groups and negatively with NA in the HC group. Conclusion: As expected, our results indicate that increased family risk of depression was associated with specific striatum reactivity to reward in a stress condition, and support previous findings that ventral striatal reward-related response is associated with PA. A new unexpected finding is the negative association between NA and reward-related ventral striatal activation in the HC group