Elements of the Nordic Leadership Framework, Origins, and Transferability

Leadership styles can be classified into different buckets based on previously developed leadership framework theories such as transformational, transactional, charismatic, and democratic leadership. This thesis explores the characteristics that define the Nordic style of leadership from a cross-cultural perspective. Under the assumption that the four Nordic nations: Denmark, Finland, Norway, and Sweden share a similar set of leadership practices, my capstone investigates the linkage between the Nordic national cultures and the influences on the leadership approach. The four small, but powerful nations are the homes to many corporations recognized for their highly innovative solutions to meet consumer needs. Nordic leaders apply the cultural norms of honesty and consensus into the Nordic work environment creating an effective set of leadership principles that competitively position Nordic companies across the global market. Is this leadership model only effective in a controlled environment with favorable external support from the society? Understanding the external conditions that support the Nordic leadership framework helps determine the possibility of transferring the model in other countries and how the leadership characteristics can be replicated

cAMP Pulsing of Denuded Mouse Oocytes Increases Meiotic Resumption Via Activation of AMP-activated Protein Kinase

cAMP plays a critical role in the control of oocyte maturation, as a high level of cAMP maintains oocyte arrest at the first meiotic prophase. Yet this study shows that pulsing meiotically arrested denuded oocytes (DO) with cAMP induces oocyte maturation through the activation of AMP-activated protein kinase (PRKA). Short-term (3 h) pulsing of meiotically arrested oocytes with forskolin, an adenyl cyclase (AC) activator, increased oocyte cAMP, led to elevated AMP, and induced oocyte meiotic resumption compared to oocytes continuously cultured in the control medium with or without forskolin. Western analysis showed that germinal vesicle (GV)-stage oocytes after forskolin pulsing contained increased levels of phospho-acetyl CoA carboxylase (pACACA), a primary substrate of PRKA. Pulsing oocytes with the phosphodiesterase (PDE)-sensitive cAMP analog, 8-bromo-cAMP (8-Br-cAMP), also increased pACACA and pPRKA levels in GV-stage oocytes and induced oocyte meiotic resumption. Moreover, the PRKA inhibitors, compound C and araA, prevented 8-Br-cAMP pulsing-induced maturation. The lack of effect on meiotic induction and PRKA activation when oocytes were pulsed with the PDE-resistant activators of cAMP-dependent protein kinase, Sp-cAMP-AM and Sp-5,6-DCI-cBIMPS, suggests that cAMP degradation is required for pulsing-induced maturation. Pulsing oocytes with the exchange protein directly activated by cAMP (Epac)-specific activator, 8-CPT-2′-O-Me-cAMP, had no stimulatory effect on oocyte maturation, suggesting Epac is not involved in the pulsing-induced maturation. Taken together, these data support the idea that a transient increase in oocyte cAMP can induce meiotic resumption via activation of PRKA

AMPK Regulation of Mouse Oocyte Meiotic Resumption in Vitro

We have previously shown that the adenosine analog 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK), stimulates an increase in AMPK activity and induces meiotic resumption in mouse oocytes [Downs, S.M., Hudson, E.R., Hardie, D.G., 2002. A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes. Dev. Biol, 245, 200–212]. The present study was carried out to better define a causative role for AMPK in oocyte meiotic maturation. When microinjected with a constitutively active AMPK, about 20% of mouse oocytes maintained in meiotic arrest with dibutyryl cAMP (dbcAMP) were stimulated to undergo germinal vesicle breakdown (GVB), while there was no effect of catalytically dead kinase. Western blot analysis revealed that germinal vesicle (GV)-stage oocytes cultured in dbcAMP-containing medium plus AICAR possessed elevated levels of active AMPK, and this was confirmed by AMPK assays using a peptide substrate of AMPK to directly measure AMPK activity. AICAR-induced meiotic resumption and AMPK activation were blocked by compound C or adenine 9-beta-d-arabinofuranoside (araA, a precursor of araATP), both inhibitors of AMPK. Compound C failed to suppress adenosine uptake and phosphorylation, indicating that it did not block AICAR action by preventing its metabolism to the AMP analog, ZMP. 2′-Deoxycoformycin (DCF), a potent adenosine deaminase inhibitor, reversed the inhibitory effect of adenosine on oocyte maturation by modulating intracellular AMP levels and activating AMPK. Rosiglitazone, an anti-diabetic agent, stimulated AMPK activation in oocytes and triggered meiotic resumption. In spontaneously maturing oocytes, GVB was preceded by AMPK activation and blocked by compound C. Collectively, these results support the proposition that active AMPK within mouse oocytes provides a potent meiosis-inducing signal in vitro

