760 research outputs found

    Enhancing Communication Within Multi-Generational organizations

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    In order to capture the essence of employee dynamics within the ever-changing landscape of modern organizations, a naturalistic inquiry using a holistic approach was employed. This technique emphasized the millennial generation’s communication strengths as compared to those of previous generation workers. The perceptions of millennial students, millennial workers, multi-generational managers, university professors, and IT professionals were analyzed through a constant, comparative analysis and grouped so that grounded theory was allowed to emerge. The products of this inquiry include practical solutions aimed at reducing the uncertainty for multi-generational managers, specifically regarding the supervision of younger generation workers. In addition, the results of this study suggest that traditional business communication practices, when coupled with an increased use of information and communication technologies that are specifically designed to bolster collaboration and interpersonal communication, have the potential to maximize internal and external communication effectiveness. The data collected within this study provided an overview of the underlying values and perceptions behind millennial behavior. This synopsis, captured through millennial focus groups and face-to-face interviews, acquiesces to the literature surrounding the millennial generation. As outwardly portrayed, the individuals within this study are technically advanced, goal-oriented people who want the freedom and balance to work efficiently and effectively. In addition, the millennials used herein respect the traditional organizational structure, but only to the limit that its hierarchical nature does not stunt innovation achieved through adaptability and collaboration

    Phosphorylation of Glutamine Synthetase on Threonine 301 Contributes to Its Inactivation During Epilepsy

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    The astrocyte-specific enzyme glutamine synthetase (GS), which catalyzes the amidation of glutamate to glutamine, plays an essential role in supporting neurotransmission and in limiting NH4+ toxicity. Accordingly, deficits in GS activity contribute to epilepsy and neurodegeneration. Despite its central role in brain physiology, the mechanisms that regulate GS activity are poorly defined. Here, we demonstrate that GS is directly phosphorylated on threonine residue 301 (T301) within the enzyme’s active site by cAMP-dependent protein kinase (PKA). Phosphorylation of T301 leads to a dramatic decrease in glutamine synthesis. Enhanced T301 phosphorylation was evident in a mouse model of epilepsy, which may contribute to the decreased GS activity seen during this trauma. Thus, our results highlight a novel molecular mechanism that determines GS activity under both normal and pathological conditions.</p

    Long-term Holocene groundwater fluctuations in a chalk catchment: evidence from Rock-Eval pyrolysis of riparian peats

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    he depositional history of peat-dominated wetlands can be used to understand palaeoclimate and palaeohydrology and also constrain the impacts of future climate change. However, in chalkland valleys, seasonal water table fluctuations and a high alkalinity have diminished key environment indicators such as pollen, and there is a need for alternative investigative techniques. The method of Rock-Eval pyrolysis can track changes in organic matter source and degradation, potentially relating to historic changes in vegetation cover. This is the first Rock-Eval on cores from a groundwater-dependent riparian chalk valley wetland combined with radiocarbon dating. The dating showed that the cores represented approximately 4000 years of depositional history. Changes in hydrocarbon chemistry including normal alkane composition of the peat indicated shifts of around 500 to 1000 years between terrestrial and more aquatic species, relating to periods of climate wetness. These climatic shifts are broadly consistent with other evidence from ombrotrophic peatland and lacustrine sediments across northwest Europe. However, the connection between climate wetness and groundwater dependent chalkland wetlands is complicated by external anthropogenically driven factors relating to land use and vegetation cover changes in the catchment. Nonetheless, this study suggests that Rock-Eval pyrolysis is a useful and cost-effective tool that can provide evidence for long-term Holocene groundwater fluctuation

    Quantum optical microcombs

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    A key challenge for quantum science and technology is to realize large-scale, precisely controllable, practical systems for non-classical secured communications, metrology and, ultimately, meaningful quantum simulation and computation. Optical frequency combs represent a powerful approach towards this goal, as they provide a very high number of temporal and frequency modes that can result in large-scale quantum systems. The generation and control of quantum optical frequency combs will enable a unique, practical and scalable framework for quantum signal and information processing. Here, we review recent progress on the realization of energy–time entangled optical frequency combs and discuss how photonic integration and the use of fibre-optic telecommunications components can enable quantum state control with new functionalities, yielding unprecedented capability

    Pathogenesis of HIV-associated sensory neuropathy: evidence from in vivo and in vitro experimental models

