Improving Portfolio Performance

The objective of this thesis is to investigate performance for dierent investment alternatives for an investor wanting to track a multidimensional stock index. Performance is measured in terms of transaction cost, active return against the index and tracking error. The problem is approached by comparing performance for a full replication strategy against a strategy in which the traded portfolio is a dimension reduction of the index as well as against a strategy, trading the dimension reduced portfolio, aiming to predict and in turn minimize transaction costs. The full replication case and the dimension reduction case trade with a volume-weighted strategy, whilst the last strategy trades at times historically being least expensive to trade at. The dimension reduction is done based on results from a principal component analysis together with empiric results on transaction costs associated with trading a certain stock. The transaction cost prediction model implemented is the PAR-model, presented by Rashkovich and Verma (2012). The results show that when reducing the dimension of the index, meaning that stocks with undesired characteristics can be excluded, performance is improved. The transaction cost minimizing strategy show some improvement against the full replication strategy, but its performance is inferior to trading a dimension reduced portfolio with a volume-weighted strategy. This highlights the diculties in predicting stock market behavior. Hence, the strategy recommended for an investor wanting to track a multidimensional index is to conduct a dimension reduction according to preferences and use a volume-weighted trading strategy

Simultaneous Assessment of White Matter Changes in Microstructure and Connectedness in the Blind Brain

Magnetic resonance imaging (MRI) of the human brain has provided converging evidence that visual deprivation induces regional changes in white matter (WM) microstructure. It remains unclear how these changes modify network connections between brain regions. Here we used diffusion-weighted MRI to relate differences in microstructure and structural connectedness of WM in individuals with congenital or late-onset blindness relative to normally sighted controls. Diffusion tensor imaging (DTI) provided voxel-specific microstructural features of the tissue, while anatomical connectivity mapping (ACM) assessed the connectedness of each voxel with the rest of the brain. ACM yielded reduced anatomical connectivity in the corpus callosum in individuals with congenital but not late-onset blindness. ACM did not identify any brain region where blindness resulted in increased anatomical connectivity. DTI revealed widespread microstructural differences as indexed by a reduced regional fractional anisotropy (FA). Blind individuals showed lower FA in the primary visual and the ventral visual processing stream relative to sighted controls regardless of the blindness onset. The results show that visual deprivation shapes WM microstructure and anatomical connectivity, but these changes appear to be spatially dissociated as changes emerge in different WM tracts. They also indicate that regional differences in anatomical connectivity depend on the onset of blindness

Regulation of glycolysis in brown adipocytes by HIF-1α

Brown adipose tissue takes up large amounts of glucose during cold exposure in mice and humans. Here we report an induction of glucose transporter 1 expression and increased expression of several glycolytic enzymes in brown adipose tissue from cold-exposed mice. Accordingly, these genes were also induced after β-adrenergic activation of cultured brown adipocytes, concomitant with accumulation of hypoxia inducible factor-1α (HIF-1α) protein levels. HIF-1α accumulation was dependent on uncoupling protein 1 and generation of mitochondrial reactive oxygen species. Expression of key glycolytic enzymes was reduced after knockdown of HIF-1α in mature brown adipocytes. Glucose consumption, lactate export and glycolytic capacity were reduced in brown adipocytes depleted of Hif-1α. Finally, we observed a decreased β-adrenergically induced oxygen consumption in Hif-1α knockdown adipocytes cultured in medium with glucose as the only exogenously added fuel. These data suggest that HIF-1α-dependent regulation of glycolysis is necessary for maximum glucose metabolism in brown adipocytes.ISSN:2045-232

Oral and Fecal Campylobacter concisus Strains Perturb Barrier Function by Apoptosis Induction in HT-29/B6 Intestinal Epithelial Cells

