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Activation measurement of the 3He(alpha,gamma)7Be cross section at low energy.

The nuclear physics input from the 3He(alpha,gamma)7Be cross section is a major uncertainty in the fluxes of 7Be and 8B neutrinos from the Sun predicted by solar models and in the 7Li abundance obtained in big-bang nucleosynthesis calculations. The present work reports on a new precision experiment using the activation technique at energies directly relevant to big-bang nucleosynthesis. Previously such low energies had been reached experimentally only by the prompt-gamma technique and with inferior precision. Using a windowless gas target, high beam intensity, and low background gamma-counting facilities, the 3He(alpha,gamma)7Be cross section has been determined at 127, 148, and 169 keV center-of-mass energy with a total uncertainty of 4%. The sources of systematic uncertainty are discussed in detail. The present data can be used in big-bang nucleosynthesis calculations and to constrain the extrapolation of the 3He(alpha,gamma)7Be astrophysical S factor to solar energies.

Journal Article↗

Unexplained fatigue syndromes in a multinational primary care sample: specificity of definition and prevalence and distinctiveness from depression and generalized anxiety.

OBJECTIVE: The authors investigated whether narrow definitions of unexplained fatigue syndromes that require additional minor somatic symptoms are more strongly associated with psychiatric morbidity than wider ones. METHOD: This was a secondary analysis of the World Health Organization Collaborative Project on Psychological Problems in General Health Care. A total of 5,438 primary care patients from 14 countries were assessed with the Composite International Diagnostic Interview. RESULTS: The prevalence of fatigue syndromes fell from 7.99 to 1.69 as somatic criteria were added. Patients with depression or anxiety were more likely to report unexplained fatigue, but this association was stronger for definitions of unexplained fatigue with more somatic criteria. CONCLUSIONS: Definitions of unexplained fatigue syndromes that require more somatic criteria selected more patients with psychiatric disorders in this culturally diverse sample. These findings might have implications for the revision of existing international diagnostic criteria for neurasthenia or chronic fatigue syndrome.

Anxiety Disorders↗

[Bibliometric study of articles published in the Revista Española de Anestesiología y Reanimación in 1996-2001].

OBJECTIVE: This evaluation of articles published by Revista Española de Anestesiología y Reanimación (REDAR) between 1996 and 2001 focused on authorship, institutional participation and citations. MATERIAL AND METHODS: Eight hundred twelve articles from 1996 through 2001 were examined for the following information: mean number of authors per article, professional categories and affiliations of the authors, inter-institutional collaboration, number of references, number of self-citations of previous work by one of the authors, rate of journal self-citation, number of citations of Spanish authors, insularity index, immediacy index, number of references that could be evaluated should REDAR analyzed as be a source journal. RESULTS: The mean number of authors per article the period analyzed was 4.26 and the mean number did not differ significantly from year to year. Anesthesiologists accounted for 89.7% of the authors. Institutional collaboration led to 259 articles and the collaboration index was 1.5. The number of references per article was 19.4, the rate of journal self-citation was 6.42%, and the rate of citation authors' own work was 2.73%. The insularity index was 11.9, and the immediacy index was 0.17; 2,430 citable works were counted for calculation of an impact factor. REDAR was the most-cited journal. CONCLUSIONS: The authorship indexes for REDAR are similar to those of other Spanish publications, although the institutional rate is lower. The number of references is similar to those in other Spanish journals. REDAR is the journal receiving the largest number of references and has the greatest effect on the immediacy index.

Anesthesiology↗

Microwell mutation assays: evaluation of ethylmethanesulphonate, benzo[a]pyrene and benzidine using the tk locus in L5178Y mouse lymphoma cells.

