Variance changes detection in multivariate time series

This paper studies the detection of step changes in the variances and in the correlation structure of the components of a vector of time series. Two procedures are considered. The first is based on the likelihood ratio test and the second on cusum statistics. These two procedures are compared in a simulation study and we conclude that the cusum procedure is more powerful. The procedures are illustrated in two examples.

Executive Privilege in the Federal Courts

Apoptosis is one type of programmed cell death, important during tissue development and to maintain the tissue homeostasis. Apoptosis comprises a complex network of internal signaling pathways, and an important part of this signaling network is the action of voltage‐gated ion channels. The aim of this thesis was to explore the role of ion channels and the role of intracellular metal ions during apoptosis in Xenopus laevis oocytes. The reasons for using these oocytes are that they are large, robust, easy to handle, and easy to study electrophysiologically. Apoptosis was induced either chemically by incubation of the oocytes in staurosporine (STS) or mechanically by centrifugation of the oocytes. Ion currents were measured by a two‐electrode voltage clamp technique, intracellular ion concentrations were measured either directly by in‐house developed K+‐selective microelectrodes or indirectly by the electrophysiological technique, and apoptosis was measured by caspase‐3 activation. Paper I describes that the intracellular K+ concentration was reduced by about 30 % during STS‐induced apoptosis. However, this reduction was prevented by excessive expression of exogenous ion channels. Despite the magnitude of the intracellular K+ concentration, either normal or reduced level, the oocytes displayed normal signs of apoptosis, suggesting that the intracellular K+ reduction was not required for the apoptotic process. Because the intracellular K+ concentration was not critical for apoptosis we searched for other ion fluxes by exploring the electrophysiological properties of X. laevis oocytes. Paper II, describes a non‐inactivating Na+ current activated at positive membrane voltages that was upregulated by a factor of five during STS‐induced apoptosis. By preventing influx of Na+, the apoptotic signaling network involving capsase‐3 was prevented. To molecularly identify this voltage‐gated Na channel, the X. tropicalis genome and conserved regions of the human SCNA genes were used as a map. Paper III, shows that the voltage‐gated Na channel corresponds to the SCN2A gene ortholog and that supression of this SCN2A ortholog using miRNA prevented cell death. In conclusion, this thesis work demonstrated that a voltage‐gated Na channel is critical for the apoptotic process in X. laevis oocytes by increasing the intracellular Na+ concentration

Mitigating Negative Impacts of Adverse Childhood Experiences: A Strength-Based Approach

Mitigating Negative Impacts of Adverse Childhood Experiences: A Strength-Based Approach Nicholas Montello, RN Purpose: Adverse Childhood Experiences (ACEs) are common among Vermont youth, and Vermont has insufficient treatment resources to address their negative impacts. A strength-based approach (SBA) mitigates the negative impacts of ACEs by using a person’s assets to build resilience to ACEs. This project is designed to increase healthcare worker and patient/caregiver knowledge of ACEs via the SBA. Methods: An evidence-based quality improvement intervention was implemented at a pediatric primary care office in rural Vermont, based on the Bodega Model for a strength-based approach. Healthcare worker knowledge and use of the SBA was assessed after an educational intervention. Materials with information on the SBA were set up for patients in the waiting room. Surveys assessed patient knowledge and perceptions of the SBA. Results: 62% of healthcare workers reported increased knowledge of SBA elements after the educational intervention, and workers reported a 50% increase in usage of SBA elements in the 3 months after the educational intervention. 60% of healthcare workers saw the SBA as cost effective. 100% of surveyed patients reported confidence in using the SBA. All patients who responded to surveys believed that the SBA could help them deal with adversity. Conclusions: The SBA can be effective in primary care for mitigating the negative impacts of ACEs, as noted by health care workers, patients and caregivers. Healthcare workers increased their usage of this evidence-based intervention after the educational session, suggesting that lack of knowledge of the SBA could be a prior barrier to use