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1.
  • Patel, Y., et al. (författare)
  • Virtual Ontogeny of Cortical Growth Preceding Mental Illness
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 92:4, s. 299-313
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
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  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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7.
  • Abolfathi, Bela, et al. (författare)
  • The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
  • 2018
  • Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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8.
  • The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
  • 2022
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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9.
  • Semb, G, et al. (författare)
  • Erratum
  • 2017
  • Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158
  • Tidskriftsartikel (refereegranskat)
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10.
  • Aguado, D. S., et al. (författare)
  • The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
  • 2019
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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  • Rovira, P, et al. (författare)
  • Shared genetic background between children and adults with attention deficit/hyperactivity disorder
  • 2020
  • Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X .- 0893-133X. ; 45:10, s. 1617-1626
  • Tidskriftsartikel (refereegranskat)abstract
    • Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.
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12.
  • Zayats, T, et al. (författare)
  • Exome chip analyses in adult attention deficit hyperactivity disorder
  • 2016
  • Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 6:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E-06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E-08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E-07); the PSD locus (P=7.58E-08) and ZCCHC4 locus (P=1.79E-06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E-05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.
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  • de Souza, Claudio M. D., et al. (författare)
  • Interaction of forsterite-91 with distilled water and artificial seawater : a prebiotic chemistry experiment
  • 2013
  • Ingår i: International Journal of Astrobiology. - 1473-5504 .- 1475-3006. ; 12:2, s. 135-143
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present work, the interactions between forsterite-91 with distilled water and forsterite-91 with artificial seawater were studied at two pHs (2.0 and 8.0) using different techniques. A large increase in pH was observed for samples incubated at an initially acidic pH (2.0) due to the dissolution of forsterite-91 in distilled water and artificial seawater. Thus, in acidic hydrothermal vents, an increase in the amount of hydrocarbons and magnetite should be expected due to the release of Fe(II). The pH(PZC) decreased and the pH(IEP) increased when forsterite-91 was treated with distilled water and artificial seawater. The ions from the artificial seawater had an effect on zeta potential. Scanning electron microscopy (SEM) images and X-ray diffractograms showed halite in the samples of forsterite-91 mixed with artificial seawater. The presence of halite or adsorption of ions on the surface of forsterite-91 could affect the synthesis of magnetite and hydrocarbons in hydrothermal vents, due to a decrease in the dissolution rates of forsterite-91. The dissolution of forsterite-91 yields low concentrations of Fe(III) and Mn(II) as detected by electron paramagnetic resonance (EPR) spectroscopy. Microanalysis of forsterite-91 showed a higher amount of Mn, with an oxidation that was likely not + II, as Mn in supernatant solutions was only detected by EPR spectroscopy after mixing with artificial seawater at pH 2.0. As Fe(III) and Mn(II) are catalyst constituents of magnetite and manganese oxide, respectively, their presence is important for synthesis in hydrothermal vents. Etch pits were observed only in the forsterite-91 sample mixed with distilled water at pH 8.0. Na, Cl, S, Ca and K were detected in the samples mixed with artificial seawater by SEM-EDS. Si, Mg, Fe and Al were detected in almost all supernatant samples due to forsterite-91 dissolution. Cr was not dissolved in the experiments, thus Cr in the mineral could serve as an effective catalyst for Fischer Tropsch Types (FTT) reactions in hydrothermal vent systems. X-ray diffractograms of the original forsterite-91 also showed peaks arising from zeolites and clinochlore. After the samples were treated with artificial seawater, X-ray diffractograms showed the dissolution of zeolite. Experiments should be performed in the natural environment to verify the potential for zeolites to act as a catalyst in hydrothermal vents.
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18.
  • Edlund, Charlotta, et al. (författare)
  • Comparative effects of moxifloxacin and clarithromycin on the normal intestinal microflora
  • 2000
  • Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 32:1, s. 81-85
  • Tidskriftsartikel (refereegranskat)abstract
    • Twelve healthy male subjects age range 24-40 y participated in the investigation. The trial was divided into 2 35-d periods. The 2 treatment regimens were: (i) 1 x 400 mg moxifloxacin tablet in the morning and 1 placebo tablet in the evening for 7 d; and (ii) 1 x 500 mg clarithromycin tablet in the morning and 1 x 500 mg clarithromycin tablet in the evening for 7 d. Each subject received firstly 1 treatment regimen and secondly the other treatment regimen. The wash-out period was 6 weeks between the two treatment regimens. Moxifloxacin caused significant decreases of enterococci and enterobacteria during the administration period while the numbers of staphylococci, streptococci, Bacillus and Candida were not affected. No impact on peptostreptococci, lactobacilli, Veillonella, Bacteroides or fusobacteria was observed, while bifidobacteria and clostridia decreased during moxifloxacin administration. The microflora was normalized after 35 d. Clarithromycin caused significant reduction of Escherichia coli while the numbers of enterococci, Enterobacter, Citrobacter, Klebsiella and Pseudomonas increased markedly. No significant changes in the numbers of staphylococci, streptococci, Bacillus and Candida were noticed. In the anaerobic microflora bifidobacteria, lactobacilli and clostridia were suppressed, while no changes in peptostreptococci, Veillonella, Bacteroides and fusobacteria were found. The microflora was normalized in all volunteers after 35 d.
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19.
  • Eftekhari, Sajedeh, et al. (författare)
  • Localization of CGRP receptor components and receptor binding sites in rhesus monkey brainstem: A detailed study using in situ hybridization, immunofluorescence and autoradiography.
  • 2016
  • Ingår i: Journal of Comparative Neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 524:1, s. 90-118
  • Tidskriftsartikel (refereegranskat)abstract
    • Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe nucleus, gracile nucleus and spinal trigeminal nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear nucleus, dorsal raphe nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens nucleus, motor trigeminal nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved.
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20.
  • Iyer, Dinesh N., et al. (författare)
  • The triggers of local and distant search : Relative magnitude and persistence in explaining acquisition relatedness
  • 2019
  • Ingår i: Long range planning. - : Elsevier. - 0024-6301 .- 1873-1872. ; 52:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Research on problemistic search has assumed negative attainment discrepancy to be the trigger of both local and distant search. Extending this research, we present and compare two additional triggers: (1) relative attainment discrepancy, which reflects how much a firm's attainment discrepancy deviates from its past negative attainment discrepancies; and (2) persistent attainment discrepancy, which reflects how often the firm experiences below-aspirations performance. Our triggers for distant search model a behavioral explanation for the timing and relatedness of acquisitions. We find support for baseline arguments of problemistic search whereby firms increase both industry- and skill-related acquisitions when they perform below aspirations. When they persistently perform below aspirations, however, this likelihood is reduced and firms engage in acquisitions that are more unrelated, thereby providing support for the notion of expanding search boundaries from local to distant search. Of the two triggers of distant search proposed, relative attainment discrepancy does not induce firms to expand search boundaries. Our results indicate that persistent attainment discrepancy is a key construct to consider when studying the expansion of search boundaries.
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  • Pasquier, David, et al. (författare)
  • Designing clinical trials based on modern imaging and metastasis-directed treatments in patients with oligometastatic breast cancer: a consensus recommendation from the EORTC Imaging and Breast Cancer Groups
  • 2023
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 24:8
  • Forskningsöversikt (refereegranskat)abstract
    • Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed.
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  • Withers, Michael C., et al. (författare)
  • Employee mobility in family and non-family firms : The role of family firm-specific human capital
  • 2020
  • Ingår i: Academy of Management: Proceedings. - : Academy of Management.
  • Konferensbidrag (refereegranskat)abstract
    • Drawing on human capital theory of employee mobility, we develop theory regarding family firm-specific human capital. Specifically, we argue that nonfamily employees of family firms are less likely to change their job than employees of nonfamily firms. We then examine employees’ mobility and the compensation outcome when such jobs changes occur. To examine these relationships, we utilize a unique dataset of all Swedish employees’ job changes from 2001 to 2012. Overall, with supportive empirical results, the present study offers a deeper understanding of employees’ mobility towards family and nonfamily private firms.
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