As part of the third UKEMS collaborative trial, ICI Central Toxicology Laboratory (CTL) tested the three study chemicals ethylmethanesulphonate (EMS), benzo[a]pyrene (B[a]P) and benzidine (BZD) in a microwell adaptation of the L5178Y gene mutation assay using the thymidine kinase (tk) locus. Cofactors for metabolic activation were optimized prior to testing the chemicals under differing expression times (48 and 72 h) and S9 levels (2,5 and 10%). The results for zero hour survival, relative total growth and mutant frequency were subjected to extensive statistical analyses. It was concluded that the methods described produce a robust and reliable assay and that for routine use a single 72 h expression time and 5% S9 level are sufficient, provided true independent replicates are used.

Animals↗

A reference material for harmonisation of D-dimer assays. Fibrinogen Subcommittee of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis.

The term "D-dimer assay" suggests, that these assays report the concentrations of the end-stage degradation product of crosslinked fibrin. This hardly occurs in patients. Degradation products of cross-linked fibrin rather occur with a wide range of molecular weights, and comprise various numbers of the D-dimer motif. Moreover, the numerical values obtained with different "D-dimer" assays vary widely. The variations are probably due to differences in reactivity of the various monoclonal antibodies used with the various D-dimer containing degradation products as they occur in patients; and to the various calibrators with a value assigned by the manufacturers. For the reasons indicated above a calibrator in the strict sense (e.g., pure D-dimer) is not feasible. This study shows that: it appears feasible to generate a conversion factor for each of the "D-dimer" assays studied, which will make the widely varying results obtained with these kits comparable; that the conversion factors can be based on a pool of real patient samples; and that the conversion factors are pool-independent. The next and final step in this study is to prepare and make available an international reference material for use by manufacturers and others facing a comparison problem. This is being carried out, in collaboration with the NIBSC (Dr. P. Gaffney), and the material is expected to be available in early 1997.

Antifibrinolytic Agents↗

Central versus lateral presentation in hemispheric sentence processing: a paradoxical finding.

There is considerable current interest in the question of the contribution of the right cerebral hemisphere to the comprehension of complex linguistic entities such as sentences and scripts. A problem in this field has been the difficulty of distinguishing between the consequences of lexical and message-level activation. The present study used a cross-modal lexical priming (CMLP) procedure to visually sample activation of word concepts at three different points during the auditory presentation of a sentence. Our aim was to contrast direct lexical activation following presentation of a word in the sentence with syntactic reactivation triggered by a subsequent anaphor. Visual word probes were presented to the right, left, and central visual fields, in order to permit hemispheric performance to be evaluated in relation to previous research confined to central presentations. The results were surprising. LVF probes revealed activation immediately following the target word, RVF probes exhibited activation three words downstream from the target, and centrally presented probes exhibited activation at all three sampling points. The most puzzling aspect of these results was the paradoxical finding that central presentations showed strong activation upon encountering an anaphor of the target, while neither lateral probe revealed any activation at all. We relate these results to recent research on the hemispheric implications of split-foveal word presentation, and suggest that simultaneous stimulation of the two hemispheres may be critical in evoking responses mediated by high-level integrative mechanisms requiring collaborative hemispheric processing.

Adolescent↗

Turbulence and tranquility in the new decade: pharmacy leader--managers in patient care.

Management challenges that face pharmacy in the 1990s are described. Tichy's rope metaphor--intertwined cultural, technical, and political strands of an organization--is applied to problems faced by pharmacy managers; effective managers keep the organization strong by preventing the strands from working at cross-purposes to unravel the rope. Pharmacy's culture--its shared beliefs and values--is changing as "altruistic" institutional pharmacists form home care businesses, pharmacists identify more strongly with the profession than with their institutions, clinical pharmacists identify more strongly with the medical team, and cost control becomes more important. Institutional pharmacy must identify its desired outcomes and apply technology to achieve them. The patient's bedside is the best place for pharmacists to influence prescribing and monitor drug therapy; technology could be used to process patient information at the bedside and to dispense medications there. Current unit dose distribution systems isolate the functions of physician, pharmacist, and nurse, which must be integrated to make the system efficient and responsive. Standardized doses and dosage forms could be developed that are consistent with patient-care protocols; use of protocols allows the effectiveness of treatment methods to be evaluated and eliminates unnecessary therapy. Pharmacy can further its patient-care goals through political success with the medical staff; a pharmacy practice plan developed for a specific clinical area and presented to the medical staff is an example. Collaboration of pharmacists and physicians in a unified institutional strategy for drug use helps ensure appropriate decisions about therapy and prevents manufacturers from attempting to isolate an institution's pharmacists from its medical staff.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Industry↗

