302 research outputs found
Employee behaviour in social media environments impacting corporate reputational risk
An employee who has a low level of awareness of how behaviours impact corporate reputation, and access to large online communities, could potentially expose the business to reputational risk. The vast number of individuals on these networks, combined with the low level of skill needed to publish on these sites, has resulted in comments and behaviours being amplified to a much greater audience. Employees and their behaviours represent the reality of the organisation to external stakeholders, and so offer a potential risk for reputational damage.This research used an online survey with Likert scales to test the hypotheses. The survey was sent out to a convenience sample, and then a snowballing technique was used to reach the employees within the identified companies.Managers and employees are equally aware of their impact on corporate reputation; however, they have a difference in opinion on what are acceptable topics to place in the public domain. A breach in the employee-employer psychological contract does not result in an increase in employee‟s willingness to post sensitive information in the public domain and employees are undecided as to how they feel about being prohibited from posting certain information in the public domain as an infringement of their person rights.Dissertation (MBA)--University of Pretoria, 2012.Gordon Institute of Business Science (GIBS)unrestricte
The Development of Excitatory Synapses and Complex Behavior
xi, 111 p. : ill. (some col.)Excitatory glutamatergic synapses facilitate important aspects of communication between the neurons that govern complex forms of behavior. Accordingly, small differences in the molecular composition of glutamatergic synapses have been suggested to underlie neurodevelopment disorders, drive evolutionary changes in brain function and behavior, and enhance specific aspects of cognition in mammals. The appropriate development and later function of these structures in the adult involves the wellcoordinated activities of hundreds of molecules. Therefore, an important goal in neuroscience is to identify and characterize how specific molecules contribute to the development of excitatory synapses as well as how manipulations of their function impact neural systems and behavior throughout life. This dissertation describes two important contributions toward this effort, (1) that the newly discovered molecule, Synaptic Cell Adhesion Molecule 1 (SynCAM1) specifically contributes to the early stages of glutamatergic synapse formation and (2) that Neuroligin1 (NL1) contributes to the mature function of glutamatergic synapses and mature forms of behavior in vivo.
In the first set of experiments, I developed an in vitro cell based assay in order to determine the minimal molecular components necessary to recruit developmentally relevant glutamate receptor subtypes to sites of adhesion mediated by SynCAM1. In these experiments we discovered that protein 4.1B interacted with SynCAM1 in order to cause the specific recruitment of the NMDA type glutamate receptor containing the NR2B subunit. In the second set of experiments, we show that expression of NL1 missing the terminal 55 amino acids enhanced short term learning and flexibility in behaving mice while increasing the number of immature excitatory postsynaptic structures. Interestingly, this behavioral profile had components more consistent with 1 month old juvenile controls than age matched control littermates. In contrast, full length NL1 overexpression impaired learning and enhanced perseverance while yielding an increase in the proportion of synapses with mature characteristics. These results suggest that NL1's C-terminus drives the synaptic maturation process that shapes the development of complex behavior. Both studies bolster our understanding of how specific molecules impact the development of excitatory synapses and complex behavior.
This dissertation includes both my previously published and unpublished co-authored material.Committee in charge: William Roberts, Chairperson;
Philip Washbourne, Advisor;
Victoria Herman, Member;
Michael Wehr, Member;
Judith Eisen, Member;
Clifford Kentros, Outside Membe
Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis.