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    HIV-associated sensory neuropathy (HIV-SN) is a frequent neurological complication of HIV infection and its treatment with some antiretroviral drugs. We review the pathogenesis of the viral- and drug-induced causes of the neuropathy, and its primary symptom, pain, based on evidence from in vivo and in vitro models of HIV-SN. Viral coat proteins mediate nerve fibre damage and hypernociception through direct and indirect mechanisms. Direct interactions between viral proteins and nerve fibres dominate axonal pathology, while somal pathology is dominated by indirect mechanisms that occur secondary to virus-mediated activation of glia and macrophage infiltration into the dorsal root ganglia. The treatment-induced neuropathy and resulting hypernociception arise primarily from drug-induced mitochondrial dysfunction, but the sequence of events initiated by the mitochondrial dysfunction that leads to the nerve fibre damage and dysfunction are still unclear. Overall, the models that have been developed to study the pathogenesis of HIV-SN, and hypernociception associated with the neuropathy, are reasonable models and have provided useful insights into the pathogenesis of HIV-SN. As new models are developed they may ultimately lead to identification of therapeutic targets for the prevention or treatment of this common neurological complication of HIV infection

    Efavirenz Is Predicted To Accumulate in Brain Tissue: an In Silico, In Vitro, and In Vivo Investigation

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    Adequate concentrations of efavirenz in the central nervous system (CNS) are necessary to suppress viral replication, but high concentrations may increase the likelihood of CNS adverse drug reactions. The aim of this investigation was to evaluate the efavirenz distribution in the cerebrospinal fluid (CSF) and the brain by using a physiologically based pharmacokinetic (PBPK) simulation for comparison with rodent and human data. The efavirenz CNS distribution was calculated using a permeability-limited model on a virtual cohort of 100 patients receiving efavirenz (600 mg once daily). Simulation data were then compared with human data from the literature and with rodent data. Wistar rats were administered efavirenz (10 mg kg of body weight(−1)) once daily over 5 weeks. Plasma and brain tissue were collected for analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The median maximum concentrations of drug (C(max)) were predicted to be 3,184 ng ml(−1) (interquartile range [IQR], 2,219 to 4,851 ng ml(−1)), 49.9 ng ml(−1) (IQR, 36.6 to 69.7 ng ml(−1)), and 50,343 ng ml(−1) (IQR, 38,351 to 65,799 ng ml(−1)) in plasma, CSF, and brain tissue, respectively, giving a tissue-to-plasma ratio of 15.8. Following 5 weeks of oral dosing of efavirenz (10 mg kg(−1)), the median plasma and brain tissue concentrations in rats were 69.7 ng ml(−1) (IQR, 44.9 to 130.6 ng ml(−1)) and 702.9 ng ml(−1) (IQR, 475.5 to 1,018.0 ng ml(−1)), respectively, and the median tissue-to-plasma ratio was 9.5 (IQR, 7.0 to 10.9). Although it is useful, measurement of CSF concentrations may give an underestimation of the penetration of antiretrovirals into the brain. The limitations associated with obtaining tissue biopsy specimens and paired plasma and CSF samples from patients make PBPK modeling an attractive tool for probing drug distribution

    Study Protocol:Understanding SARS-Cov-2 infection, immunity and its duration in care home residents and staff in England (VIVALDI)

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    Global infection and mortality rates from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are disproportionately high in certain populations, including amongst older people. Care home residents are frequently exposed to infection due to contact with staff and other residents, and are highly susceptible to infection due to their age and co-morbidity. In England, official statistics suggest that at least 25% of all deaths in care home residents since the start of pandemic are linked to coronavirus disease 2019 (COVID-19), but limited testing for SARS-CoV-2 early in the pandemic means estimates of the true burden of disease are lacking. Additionally, little is known about patterns of transmission between care homes, the community and hospitals, or the relationship between infection and immunity in care home staff and residents. The VIVALDI study plans to address these questions. VIVALDI is a prospective cohort study aiming to recruit 6,500 staff and 5000 residents from 105 care homes across England. Successive rounds of testing for infection will be performed over a period of 12 months. Nasopharyngeal swabs will detect evidence of viral RNA and therefore active infection (accompanied by collection of data on symptoms), whereas blood tests will detect antibodies and evidence of cellular immunity to SARS-CoV-2. Whole genome sequencing of viral isolates to investigate pathways of transmission of infection is planned in collaboration with the COVID-19 Genomics UK Consortium. Qualitative interviews with care home staff will investigate the impact of the pandemic on ways of working and how test results influence infection control practices and behaviours. Data from residents and staff will be linked to national datasets on hospital admissions, antibody and PCR test results, mortality and care home characteristics. Data generated will support national public health efforts to prevent transmission of COVID-19 and protect care home staff and residents from infection.</p
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