T-rex: standardized analysis of germline variants in whole-exome sequencing trios.

Whole-exome sequencing (WES) enables the identification of rare germline variants contributing to pediatric diseases. Trio-based sequencing, comparing affected children with their parents, is particularly effective for rare disease genetics. However, WES data analysis requires bioinformatics expertise, varies across institutions, and is often incompatible with clinical workflows. We developed T-Rex (Trio Rare variant analysis of EXomes), a cross-platform desktop application that enables the standardized and local analysis of WES germline Trio data without the need for programming knowledge. T-Rex integrates state-of-the-art tools for alignment, dual-variant calling (GATK HaplotypeCaller + VarScan2), annotation (SNPEff/SNPSift), rare-variant filtering based on population frequencies (gnomAD), and family-based statistical testing, including the Transmission Disequilibrium Test with multiple-testing correction. Benchmarking of the dual-caller strategy on the Genome in a Bottle Ashkenazim Trio demonstrates high precision (99.2%) while maintaining robust sensitivity (91.1%). User testing (n = 13) confirmed quick learning across clinicians and researchers. Application to a cohort of n = 121 pediatric cancer Trio datasets, filtering for rare protein-coding variants (MAF ≤ 0.1% in gnomAD v4.1), validated all assessable previously reported pathogenic variants. Overall, T-Rex enables clinicians to robustly analyze WES Trio data in compliance with data protection regulations without requiring additional software licenses. As one of the first platforms for comprehensive WES Trio analysis that requires no programming expertise while providing reproducible, end-to-end workflows for clinical genomics, T-Rex facilitates collaborative research between clinics and reduces reliance on external providers.

Humans↗

Molecular and functional analysis of Caenorhabditis elegans CHIP, a homologue of Mammalian CHIP.

A recently identified molecule C-terminus of Hsc70 interacting protein (CHIP) has been reported to be an E3 ubiquitin ligase collaborating with molecular chaperones for the degradation of misfolded or unfolded proteins. The physiological roles of CHIP in animal and plant development remain largely unknown. Here, we show that the knockdown of CeCHIP by RNAi and knockout by a deletion mutation arrests the development of the animal at the larval stage. CeCHIP expresses ubiquitously in all tissues but there are tissue specific variations of expression level. CeCHIP produces dose dependent phenotypes in vivo. Over expression of CHIP causes embryonic lethality, while a comparatively lower level of over expression causes locomotion and egg laying defects, and the CHIP over expressed animals form dauers at a higher temperature.

Amino Acid Sequence↗

Culture and schizophrenia and other psychotic disorders.

The comparative study of schizophrenia and related disorders across cultures has come a long way since Kraepelin advocated its cause, following his trip to Java at the beginning of the last century. The principal development since then has been the burgeoning of interest in the field, culminating in innovative and ambitious international collaborative research by the WHO. Despite reservations about covert ideology or about the more overt methodologic difficulties, the balance of evidence from these and similar studies suggests that: It is feasible to conduct such research despite the numerous hazards. There is a certain uniformity to the way schizophrenia presents globally; there are equally significant cultural differences. The outcome of schizophrenia appears to be better in developing, than developed cultures; reasons for this are far from clear, nevertheless, it can be safely assumed that culturally-determined processes, whether social or environmental, are partly responsible. Overall, the study of schizophrenia in different cultures has proved useful in establishing the pancultural and the culture-specific properties of this and related disorders.

Cross-Cultural Comparison↗

[HIV infection in pregnancy and childhood].

In two ongoing nationwide collaborative studies 375 children of 337 HIV infected mothers (Neonatal HIV Study [started in October 1986], C. Kind, M. D., St. Gall) and 154 pregnancies/induced abortions in 148 HIV infected women (HIV and Pregnancy [started in May 1989], Ch. Rudin, M. D., Basel) have been registered and studied to date. Experiences gained from the two ongoing projects are presented. Viral load during pregnancy seems to influence the vertical transmission rate. There are many differences between HIV infections in children and adults. This is also true for ophthalmologic involvement. Psychosocial problems may be prominent in the care of children born to HIV infected mothers. Recruitment of foster parents is the most serious problem in this context.

AIDS-Related Opportunistic Infections↗

Incidence of complete atrioventricular block following attempted radiofrequency catheter modification of the atrioventricular node in 880 patients. Results of the Multicenter European Radiofrequency Survey (MERFS) The Working Group on Arrhythmias of the European Society of Cardiology.

UNLABELLED: The Multicenter European Radiofrequency Survey (MERFS) retrospectively analysed the incidence of procedure-related complications in 4463 patients who had undergone radiofrequency catheter ablation in 69 European institutions between 1987 and 1992. Of these 4463 patients, 880 underwent modification of the atrioventricular node to cure atrioventricular nodal reentrant tachycardia. This report presents a detailed analysis of the incidence of complete atrioventricular block with respect to the target site and the number of patients reported per institution. The most common complication of modification of the atrioventricular node was the unintended induction of complete atrioventricular block (41 of 880 patients, 4.7%). In 684 of 880 patients (78%), detailed information about the approached target site for modification of the atrioventricular node was available. Complete atrioventricular block occurred significantly more often in patients who underwent ablation of the fast pathway (19/361, 5.3%) or in whom ablation of the slow and fast pathway was attempted after failure at the initial site (4/25, 16%) than in patients who underwent slow pathway ablation (6/298, 2.0%, P < 0.05). The overall incidence of complete atrioventricular block was significantly higher (6.3%) in centres with limited experience in radiofrequency modification of the atrioventricular node ( < or = 30 patients treated; group I: n = 526) compared to centres that had treated > 30 patients (group II: n = 354; 2.3%; P < 0.05). In addition, in those patients in whom the target site was available, the incidence of complete atrioventricular block after fast pathway ablation was significantly higher in group I (n = 168 patients) when compared to group II (n = 193 patients) (7.7% vs 3.1%, P < 0.05) and also tended to be higher after slow pathway ablation in group I (2.4% in group I vs 1.5% in group II; P = ns). CONCLUSIONS: In this analysis of collaborative data, radiofrequency catheter modification of the atrioventricular node carried a risk of approximately 5% of complete atrioventricular block. The incidence of complete atrioventricular block was significantly higher in patients who underwent fast pathway ablation or fast and slow pathway ablation after failure at the initial site compared with slow pathway ablation. In addition, the results indicate that there is a learning curve, regarding the incidence of complete atrioventricular block, which is a significant complication of the procedure, when modifying the atrioventricular node. Thus, caution is recommended when performing radiofrequency modification of the atrioventricular node using the so-called anterior approach to abolish fast pathway conduction, especially when the experience of the institution or investigator/s is limited.

Atrioventricular Node↗

Genetic analysis of the mouse brain proteome.

Proteome analysis is a fundamental step in systematic functional genomics. Here we have resolved 8,767 proteins from the mouse brain proteome by large-gel two-dimensional electrophoresis. We detected 1,324 polymorphic proteins from the European collaborative interspecific backcross. Of these, we mapped 665 proteins genetically and identified 466 proteins by mass spectrometry. Qualitatively polymorphic proteins, to 96%, reflect changes in conformation and/or mass. Quantitatively polymorphic proteins show a high frequency (73%) of allele-specific transmission in codominant heterozygotes. Variations in protein isoforms and protein quantity often mapped to chromosomal positions different from that of the structural gene, indicating that single proteins may act as polygenic traits. Genetic analysis of proteomes may detect the types of polymorphism that are most relevant in disease-association studies.