Campylobacter concisus infections of the gastrointestinal tract can be accompanied by diarrhea and inflammation, whereas colonization of the human oral cavity might have a commensal nature. We focus on the pathophysiology of C. concisus and the effects of different clinical oral and fecal C. concisus strains on human HT-29/B6 colon cells. Six oral and eight fecal strains of C. concisus were isolated. Mucus-producing HT-29/B6 epithelial monolayers were infected with the C. concisus strains. Transepithelial electrical resistance (Rt) and tracer fluxes of different molecule size were measured in Ussing chambers. Tight junction (TJ) protein expression was determined by Western blotting, and subcellular TJ distribution was analyzed by confocal laser-scanning microscopy. Apoptosis induction was examined by TUNEL-staining and Western blot of caspase-3 activation. All strains invaded confluent HT-29/B6 cells and impaired epithelial barrier function, characterized by a time- and dose-dependent decrease in Rt either after infection from the apical side but even more from the basolateral compartment. TJ protein expression changes were sparse, only in apoptotic areas of infected monolayers TJ proteins were redistributed. Solely the barrier-forming TJ protein claudin-5 showed a reduced expression level to 66±8% (P<0.05), by expression regulation from the gene. Concomitantly, Lactate dehydrogenase release was elevated to 3.1±0.3% versus 0.7±0.1% in control (P<0.001), suggesting cytotoxic effects. Furthermore, oral and fecal C. concisus strains elevated apoptotic events to 5-fold. C. concisus-infected monolayers revealed an increased permeability for 332 Da fluorescein (1.74±0.13 vs. 0.56±0.17 10−6 cm/s in control, P<0.05) but showed no difference in permeability for 4 kDa FITC-dextran (FD-4). The same was true in camptothecin-exposed monolayers, where camptothecin was used for apoptosis induction

The SHED-IT community trial study protocol: a randomised controlled trial of weight loss programs for overweight and obese men

<p>Abstract</p> <p>Background</p> <p>Obesity is a major cause of preventable death in Australia with prevalence increasing at an alarming rate. Of particular concern is that approximately 68% of men are overweight/obese, yet are notoriously difficult to engage in weight loss programs, despite being more susceptible than women to adverse weight-related outcomes. There is a need to develop and evaluate obesity treatment programs that target and appeal to men. The primary aim of this study is to evaluate the efficacy of two relatively low intensity weight loss programs developed specifically for men.</p> <p>Methods and Design</p> <p>The study design is an assessor blinded, parallel-group randomised controlled trial that recruited 159 overweight and obese men in Newcastle, Australia. Inclusion criteria included: BMI 25-40 (kg/m²); no participation in other weight loss programs during the study; pass a health-screening questionnaire and pre-exercise risk assessment; available for assessment sessions; access to a computer with e-mail and Internet facilities; and own a mobile phone. Men were recruited to the SHED-IT (Self-Help, Exercise and Diet using Internet Technology) study via the media and emails sent to male dominated workplaces. Men were stratified by BMI category (overweight, obese class I, obese class II) and randomised to one of three groups: (1) SHED-IT <it>Resources </it>- provision of materials (DVD, handbooks, pedometer, tape measure) with embedded behaviour change strategies to support weight loss; (2) SHED-IT <it>Online </it>- same materials as SHED-IT <it>Resources </it>plus access to and instruction on how to use the study website; (3) Wait-list Control. The intervention programs are three months long with outcome measures taken by assessors blinded to group allocation at baseline, and 3- and 6-months post baseline. Outcome measures include: weight (primary outcome), % body fat, waist circumference, blood pressure, resting heart rate, objectively measured physical activity, self-reported dietary intake, sedentary behaviour, physical activity and dietary cognitions, sleepiness, quality of life, and perceived sexual health. Generalised linear mixed models will be used to assess all outcomes for the impact of group (<it>Resources</it>, <it>Online</it>, and <it>Control</it>), time (treated as categorical with levels baseline, 3-months and 6-months) and the group-by-time interaction. These three terms will form the base model. 'Intention-to-treat' analysis will include all randomised participants.</p> <p>Discussion</p> <p>Our study will compare evidence-based and theoretically driven, low cost and easily disseminated strategies specifically targeting weight loss in men. The SHED-IT community trial will provide evidence to inform development and dissemination of sustainable strategies to reduce obesity in men.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry (ACTRN12610000699066)</p

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)