BACKGROUND: Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate. METHODS: In a multinational retrospective cohort study, LA was defined as arterial blood pH5 mmol/l. Logistic regression was used to identify factors associated with fatality. Sensitivity and specificity of different case definitions as predictors of death were compared. RESULTS: The overall case-fatality rate was 19/110 (17.3%), but among acidotic patients it was 33% (16/49 cases). There were 10 asymptomatic patients and none of them died as a consequence of the event. The median lactate for fatal, non-fatal and all patients was 8.3 mmol/l (IQR 7.2-13.1), 6.4 mmol/l (IQR 5.4-7.8) and 6.7 mmol/l (IQR 5.5-8.1), respectively. After adjusting for age and current CD4(+) T-cell count, lactate >7 mmol/l (OR 6.27, 95% CI 1.13-34.93), blood bicarbonate 18 mmol/l, 95% CI 1.33-75.65) and concurrent opportunistic infections (OR 8.69, 95% CI 1.45-52.22) were independently associated with case fatality. Blood lactate >7 mmol/l showed a sensitivity of 84% for fatality with a specificity of 60%, whereas bicarbonate 7 mmol/l and blood bicarbonate <18 mmol/l appear to predict death and might help clinicians in selecting patients who may benefit from more intense monitoring
Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion
SummarySensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR’s effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion
Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia
We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol) according to exposure to different combination antiretroviral regimens in Asian (n = 2051) and Australian (predominantly Caucasian, n = 794) cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs) and either of at least one protease inhibitor (PI) or non-nucleoside-reverse transcriptases (NNRTIs). We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both); and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: <0.001) but not in case of other lipids (P for interaction: >0.05). The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations
Recommendations for evaluation and management of bone disease in HIV
Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ≥40 years. DXA should be performed in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated
Physical function limitation among gay and bisexual men aged ≥55years with and without HIV: findings from the Australian Positive and Peers Longevity Evaluation Study (APPLES)
Background. As people living with HIV now have a life expectancy approaching that of the general population, clinical care focuses increasingly on the management and prevention of comorbidities and conditions associated with aging. We aimed to assess the prevalence of physical function (PF) limitation among gay and bisexual men (GBM) and determine whether HIV is associated with severe PF limitation in this population. Methods. We analysed cross-sectional data from GBM aged ≥55 years in the Australian Positive and Peers Longevity Evaluation Study who completed a self-administered survey on health and lifestyle factors. PF was measured using the Medical Outcomes Study–Physical Functioning scale. Factors associated with severe PF limitation were assessed using logistic regression. Results. The survey was completed by 381 men: 186 without HIV and 195 with HIV. Median age was 64.3 years for GBM without HIV and 62.1 years for GBM with HIV. Compared with men without HIV, those with HIV had higher proportions of severe (13.3% vs 8.1%) and moderate-to-severe (26.7% vs 24.2%) PF limitation. Severe PF limitation commonly involved difficulty with vigorous activity (95% with severe PF limitation described being limited a lot), climbing several flights of stairs (68.4% limited a lot), bending, kneeling or stooping (60.5% limited a lot), and walking 1 km (55.0% limited a lot). In a model adjusted for age, body mass index, typical duration of physical activity, psychological distress, and number of comorbidities, we found a significant association between HIV and severe PF limitation (adjusted odds ratio 3.3 vs not having HIV, 95% confidence interval 1.3–8.7). Conclusions. The biological mechanisms underlying this association require further investigation, particularly given the growing age of the HIV population and inevitable increase in the burden of PF limitation
A Randomised Trial Comparing Genotypic and Virtual Phenotypic Interpretation of HIV Drug Resistance: The CREST Study
OBJECTIVES: The aim of this study was to compare the efficacy of different HIV drug resistance test reports (genotype and virtual phenotype) in patients who were changing their antiretroviral therapy (ART). DESIGN: Randomised, open-label trial with 48-week followup. SETTING: The study was conducted in a network of primary healthcare sites in Australia and New Zealand. PARTICIPANTS: Patients failing current ART with plasma HIV RNA > 2000 copies/mL who wished to change their current ART were eligible. Subjects were required to be > 18 years of age, previously treated with ART, have no intercurrent illnesses requiring active therapy, and to have provided written informed consent. INTERVENTIONS: Eligible subjects were randomly assigned to receive a genotype (group A) or genotype plus virtual phenotype (group B) prior to selection of their new antiretroviral regimen. OUTCOME MEASURES: Patient groups were compared for patterns of ART selection and surrogate outcomes (plasma viral load and CD4 counts) on an intention-to-treat basis over a 48-week period. RESULTS: Three hundred and twenty seven patients completing > one month of followup were included in these analyses. Resistance tests were the primary means by which ART regimens were selected (group A: 64%, group B: 62%; p = 0.32). At 48 weeks, there were no significant differences between the groups for mean change from baseline plasma HIV RNA (group A: 0.68 log copies/mL, group B: 0.58 log copies/mL; p = 0.23) and mean change from baseline CD4+ cell count (group A: 37 cells/mm(3), group B: 50 cells/mm(3); p = 0.28). CONCLUSIONS: In the absence of clear demonstrated benefits arising from the use of the virtual phenotype interpretation, this study suggests resistance testing using genotyping linked to a reliable interpretive algorithm is adequate for the management of HIV infection
Asymptomatic people with well-controlled HIV do not have abnormal left ventricular global longitudinal strain
BackgroundPrevious studies have reported impairment in systolic and diastolic function in people with HIV (PWHIV). Our aim was to determine if echocardiographically measured left ventricular (LV) global longitudinal strain (GLS) is abnormal in asymptomatic PWHIV.MethodsA cross-sectional study of PWHIV (n = 98, 89% male, median age 53 years) and HIV-negative people (n = 50, median age 53 years) without known cardiovascular disease were recruited from a single centre. All participants completed a health/lifestyle questionnaire, provided a fasting blood sample, and underwent a comprehensive echocardiogram for assessment of diastolic and systolic LV function, including measurement of GLS.ResultsAll PWHIV were receiving antiretroviral therapy (ART) for a median of 12 years (IQR: 6.9, 22.4), the majority with good virological control (87% suppressed) and without immunological compromise (median CD4 598 cells/µl, IQR: 388, 841). Compared with controls of similar age and gender, there was no difference in GLS [mean GLS −20.3% (SD 2.5%) vs. −21.0% (SD 2.5%), p = 0.14] or left ventricular ejection fractions [65.3% (SD 6.3) vs. 64.8% (SD 4.8), p = 0.62]. Following adjustment for covariates (gender, heart rate, systolic and diastolic blood pressure, and fasting glucose), the difference in GLS remained non-significant. There were no differences in LV diastolic function between the groups. Exposure to at least one mitochondrially toxic ART drug (didanosine, stavudine, zidovudine, or zalcitabine) was not associated with impairment of LV systolic function.ConclusionNo clinically significant impairment of myocardial systolic function, as measured by LV GLS, was detected in this predominantly Caucasian male population of PWHIV on long-term ART, with no history of cardiovascular disease
Burned area and carbon emissions across northwestern boreal North America from 2001-2019
Fire is the dominant disturbance agent in Alaskan and Canadian boreal ecosystems and releases large amounts of carbon into the atmosphere. Burned area and carbon emissions have been increasing with climate change, which have the potential to alter the carbon balance and shift the region from a historic sink to a source. It is therefore critically important to track the spatiotemporal changes in burned area and fire carbon emissions over time. Here we developed a new burned-area detection algorithm between 2001-2019 across Alaska and Canada at 500 m (meters) resolution that utilizes finer-scale 30 m Landsat imagery to account for land cover unsuitable for burning. This method strictly balances omission and commission errors at 500 m to derive accurate landscape- and regional-scale burned-area estimates. Using this new burned-area product, we developed statistical models to predict burn depth and carbon combustion for the same period within the NASA Arctic-Boreal Vulnerability Experiment (ABoVE) core and extended domain. Statistical models were constrained using a database of field observations across the domain and were related to a variety of response variables including remotely sensed indicators of fire severity, fire weather indices, local climate, soils, and topographic indicators. The burn depth and aboveground combustion models performed best, with poorer performance for belowground combustion. We estimate 2.37×106 ha (2.37 Mha) burned annually between 2001-2019 over the ABoVE domain (2.87 Mha across all of Alaska and Canada), emitting 79.3 ± 27.96 Tg (±1 standard deviation) of carbon (C) per year, with a mean combustion rate of 3.13 ± 1.17 kg C m-2. Mean combustion and burn depth displayed a general gradient of higher severity in the northwestern portion of the domain to lower severity in the south and east. We also found larger-fire years and later-season burning were generally associated with greater mean combustion. Our estimates are generally consistent with previous efforts to quantify burned area, fire carbon emissions, and their drivers in regions within boreal North America; however, we generally estimate higher burned area and carbon emissions due to our use of Landsat imagery, greater availability of field observations, and improvements in modeling. The burned area and combustion datasets described here (the ABoVE Fire Emissions Database, or ABoVE-FED) can be used for local- to continental-scale applications of boreal fire science
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