A new actigraph for long-term registration of the duration andintensity of tremor and movement

Actigraphy, the long-term measurement of human movement with a small solid state recorder, is gaining acceptance as a useful method in many research fields. Currently available actigraphs assess or estimate the movement duration per time interval. However, the output gives no information on movement type or intensity, and cannot be used in subjects suffering from tremor. The present paper describes a new type of actigraph, that has been developed primarily for the long-term evaluation of motor symptoms in Parkinson patients. The device is the first to discriminate tremor from other movements and to assess both duration and intensity of the two types of movement. It is based on a Motorola 68HC805B6 microcontroller and contains: an accelerometer, programmable gain stages, programmable low- and highpass filters, a programmable level comparator, a peak detector, interface circuits, a real time clock, data storage, and control circuitry. The micro-controller performs a period amplitude sequence analysis (PASA) on the conditioned accelerometer signal, and stores four output variables (tremor duration, tremor amplitude, movement duration, and movement amplitude) at the end of programmable time intervals. The analysis of fluctuations in the motor symptoms of, e.g., Parkinson patients using this actigraph can be of great help in the pharmacological management of symptoms     

Processing attitude statements from in-group and out-group members: Effects of within-group and within-person inconsistencies on reading times.

The authors examined reading times of attitude statements made by group members as a function of consistency of statements with stereotypic expectancies (between-member) and consistency of statements with other statements from the same member (within-member). Stereotype-inconsistent statements were studied longer than consistent statements only when the target group was an outgroup or when subjects were instructed to focus on the group as a whole. Results suggested that the out-group was perceived as a single homogeneous whole regardless of experimental instructions. Inconsistencies within individual group members instigated the longest reading times. This effect was stronger for inconsistencies within out-group members than within in-group members, suggesting that subjects not only expected more within-group variability in in-groups than in out-groups, but they also expected more within-person variability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A survey on the history of transaction management: from flat to grid transactions

Transactions have been around since the Seventies to provide reliable information processing in automated information systems. Originally developed for simple ‘debit-credit’ style database operations in centralized systems, they have moved into much more complex application domains including aspects like distribution, process-orientation and loose coupling. The amount of published research work on transactions is huge and a number of overview papers and books already exist. A concise historic analysis providing an overview of the various phases of development of transaction models and mechanisms in the context of growing complexity of application domains is still missing, however. To fill this gap, this paper presents a historic overview of transaction models organized in several ‘transaction management eras’, thereby investigating numerous transaction models ranging from the classical flat transactions, via advanced and workflow transactions to the Web Services and Grid transaction models. The key concepts and techniques with respect to transaction management are investigated. Placing well-known research efforts in historical perspective reveals specific trends and developments in the area of transaction management. As such, this paper provides a comprehensive, structured overview of developments in the area.     

Classroom ventilation and indoor air quality—results from the FRESH intervention study

Inadequate ventilation of classrooms may lead to increased concentrations of pollutants generated indoors in schools. The FRESH study, on the effects of increased classroom ventilation on indoor air quality, was performed in 18 naturally ventilated classrooms of 17 primary schools in the Netherlands during the heating seasons of 2010–2012. In 12 classrooms, ventilation was increased to targeted CO₂ concentrations of 800 or 1200 ppm, using a temporary CO₂ controlled mechanical ventilation system. Six classrooms were included as controls. In each classroom, data on endotoxin, β(1,3)‐glucans, and particles with diameters of <10 μm (PM₁₀) and <2.5 μm (PM_2.5) and nitrogen dioxide (NO₂) were collected during three consecutive weeks. Associations between the intervention and these measured indoor air pollution levels were assessed using mixed models, with random classroom effects. The intervention lowered endotoxin and β(1,3)‐glucan levels and PM₁₀ concentrations significantly. PM₁₀ for instance was reduced by 25 μg/m³ (95% confidence interval 13–38 μg/m³) from 54 μg/m³ at maximum ventilation rate. No significant differences were found between the two ventilation settings. Concentrations of PM_2.5 and NO₂ were not affected by the intervention. Our results provide evidence that increasing classroom ventilation is effective in decreasing the concentrations of some indoor‐generated pollutants.     