Cost-effectiveness of compression technologies for evidence-informed leg ulcer care: results from the Canadian Bandaging Trial

BACKGROUND: Venous leg ulcers, affecting approximately 1% of the population, are costly to manage due to poor healing and high recurrence rates. We evaluated an evidence-informed leg ulcer care protocol with two frequently used high compression systems: ‘four-layer bandage’ (4LB) and ‘short-stretch bandage’ (SSB). METHODS: We conducted a cost-effectiveness analysis using individual patient data from the Canadian Bandaging Trial, a publicly funded, pragmatic, randomized trial evaluating high compression therapy with 4LB (n = 215) and SSB (n = 209) for community care of venous leg ulcers. We estimated costs (in 2009–2010 Canadian dollars) from the societal perspective and used a time horizon corresponding to each trial participant’s first year. RESULTS: Relative to SSB, 4LB was associated with an average 15 ulcer-free days gained, although the 95% confidence interval [−32, 21 days] crossed zero, indicating no treatment difference; an average health benefit of 0.009 QALYs gained [−0.019, 0.037] and overall, an average cost increase of $420 [$235, $739] (due to twice as many 4LB bandages used); or equivalently, a cost of$46,667 per QALY gained. If decision makers are willing to pay from $50,000 to$100,000 per QALY, the probability of 4LB being more cost effective increased from 51% to 63%. CONCLUSIONS: Our findings differ from the emerging clinical and economic evidence that supports high compression therapy with 4LB, and therefore suggest another perspective on high compression practice, namely when delivered by trained registered nurses using an evidence-informed protocol, both 4LB and SSB systems offer comparable effectiveness and value for money. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0020226

Comparing Influenza Vaccine Efficacy Against Mismatched And Matched Strains: A Systematic Review And Meta-Analysis

Background: Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains. Methods: We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk x 100%). Results: We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I-2 < 50%) across all meta-analyses, except for the LAIV meta-analyses among children (I-2 = 79%). Conclusions: The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.Canadian Institutes for Health Research/Drug Safety and Effectiveness Network New Investigator Award in Knowledge Synthesi

Following 411 Cochrane Protocols to Completion: A Retrospective Cohort Study

Cochrane reviews are regarded as being scientifically rigorous and are increasingly used by a variety of stakeholders. However, factors predicting the publication of Cochrane reviews have never been reported. This is important because if a higher proportion of Cochrane protocols with certain characteristics (e.g., funding) are being published, this may lead to inaccurate decisions. We examined the frequency of published and unpublished Cochrane reviews and protocol factors that predict the publication of Cochrane reviews.Retrospective cohort study of Cochrane protocols published in 2000 (Issues 2 to 4) and 2001 (Issue 1). The publication status of these reviews was followed up to Issue 1, 2008 in The Cochrane Library. Survival analysis of the time from protocol publication to the first review publication and protocol factors predicting the time to publication was conducted. There were 411 new Cochrane protocols in the cohort. After excluding 39; 71/372 (19.1%) were unpublished and 301/372 (80.9%) were published as full Cochrane reviews at the time of study analysis (January 2008). The median time to publication was 2.4 years (range: 0.15 to 8.96). Multivariate analyses revealed that shorter time to publication was associated with the review subsequently being updated (hazard ratio, HR: 1.80 [95% confidence interval, CI: 1.39 to 2.33 years]) and longer time to publication was associated with the review having two published protocols, indicating changes to the review plan (HR: 0.33 [95% CI: 0.12 to 0.90 years]).Only about 80% Cochrane protocols were published as full reviews after over 8 years of follow-up. The median time to publication was 2.4 years and some reviews took much longer. Strategies to decrease time to publication should be considered, such as streamlining the review process, increased support for authors when protocol amendments occur, and better infrastructure for updating Cochrane reviews

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P &lt; 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T&gt;C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P &lt; .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of \u3e3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10-11) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10-10). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10 -8). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10-7), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations. © 2013 Nature America, Inc. All rights reserved