THE IMPACT OF EMPLOYEE COMPETENCE ON ORGANIZATIONAL AGILITY: THE MEDIATING ROLE OF IT ALIGNMENT

Scholars have proposed that IT enables organizational agility by extending the reach and richness of firm knowledge and processes. However, this relationship is still open to debate. Based on the dynamic capabilities perspective, this paper proposes a model to investigate how employee competence (i.e., IT competence of business people and business competence of IT professionals) affects organizational agility through IT alignment. Data analysis results show that IT alignment fully mediates the influence of IT competence of business people and partially mediates the influence of business competence of IT professionals on organizational agility. In addition, the two kinds of competence are also positively interacting with each other to enhance IT alignment. We summarize with implications and suggestions for future research

Assessment of Cardiovascular Health of Children Ages 6 to 10 Years Conceived by Assisted Reproductive Technology

Importance: Assisted reproductive technology (ART) has been widely used for treatment of infertility and has brought millions of births worldwide. The health of offspring conceived by ART has been of much concern, and adverse cardiovascular health outcomes have been reported by previous studies.Objective: To assess the cardiovascular health of children conceived by ART.Design, setting, and participants: This cohort study was conducted among participants recruited from November 2017 to February 2019. Participants were 382 children conceived by ART who were selected from a single reproductive center and 382 children who were naturally conceived, randomly selected from a primary school, and matched by sex, age, and maternal age at the child's birth (2 years older or younger). Data were analyzed from March 2019 through December 2019.Exposures: Conception by ART.Main outcomes and measures: Blood pressure was measured, and echocardiography was performed to determine left ventricular structural and functional parameters. Adjusted relative wall thickness (aRWT) was found for age, with high RWT defined as an aRWT of 0.375 or more.Results: Among 764 children aged 6 to 10 years, 382 children were conceived by ART (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys) and 382 children were naturally conceived (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys). Children conceived by ART had statistically significantly increased mean (SD) height (130.2 [9.5] cm vs 128.5 [8.1] cm; P = .007) and body mass index (17.6 [3.6] vs 17.1 [2.7]; P = .03). Those conceived by ART, compared with children in the matched control group, had statistically significantly increased blood pressure (mean [SD] systolic blood pressure, 105.5 [6.9] mm Hg vs 103.5 [8.4] mm Hg; adjusted P P P P 2.7 vs 28.28 [3.54] g/m2.7; adjusted P P P = .03), high RWT (61 children [16.0%] vs 0 children; P P for left ventricle remodeling Conclusions and relevance: This study found that children conceived by ART had increased blood pressure and unfavorable changes in left ventricular structure and function compared with children who were naturally conceived. These findings suggest that further studies are needed to investigate the potential mechanisms and long-term outcomes associated with these differences.</p

A-6G and A-20C Polymorphisms in the Angiotensinogen Promoter and Hypertension Risk in Chinese: A Meta-Analysis

BACKGROUND: Numerous studies in Chinese populations have evaluated the association between the A-6G and A-20C polymorphisms in the promoter region of angiotensinogen gene and hypertension. However, the results remain conflicting. We carried out a meta-analysis for these associations. METHODS AND RESULTS: Case-control studies in Chinese and English publications were identified by searching the MEDLINE, EMBASE, CNKI, Wanfang, CBM, and VIP databases. The random-effects model was applied for dichotomous outcomes to combine the results of the individual studies. We finally selected 24 studies containing 5932 hypertensive patients and 5231 normotensive controls. Overall, we found significant association between the A-6G polymorphism and the decreased risk of hypertension in the dominant genetic model (AA+AG vs. GG: P=0.001, OR=0.71, 95%CI 0.57-0.87, P(heterogeneity)=0.96). The A-20C polymorphism was significantly associated with the increased risk for hypertension in the allele comparison (C vs. A: P=0.03, OR=1.14, 95%CI 1.02-1.27, P(heterogeneity)=0.92) and recessive genetic model (CC vs. CA+AA: P=0.005, OR=1.71, 95%CI 1.18-2.48, P(heterogeneity)=0.99). In the subgroup analysis by ethnicity, significant association was also found among Han Chinese for both A-6G and A-20C polymorphisms. A borderline significantly decreased risk of hypertension between A-6G and Chinese Mongolian was seen in the allele comparison (A vs. G: P=0.05, OR=0.79, 95%CI 0.62-1.00, P(heterogeneity)=0.84). CONCLUSION: Our meta-analysis indicated significant association between angiotensinogen promoter polymorphisms and hypertension in the Chinese populations, especially in Han Chinese

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.

Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types.This work was supported by the National Health and Medical Research Council of Australia (ID#1031333 to A B Spurdle, DF, A M Dunning, ID#39435 to ANECS, ID#552402, QIMR Controls); National Health and Medical Research Council of Australia Fellowship Scheme (to A B Spurdle); Principal Research Fellow of Cancer Research UK (to D F Easton); Joseph Mitchell Trust (to A M Dunning); Oxford Comprehensive Biomedical Research Centre (to I Tomlinson); The European Community's Seventh Framework Programme (grant agreement number 22175 (HEALTH-F2-2009-223175) (COGS); Cancer Research UK (C1287/A10118 to COGS and BCAC, C1287/A10710, C12292/A11174, C1281/A12014 to COGS and BCAC, C5047/A15007, C5047/A10692, C8197/A16565, C490/A10124 to SEARCH, CORGI - NSECG, to I Tomlinson); National Institutes of Health (CA128978, R01 CA122443 to MECS and MAY, P30 CA15083 to MECS, P50 CA136393 to MECS and MAY, CAHRES); Post-Cancer GWAS Initiative (1U19 CA148537, 1U19 CA148065, 1U19 CA148112 – the GAME-ON initiative); Department of Defence (W81XWH-10-1-0341); Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; The Breast Cancer Research Foundation; Ovarian Cancer Research Fund (to COGS); Cancer Council Queensland (ID#4196615 to ANECS); Council Cancer Tasmania (ID#403031, #ID457636 to ANECS); Medical Research Council (G0000934 to the British 1958 Birth Cohort); Wellcome Trust (068545/Z/02, 085475 to the British 1958 Birth Cohort); Wellcome Trust Human Genetics Grant (090532/Z/09/Z to NSECG); European Union (EU FP7 CHIBCHA to NSECG); The University of Newcastle (to QIMR Controls, to NECS); Gladys M Brawn Senior Research Fellowship (QIMR Controls); The Vincent Fairfax Family Foundation (QIMR Controls); Hunter Medical Research Institute (HCS, NECS); Hunter Area Pathology Service (HCS); ELAN fund of the University of Erlangen (BECS); Verelst Foundation for endometrial cancer (LES); Fred C and Katherine B Anderson Foundation (to MECS, to MAY); Mayo Foundation (to MECS, to MAY); Ovarian Cancer Research Fund with support of the Smith family, in memory of Kathryn Sladek Smith (MECS, PPD/RPCI.07 to OCAC); Helse Vest Grant (MoMaTEC); University of Bergen (MoMaTEC); Melzer Foundation (MoMaTEC); The Norwegian Cancer Society – Harald Andersens legat (MoMaTEC); The Research Council of Norway (MoMaTEC); Haukeland University of Hospital (MoMaTEC); NBN Children's Cancer Research Group (NECS); Ms Jennie Thomas (NECS); regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet (20110222, 20110483, 20110141 and DF 07015 all to RENDOCAS, to KARBAC); The Swedish Labor Market Insurance (100069 to RENDOCAS); The Swedish Cancer Society (11 0439 to RENDOCAS); Agency for Science, Technology and Research of Singapore (CAHRES); Susan G Komen Breast Cancer Foundation (CAHRES); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge (OCAC); Baden-Württemberg state Ministry of Science, Research and Arts (ESTHER); Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (ESTHER); Federal Ministry of Education and Research (BMBF) Germany (01KW9975/5 to GENICA, 01KW9976/8 to GENICA, 01KW9977/0 to GENICA, 01KW0114 to GENICA, to ESTHER); Robert Bosch Foundation (GENICA); Deutsches Krebsforschungszentrum – DKFZ (GENICA); Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, IPA (GENICA); Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus (GENICA); Deutsche Krebshilfe e.V. (70-2892-BR I to MARIE); Hamburg Cancer Society (MARIE); German Cancer Research Center (MARIE); Breast Cancer Research Foundation (MCBCS); David F. and Margaret T. Grohne Family Foundation (MCBCS); Ting Tsung and Wei Fong Chao Foundation (MCBCS); VicHealth (MCCS); Cancer Council Victoria (MCCS); Breakthrough Breast Cancer (UKBGS); Institute of Cancer Research (UKBGS); and NHS funding to the NIHR Biomedical Research Centre (UKBGS/ICR).This is the final version of the article. It first appeared from the Society for Endocrinology via http://dx.doi.org/10.1530/ERC-15-031

CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer.

Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10(-11)). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10(-8)). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.Fine-mapping analysis was supported by NHMRC project grant [ID#1031333] to ABS, DFE and AMD. ABS, PW, GWM, and DRN are supported by the NHMRC Fellowship scheme. AMD is supported by the Joseph Mitchell Trust. IT is supported by Cancer Research UK and the Oxford Comprehensive Biomedical Research Centre. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 [HEALTH-F2-2009-223175] [COGS], Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565], the National Institutes of Health [CA128978] and Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative], the Department of Defence [W81XWH-10-1-0341], the Canadian Institutes of Health Research [CIHR] for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. ANECS recruitment was supported by project grants from the NHMRC [ID#339435], The Cancer Council Queensland [ID#4196615] and Cancer Council Tasmania [ID#403031 and ID#457636]. SEARCH recruitment was funded by a programme grant from Cancer Research UK [C490/A10124]. Stage 1 and stage 2 case genotyping was supported by the NHMRC [ID#552402, ID#1031333]. This study 647 makes use of data generated by the Wellcome Trust Case-Control Consortium (WTCCC). A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02 - funding for this project was provided by the Wellcome Trust under award 085475. NSECG was supported by the EU FP7 CHIBCHA grant and Wellcome Trust Centre for Human Genetics Grant 090532/Z/09Z, and CORGI by Cancer Research UK. Recruitment of the QIMR Berghofer controls was supported by the NHMRC. The University of Newcastle, the Gladys M Brawn Senior Research Fellowship scheme, The Vincent Fairfax Family Foundation, the Hunter Medical Research Institute and the Hunter Area Pathology Service all contributed towards the costs of establishing the Hunter Community Study. The Bavarian Endometrial Cancer Study (BECS) was partly funded by the ELAN fund of the University of Erlangen. The Leuven Endometrium Study (LES) was supported by the Verelst Foundation for endometrial cancer. The Mayo Endometrial Cancer Study (MECS) and Mayo controls (MAY) were supported by grants from the National Cancer Institute of United States Public Health Service [R01 CA122443, P30 CA15083, P50 CA136393, and GAME-ON the NCI Cancer Post-GWAS Initiative U19 CA148112], the Fred C and Katherine B Andersen Foundation, the Mayo Foundation, and the Ovarian Cancer Research Fund with support of the Smith family, in memory of Kathryn Sladek Smith. MoMaTEC received financial support from a Helse Vest Grant, the University of Bergen, Melzer Foundation, The Norwegian Cancer Society (Harald Andersens legat), The Research Council of Norway and Haukeland University Hospital. 672 The Newcastle Endometrial Cancer Study (NECS) acknowledges contributions from the University of Newcastle, The NBN Children’s Cancer Research Group, Ms Jennie Thomas and the Hunter Medical Research Institute. RENDOCAS was supported through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet [numbers: 20110222, 20110483, 20110141 and DF 07015], The Swedish Labor Market Insurance [number 100069] and The Swedish Cancer Society [number 11 0439]. The Cancer Hormone Replacement Epidemiology in Sweden Study (CAHRES, formerly called The Singapore and Swedish Breast/Endometrial Cancer Study; SASBAC) was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institutes of Health and the Susan G. Komen Breast Cancer Foundation. The Breast Cancer Association Consortium (BCAC) is funded by Cancer Research UK [C1287/A10118, C1287/A12014]. The Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith [PPD/RPCI.07], and the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge. Additional funding for individual control groups is detailed in the Supplementary Information. EPIC-Norfolk was funded by research programme grant funding from Cancer Research UK and the Medical Research Council with additional support from the Stroke Association, British Heart Foundation, Department of Health, Research into Ageing and Academy of Medical Sciences. The SIBS study was supported by program grant C1287/A10118 and project grants from Cancer Research 697 UK (grant numbers C1287/8459).This is the author accepted manuscript. The final version is available from Bioscientifica via http://dx.doi.org/10.1530/ERC-15-038

Five endometrial cancer risk loci identified through genome-wide association analysis.

We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.I.T. is supported by Cancer Research UK and the Oxford Comprehensive Biomedical Research Centre. T.H.T.C. is supported by the Rhodes Trust and the Nuffield Department of Medicine. Funding for iCOGS infrastructure came from the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565), the US National Institutes of Health (R01 CA128978, U19 CA148537, U19 CA148065 and U19 CA148112), the US Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Susan G. Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund. SEARCH recruitment was funded by a programme grant from Cancer Research UK (C490/A10124). Stage 1 and stage 2 case genotyping was supported by the NHMRC (552402 and 1031333). Control data were generated by the WTCCC, and a full list of the investigators who contributed to the generation of the data is available from the WTCCC website. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by UK Medical Research Council grant G0000934 and Wellcome Trust grant 068545/Z/02; funding for this project was provided by the Wellcome Trust under award 085475. NSECG was supported by the European Union's Framework Programme 7 CHIBCHA grant and Wellcome Trust Centre for Human Genetics Core Grant 090532/Z/09Z, and CORGI was funded by Cancer Research UK. BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014). OCAC is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07) and the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.356

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P <5 x 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain similar to 7.4% of the population variance in age at menarche, corresponding to similar to 25% of the estimated heritability. We implicate similar to 250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049