Strategic Alliances as a form of Coopetition and its impact on the Performance of Airlines: A Case Study analysis of Lufthansa, Finnair, and Alitalia

The research on coopetition (i.e., simultaneous cooperation and competition) has increased significantly over the last two decades. Noteworthy findings have been made, including the benefits that a firm gains from such a relationship. However, only limited studies centralize the impact on performance through coopetition. Existing studies on coopetition and the effect on performance show mixed outcomes, and researchers claim that the results depend on the firm's industry. Thus, it is relevant to analyze the impact of coopetition on market performance. The following study will examine the aforementioned research gap by looking into the airline industry where coopetition relationship has been practiced in the form of strategic alliances for more than 20 years. The empirical analysis was based on a multiple case study of three airlines, from three different countries, operating in three different alliances. That allowed to investigate similarities and differences among the diverse sized companies in terms of the performance impact. Primary data were collected through semi-structured interviews. Additionally, annual reports were used as secondary data and to enhance credibility through triangulation. Findings show that in general, coopetition through strategic alliances contributes positively to airlines. Nevertheless, the degree of how much airlines benefit from alliances depends on the position in the network and the airline's size. Airlines of small size gain most from the relationship, and airlines with a central position in the alliance give more to the strategic alliances than they get out. The findings reveal that airlines of large size gain less from alliances and increasingly form other types of partnerships like joint ventures that create a more balanced give and gain relationship. Notwithstanding, the COVID epidemic will have a crucial impact on airlines and increase the importance of strategic alliances and partnerships further

Rückenmarksstimulation (SCS) bei chronischen neuropathischen Schmerzen: Vergleich von BurstDR™- und Hochfrequenzstimulation (HF10™)

Hintergrund: BurstDR™ und HF10™ als neue Stimulationsformen der SCS-Therapie zeichnen sich im Vergleich zur konventionellen tonischen Stimulation durch effektivere Schmerzlinderung, Wirksamkeit bei schwierigen Patientengruppen (Nonresponder u. a.) und verminderte Parästhesien aus. Außerdem könnten sie sich durch Modulation des für affektiv-kognitive Aspekte zuständigen medialen Schmerzwegs auf diese positiv auswirken. Ziel der Studie war die vergleichende Betrachtung der Wirkung von BurstDR™ und HF10™ mit Fokus auf die affektiv-kognitive Schmerzverarbeitung. Die Untersuchung weiterer Schmerzaspekte und Zusammenhänge soll die klinische Situation möglichst umfassend abbilden. Methoden: 41 von 70 chronischen Schmerzpatienten, die am Universitätsklinikum Tübingen zwischen 2014 und 2016 einen BurstDR™- oder HF10™-Generator implantiert bekommen hatten, nahmen an der Studie teil. Anamnestische Daten, Schmerzstärke (NRS), Schmerzakzeptanz (CPAQ), Schmerzkatastrophisieren (PCS), Schmerzaufmerksamkeit (PVAQ), erlebte Behinderung im Alltag (PDI) und depressive Symptome (BDI-II) wurden mittels Fragebögen für den aktuellen Zeitpunkt T1 und retrospektiv für den Zeitpunkt T0 (Interpretation durch Recall Bias limitiert) vor Therapie erhoben. Ergebnisse: BurstDR™ bewirkte eine signifikante Verbesserung der untersuchten Schmerzaspekte. Für HF10™ zeigten sich positive Tendenzen (eingeschränkt aussagekräftig aufgrund kleiner Fallzahl). Im Verlauf der Studie erwies es sich als sinnvoll, die Untersuchung der BurstDR™-Gruppe in BurstDR™, BurstDR™/Tonisch und Tonisch zu differenzieren. Die Burst/Tonisch-Gruppe zeigte eine homogen positive Entwicklung. Zwischen den erfragten Schmerzaspekten bestanden in der untersuchten Patientengruppe mit wenigen Ausnahmen deutlich positive Korrelationen. Schlussfolgerung: Die positive Wirkung von BurstDR™ auf die affektiv-kognitiven Schmerzaspekte (Schmerzakzeptanz, Schmerzkatastrophisieren und Schmerzaufmerksamkeit) konnte bestätigt werden und könnte mit einer Modulation des medialen Schmerzweges zusammenhängen, für HF10™ waren hierzu keine abschließenden Aussagen möglich. Der Wechsel zwischen BurstDR™ und Tonisch könnte eine vielversprechende Ergänzung sein im Sinne einer effektiven Therapieoption. Die Wirksamkeit von BurstDR™ sowie die positiven Effekte des BurstDR™/Tonisch-Wechsels konnten gezeigt werden und sind vielversprechende Entwicklungen auf dem Weg zu einer individualisierten SCS der Zukunft

Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice

IntroductionCaloric restriction (CR) is a nutritional intervention that increases life expectancy while lowering the risk for cardio-metabolic disease. Its effects on bone health, however, remain controversial. For instance, CR has been linked to increased accumulation of bone marrow adipose tissue (BMAT) in long bones, a process thought to elicit detrimental effects on bone. Qualitative differences have been reported in BMAT in relation to its specific anatomical localization, subdividing it into physiological and potentially pathological BMAT. We here examine the local impact of CR on bone composition, microstructure and its endocrine profile in the context of aging.MethodsYoung and aged male C57Bl6J mice were subjected to CR for 8 weeks and were compared to age-matched littermates with free food access. We assessed bone microstructure and BMAT by micro-CT, bone fatty acid and transcriptomic profiles, and bone healing.ResultsCR increased tibial BMAT accumulation and adipogenic gene expression. CR also resulted in elevated fatty acid desaturation in the proximal and mid-shaft regions of the tibia, thus more closely resembling the biochemical lipid profile of the distally located, physiological BMAT. In aged mice, CR attenuated trabecular bone loss, suggesting that CR may revert some aspects of age-related bone dysfunction. Cortical bone, however, was decreased in young mice on CR and remained reduced in aged mice, irrespective of dietary intervention. No negative effects of CR on bone regeneration were evident in either young or aged mice.DiscussionOur findings indicate that the timing of CR is critical and may exert detrimental effects on bone biology if administered during a phase of active skeletal growth. Conversely, CR exerts positive effects on trabecular bone structure in the context of aging, which occurs despite substantial accumulation of BMAT. These data suggest that the endocrine profile of BMAT, rather than its fatty acid composition, contributes to healthy bone maintenance in aged mice

Inflammatory bowel disease in South-Eastern Norway III (IBSEN III): a new population-based inception cohort study from South-Eastern Norway

Background and aim: Modern treatment strategies for inflammatory bowel disease (IBD) are postulated to change the natural disease course. Inception cohort studies are the gold standard for investigating such changes. We have initiated a new population-based inception cohort study; Inflammatory bowel disease in South Eastern Norway III (IBSEN III). In this article, we describe the study protocol and baseline characteristics of the cohort. Methods: IBSEN III is an ongoing, population-based observational inception cohort study with prospective follow-up. Adult and pediatric patients with suspected IBD in the South-Eastern Health Region of Norway (catchment area of 2.95 million inhabitants in 2017), during the 3-year period from 2017 to 2019, were eligible for inclusion. Comprehensive clinical, biochemical, endoscopic, demographic, and patient-reported data were collected at the time of diagnosis and throughout standardized follow-up. For a portion of the patients, extensive biological material was biobanked. Results: The study included 2168 patients, of whom 1779 were diagnosed with IBD (Crohn's disease: 626, ulcerative colitis: 1082, IBD unclassified: 71). In 124 patients, there were subtle findings indicative of, but not diagnostic for, IBD. The remaining 265 patients were classified as symptomatic non-IBD controls. Conclusion: We have included patients in a comprehensive population-based IBD cohort from a catchment population of 2.95 million, and a unique biobank with materials from newly diagnosed and treatment-naïve IBD patients and symptomatic non-IBD controls. We believe this cohort will add important knowledge about IBD in the years to come.publishedVersio

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics

Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)

Genetic Variants For Head Size Share Genes and Pathways With Cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele