Exploring the impact of rebranding on stakeholders: a case study of Hotel Management School NHL Stenden

The purpose of this study is to provide a better insight into the impact of rebranding on stakeholders; the case for this study is the rebranding of the  Hotel Management School (HMS). This research has explored how the stakeholders have experienced rebranding and how the rebranding has  affected the brand identity, image and loyalty. A qualitative research method was used and data was gathered conducting semi-structured, face-to-  face interviews with the students, staff and industry partners. The data illustrates that due to effective internal communication the employees were not  affected by the rebranding. Nevertheless, the brand identity, image and loyalty did not have the same effect on the students and industry  partners. Thus, it is recommended that HMS pay more attention to improving the communication, rebuilding and expansion of the brand identity

A total productive maintenance & reliability framework for an active pharmaceutical ingredient plant utilising design for Lean Six Sigma

publishedVersio

Predictive accuracy of boosted regression model in estimating risk of venous thromboembolism following minimally invasive radical surgery in pharmacological prophylaxis-naïve men with prostate cancer

Background: Venous thromboembolism (VTE) is a potentially life-threatening but preventable complication after urological surgery. Physicians are faced with the challenges of weighing the risks and benefits of thromboprophylaxis given scanty evidence for or against and practice variation worldwide.Objective: The primary objective of the study was to explore the possibility of a risk-stratified approach for thromboembolism prophylaxis following radical prostatectomy.Design, setting, and participants: A prospective database was accessed to cross-link venous thromboembolism events in 522 men who underwent minimally invasive prostatectomy between February 2010 and October 2021. A deterministic data linkage method was used to record events through electronic systems. Community Health Index (CHI) numbers were used to identify patients via electronic health records. Patient demographics and clinical characteristics such as age, comorbidities, Gleason staging, and readmission details accrued.Outcomes: VTE within 90 days and development of a risk-stratified scoring system. All statistical analysis was performed using R-Statistical Software and the risk of VTE within 90 days of surgery was estimated via gradient-boosting decision trees (BRT) model.Results and limitations: 1.1% (6/522) of patients developed deep vein thrombosis or pulmonary embolism within 3 months post-minimally invasive prostatectomy. Statistical analysis demonstrated a significant difference in the body mass index (p = 0.016), duration of hospital stay (p &lt; 0.001), and number of readmissions (p = 0.036) between patients who developed VTE versus patients who did not develop VTE. BRT analysis found 8 variables that demonstrated relative importance in predicting VTE. The receiver operating curves (ROC) were constructed to assess the discrimination power of a new model. The model showed an AUC of 0.97 (95% confidence intervals [CI]: 0.945,0.999). For predicting VTE, a single-center study is a limitation.Conclusions: The incidence of VTE post-minimally invasive prostatectomy in men who did not receive prophylaxis with low molecular weight heparin is low (1.1%). The proposed risk-scoring system may aid in the identification of higher-risk patients for thromboprophylaxis. Patient summary: In this report, we looked at the outcomes of venous thromboembolism following minimally invasive radical prostatectomy for prostate cancer in consecutive men. We developed a new scoring system using advanced statistical analysis. We conclude that the VTE risk is very low and our model, if applied, can risk stratify men for the development of VTE following radical surgery for prostate cancer.</p

Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity

Activity-dependent modifications strongly influence neural development. However, molecular programs underlying their context and circuit-specific effects are not well understood. To study global transcriptional changes associated with chronic elevation of synaptic activity, we performed cell-type-specific transcriptome profiling of Drosophila ventral lateral neurons (LNvs) in the developing visual circuit and identified activity-modified transcripts that are enriched in neuron morphogenesis, circadian regulation, and lipid metabolism and trafficking. Using bioinformatics and genetic analyses, we validated activity-induced isoform-specific upregulation of Drosophila lipophorin receptors LpR1 and LpR2, the homologs of mammalian low-density lipoprotein receptor (LDLR) family proteins. Furthermore, our morphological and physiological studies uncovered critical functions of neuronal lipophorin receptors (LpRs) in maintaining the structural and functional integrities in neurons challenged by chronic elevations of activity. Together, our findings identify LpRs as molecular targets for activity-dependent transcriptional regulation and reveal the functional significance of cell-type-specific regulation of neuronal lipid uptake in experience-dependent plasticity and adaptive responses

