Clonal Analysis of Regulatory T Cell Defect in Patients with Autoimmune Polyendocrine Syndrome Type 1 Suggests Intrathymic Impairment.

Mutations in the autoimmune regulator gene disrupt thymic T cell development and negative selection, leading to the recessively inherited polyendocrine autoimmune disease autoimmune polyendocrine syndrome type 1 (APS-1). The patients also have a functional defect in the FOXP3+ regulatory T cell population, but its origin is unclear. Here, we have used T cell receptor sequencing to analyse the clonal relationship of major CD4+ T cell subsets in three patients and three healthy controls. The naive regulatory T cells showed little overlap with helper T cell subsets, supporting divergence in the thymus. The activated/memory regulatory T cell subset displayed more sharing with helper T cells, but was mainly recruited from the naive regulatory T cell population. These clonal patterns were very similar in both patients and controls. However, naive regulatory T cells isolated from the patients had a significantly longer T cell receptor complementarity-determining region 3 than any other population, suggesting failure of thymic selection. These data indicate that the peripheral differentiation of regulatory T cells in APS-1 patients is not different from that in healthy controls. Rather, the patients' naive regulatory T cells may have an intrinsic defect imprinted already in the thymus.

Influence of shear viscosity of quark-gluon plasma on elliptic flow in ultrarelativistic heavy-ion collisions.

We investigate the influence of a temperature-dependent shear viscosity over entropy density ratio η/s on the transverse momentum spectra and elliptic flow of hadrons in ultrarelativistic heavy-ion collisions. We find that the elliptic flow in √S(NN)=200 GeV Au+Au collisions at RHIC is dominated by the viscosity in the hadronic phase and in the phase transition region, but largely insensitive to the viscosity of the quark-gluon plasma (QGP). At the highest LHC energy, the elliptic flow becomes sensitive to the QGP viscosity and insensitive to the hadronic viscosity.

Design principles for simulation games for learning clinical reasoning: A design-based research approach.

BACKGROUND: Nurses sometimes lack the competence needed for recognising deterioration in patient conditions and this is often due to poor clinical reasoning. There is a need to develop new possibilities for learning this crucial competence area. In addition, educators need to be future oriented; they need to be able to design and adopt new pedagogical innovations. The purpose of the study is to describe the development process and to generate principles for the design of nursing simulation games. METHOD: A design-based research methodology is applied in this study. Iterative cycles of analysis, design, development, testing and refinement were conducted via collaboration among researchers, educators, students, and game designers. RESULTS: The study facilitated the generation of reusable design principles for simulation games to guide future designers when designing and developing simulation games for learning clinical reasoning. CONCLUSION: This study makes a major contribution to research on simulation game development in the field of nursing education. The results of this study provide important insights into the significance of involving nurse educators in the design and development process of educational simulation games for the purpose of nursing education.

Effect of smoking on neuroleptics in schizophrenia.

OBJECTIVE: The effect of smoking on daily doses and plasma levels of neuroleptics prescribed for schizophrenic patients was studied. METHODS: 90 outpatients with schizophrenic disorder (DSM-III-R) who were on a stable regimen of psychotropic medication and showed a stable clinical state were included in a double-blind placebo-controlled trial. Data were collected and blood tests taken at the baseline interview. The plasma levels were obtained for 52 patients. RESULTS: Daily neuroleptic doses converted to chlorpromazine equivalents correlated significantly (r = 0.436) with the plasma levels of their unmetabolised fractions. The neuroleptic doses increased with age in smokers, while in nonsmokers they decreased. Neither sex, age nor smoking had a significant association with the neuroleptic plasma levels. CONCLUSIONS: Smoking seems to lead to increased neuroleptic dosages in postmenopausal schizophrenics by increasing hepatic metabolism and renal excretion of the drugs and possibly enhancing dopamine release. It is also possible that older smoking patients form a selected group of heavy smoker and they, therefore, need exceptionally high neuroleptic doses.

Citalopram as an adjuvant in schizophrenia: further evidence for a serotonergic dimension in schizophrenia.

There is increasing evidence suggesting that symptoms of depression and anxiety may also be associated with serotonergic dysfunction in schizophrenic patients. The effect of the adjuvant selective serotonin reuptake inhibitor citalopram was assessed regarding the symptom dimensions of schizophrenia measured with the Positive and Negative Syndrome Scale (PANSS) and with the Hamilton Rating Scale for Depression (HRSD). Citalopram alleviated symptoms of the depression/anxiety dimension of the PANSS, but not the symptoms of the four other PANSS domains or depressive symptoms measured with the HRSD. The results support the hypothesis of a serotonergic dimension in schizophrenia.

Mercury adsorption on gold surfaces employed in the sampling and determination of vaporous mercury: a scanning tunneling microscopy study.

To clarify the mechanism of mercury adsorption on gold surfaces thin epitaxial gold films have been exposed to trace amounts of gaseous mercury under laboratory conditions for different periods of time. The changes in the surface morphology of the thin films caused by the exposure have been studied by scanning tunneling microscopy (STM). The evolution of the surface structures with time has been also investigated, in the course of a few days after the exposure. The adsorption of mercury on the gold surfaces has caused drastic changes in the morphology of the surfaces. Pits and islands of 2 to 30 nm in diameter have appeared on the surface, their size and density per unit area depending on the amount of exposure to mercury. The formation of pits and islands followed a certain path of events.

Smoking and cognitive deficits in schizophrenia: a pilot study.

The cross-sectional study assessed the associations among smoking status, number of cigarettes smoked per day, and psychiatric symptoms in 88 chronic schizophrenic outpatients with a stable psychic condition. Among the 49 smokers, the number of cigarettes smoked per day was associated with the severity of cognitive symptoms of the Positive and Negative Syndrome Scale. The authors suggest that smoking may alleviate cognitive deficits in schizophrenia by increasing dopaminergic neurotransmission in the prefrontal areas of the brain.

Citalopram causes no significant alterations in plasma neuroleptic levels in schizophrenic patients.

Steady-state plasma concentrations of commonly used neuroleptic drugs were measured in 90 schizophrenic patients before and after adding placebo or citalopram (40 mg/day) to their treatment regimen. Plasma concentrations of citalopram and its main metabolite, desmethylcitalopram, were also measured. In addition, patients with exceptionally high neuroleptic levels or an increase in adverse effects during the 12-week study period were evaluated for their debrisoquine/sparteine hydroxylase (CYP2D6) genotype, an enzyme responsible for oxidative metabolism of several neuroleptics and selective serotonin re-uptake inhibitors. There were no significant changes in plasma concentrations of haloperidol, chlorpromazine, zuclopenthixol, levomepromazine, thioridazine or perphenazine during the study. Plasma concentrations of citalopram and desmethylcitalopram were well within the levels reported previously with monotherapy, and remained stable throughout the study. None of the 15 patients analysed for the CYP2D6 genotype was a poor metabolizer. It is concluded that clinically important pharmacokinetic drug interactions do not play a crucial role when citalopram is used as an augmentation therapy in neuroleptic-treated schizophrenic patients.

A new method for protein crystallization using high pressure.

Crystallization methods for proteins have been the subject of decades of development yet protein crystallization remains the limiting step in structural studies. We present here a new method for protein crystallization--based on the use of high pressure--that enabled us to accelerate dramatically the growth of glucose isomerase crystals. We think this method may have a more general utility.

Child protection at home: a Finnish model.

When applied to a new social services program in Finland, the term home care has a whole new meaning. The Alvari home care project combines intensive home care, psychology and social work, and social rehabilitation, all with the purpose of increasing child protection.

Relativistic shock waves in viscous gluon matter.

We solve the relativistic Riemann problem in viscous gluon matter employing a microscopic parton cascade. We demonstrate the transition from ideal to viscous shock waves by varying the shear viscosity to entropy density ratio eta/s from zero to infinity. We show that an eta/s ratio larger than 0.2 prevents the development of well-defined shock waves on time scales typical for ultrarelativistic heavy-ion collisions. Comparisons with viscous hydrodynamic calculations confirm our findings.

Characteristics of the Flash-induced 515 Nanometer Absorbance Change of Intact Isolated Chloroplasts.

In intact (type A) chloroplasts isolated from mesophyll protoplasts of maize (Zea mays L. convar. KSC 360) the flash-induced 515 nanometer absorbance change was much higher than in conventionally prepared (types B and C) chloroplasts. The 515 nanometer signal of type A chloroplasts exhibited a biphasic rise: the initial very fast rise (rise time <<1 millisecond) was followed by a slow increase of absorbance (rise time 10 to 20 milliseconds). With decreasing degree of envelope retention the slow phase disappeared. Thus the biphasic rise of the flash-induced 515 nanometer absorbance change can be regarded as an attribute of intact chloroplasts.The 515 nanometer signal of intact chloroplasts was studied at various pH values of the external medium, with various dark intervals between the flashes and at different temperatures. The absorbance change was probed with electron transport inhibitors and ionophores. The data show that the fast phase of the absorbance increase was similar in chloroplasts isolated from protoplasts and in conventional chloroplast preparations. The slow rise, which has not been hitherto recognized in isolated chloroplasts, can be due to a contribution of the proton pump to the electric field which is generated across the thylakoid membranes.

Medication calculation skills of graduating nursing students in Finland.

The aim of this study was to describe the basic mathematical proficiency and the medication calculation skills of graduating nursing students in Finland. A further concern was with how students experienced the teaching of medication calculation. We wanted to find out whether these experiences were associated with various background factors and the students' medication calculation skills. In spring 1997 the population of graduating nursing students in Finland numbered around 1280; the figure for the whole year was 2640. A convenience sample of 204 students completed a questionnaire specially developed for this study. The instrument included structured questions, statements and a medication calculation test. The response rate was 88%. Data analysis was based on descriptive statistics. The students found it hard to learn mathematics and medication calculation skills. Those who evaluated their mathematical and medication calculation skills as sufficient successfully solved the problems included in the questionnaire. It was felt that the introductory course on medication calculation was uninteresting and poorly organised. Overall the students' mathematical skills were inadequate. One-fifth of the students failed to pass the medication calculation test. A positive correlation was shown between the student's grade in mathematics (Sixth Form College) and her skills in medication calculation.

Prediction of positive placebo response among chronic schizophrenic outpatients.

We undertook this study to determine whether predictors of positive placebo response in chronic schizophrenic outpatients could be identified. Twelve placebo responders and 33 placebo nonresponders who participated in a parallel-group, double-blind, 12-week clinical drug trial were compared. No significant differences between the groups were found with regard to 16 anamnestic and symptom variables. To investigate further which variables at baseline predicted positive placebo response, a stepwise linear regression model was created. Of the seven variables entered into the model, only high scores in the positive domain of the Positive and Negative Syndrome Scale (delusions, unusual thought content, grandiosity, and suspiciousness/persecution) at baseline predicted significantly positive placebo response (p = .0047). Because the onset of placebo response was gradual, the authors hypothesize that placebo response in chronic schizophrenia consists mainly of two ingredients: nonspecific psychotherapeutic effect caused by the several assessments carried out during the study, and regression toward the mean.

Citalopram as an adjuvant in chronic schizophrenia: a double-blind placebo-controlled study.

The effects of citalopram--the most selective serotonin reuptake inhibitor on the market--on psychopathological symptoms were studied in chronic schizophrenic patients on a stable regimen of neuroleptic medication. Outpatients suffering from schizophrenic disorder (DSM-III-R) with Positive and Negative Symptom Scale (PANSS) scores higher than 50 were included in a double-blind placebo-controlled add-on study. The daily dose of citalopram was 20 mg in the first week and 40 mg for the remaining period. A total of 90 patients (45 patients receiving citalopram and 45 receiving placebo) completed the 12-week trial. There were no changes in neuroleptic plasma levels during the trial. There was a significant decrease in total PANNS scores during the trial, although no statistically significant differences between the citalopram group and the placebo group were revealed. The number of responders in terms of severity of illness (CGI) was higher and the increase in subjective well-being (VAS) was greater in patients on citalopram than in those receiving placebo. There were no significant differences in the occurrence of side-effects. It is concluded that, in chronic schizophrenic out-patients, citalopram has no clear effect on the psychopathological symptoms; it may improve the general clinical condition, and it appears to increase the subjective well-being of these patients. Citalopram appears to be safe when used to treat schizophrenic patients who are receiving concomitant neuroleptic treatment.