Juvenile neuronal ceroid lipofuscinosis; psychiatric symptoms, GAD-autoantibodies, and response to medication

Juvenile neuronal ceroid lipofuscinosis (JNCL) is one of the most common neurodegenerative diseases in childhood. Its clinical onset, with visual failure as the first sign, is between the ages of 4 to 8 years. During the disease progress, epilepsy, motor symptoms, cognitive decline, and psychiatric symptoms become apparent. It leads to premature death between ages 15 and 30. Treatment consists of symptomatic drug administration and various forms of rehabilitation, but to date, no curative treatment exists. To gain a more comprehensive picture of psychiatric problems, symptoms were evaluated by the Child Behavior Checklist, the Teacher Report Form, and the Children s Depression Inventory. The JNCL patients had a great number of severe psychiatric symptoms, with wide inter-individual variability. The most common symptoms were social, thought, attention, and sleep problems, somatic complaints, and aggressive behaviour. Patients with psychotropic treatment had more problems than did those without psychotropic treatment, and female patients had more problems than did males. Between 10 and 20% of the patients reported depressive symptoms. In a 5-year follow-up, [123I]β-CIT SPECT and MRI revealed a tendency of decreasing serotonin transporter (SERT) availability and progressive brain atrophy. The correlation between changes in midbrain SERT and total brain volume was positive; no correlation appeared between SERT or brain atrophy and depressive symptoms. Thus, it seems likely that the low SERT availability is associated with progressive brain atrophy; it may also predispose towards depression, however. An open survey of psychotropic drugs and their efficacy was performed on JNCL patients in Finland. The most commonly used psychotropic drugs were the antidepressant citalopram and the antipsychotic risperidone. Their efficacy was good or satisfactory in the majority of cases and they seemed well tolerated. Quetiapine had a marked effect on one patient with a history of severe psychotic symptoms. Glutamate decarboxylase 65 autoantibodies (GAD65ab), found in JNCL patients, indicate that an immunomediated reaction against GAD or GABAergic neurons may play a part in the underlying pathogenetic mechanism. GAD65ab s also appeared in the serum of all eight JNCL patients included and intermittent corticosteroid therapy was initiated in all cases. After one year, the GAD65ab s had disappeared in the two oldest patients, who experienced an improvement in motor symptoms and alertness associated with their prednisolone therapy. Two younger patients experienced a significant IQ increase, but no change in GADab s. A randomized study with longer follow-up time is needed, however, to clarify the effect of prednisolone on disease progression.

Factors associated with medication adherence among tuberculosis patients in Timor-Leste

This thesis investigated medication adherence among people living with tuberculosis in Timor Leste. Suboptimal adherence was commonly reported, and was influenced by service inaccessibility, family poverty, patients' absence of disease symptoms and misperception of recovery, untreated depression and a popular cultural belief that luck or chance determines health outcomes. The study has implications for improving health literacy and counselling programs to achieve effective adherence to medication and good health outcomes.

Individual variation in in vitro efficacy of antiplatelet medication - aspirin and clopidogrel

Antiplatelet medication is known to decrease adverse effects in patients with atherothrombotic disease. However, despite ongoing antiplatelet medication considerable number of patients suffer from atherothrombotic events. The aims of the study were 1) to evaluate the individual variability in platelet functions and compare the usability of different methods in detecting it, 2) to assess variability in efficacy of antiplatelet medication with aspirin (acetylsalicylic acid) or the combination of aspirin and clopidogrel and 3) to investigate the main genetic and clinical variables as well as potential underlying mechanisms of variability in efficacy of antiplatelet medication. In comparisons of different platelet function tests in 19 healthy individuals PFA-100® correlated with traditional methods of measuring platelet function and was thus considered appropriate for testing individual variability in platelet activity. Efficacy of ongoing 100mg aspirin daily was studied in 101 patients with coronary artery disease (CAD). Aspirin response was measured with arachidonic acid (AA)-induced platelet aggregation, which reflects cyclo-oxygenase (COX)-1 dependent thromboxane (Tx) A2 formation, and PFA-100®, which evaluates platelet activation under high shear stress in the presence of collagen and epinephrine. Five percent of patients failed to show inhibition of AA-aggregation and 21% of patients had normal PFA-100® results despite aspirin and were thus considered non-responders to aspirin. Interestingly, the two methods of assessing aspirin efficacy, platelet aggregation and PFA-100®, detected different populations as being aspirin non-responders. It could be postulated that PFA-100® actually measures enhanced platelet function, which is not directly associated with TxA2 inhibition exerted by aspirin. Clopidogrel efficacy was assessed in 50 patients who received a 300mg loading dose of clopidogrel 2.5 h prior to percutaneous coronary intervention (PCI) and in 51 patients who were given a loading dose of 300mg combined with a five day treatment of 75mg clopidogrel daily mimicking ongoing treatment. Clopidogrel response was assessed with ADP-induced aggregations, due to its mechanism of action as an inhibitor of ADP-induced activation. When patients received only a loading dose of clopidogrel prior to PCI, 40% did not gain measurable inhibition of their ADP-induced platelet activity (inhibition of 10% or less). Prolongation of treatment so that all patients had reached a plateau of inhibition exerted by clopidogrel, decreased the incidence of non-responders to 20%. Polymorphisms of COX-1 and GP VI, as well as diabetes and female gender, were associated with decreased in vitro aspirin efficacy. Diabetes also impaired the in vitro efficacy of short-term clopidogrel. Decreased response to clopidogrel was associated with limited inhibition by ARMX, an antagonist of P2Y12-receptor, suggesting the reason for clopidogrel resistance to be receptor-dependent. Conclusions: Considerable numbers of CAD patients were non-responders either to aspirin, clopidogrel or both. In the future, platelet function tests may be helpful to individually select effective and safe antiplatelet medication for these patients.

Migration-Development Nexus in the Malawian Health Sector: European Union Blue Card – circular migration for development?

The European Union has agreed on implementing the Policy Coherence for Development (PCD) principle in all policy sectors that are likely to have a direct impact on developing countries. This is in order to take account of and support the EU development cooperation objectives and the achievement of the internationally agreed Millennium Development Goals. The common EU migration policy and the newly introduced EU Blue Card directive present an example of the implementation of the principle in practice: the directive is not only designed to respond to the occurring EU labour demand by attracting highly skilled third-country professionals, but is also intended to contribute to the development objectives of the migrant-sending developing countries, primarily through the tool of circular migration and the consequent skills transfers. My objective in this study is to assess such twofold role of the EU Blue Card and to explore the idea that migration could be harnessed for the benefit of development in conformity with the notion that the two form a positive nexus. Seeing that the EU Blue Card fails to differentiate the most vulnerable countries and sectors from those that are in a better position to take advantage of the global migration flows, the developmental consequences of the directive must be accounted for even in the most severe settings. Accordingly, my intention is to question whether circular migration, as claimed, could address the problem of brain drain in the Malawian health sector, which has witnessed an excessive outflow of its professionals to the UK during the past decade. In order to assess the applicability, likelihood and relevance of circular migration and consequent skills transfers for development in the Malawian context, a field study of a total of 23 interviews with local health professionals was carried out in autumn 2010. The selected approach not only allows me to introduce a developing country perspective to the on-going discussion at the EU level, but also enables me to assess the development dimension of the EU Blue Card and the intended PCD principle through a local lens. Thus these interviews and local viewpoints are at the very heart of this study. Based on my findings from the field, the propensity of the EU Blue Card to result in circular migration and to address the persisting South-North migratory flows as well as the relevance of skills transfers can be called to question. This is as due to the bias in its twofold role the directive overlooks the importance of the sending country circumstances, which are known to determine any developmental outcomes of migration, and assumes that circular migration alone could bring about immediate benefits. Without initial emphasis on local conditions, however, positive outcomes for vulnerable countries such as Malawi are ever more distant. Indeed it seems as if the EU internal interests in migration policy forbid the fulfilment of the PCD principle and diminish the attempt to harness migration for development to bare rhetoric.