Immune Response to HIV-1 Infection and Vaccine Development

Human immunodeficiency virus (HIV)-1 infection represents an ongoing challenging public health epidemic. This is in part because of the socioeconomic burden on low-income countries, lack of access to highly active antiretroviral therapy and other medical treatment, and progression to acquired immunodeficiency syndrome (AIDS) over the course of years. To control or eradicate this virus, a prophylactic vaccine must be generated. Despite several decades of research, development, and clinical trials, there is not yet an effective immunization. This chapter focuses on unique aspects of the immune response to this infection, challenges of vaccine development, key clinical trials, and promising vaccine strategies

Safety and efficacy of the partial adenosine A1 receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced ejection fraction:a phase IIb, randomized, double-blind, placebo-controlled trial

Aims Neladenoson bialanate is a partial adenosine A1 receptor agonist with demonstrated beneficial effects on cardiac function in animal models. We aimed to assess the dose-response effect of neladenoson bialanate on cardiac structure and function, clinical outcome, and safety in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results PANTHEON was a dose-finding, phase IIb, randomized, double-blind, placebo-controlled trial conducted in 92 centres in 11 countries including 462 patients with chronic HFrEF, randomized to once daily oral dose of neladenoson bialanate (5, 10, 20, 30, and 40 mg) or placebo. The primary endpoints were change from baseline to 20 weeks in left ventricular ejection fraction (LVEF) (echocardiography) and in N-terminal pro-B-type natriuretic peptide (NT-proBNP). Mean age of the patients was 67 years, 17% were female, mean LVEF was 28%, mean NT-proBNP was 2085 ng/L. After 20 weeks of treatment, there was no dose-effect of neladenoson bialanate on changes in NT-proBNP or LVEF (primary endpoints). No effect of neladenoson bialanate was found on left ventricular volumes, high-sensitivity troponin T, or cardiovascular mortality, HF hospitalization, and urgent visits for HF (secondary endpoints). There was a dose-dependent increase in creatinine and cystatin C, and a dose-dependent decrease in estimated glomerular filtration rate and heart rate. Conclusions In patients with chronic HFrEF, treatment with neladenoson bialanate was not associated with dose-dependent favourable effects on cardiac structure and function, cardiac risk markers, or clinical outcome but was associated with a dose-dependent decrease in renal function. Clinical Trial Registration: identifier NCT02992288

Hematopoietic stem/progenitor cell sources to generate reticulocytes for Plasmodium vivax culture.

The predilection of Plasmodium vivax (P. vivax) for reticulocytes is a major obstacle for its establishment in a long-term culture system, as this requires a continuous supply of large quantities of reticulocytes, representing only 1-2% of circulating red blood cells. We here compared the production of reticulocytes using an established in vitro culture system from three different sources of hematopoietic stem/progenitor cells (HSPC), i.e. umbilical cord blood (UCB), bone marrow (BM) and adult peripheral blood (PB). Compared to CD34+-enriched populations of PB and BM, CD34+-enriched populations of UCB produced the highest amount of reticulocytes that could be invaded by P. vivax. In addition, when CD34+-enriched cells were first expanded, a further extensive increase in reticulocytes was seen for UCB, to a lesser degree BM but not PB. As invasion by P. vivax was significantly better in reticulocytes generated in vitro, we also suggest that P. vivax may have a preference for invading immature reticulocytes, which should be confirmed in future studies

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features

Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms.National Institute of Neurological Diseases and Stroke (U.S.) (R01NS035129)United States. National Institutes of Health (R21TW008223)National Cancer Institute (U.S.) (R01CA157996

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy