<AbstractText>The Brief Negative Symptom Scale (BNSS) includes five domains of negative symptoms suggested by the NIMH Consensus Development Conference (anhedonia, asociality, avolition, blunted affect, and alogia), which could be clustered into two factors - Motivation-Pleasure (MAP) and Emotional Expressivity (EE). Our study aims to examine the psychometric properties of BNSS, and its association with functioning.</AbstractText><AbstractText>274 individuals with schizophrenia were assessed on the BNSS, Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Global Assessment of Functioning Scale (GAF), Calgary Depression Scale for Schizophrenia (CDSS), and Simpson-Angus Extrapyramidal Side Effects Scale (<em>SAS</em>). Internal consistency was examined using Cronbach's <em>alpha</em>. Concurrent, discriminant, and construct validity were examined. Factor structure of BNSS was explored using confirmatory factor analyses. Association between GAF and BNSS was examined with GAF as the dependent variable and BNSS Total, MAP and EE, and BNSS five domains as independent variables in three multiple regression models after controlling for covariates.</AbstractText><AbstractText>BNSS showed good internal consistency (Cronbach's <em>alpha</em> = 0.880) and validity. The five-factor model fit the data better than the two-factor model; a second-order model was superior to both models. More severe symptoms on BNSS Total (B = -0.438, p < .001), MAP (B = -0.876, p < .001), Avolition (B = -2.503, p < .001) and Asociality (B = -0.950, p = .001) were associated with lower GAF.</AbstractText><AbstractText>Our results lend support to the use of BNSS in clinical practice and in future research into negative symptoms. Composite scores could be computed using either the five-factor or second-order models. Negative symptoms, particularly MAP, avolition and asociality, were associated with functioning.</AbstractText>

This study tested the sensitization model proposed by Bell et al. [Bell I.R., Miller C.S. and Schwartz G.E. An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationship to kindling and affective spectrum disorders. Biol. Psychiatry 1992: 32: 218-242] to study chemical sensitivity. The sensitization model indicates that a pharmacological stimulus or a traumatic event which elicits a strong response can sensitize limbic and/or mesolimbic pathways; and subsequent less intense trauma or stimuli, in the same or different modality, can elicit an amplified response. Three groups of subjects were tested: (1) women who reported chemical sensitivity and no sexual abuse (chemically sensitive, CS); (2) sexually abused (SA) women without chemical sensitivity; and (3) healthy women without chemical sensitivity or sexual abuse history (normal, N). All subjects were exposed to odorant and nonodorous control stimuli once a week for 3 weeks. Electroencephalographic activity was recorded while subjects sniffed the odorant and control stimuli. Results of the study revealed that both the CS and the SA group showed electroencephalogram (EEG) alpha sensitization across experimental sessions, while the N group showed little change over time. Additionally, EEG findings revealed that the CS group generated significantly greater alpha activity than the other two groups. Finally, while the groups were different on measures of psychological distress, these differences did not diminish the EEG findings. In summary, these findings suggest that intermittent exposure to chemicals elicits sensitization in CS and SA women without chemical sensitivity, supporting our expectations that chemical sensitivity is, in part, a manifestation of time-dependent sensitization (TDS). Additionally, these EEG findings indicate that CS women are unlike SA and healthy women in the amount of EEG alpha activity they generate. Finally, these findings indicate that psychological factors as assessed in this study do not explain electrophysiological differences between chemically and non-chemically-sensitive women.

Seven patients (one man and six women) with a diagnosis of pulmonary thromboembolism (PTE) were examined by polysomnography in order to clarify the relationship between sleep-related breathing disorders and PTE. In the chronic stage of PTE, sleep apnea syndrome (SAS) was recognized in two patients (a man and a woman) among the subjects. Four of the five patients without SAS showed nocturnal hypoxemia. The female predominance was different from ordinary SAS without the disease background of PTE even though PTE is accompanied by hypoxemia and pulmonary hypertension like SAS. A pathophysiological relationship between PTE and SAS was not found in this study.

OBJECTIVE

The spatial QRS-T angle (SA), a predictor of sudden cardiac death, is a vectorcardiographic variable. Gold standard vertorcardiograms (VCGs) are recorded by using the Frank electrode positions. However, with the commonly available 12-lead ECG, VCGs must be synthesized by matrix multiplication (inverse Dower matrix/Kors matrix). Alternatively, Rautaharju proposed a method to calculate SA directly from the 12-lead ECG. Neither spatial angles computed by using the inverse Dower matrix (SA-D) nor by using the Kors matrix (SA-K) or by using Rautaharju's method (SA-R) have been validated with regard to the spatial angles as directly measured in the Frank VCG (SA-F). Our present study aimed to perform this essential validation.

METHODS

We analyzed SAs in 1220 simultaneously recorded 12-lead ECGs and VCGs, in all data, in SA-F-based tertiles, and after stratification according to pathology or sex.

RESULTS

Linear regression of SA-K, SA-D, and SA-R on SA-F yielded offsets of 0.01 degree, 20.3 degrees, and 28.3 degrees and slopes of 0.96, 0.86, and 0.79, respectively. The bias of SA-K with respect to SA-F (mean +/- SD, -3.2 degrees +/- 13.9 degrees) was significantly (P < .001) smaller than the bias of both SA-D and SA-R with respect to SA-F (8.0 degrees +/- 18.6 degrees and 9.8 degrees +/- 24.6 degrees, respectively); tertile analysis showed a much more homogeneous behavior of the bias in SA-K than of both the bias in SA-D and in SA-R. In pathologic ECGs, there was no significant bias in SA-K; bias in men and women did not differ.

CONCLUSIONS

SA-K resembled SA-F best. In general, when there is no specific reason either to synthesize VCGs with the inverse Dower matrix or to calculate the spatial QRS-T angle with Rautaharju's method, it seems prudent to use the Kors matrix.

The determination of protein structures has furthered our understanding of how various proteins perform their functions. With the large number of structures currently available in the PDB, it is necessary to be able to easily study these proteins in detail. Here new software tools are presented which aim to facilitate this analysis; these include the PDBsum WWW site which provides a summary description of all PDB entries, the programs TOPS and NUCPLOT to plot schematic diagrams representing protein topology and DNA-binding interactions, SAS a WWW-based sequence-analysis tool incorporating structural data, and WWW servers for the analysis of protein-protein interfaces and analyses of over 300 haem-binding proteins.

Descriptive diagnoses of nonsuicidal self-injury (NSSI) and suicide attempts (SAs) may detract from underlying dimensional borderline personality pathology (D-BPP). This study aimed to investigate D-BPP in adolescent inpatients with NSSI and SAs. A consecutive sample of 359 adolescent inpatients was assessed for current and past NSSI and life-time SAs. D-BPP and current mental health problems were measured using the Dimensional Assessment of Personality Pathology and the Strengths and Difficulties Questionnaire, respectively. D-BPP was significantly associated with both current (p < 0.001) and past NSSI (p = 0.025) and life-time SAs (p < 0.001) compared to their non-self-harming peers. Patients with current and past NSSI did not differ in terms of D-BPP or current mental health problems. A multivariate model did not show any additional influence of current mental health problems over and above D-BPP in predicting NSSI and SAs. It can be hypothesized that D-BPP underlies adolescent self-harm and may persist even after its termination, promoting a higher burden of mental health problems.

Adhesion of endothelial cells (EC) to surfaces can be enhanced by supplementing the integrin-mediated adhesion with high-affinity streptavidin (SA) that links a biotinylated EC to a biotinylated surface. Biotin pullout from the EC membrane limits the effectiveness of this treatment, leading to a predominance of EC detachment by cohesive failure. In this study we investigated whether a RGD-SA mutant that links SA to EC integrin receptors, and eliminates EC biotinylation, improves EC adhesion. Suspended EC were incubated with the RGD-SA mutant prior to cell seeding, primarily via attachment to the RGD binding site on alpha(v)beta(3) integrin. RGD-SA-incubated EC were subsequently seeded onto a surface preadsorbed with a mixture of fibronectin (Fn) and biotinylated bovine serum albumin (b-BSA). Results showed EC adhesion supplemented with the RGD-SA-biotin system significantly increased cell retention under flow, critical shear stresses for detachment, focal contact area, and force per bond relative to SA used with biotinylated EC. These increases were accompanied by significant reductions in membrane fragments left behind following EC detachment, which suggested cohesive failure via cell membrane rupture was significantly reduced, and enhanced phosphorylation of focal adhesion kinase, which suggested activation and clustering of integrin receptors. Together, these results show that the integrin-independent augmentation of EC adhesion using SA-biotin can be further improved through use of an RGD-SA mutant.

Salicylic acid (SA), a cell-signaling metabolite in plants, is involved in resistance of plants to pathogens and environmental stresses; however, there is little information available on the responses of fungi to SA. Conidia of Metarhizium robertsii (ARSEF 2575) (Hypocreales: Clavicipitaceae) were produced on potato dextrose agar medium plus yeast extract (PDAY) supplemented with 1, 2, 4, or 8 mM SA (pH adjusted to 6.9) and incubated under constant-dark conditions. Then the tolerance of conidia against wet heat (45 °C, 3 h) and UV-B radiation (7.0 kJ m(-2)) was tested. For comparison, conidia were also produced on minimal medium (MM) that contained no carbon source (carbon starvation), a condition known to induce elevated conidial tolerance to heat and UV-B radiation in M. robertsii. The heat tolerance of conidia produced on PDAY containing 1, 2, or 4 mM SA were two-fold higher than that of conidia produced on PDAY alone; which is the same level of thermotolerance induced by growth on MM. Conidia produced on PDAY with 8 mM SA, however, did not exhibit increased heat tolerance. Growth on PDAY + SA did not increase conidial UV-B tolerance at any of the SA concentrations tested. The conidial yields of M. robertsii produced on PDAY with all levels of SA were somewhat reduced in comparison to the yield on PDAY alone. Nevertheless, conidial yields on PDAY + SA were 20-40 times greater than that obtained on MM alone. In conclusion, M. robertsii conidia produced on PDAY medium containing low concentrations of SA demonstrated increased tolerance to heat, but not to UV-B radiation. In comparison to PDAY alone, SA-amended PDAY afforded somewhat reduced conidial yields; however, in a mass-production situation, yield reductions would be offset by the fact that the conidia obtained would have relatively high heat tolerance.

We report the imaging of hepatocellular carcinoma cells and the immunoassay for alpha fetoprotein (AFP) using CdTe/CdS/ZnS core-shell-shell QDs. Stable and high PLQY (20%-48%) CdTe/CdS/ZnS core-shell-shell QDs were synthesized by a stepwise process. Bioconjugation of the core-shell-shell QDs with streptavidin (SA) was successfully applied in immunofluorescent imaging of the human hepatocellular carcinoma (HCC) cell line HepG2.2.15. Furthermore, the thioglycolic acid (TGA)-capped CdTe/CdS/ZnS core-shell-shell QDs fluorescence lifetime is longer than fluorescein, so it was first engaged to conjugate with antigen for the determination of protein (AFP) by fluorescence polarization immunoassay.

We propose a new six-compartment model of intracellular muscle kinetics of leucine and of its transamination product alpha-ketoisocaproic acid (KIC) by combining systemic tracer infusions of [14C]- and [15N]leucine with the arterial-deep venous catheterization of the human forearm. Venous [14C]KIC specific activity (SA) is taken as representative of intracellular [14C]leucine SA, whereas net [15N]leucine disposal is used to calculate leucine inflow and outflow across forearm cell membrane(s). In post-absorptive normal subjects, model-derived rates of intracellular leucine release from and incorporation into protein were approximately 32% (P = 0.03) and approximately 37% greater (P = 0.025), respectively, than those calculated using a conventional arteriovenous approach. Forearm fasting proteolysis exceeded protein synthesis (P < 0.025), whereas leucine oxidation was greater than zero (P < 0.01), suggesting a net negative leucine (i.e., protein) balance. Leucine inflow from blood to cell represented approximately 30% of arterial leucine delivery; therefore approximately 70% of arterial leucine bypassed intracellular metabolism. This model provides a comprehensive description of regional leucine and KIC kinetics and new estimates of protein degradation and synthesis across the human forearm.

The cell surface protein apolipoprotein 1 (APO1) is expressed on various cell types including malignant lymphoid cells. Triggering of APO1 protein with antibody (Ab) induces apoptosis in APO1-expressing cells. We examined the effect of anti (alpha) APO1 Ab on spontaneous apoptosis (SA) and bcl-2 expression in B cell chronic lymphocytic leukaemia (B-CLL) in vitro. We also investigated the anti-apoptotic activity of interleukin 4 (IL4) on the aAPO1-induced apoptosis in B-CLL cells. Although expression of APO1 on B-CLL cells was not detectable by immunofluorescence, alpha APO1 Ab induced apoptosis in these cells. At 24 hours in culture the number of apoptotic cells was increased by a mean percentage (%) of 27% (range: 21-38) in only half of the cases studied. But in all twelve cases studied, at 48 hours alpha APO1 increased SA by a mean of 72% (range: 26-114) (P < .001) and at 72 hours, the mean % increase was 69% (range: 31-96) in 6/7 cases (P < .001). This effect was alpha APO1 concentration dependent. Interleukin 4 significantly protected B-CLL cells against alpha APO1-induced apoptosis by a mean of 53% (range: 28-76) (P < .001). This protection was specific to IL4 and it was significantly reduced or abolished with alpha IL4 Ab. Expression of bcl-2 protein in untreated cultures was not significantly different from that of the alpha APO1-treated cells; the mean equivalent of soluble fluorochrome (MESF) (range) was 4.9 (3.0-6.8) and 5.2 (3.5-6.0) respectively (P>> 0.2). In fresh B-CLL cells the MESF (range) was 4.5 (2.4-6.6). Thus alpha APO1 Ab induced apoptosis in B-CLL cells by a pathway that is independent of bcl-2 expression and partially blocked by IL4.

Phytotoxic effects of phenolic compounds have been extensively studied, but less attention has been given to the effects of these compounds on soil microbial communities, which are crucial to the productivity of agricultural systems. Responses of cucumber rhizosphere bacterial and fungal communities to syringic acid (SA), a phenolic compound with autotoxicity to cucumber, were analyzed by high-throughput sequencing of 16S rRNA gene and internal transcribed spacer amplicons. SA at the concentration of 0.1 μmol g-1 soil changed rhizosphere bacterial and fungal community compositions, decreased bacterial community diversity but increased fungal community richness and diversity (P<0.05). Moreover, SA increased the relative abundances of bacterial phylum Proteobacteria and fungal classes Leotiomycetes, Pezizomycetes, Tremellomycetes and Eurotiomycetes, but decreased the relative abundances of bacterial phylum Firmicutes and fungal class Sordariomycetes (P<0.05). At the genus level, SA decreased the relative abundances of microbial taxa with pathogen-antagonistic and/or plant growth promoting potentials, such as Pseudomonas spp. (P<0.05). Real-time PCR validated that SA decreased cucumber rhizosphere Pseudomonas spp. abundance (P<0.05). In vitro study showed that SA (0.01 to 10 mM) inhibited the growth of a strain of Pseudomonas spp. with pathogen-antagonistic activities to cucumber pathogen Fusarium oxysporum f.sp. cucumerinum Owen (P<0.05). Overall, SA changed cucumber rhizosphere bacterial and fungal community compositions, which may exert negative effects on cucumber seedling growth through inhibiting plant-beneficial microorganisms.

BACKGROUND

Although everyone working in routine mental health services recognizes the scientific and ethical importance to ensure that treatments being provided are of highest quality, there is a clear lack of consensus regarding what outcome domains to include, what measure of assessment to use and, moreover, who to question when assessing.

RESULTS

Since the fifties, social functioning is considered as an important dimension to take into account for treatment planning and outcome measuring. But for many years, symptoms scales have been considered as sufficient outcome measures and social functioning improvement expected on the basis of symptoms alleviation. As symptoms and social adjustment sometimes appear relatively independent, no accurate conclusion concerning the patient's social functioning can so be driven on the basis of his clinical symptoms. More attention has then been directed toward the development of instruments specifically intended to measure the extent and nature of social functioning impairments observed in most psychiatric syndromes. Many of these instruments are designed to be completed by caregivers or remain time consuming and difficult to use routinely. Presently, in clinical practice, there is a need to rely on simple and brief instruments considering patients'perspective about their social adjustment as a function of time.

OBJECTIVE

The aim of this study is to present a new instrument, the QFS, initially developed in order to assess social functioning in patients involved in group psychotherapy programs conducted in a specialist mental health setting, as well as its psychometric characteristics.

METHODS

It was designed to be completed in less than 10 minutes and the questions are phrased in a simple and redundant way, in order to limit problems inherent to illiteracy or language comprehension. The QFS is a 16 items self-report instrument that assesses both the frequency of (8 items) and the satisfaction with (8 items) various social behaviours adopted during the 2 weeks period preceding the assessment. It yields three separate indexes of social functioning, defined a priori and labelled "frequency", "satisfaction" and "global". The higher the scores, the better the social functioning. The QFS was administered to 457 subjects, aged between 18 and 65, including 176 outpatients (99 with anxious or depressive disorders, 25 with personality disorders and 52 with psychotic disorders) and 281 healthy control subjects.

RESULTS

No significant difference was found between patients and controls according to age or gender distribution. Acceptance rate was high (>95%). Moreover, the QFS was generally acceptable to the clinicians who used it. Internal consistency calculated for each index ranged from 0.65 to 0.83 (Cronbach alpha). Test-retest reliability, calculated within a 15 days time interval on a sample of 49 healthy controls, ranged from 0.69 to 0.71 (intraclass correlation coefficient). Discriminant validity was calculated on healthy controls and patients divided into sub-groups according to their diagnosis. It showed to be excellent, with significantly higher scores in control subjects than in psychiatric patients and significant differences across diagnostic categories (Kruskal-Wallis ANOVA with post-hoc tests, all p<0.05). The convergent validity of the QFS with other measures of social functioning was calculated, using the Social Adaptation Self-Evaluation Scale (SASS) and the Social Adjustment Scale Self-Report (SAS-SR). With the SASS, the convergent validity was higher among patients (Spearman rS 0.71 to 0.92, p<0.01) than controls (rS from 0.49 to 0.66, p<0.001). In healthy controls, correlation with the SAS-SR was moderate but statistically significant (rS from - 0.21 to - 0.44, p<0.05). When comparing QFS scores with self-rated symptoms severity, lower levels of social functioning were significantly associated with more severe symptoms according to the Brief Symptom Inventory (BSI: rS from - 0.38 to - 0.65, p<0.001). The QFS indexes demonstrated sensitivity to change (Wilcoxon: all p<0.05) on a sample of 27 out-patients suffering from anxious-depressive disorders questioned before and after 4 months of cognitive behavioural group therapy running on a weekly basis during 16 sessions of 2 hours each.The factorial validity of the QFS was measured through 3 separate factor analysis conducted using the data of 457 subjects. The first analysis considered only Frequency items; 7 out of 8 items had loadings above 0.5 on Factor 1 accounting for 30.7% (unrotaded) of the variance. The second analysis considered only Satisfaction items; all items had loadings above 0.6 on Factor 1 explaining 43.4% (unrotaded) of the variance. And finally, in the third factor analysis, all QFS items were included; 15 out of 16 items had loadings above 0.4 on Factor 1 accounting for 30% (unrotated) of the variance. Concerning the factorial validity of the instrument, these results suggest that all QFS items belong to the same underlying dimension.

CONCLUSIONS

Finally, provisional norms for the QFS are provided for healthy controls, in order to characterise individual patients or patient subgroups. In conclusion, the need for assessment in clinical routine, in order to estimate different aspects of patients conditions as well as the quality of the treatment provided, has contributed to the development of a large variety of instruments measuring several domains. Concerning the level of social functioning, many instruments fail to meet chief criterion of feasibility, remaining often too complex or time onsuming. Moreover, only few of them are available in French.

CONCLUSIONS

The QFS presented here is a brief, simple and easy to administer self-rating scale that displays satisfactory psychometric properties. It seems to be a valuable instrument for the monitoring of social functioning in psychiatric patients which, from a therapeutic point of view, may have a clear impact as it sets up expectation of change and allows both to reality test patients and therapists beliefs about the presence of progress or not and to identify if therapy is working on this specific outcome domain. Though, to date, the administration of the QFS to other populations and treatment modalities requires further investigation.

We have studied the regeneration of T cell subsets and function after BMT in 21 children affected by combined immunodeficiency after BMT. In the first months, the striking predominance of CD4+ cells displayed the primed CD45R0+ phenotype and a high number of activated (HLA-DR+) T cells were observed. Regeneration of naive CD4+CD45RA+ cells correlated with the recovery of proliferative responses to mitogens (r = 0.64, P<0.001). Peripheral blood lymphocytes circulating after BMT undergo an increased process of in vitro cell death, resulting from two mechanisms: spontaneous apoptosis (SA), a consequence of defective production of IL-2 and down-regulation of Bcl-2 (P = 0.02 vs. healthy controls), and high susceptibility to activation-induced cell death (AICD) after restimulation with mitogens. In accordance with the role of CD95/Fas in this latter process, we have observed a high level of CD95 expression (P<0.001 vs. healthy controls), correlated with AICD (P<0.001) but not with SA, and decreasing with time after BMT (P<0.001). Both SA and AICD levels correlated with the presence of activated T cells and decreased with the progressive recovery of T cell proliferative response. Therefore, the lymphocyte hyperactivated status might explain their susceptibility to apoptosis and contribute to the genesis of immunodeficiency that follows BMT.

OBJECTIVE

Sleep apnoea (SA) is a common breathing disorder that affects 5% of the North American adult population. It has been suggested that suppressing periods of bradycardia associated with apnoea may reduce the autonomic imbalance associated with SA, thereby improving the respiratory condition. The goals of this study were to conduct a systematic review to identify all randomized clinical trial data evaluating atrial overdrive pacing (AOP) for the treatment of SA and to perform a meta-analysis to estimate the true effect of AOP on SA.

RESULTS

A systematic review of the literature was performed to identify all reports of the effect of AOP for the treatment of SA. To be eligible for analysis, studies had to be randomized and controlled, and use the apnoea-hypopnoea index (AHI) to determine the severity of SA. A total of 10 studies were identified, which included 175 patients with intermediate to severe SA. Overall, AOP reduced the AHI by -4.65 episodes/h [95% confidence interval (CI) -8.27 to -1.03, P = 0.01]. In comparison, studies that included a continuous positive airway pressure (CPAP) arm found a greater reduction in AHI with CPAP: -46.3 episodes/h (CI -56.2 to -36.5, P < 0.001).

CONCLUSIONS

Although it appears that AOP is associated with a statistically significant reduction in AHI, the magnitude of this benefit is small and likely not of clinical significance. Atrial overdrive pacing should not be universally indicated in patients with SA, unless they have a conventional indication for cardiac pacing.

Different matrices and sample-matrix preparation procedures have been tested in order to study their influence on the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectra of intact glycoproteins, which present different degrees of glycosylation (human transferrin; bovine fetuin; bovine alpha(1)-acid-glycoprotein; recombinant human erythropoietin; and the novel erythropoiesis stimulating protein). Using sinapinic acid (SA) and the fast evaporation method, the studied glycoproteins became susceptible to fragmentation at any laser intensity, suggesting that this 'hot' matrix is unsuitable for a reliable molecular mass determination of glycosylated compounds. In contrast, 2,5-dihydroxybenzoic acid (DHB) and 6-aza-2-thiothymine (ATT), with an adequate sample-matrix preparation, provided improved results. Samples containing DHB after crystallization by vacuum drying demonstrated the best performance because the labile functional groups from the glycoforms were apparently fragmented to a lower extent. The average molecular masses obtained using this methodology were in all cases a better estimation than those values reported in the literature. The results were reproducible, and sensitivity was similar to that obtained with SA and the fast evaporation method. These excellent results suggest that this MALDI-TOF-MS methodology could be useful for an improved determination of the average molecular mass values of microheterogeneous compounds such as glycoproteins, glycosylated compounds or, in general, molecular mass values of molecules with similar labile functional groups.

BACKGROUND

Chronic orthostatic intolerance (COI) is a common and disabling autonomic syndrome of unclear pathophysiology. We tested the hypothesis that baroreflex and autonomic responses to graded lower body suction (LBNP, up to -40 mmHg) could be altered in COI patients.

METHODS

Electrocardiogram (ECG), non-invasive arterial blood pressure and respiratory activity were measured during progressive LBNP (seven patients and seven volunteers). Lumped arterial baroreflex sensitivity (alpha index), and its arterial and cardiopulmonary components, were assessed by multivariate closed-loop analysis of RR interval and systolic arterial pressure (SAP) spontaneous variabilities and respiration. Monovariate spectral analysis of RR interval and SAP variability provided markers of autonomic regulation of the sinoatrial (SA) node and of vascular sympathetic modulation.

RESULTS

Similar reductions in overall and cardiopulmonary baroreflex gain were observed in both groups in response to graded LBNP. In contrast, only controls demonstrated a selective increase in arterial baroreflex sensitivity, at low-grade LBNP. Clear increases in the low-frequency component of RR interval variability (LFRR) [and decreases in the high-frequency component of RR interval variability (HFRR), both in normalized units] were observed in controls with graded LBNP, while insignificant changes occurred in COI patients, who showed, conversely, exaggerated sympathetic vasomotor responses [as assessed by the low frequency component of SAP variability (LFSAP)].

CONCLUSIONS

Patients with chronic orthostatic intolerance show distinct signs of altered baroreflex and autonomic regulation of the SA node and of the vasculature in response to graded LBNP.

Wilms' tumour (WT) and soft tissue sarcomas (SA) in children lack reliable biochemical markers. This study was carried out to determine the clinical significance of serum soluble interleukin-2 receptor alpha (sIL-2Ralpha) in the diagnostics and treatment monitoring of children with WT and SA. The study included 48 children: ten with WT, eight with SA and 30 healthy controls. The sIL-2Ralpha levels (ELISA) and rates of elevated sIL-2Ralpha values were estimated prospectively at diagnosis and in complete remission during treatment and after therapy. As the dependence on age was determined, the levels of sIL-2Ralpha were expressed as multiplications of the upper value of the normal range for a particular age ( xN). Median pretreatment levels of sIL-2Ralpha in patients exceeded those of healthy controls (1.79 xN for WT and 1.53 for SA vs. 0.61 for controls; p < 0.001) as did the rates of elevated sIL-2Ralpha values (80% of WTand 87.5% of SA patients vs. 0% of controls). Good response to therapy was paralleled by a significant decline of pretreatment sIL-2Ralpha levels and its elevated rates. Thus, sIL-2Ralpha determination may be of some value in the diagnostics and treatment monitoring of childhood WT and SA.

The aim of this study was to show the presence of an imbalance between pro-inflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumor necrosis factor (TNF)alpha, which are well known to possess pro-inflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity, in two groups of 30 patients affected by acute myocardial infarction (AMI) and unstable angina (UA), compared with two equivalent groups of patients with stable angina (SA) and of healthy volunteers. We found a significant increase of IFNgamma and TNFalpha production (p<0.01) and a significant decrease of IL-10 production (p<0.01) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes were found between AMI and UA patients and SA patients and controls. We conclude that a relevant imbalance in cytokine release is present in ACS, markedly favoring pro-inflammatory effects.

The cucumber mosaic virus (CMV) 2b silencing suppressor protein allows the virus to overcome resistance to replication and local movement in inoculated leaves of plants treated with salicylic acid (SA), a resistance-inducing plant hormone. In Arabidopsis thaliana plants systemically infected with CMV, the 2b protein also primes the induction of SA biosynthesis during this compatible interaction. We found that CMV infection of susceptible tobacco (Nicotiana tabacum) also induced SA accumulation. Utilization of mutant 2b proteins expressed during infection of tobacco showed that the N- and C-terminal domains, which had previously been implicated in regulation of symptom induction, were both required for subversion of SA-induced resistance, while all mutants tested except those affecting the putative phosphorylation domain had lost the ability to prime SA accumulation and expression of the SA-induced marker gene PR-1.

BACKGROUND

Sample sizes for single-stage phase II clinical trials in the literature are often based on exact (binomial) tests with levels of significance (alpha (α) <5% and power >80%). This is because there is not always a sample size where α and power are exactly equal to 5% and 80%, respectively. Consequently, the opportunity to trade-off small amounts of α and power for savings in sample sizes may be lost.

METHODS

Sample-size tables are presented for single-stage phase II trials based on exact tests with actual levels of significance and power. Trade-off in small amounts of α and power allows the researcher to select from several possible designs with potentially smaller sample sizes compared with existing approaches. We provide SAS macro coding and an R function, which for a given treatment difference, allow researchers to examine all possible sample sizes for specified differences are provided.

RESULTS

In a single-arm study with P(0) (standard treatment)=10% and P(1) (new treatment)=20%, and specified α=5% and power=80%, the A'Hern approach yields n=78 (exact α=4.53%, power=80.81%). However, by relaxing α to 5.67% and power to 77.7%, a sample size of 65 can be used (a saving of 13 patients).

CONCLUSIONS

The approach we describe is especially useful for trials in rare disorders, or for proof-of-concept studies, where it is important to minimise the trial duration and financial costs, particularly in single-arm cancer trials commonly associated with expensive treatment options.

The motion of particles and feeding currents created by micro-organisms due to a flagellum are considered. The calculations are pertinent to a range of sessile organisms, but we concentrate on a particular organism, namely Salpingoeca amphoridium (SA) (a choanoflagellate), due to the availability of experimental data (Pettitt, 2000). These flow fields are characterized as having very small Reynolds numbers, which implies that viscous forces dominate over inertial ones consistent with using the Stokes flow equations. The flow generated by the flagellum is modelled via the consideration of a point force known as a stokeslet. The interaction between the boundary, to which the organism is attached, and its flagellum leads to toroidal eddies, which serve to transport particles towards the micro-organism, promoting filtering of nutrients by the microvilli which constitute the cell's collar (the filtering mechanism in SA). It is our conjecture that the interaction of multiple toroidal eddies will lead to chaotic advection and hence enhance the domain of feeding for these organisms. The degree of mixing in the region around SA is investigated using chaotic and statistical measures to study the influence the flagellum has on the surrounding fluid. The three-dimensional particle paths around such organisms are also considered with the aim of showing that the plane within which they are situated is an attractor.

Globin synthesis ratios were measured on reticulocytes from nine patients with primary acquired sideroblastic anaemia (SA), four patients with hereditary or congenital SA, two patients with secondary acquired SA and three patients with iron deficiency (ID). Ten of the samples from patients with SA and all the samples from patients with ID had normal ratios. Samples from three patients had significantly abnormal ratios, one from a patient with SA and acquired Hb H disease (alpha/beta 0 X 26), one from a patient with secondary acquired SA (alpha/beta 0 X 88), and one from a patient who went on to develop acute myeloblastic leukaemia (alpha/beta 1 X 36). Globin synthesis was stimulated by 100 microM haem similarly in normal, SA and ID reticulocytes. Any limitation of globin synthesis in SA and ID is therefore not easily reversible by adding haem. Inhibition of haem synthesis in nonsideroblastic reticulocytes using 4 mM isonicotinic acid hydrazide for 1 h incubation affected neither total globin synthesis nor the alpha/beta ratio. These results contradict the view that decreased haem synthesis decreases globin chain synthesis and decreases the alpha/beta globin chain synthesis ratios in human reticulocytes. Previously reported findings that haem could reverse globin chain synthesis inhibition in SA were good evidence for a primary deficiency of haem synthesis in the erythroblasts of these patients. Our inability to substantiate these findings emphasizes the need for a re-evaluation of the aetiology of sideroblastic anaemia.

This study addressed the question if socially anxious adolescents have a negatively biased perception of the way they are treated by their peers. A total of 998 high school students from Grades 8-10 were categorized as socially low, middle, or high anxious on the basis of their SAS-A score. The perceived behavior of classmates was measured using three lists that described class behaviors during oral presentations of students, one list was concerned with the behaviors directed towards the student him/herself and the other two with behaviors directed towards a hypothetical high and low socially anxious peer, respectively. The results indicated that high socially anxious students felt negatively treated by their peers and that the other students too perceived that socially anxious classmates were treated more negatively. This suggests that the perception of the high socially anxious students is not distorted but based on the actual treatment they receive from their classmates.