The Generational Divide: Generational Differences in Psychological Capital

Human resource development has customarily focused on social and human capital; however, an innovative new theory within positive organizational behavior focuses on psychological resources. The purpose of this research was to examine the differences across generations on dimensions of psychological resources using the core construct psychological capital. Using a quantitative survey research approach, this study focused on the differences among the three largest generations in the current workforce: Baby Boomers, Generation X, and Generation Y. The independent variable, generations, was defined through a self-identified connection with age and significant events. The dependent variable, psychological capital (PsyCap), was defined as a numeric score representing respondent’s psychological state of development determined through the PCQ-24 instrument. The sample for this study consisted of 347 participants obtained through personal and professional contacts. The results of the ANOVA suggested there is a statistically significant difference among the generations. Specifically, Baby Boomers had higher PsyCap scores than the younger generations. There was also evidence suggesting a difference among generations in three of the four subscales: both Baby Boomers and Generation Y were higher than Generation X in PsyCap efficacy; Baby Boomers were highest, Generation X were in the middle, and Generation Y were the lowest in PsyCap resiliency; and Baby Boomers were higher than both Generation X and Generation Y in PsyCap optimism. The three generations showed equivalent levels of hopefulness. Evidence of differences imply that generational consideration be given in strategies to maximize job satisfaction, commitment, and retention for different generations, specifically training to increase PsyCap among employees within the younger generations. This finding also contributed to the growing field of research on both generations and PsyCap

New Developments in Practice I: Risk Management in Information Systems: Problems and Potential

Risk management can be an extremely powerful approach to dealing with the complexities and uncertainties that increasingly surround technological change and its management. Conventionally in information technology (IT) projects, risks have been narrowly defined. Today, with IT becoming integral to a company\u27s existence, the stakes are considerably higher and broader in scope. However, risk is sometimes seen a negative concept in information systems (IS) organizations because it implies that something could go wrong with an IT project. To understand effective risk management in IS, the authors convened a focus group of senior IS managers from a number of organizations in a variety of industries. The results of this discussion, the managers\u27 presentations, and a review of the current research on risk management, were integrated and are presented in this paper. The nature of risk, identifying risk in IT initiatives, determining appropriate levels of risk, and dealing with unacceptable types and levels of risk are discussed. The following conclusions were reached. Risk management is a means to an end - whether it is a successful IS project; stable, secure technical operations; or a properly implemented business strategy using technology. It is not a one-time activity, but rather an ongoing process of identification, assessment, and action, which needs to be well integrated into every part of IS management. IS managers must learn to control both the problems and the potential that risk represents. Several general principles to help IS managers deal effectively with risks were identified. Effective risk management involves taking a holistic approach to risk, developing a risk management policy, establishing clear accountabilities and responsibilities, balancing risk exposure against controls, being open about risks to reduce conflict and information hiding, enforcing risk management practices, and learning what works and doesn\u27t from past experience

Review: Systematic review and metasynthesis of qualitative literature on young people's experiences of going to A&E/emergency departments for mental health support

Background: There has been an increase in children and young people attending emergency departments for mental health reasons, including self‐harm. Patients often report having poor experiences when attending emergency departments for mental health support. However, there has yet to be a review exploring the experiences of young people. Our aim in this study was to synthesise qualitative literature on young people's experiences of going to emergency departments for mental health support. Methods: A systematic review and metasynthesis were conducted. Five databases and grey literature were searched for relevant studies. Five articles met study criteria and were analysed using an iterative process of thematic synthesis. Results: The synthesis yielded four overarching themes: (a) emergency departments' inability to meet the mental health needs of young people, (b) emergency departments exacerbating patient distress, (c) patients feeling like a burden or undeserving of treatment and (d) consequences of poor emergency department experiences. Conclusions: These findings (based on a still very limited literature) highlight the role that emergency departments have in relation to being a key point of contact with young people who self‐harm. To properly engage with patients, emergency departments need to have the resources to provide compassionate care and follow clinical guidelines regarding assessments

Optimization of tricyclic Nec-3 necroptosis inhibitors for in vitro liver microsomal stability

Necroptosis is a regulated caspase-independent cell death pathway with morphological features resembling passive non-regulated necrosis. Several diverse structure classes of necroptosis inhibitors have been reported to date, including a series of 3,3a,4,5-tetrahydro-2H-benz[g]indazoles (referred to as the Nec-3 series) displaying potent activity in cellular assays. However, evaluation of the tricyclic necroptosis inhibitor’s stability in mouse liver microsomes indicated that they were rapidly degraded. A structure–activity relationship (SAR) study of this compound series revealed that increased liver microsomal stability could be accomplished by modification of the pendent phenyl ring and by introduction of a hydrophilic substituent (i.e., ?-hydroxyl) to the acetamide at the 2-position of the tricyclic ring without significantly compromising necroptosis inhibitory activity. Further increases in microsomal stability could be achieved by utilizing the 5,5-dioxo-3-phenyl-2,3,3a,4-tetrahydro-[1]benzothiopyrano[4,3-c]pyrazoles. However, in this case necroptosis inhibitory activity was not maintained. Overall, these results provide a strategy for generating potent and metabolically stable tricyclic necrostatin analogs (e.g., 33, LDN-193191) potentially suitable for in vivo studies

Intramolecular homolytic substitution in selenoxides and selenones

G3(MP2)-RAD calculations provide activation energies for intramolecular homolytic substitution in the 4-(alkylselenoxo)butyl and 4-(alkylselendioxo)butyl radicals ranging from 21–39 kJ mol−1, and 143–170 kJ mol−1 for the selenoxide and selenone, respectively. Arrhenius data translate into rate constants for ring-closure of 1.5×105−2.5×108 s−1 (80°) for the selenoxides, and 5.4×10−14−5.1×10−11 s−1 (80°) for the corresponding selenones. NBO analyses show alkyl radicals are electrophilic during homolytic substitution at selenoxide selenium. The dominant orbital interaction in the transition state is worth 2413 kJ mol−1 and involves the SOMO and the lone-pair of electrons on selenium. The corresponding selenones are calculated to ring-close through transition states in which alkyl radicals are nucleophilic, but involve weak (SOMO--> σ* and SOMO--> π*) interactions. Consequently, this chemistry is not viable for selenones because of the lack of lone-pairs of electrons on the chalcogen

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)