Ventilation and perfusion imaging by electrical impedance tomography: a comparison with radionuclide scanning

Cytokine gene transfer into tumor cells has been shown to mediate tumor regression and antimetastatic effects in several animal models via immunomodulation. Therefore, clinical protocols have been developed to treat cancer patients with cytokine gene-modified tumor cells. We inserted the genes coding for the p35 and p40 chain of interleukin-12 (IL-12) in two independent eukaryotic expression vectors and transduced melanoma cells of 15 different primary tumor cultures with both plasmids by a ballistic gene transfer approach. Secreted IL-12 demonstrated strong bioactivity by inducing interferon-gamma release from peripheral blood lymphocytes upon coculture with cell culture supernatants after IL-12 gene transfer which could at least partly be blocked by IL-12-specific antisera. Further enrichment of transduced tumor cells by magnetic separation directly after gene transfer increased cytokine secretion from a mean of 119 pg in the unsorted to 507 pg IL-12 (24 h/10(8) cells) in the magnetically enriched cell fraction. Irradiation of these cells led to a further elevation of secreted IL-12 (mean 987 pg). Elevated IL-12 levels were detected over 7 days after irradiation in vitro. In a subsequent first clinical phase I study six patients with metastatic melanoma were vaccinated with autologous, interleukin-12 gene-modified tumor cells. Melanoma cells were expanded in vitro from surgically removed metastases, transduced by ballistic gene transfer, irradiated and were then injected subcutaneously (s.c.) at weekly intervals. Clinically, there was no major toxicity except for mild fever. All patients completed more than four s.c. vaccinations over 6 weeks and were eligible for immunological evaluation. Post-vaccination, peripheral mononuclear cells were found to contain an increased number of tumor-reactive proliferative as well as cytolytic cells as determined by a limiting dilution analysis in two patients. Two patients developed DTH reactivity against autologous melanoma cells and one had a minor clinical response. Biopsies taken from that patient's metastases revealed a heavy infiltration of CD4+ and CD8+ T lymphocytes. In conclusion, vaccination induced immunological changes even in a group of advanced, terminally ill patients. These changes can be interpreted as an increased antitumor immune response.     

A Genus-Wide Bioactivity Analysis of Daboia (Viperinae: Viperidae) Viper Venoms Reveals Widespread Variation in Haemotoxic Properties

The snake genus Daboia (Viperidae: Viperinae; Oppel, 1811) contains five species: D. deserti, D. mauritanica, and D. palaestinae, found in Afro-Arabia, and the Russell’s vipers D. russelii and D. siamensis, found in Asia. Russell’s vipers are responsible for a major proportion of the medically important snakebites that occur in the regions they inhabit, and their venoms are notorious for their coagulopathic effects. While widely documented, the extent of venom variation within the Russell’s vipers is poorly characterised, as is the venom activity of other species within the genus. In this study we investigated variation in the haemotoxic activity of Daboia using twelve venoms from all five species, including multiple variants of D. russelii, D. siamensis, and D. palaestinae. We tested the venoms on human plasma using thromboelastography, dose-response coagulometry analyses, and calibrated automated thrombography, and on human fibrinogen by thromboelastography and fibrinogen gels. We assessed activation of blood factors X and prothrombin by the venoms using fluorometry. Variation in venom activity was evident in all experiments. The Asian species D. russelii and D. siamensis and the African species D. mauritanica possessed procoagulant venom, while D. deserti and D. palaestinae were net-anticoagulant. Of the Russell’s vipers, the venom of D. siamensis from Myanmar was most toxic and D. russelli of Sri Lanka the least. Activation of both factor X and prothrombin was evident by all venoms, though at differential levels. Fibrinogenolytic activity varied extensively throughout the genus and followed no phylogenetic trends. This venom variability underpins one of the many challenges facing treatment of Daboia snakebite envenoming. Comprehensive analyses of available antivenoms in neutralising these variable venom activities are therefore of utmost importance.     

Role of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids in the Treatment of Large Chondral Defects in the Knee: A Systematic Review

Autologous chondrocyte implantation (ACI) is a cell therapy for the treatment of focal cartilage defects. The ACI product that is currently approved for use in the European Union (EU) consists of spheroids of autologous matrix-associated chondrocytes. These spheroids are spherical aggregates of ex vivo expanded human autologous chondrocytes and their self-synthesized extracellular matrix. The aim is to provide an overview of the preclinical and nonclinical studies that have been performed to ensure reproducible quality, safety, and efficacy of the cell therapy, and to evaluate the clinical data on ACI with spheroids. A systematic review was performed to include all English publications on self-aggregated spheroids of chondrocytes cultured in autologous serum without other supplements. A total of 20 publications were included, 7 pre- and nonclinical and 13 clinical research publications. The pre- and nonclinical research publications describe the development from concept to in vivo efficacy and quality- and safety-related aspects such as biodistribution, tumorigenicity, genetic stability, and potency. The evaluation of clinical research shows short- to mid-term safety and efficacy for the ACI with spheroid-based treatment of cartilage defects in both randomized clinical trials with selected patients, as well as in routine treatment providing real-world data in more complex patients.     

Ambulatory monitoring of tremor and other movements before and after thalamotomy: a new quantitative technique

Tremor, e.g. in Parkinson patients, often shows large spontaneous fluctuations in severity over the day, to such an extent that a short observation is usually not sufficient to assess the overall severity or the effect of a treatment. Since momentary impressions of the tremor can thus be misleading, long-term ambulatory recordings would be helpful in the evaluation of severity and treatment effectiveness. As existing methods for long-term tremor registration have several shortcomings, a new method is proposed: an algorithm was designed to discriminate tremor from other movements and to describe the amount (i.e. the proportion of tremor or movements per time unit) as well as the intensity (i.e. average acceleration amplitude) of the two types of movement. In the evaluation of the severity of tremor both the amount and intensity of tremor episodes are of importance. The algorithm was tested on 24-h analog tape recordings of wrist-movement in 10 young and 10 aged controls, as well as in 8 patients with tremor--both before and after a tremor relieving thalamotomy. The algorithm scored movements as 'tremor' exclusively in patients prior to the operation. Fluctuations in tremor severity over the day were detected, and tremor could be discriminated from non-pathological movements. Moreover, following thalamotomy, motor slowing (bradykinesia) was detectable using this algorithm. Based on these test results, a miniaturized device in wrist-watch format is now being developed for long-term registrations.     

Short-term effects of ambient oxidant exposure on mortality: a combined analysis within the APHEA project. Air Pollution and Health: a European Approach

The Air Pollution and Health: a European Approach (APHEA) project is a coordinated study of the short-term effects of air pollution on mortality and hospital admissions using data from 15 European cities, with a wide range of geographic, sociodemographic, climatic, and air quality patterns. The objective of this paper is to summarize the results of the short-term effects of ambient oxidants on daily deaths from all causes (excluding accidents). Within the APHEA project, six cities spanning Central and Western Europe provided data on daily deaths and NO2 and/or O3 levels. The data were analyzed by each center separately following a standardized methodology to ensure comparability of results. Poisson autoregressive models allowing for overdispersion were fitted. Fixed effects models were used to pool the individual regression coefficients when there was no evidence of heterogeneity among the cities and random effects models otherwise. Factors possibly correlated with heterogeneity were also investigated. Significant positive associations were found between daily deaths and both NO2 and O3. Increases of 50 micrograms/m3 in NO2 (1-hour maximum) or O3 (1-hour maximum) were associated with a 1.3% (95% confidence interval 0.9-1.8) and 2.9% (95% confidence interval 1.0-4.9) increase in the daily number of deaths, respectively. Stratified analysis of NO2 effects by low and high levels of black smoke or O3 showed no significant evidence for an interaction within each city. However, there was a tendency for larger effects of NO2 in cities with higher levels of black smoke. The pooled estimate for the O3 effect was only slightly reduced, whereas the one for NO2 was almost halved (although it remained significant) when two pollutant models including black smoke were applied. The internal validity (consistency across cities) as well as the external validity (similarities with other published studies) of our results on the O3 effect support the hypothesis of a causal relation between O3 and all cause daily mortality. However, the short-term effects of NO2 on mortality may be confounded by other vehicle-derived pollutants. Thus, the issue of independent NO2 effects requires additional investigation.