Alleles↗

Advances in quality of life measurements in oncology patients.

Accurate assessment of the quality of life (QOL) of patients can provide important clinical information to physicians, especially in the area of oncology. Changes in QOL are important indicators of the impact of a new cytotoxic therapy, can affect a patient's willingness to continue treatment, and may aid in defining response in the absence of quantifiable endpoints such as tumor regression. Because QOL is becoming an increasingly important aspect in the management of patients with malignant disease, it is vital that the instruments used to measure QOL are reliable and accurate. Assessment of QOL involves a multidimensional approach that includes physical, functional, social, and emotional well-being, and the most comprehensive instruments measure at least three of these domains. Instruments to measure QOL can be generic (eg, the Nottingham Health Profile), targeted toward specific illnesses (eg, Functional Assessment of Cancer Therapy - Lung), or be a combination of generic and targeted. Two of the most widely used examples of the combination, or hybrid, instruments are the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items and the Functional Assessment of Chronic Illness Therapy. A consequence of the increasing international collaboration in clinical trials has been the growing necessity for instruments that are valid across languages and cultures. To assure the continuing reliability and validity of QOL instruments in this regard, item response theory can be applied. Techniques such as item response theory may be used in the future to construct QOL item banks containing large sets of validated questions that represent various levels of QOL domains. As QOL becomes increasingly important in understanding and approaching the overall management of cancer patients, the tools available to clinicians and researchers to assess QOL will continue to evolve. While the instruments currently available provide reliable and valid measurement, further improvements in precision and application are anticipated.

Cross-Cultural Comparison↗

Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients.

OBJECTIVES: To confirm early, marked decrease in plasma selenium concentrations in patients admitted to a surgical and medical intensive care unit (ICU), and to study this decrease according to the presence or absence of systemic inflammatory response syndrome (SIRS), sepsis, or direct ischemia-reperfusion. DESIGN: Prospective, observational study. SETTINGS: Collaboration between the adult ICU of a 1,100-bed general hospital and a biochemical research laboratory of a university medical center. PATIENTS: One hundred thirty-four consecutive surgical and medical ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the first 31 patients, plasma and urine selenium concentrations were measured by electrothermal atomic absorption spectrometry on admission and once weekly during their ICU stay. These values were compared first with severity scores, criteria for SIRS, sepsis, and organ system failure taken on admission, and then with nosocomial infection, organ system failure during ICU stay, and hospital mortality. An early, low mean plasma selenium concentration was observed in these patients compared with selenium laboratory reference values. Plasma selenium, measured on ICU admission, inversely correlated with Acute Physiology and Chronic Health Evaluation II or Simplified Acute Physiology II scores. Patients with SIRS had lower selenium concentrations than those without SIRS. Mean urine selenium losses were normal in the first 31 patients. Plasma selenium concentration was low in all patients with severe sepsis and septic shock (range 0.20 to 0.72 micromol/L) and in those patients with ischemia-reperfusion from aortic cross-clamping (range 0.34 to 0.68 micromol/L). Despite recommended specific selenium supplementation, plasma selenium concentrations remained low for >2 wks in patients with SIRS. However, there was a slight increase in plasma selenium concentrations in surviving SIRS patients, whereas plasma selenium concentrations decreased in nonsurviving patients. The frequency of ventilator-associated pneumonia, organ system failure, and mortality was three times higher in patients with low plasma selenium concentration at the time of admission (selenium < or =0.70 micromol/L) than for the other patients. CONCLUSIONS: In severely ill ICU patients with SIRS, we observed an early 40% decrease in plasma selenium concentrations, reaching values observed in deleterious nutritional selenium deficiency. This prolonged decrease in selenium concentrations could explain the three-fold increase in morbidity and mortality rates in these patients compared with other ICU patients. The efficacy of selenium treatment in SIRS patients with a high gravity index score or hypoperfusion needs further investigation.

APACHE↗

[Social psychiatry as practical application of epidemiology].

The paper describes the development of an epidemiologically oriented community mental health service (the external psychiatric services of the Canton of Baselland). Because helpful intervention is intended not only to those labelled as patients as is the case in outpatient clinics, the main emphasis is on outreach toward the prospective endangered population, those suffering from chronic mental disease or those in danger of relapses. To this end it is of utmost importance to create networks of collaboration with all other social helping institutions as well as with family physicians, psychiatrists, community officials, ministers, public health nurses as well as with voluntary helpers. The creation of transitional and rehabilitative institutions for sheltered living, rehabilitation for work and for leisure time structuring can take place through the service itself or in collaboration with existing voluntary or charitable organizations. The described service has, on account of extremely restricted personnel, chosen to seek collaboration with a great number of community organizations. The offices of the two ambulatory services (there are two for two somewhat unequal parts of the Canton), function therefore, next to their treatment function, also as centers of coordination for rehabilitative efforts. Coordination of social and health services in the community has been realized in a number of towns. A decentralized but relatively fine-meshed network of caring for the psychically ill or handicapped could be established in the relatively short time of eight years. Network formation is recommended as an epidemiologic technique for the treatment and care of a population at risk, this especially in view of prophylaxis of relapses of severe psychiatric disease.

Chronic Disease↗

Development of a heterologous radioimmunoassay for eel (Anguilla anguilla) gonadotropin.

A heterologous radioimmunoassay (RIA) for eel gonadotropin (GTH) was developed, using an antiserum to the beta subunit of carp GTH (cGTHbeta). Partially purified eel GTH preparations or crude eel pituitary extracts produced partial cross-reactions: the inhibition curves reached a plateau before complete inhibition of the binding of the tracer and the slopes were lower than those for cGTH. However, the parallelism between the inhibition curves produced by all the eel samples allowed estimation of their GTH activity relative to an eel GTH standard; under these conditions, the RIA exhibited good reproducibility within and between assays. Three different RIA systems for cGTHbeta using different antisera gave similar estimations of immunoreactive GTH (irGTH) content of eel GTH preparations and pituitary extracts. The specificity of teh heterologous RIA for eel GTH was first assessed by comparing RIA and bioassay data: as with carp pituitary extracts, no significant difference was found between immunological and biological estimations of GTH activity for partially purified or crude pituitary extracts from normal female eel. Further validation of the specificity of the RIA for eel GTH was provided by the variation of the eel pituitary irGTH content under different hormonal treatments: a significant increase in female eel pituitary irGTH content was produced by treatment with estradiol-17 beta or with carp pituitary extract, a result in agreement with previous histological reports of Olivereau and collaborators. The heterologous RIA for eel GTH, in view of its sensitivity, reproducibility, and specificity, is a useful tool for physiological studies in the eel.

Anguilla↗

Extension of Luria's psycholinguistic studies in Poland.

One of Luria's basic interests was the organization of human cognitive processes, and thinking in particular. He believed that language and thought are closely related, and hence the manner in which we speak reflects the way we think. To verify this assumption, he and his collaborators performed a number of interesting psycholinguistic experiments with subjects of various ages and cultural backgrounds. The tasks used made the evaluation of both receptive and expressive language possible. The Narrative Ability Test described here stems from Luria's observations to a considerable degree. The test was administered to preschool children (N = 106), schoolchildren (N = 143), adolescents (N = 89), adults (N = 126), and older persons (N = 175). Findings of the 20-year studies with normal and deviant populations indicate close relationships among thought, language, and self-control. It was found that difficulty in developing narratives corresponds with a disability to process complex information. Correlations between narrative skills and age, sex, and social background were also noted.

Adult↗