Gate Drive Card for High Power Three Phase PWM Converters

Gate driver is an integral part of every power converter, drives the power semiconductor devices and also provides protection for the switches against short-circuit events and over-voltages during shut down. Gate drive card for IGBTs and MOSFETs with basic features can be designed easily by making use of discrete electronic components. Gate driver ICs provides attractive features in a single package, which improves reliability and reduces effort of design engineers. Either case needs one or more isolated power supplies to drive each power semiconductor devices and provide isolation to the control circuitry from the power circuit. The primary emphasis is then to provide simplified and compact isolated power supplies to the gate drive card with the requisite isolation strength and which consumes less space, and for providing thermal protection to the power semiconductor modules for 3-� 3 wire or 4 wire inverters.

A Drift Card Study in Monterey Bay, California, September 1971 to April 1973: Annual Report, Part 4, 1973

Drift cards were released in Monterey Bay, California, to detect seasonal variations in the California Current system, and seasonal and diurnal wind variations in the immediate vicinity of the bay. About 23% of the cards were recovered, although the recovery rate varied from about 5% in the winter to about 60% in the late summer. Drift card speeds ranged from 1 to 8 km/day, in the winter and summer months respectively. Good agreement was observed between geostrophic current, wind, drogue, and drift card data, although drift cards were observed to be primarily wind driven. A weekend bias in drift card recoveries was observed for the entire period of study; however, it was less pronounced for those cards released during the summer months. Two bogus releases were used to estimate the discovery lag time, reported position accuracy, and longshore drift currents. Diurnal winds were observed during a 24-hour study, and indicated daily variations in the wind field may be as important as seasonal changes in moving surface water. The drift card speed was observed to be about 3% of the wind velocity, and 1 m/sec was estimated as the minimum effective wind. The wind factor, ranging from 2.2% to 4.0%, was used to estimate the actual paths of drift cards and to examine the role of diurnal winds in affecting surface water movement. (PDF contains 79 pages)

Biodiversity study of Southern Biscayne Bay and Card Sound 1968-1973

A multi-disciplinary investigation was conducted in southern Biscayne Bay and Card Sound from 1968 to 1973. The purpose of the investigation was to conduct an integrated study of the ecology of southern Biscayne Bay with special emphasis on the effects of the heated effluent from the Turkey Point fossil fuel power plant, and to predict the impact of additional effluent from the planned conversion of the plant to nuclear fuel. The results of this investigation have been discussed in numerous publications. This report contains the unpublished biology data that resulted from the investigation. (PDF contains 44 pages)

2002-03 Florida Keys National Marine Sanctuary science report: An ecosystem report card after five years of marine zoning

Executive Summary: Circulation and Exchange of Florida Bay and South Florida Coastal Waters The coastal ecosystem of South Florida is comprised of distinct marine environments. Circulation of surface waters and exchange processes, which respond to both local and regional forcings, interconnect different coastal environments. In addition, re-circulating current systems within the South Florida coastal ecosystem such as the Tortugas Gyre contribute to retention of locally spawned larvae. Variability in salinity, chlorophyll, and light transmittance occurs on a wide range of temporal and spatial scales, in response to both natural forcing, such as seasonal precipitation and evaporation and interannual “El Niño” climate signals, and anthropogenic forcing, such as water management practices in south Florida. The full time series of surface property maps are posted at www.aoml.noaa.gov/sfp. Regional surface circulation patterns, shown by satellite-tracked surface drifters, respond to large-scale forcing such as wind variability and sea level slopes. Recent patterns include slow flow from near the mouth of the Shark River to the Lower Keys, rapid flow from the Tortugas to the shelf of the Carolinas, and flow from the Tortugas around the Tortugas Gyre and out of the Florida Straits. The Southwest Florida Shelf and the Atlantic side of the Florida Keys coastal zone are directly connected by passages between the islands of the Middle and Lower Keys. Movement of water between these regions depends on a combination of local wind-forced currents and gravitydriven transports through the passages, produced by cross-Key sea level differences on time scales of several days to weeks, which arise because of differences in physical characteristics (shape, orientation, and depth) of the shelf on either side of the Keys. A southeastward mean flow transports water from western Florida Bay, which undergoes large variations in water quality, to the reef tract. Adequate sampling of oceanographic events requires both the capability of near real-time recognition of these events, and the flexibility to rapidly stage targeted field sampling. Capacity to respond to events is increasing, as demonstrated by investigations of the 2002 “blackwater” event and a 2003 entrainment of Mississippi River water to the Tortugas. (PDF contains 364 pages.)