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[Are Nobel prize winners gettting older? Mathematical analysis of age and life span of the Nobel prize winners, 1901-2003].

Data on the distribution by the age of 647 Nobel prizewinner in physics, chemistry, physiology or medicine, economics and literature and time dynamics of the age during 1901-2003 are presented in the paper. The mean survival and the expected life span of the prizewinners was also calculated. The mean life span of the Nobelists in natural sciences steadily increases from the first to the fourth quartile of the 20th century. The rate of the prizewinners selected at the age of 61 and more years increases from the 23% at 1901-1925 to 53.1% at 1975-2003, whereas the rate of the winners selected before the age of 40 years decreases from 19% to 2.7% during the same period. Analysis of available data on the Nobel Prizes for chemistry or physiology or medicine has shown that the majority of the Prizes was awarded to researcher discovered his main results at the age of 31-40 (41.8% and 47.4%, correspondingly). The mean interval between a discovery and a selection for Nobel Prize in chemistry increases from 12.6 years in 1901-1925 to 23.7 years in 1975-2003, whereas corresponding parameters for prizewinners in physiology or medicine increases from to 16.9 to 20.1 years. The mean life span of deceased Nobelists is 77.8 years, varying from 76.0 years in chemists to 84.8 years in economists. The mean life span after the selection is 20.3 years (from 13.6 years in writers to 24.6 in physicists). The expected life span after the selection adjusted by the age and the year of the selection of the Nobelists in physics, chemistry, economics and literature in 1959-1999 failed to reveal any increase, whereas the life expectancy of the prizewinners in physiology or medicine is increased as compared with the male population of USA.

Adult↗

The influence of the full moon on seizure frequency: myth or reality?

To investigate a possible relationship between seizure frequency and the lunar cycle, we reviewed the occurrence of seizures recorded in our epilepsy monitoring unit over a 3-year period. Analysis of the total number of seizures (epileptic plus nonepileptic) showed no significant association. A separate analysis revealed that for nonepileptic seizures, there was an increase at the full moon, and for epileptic seizures, an increase in the last quarter. We conclude that there is no "full moon" effect on seizures as a whole, although there is a possible effect on nonepileptic seizures.

Chi-Square Distribution↗

Effects of an intensive 12-wk training program by elite swimmers on neutrophil oxidative activity.

The effects of an intensive 12-wk training program by 12 national-level swimmers on neutrophil oxidative activity were studied. Eleven sedentary (untrained) subjects (6 males and 5 females) served as environmental controls. Blood samples (10 ml) were taken at rest from an antecubital vein and neutrophils isolated by standard separation techniques. The oxidative burst activity of isolated neutrophils was assessed with an in vitro flow cytometric assay that used the fluorescent probe dihydrorhodamine 123. Two-way ANOVA (repeated measures) showed that oxidative activity was lower (P < 0.05) in the elite swimmers compared with the sedentary control group across the 12-wk period. Analysis of cells from swimmers in training was made: repeated measures ANOVA provided evidence of a significant decline (P < 0.05) in the number of cells responding positively ito in vitro challenge. Despite this decline, there was no significant difference in self-reported upper respiratory tract infection rate between the swimmers and sedentary individuals. These data show that: (i) elite swimmers undertaking intensive training have a significantly lower neutrophil oxidative activity at rest than do age- and sex-matched sedentary individuals; (ii) aspects of oxidative activity in swimmers are further suppressed during periods of strenuous training, and (iii) the extent of the suppression does not appear to be of clinical significance.

Adult↗

The transfer of docosahexaenoic acid from the yolk to the tissues of the chick embryo.

Changes in the amounts of the major fatty acids present in the lipids of the yolk complex and the embryo were delineated during embryogenesis of the chicken. The rates of transfer of palmitic, oleic, linoleic, linolenic and arachidonic acids from the lipids of the yolk complex were essentially identical. In contrast, docosahexaenoic acid (DHA) was preferentially transferred from the yolk complex at a rate which was significantly higher than that exhibited by the other major fatty acids. The rates of accumulation of both arachidonic acid and DHA in the lipids of the whole embryo were significantly greater than the rates observed for the C16 and C18 fatty acids, particularly between days 12 and 16 of the 21-day embryonic period. Analysis of the fatty acid composition of plasma lipid throughout development indicated that the triacylglycerol fraction contained relatively high proportions (up to approx. 14% w/w of total fatty acids) of DHA, but much lower proportions (approx. 3%) of arachidonic acid. In contrast, plasma phospholipid was enriched in arachidonic acid (up to approx. 18%), but contained much lower proportions (generally less than 3%) of DHA. A considerable amount of DHA was incorporated into adipose tissue triacylglycerol, so that by the time of hatching, the tissue represented a major store of this fatty acid. Over the hatching period, the amount of DHA in adipose triacylglycerol decreased dramatically, by up to 85%, whereas there was little or no change in the amounts of the other major fatty acyl components in this tissue. The amount of DHA as a component of brain phospholipid increased continuously throughout the developmental period studied. However, by the time of hatching, the amount of DHA in brain phospholipid represented less than 10% of the amount of this fatty acid originally present in the lipids of the yolk.

Adipose Tissue↗

Analysis of cell division by time-lapse cinematographic studies of hydrocortisone-treated embryonic lung fibroblasts.

Hydrocortisone is a modulator of cell division and has been shown to prolong the replicative in vitro life span of human embryonic lung fibroblasts. Time lapse cinematography was used to analyze the proliferative behavior of individual cells in populations of fibroblasts exposed to hydrocortisone in young cultures during a single growth cycle and in aged cultures that had been continuously exposed to hydrocortisone. Results indicate that hydrocortisone causes a decrease in the interdivision time (IDT) of a portion of the cells in the population and this effect is augmented after continuous exposure to hydrocortisone. Hydrocortisone does not appear to increase the number of initial dividers in the population but increases growth rate in the early stages of the culture period. Analysis of mother-daughter IDT pairs further suggests that hydrocortisone exerts its effects on IDT independently for a given cell.

Cell Cycle↗

Morbidity and mortality of early postoperative intraperitoneal chemotherapy as adjuvant therapy for gastric cancer.

Intraperitoneal chemotherapy (IC) is emerging as a valuable adjuvant therapeutic modality in patients with gastric cancer. The purpose of this study was to assess morbidity and mortality of early postoperative IC (EPIC) in gastric cancer patients. Two hundred forty-eight gastric cancer patients thought to have resectable cancer were randomized intraoperatively to receive EPIC with mitomycin C on postoperative day 1 and 5-fluorouracil on postoperative days 2 to 5 versus surgery only. Sixty-four patients who were stage IV at histopathologic examination remain in the analysis. Morbidity and mortality were compared using Fisher's exact test. All patients completed the therapy. In the study group, overall morbidity was higher than in the control group (28.8% versus 20.3%, respectively), although the difference was not significant (P = 0.121). Intra-abdominal sepsis without anastomotic leak (P = 0.008) and bleeding (P = 0.002) occurred significantly more often in the study group. Also, 37.6 per cent of patients who received EPIC experienced a variety of minor complications attributable to EPIC. Postoperative mortality was higher in the study group (5.6%) than in controls (0.8%), but not significantly (P = 0.299). Patients treated with EPIC stayed in the hospital an average of 4 days longer (P = 0.002); in patients with morbidity, however, there was no difference with the control group. A period analysis of the morbidity demonstrated that it followed the pattern of a learning curve. Surgery with EPIC tended to increase the postoperative morbidity and mortality. The therapy-associated risk must be justified by a significant improvement in survival of treated patients with stage III disease. Selective application of perioperative IC may be indicated.

Antineoplastic Combined Chemotherapy Protocols↗

Construction of vaccinia virus recombinants expressing several measles virus proteins and analysis of their efficacy in vaccination of mice.

Measles virus genes encoding the haemagglutinin (HA), fusion protein (F) or nucleoprotein (NP) have been inserted into the vaccinia virus genome either alone or in various combinations. In each case the measles virus genes were expressed from the 7.5K promoter and were incorporated into the thymidine kinase (tk) or K1L loci of the Copenhagen strain of vaccinia virus. Cells infected by the recombinants synthesized measles virus proteins indistinguishable from those induced in measles virus-infected cells. However, in some instances the level of expression in cells infected by recombinants expressing more than one measles virus gene was reduced when compared to those encoding a single gene. The sera from mice immunized with recombinants containing either HA, HA.F, HA.NP or HA.F.NP had similar levels of measles virus neutralizing antibodies which remained constant throughout a 7 month period. Analysis of these sera by immunoprecipitation of radiolabelled measles virus confirmed the presence of specific antibody to each of the antigens where appropriate. The introduction of the measles virus genes into the K1L and the tk sites despite attenuating the virus for mice by 10-fold and 1000-fold respectively did not affect the vaccination efficiency, i.e. ability to induce measles virus antibody and protect mice. Vaccination of BALB/c (H2d) mice with HA and F, but not NP, recombinants completely protected the animals against a lethal measles virus challenge. In contrast, although the HA recombinant protected CBA (H2k) mice, the F recombinant did so poorly. However, by immunizing CBA mice with a recombinant expressing both F and NP, protection was increased to more than 75%. Our findings demonstrate the ability of three measles virus antigens expressed from the vaccinia virus genome alone or in combination to contribute to protective immunity against measles virus infection of mice. They also suggest that the association of measles virus antigens in a single recombinant DNA vaccine could be beneficial to overcome host-related restriction of the immune response to particular antigens.

Animals↗

Mitotic activity of the pars intermedia in the female mouse: age-associated variations in proliferation rate and circadian periodicity.

We previously reported daily variations in the mitotic activity of the endocrine cells in the pars intermedia of 21- and 28-day-old male mice. Since cellular proliferation might be affected by factors such as sex and age, we undertook the present experiments to study the mitotic activity of the pars intermedia from 14-, 28-, and 150-day-old female mice. Inbred C3H/S mice, grouped according to age, were housed under standard conditions (12h each of light and dark [LD 12:12]) for periodicity analysis and were killed in lots of 5-11 animals every 4h over a single 24h cycle, with each mouse receiving 2 microg/g of colchicine 4h before decapitation. Pituitaries were excised, extracted, fixed in buffered formaldehyde, embedded in celloidin-paraffin, sectioned at 5 microm, and stained with hematoxylin and eosin. We counted the total number of nuclei to estimate the total number of cells monitored and then calculated the mitotic index (metaphases/1000 nuclei). Differences were analyzed for statistical significance by the Student t test. While the 14-day-old animals manifested no significant changes in mitotic activity during the 24h cycle, the 28- and 150-day-old mice showed higher mitotic indices during the period of darkness. The average mitotic activity over the entire cycle, however, was higher in the two groups of younger animals than in the 150-day-old mice. Moreover, the averages for the 28-day-old females were higher than the corresponding values previously reported by us for male mice of the same age.

Aging↗

Statistical process control as a tool for monitoring nonoperative time.

BACKGROUND: Administrators need simple tools to quickly identify even small changes in the performance of perioperative systems. This applies both to established systems and to impact assessments of deliberate perioperative system design changes. METHODS: Statistical process control was originally developed to detect nonrandom variation in manufacturing processes by continuous comparison to previous performance. The authors applied the technique to assess the nonoperative time performance between successive cases for same surgeon following themselves in a redesigned operating room. This operating room specifically implemented a new patient care pathway that improves throughput by reducing the nonoperative time. The authors tested how quickly statistical process control detected reductions in nonoperative time. They also tested the ability of statistical process control to detect successively smaller performance changes and investigated its utility for longitudinal process monitoring. RESULTS: Statistical process control detected a clear reduction in nonoperative time after the new operating room had been used for only 2 days. The method could detect nonoperative time changes of between 5 and 10 min per case for a single operating room within one fiscal quarter. Nonoperative time for the new process was globally stable over the 31 months analyzed, but late in the analysis period, the authors detected small performance decrements, mostly attributable to factors external to the new operating room. CONCLUSIONS: Statistical process control is useful for detecting changes in perioperative system performance, represented in this study by nonoperative time. The technique is able to detect changes quickly and to detect small changes over time.

Algorithms↗

[Influence of the disco-scene on the psyche and soma of young people: psychometric, computerized-EEG and physiological studies (author's transl)].

Investigating the personality profile of 90 young disco-visitors, it was found that the group on the whole did not differ from the norm. However, a more detailed analysis according to age and sex demonstrated that young female "disco-fans" (under the age of 20 years) exhibited an increased desire for communication and contacts but also a less critical and a more pronounced self-admiring attitude than controls, while this was not observed in males. Subsequently, the effect of a typical disco-night on physiological, neurophysiological and psychometric variables was studied in 13 young disco-visitors. The results suggested an increased activation and arousal as reflected by the increased critical flicker fusion frequency, heart rate and blood pressure. Moreover, psychomotor activity, drive and mood were found to be improved, while attention, concentration, attention variability, reaction time and mnestic function deteriorated as compared with a control night. Digital computer period analysis of the electroencephalogram revealed an increased of theta and beta activity, and a decrease of alpha activity. The profile of the latter CNS changes shows a certain similarity to the pharmaco-EEG profiles of antidepressants. The findings are discussed.

Adult↗

[A system for continuous digitizing and evaluation of 32 biosignals from all-night sleep leads].

In all-night sleep recordings usually 12 to 16 channel electroencephalographs are used to record the electrical activity of the brain. A detailed analysis of EEG sleep activity, however, requires the inclusion of at least 19 electrodes placed according to the international 10-20 system in order to compare the variations of the activities in different brain areas. In addition polygraphic parameters such as ECG, respiration and actogram, to mention just a few, have to be recorded depending on the type of study. Therefore the number of recording channels has to be increased for a complete polygraphic investigation. We developed a 32 channel unit with a personal computer and corresponding hardware interfaces allowing the continuous digitalization of up to 32 bioelectrical signals throughout the whole night (8 hours). The recorded data can be presented graphically and evaluated according to the usual methods such as power spectrum, coherence and periodicity analysis. Additionally the use of algorithms for pattern detection permits automatic analysis of EEG segments regarding particular sleep patterns e.g. sleep spindles and K-complexes.

Electroencephalography↗

A study of prostane in the treatment of benign prostatic hyperplasia.

A clinical trial was conducted in a study group of 70 males diagnosed with symptomatic benign prostatic hypertrophy (BPH) (synonym of benign prostatic hyperplasia). They were administered Prostane, a herbal formulation, at a dose of two tablets a day for 1 year and monitored every 4 months during the study period. Analysis of the results showed an improvement in the symptom score of the American Urological Association symptom index rating. There was total relief in pain and haematuria in all the patients (100%); dribbling of urine decreased in 67%, dysuria in 50%, urgency in 60% and hesitancy in 40%. Blood urea levels were within the normal range in 70% of the patients and in the range 31-40 mg/dL in the remaining patients of the study group. Serum prostate specific antigen levels returned to normal in 56% of patients and were in the range 4.1-5.0 ng/mL in 25% of patients. There was a decrease in prostate specific antigen values which were >6 ng/mL in 9 patients at the commencement of the trial. Uroflowmetry studies showed that the peak flow increased from 12.6 to 30.7 s (p<0.001) and the void volume from 60.72 to 660 mL (p<0.001), the latent period reduced from 12.78 s to 2.61 s; the flow time from 57.01 s to 20.17 s and the residual volume from 620 mL to 20 mL (p<0.001). From these results, it is evident that Prostane was effective in alleviating symptoms, reducing prostate specific antigen values and normalizing uroflow dynamics in patients with benign prostatic hypertrophy.

Aged↗

The sensitivity of ecosystem carbon exchange to seasonal precipitation and woody plant encroachment.

Ongoing, widespread increases in woody plant abundance in historical grasslands and savannas (woody encroachment) likely will interact with future precipitation variability to influence seasonal patterns of carbon cycling in water-limited regions. To characterize the effects of woody encroachment on the sensitivity of ecosystem carbon exchange to seasonal rainfall in a semi-arid riparian setting we used flux-duration analysis to compare 2003-growing season NEE data from a riparian grassland and shrubland. Though less seasonally variable than the grassland, shrubland NEE was more responsive to monsoon rains than anticipated. During the 2004-growing season we measured leaf gas exchange and collected leaf tissue for delta(13)C and nitrogen content analysis periodically among three size classes of the dominant woody-plant, Prosopis velutina and the dominant understory species, Sporobolus wrightii, a C(4) bunchgrass, present at the shrubland. We observed size-class and plant functional type independent patterns of seasonal plant performance consistent with greater-than-anticipated sensitivity of NEE in the shrubland. This research highlights the complex interaction between growing-season precipitation, plant-available alluvial groundwater and woody plant abundance governing ecosystem carbon balance in this semi-arid watershed.

Analysis of Variance↗

Protein databases for compacted eight-cell and blastocyst-stage mouse embryos.

High-resolution two-dimensional sodium dodecyl sulfate-polyacrylamide (2D-SDS) gel electrophoresis combined with computerized analysis of gel images was used to construct and analyze protein data-bases for two stages of preimplantation mouse embryogenesis, the compacted eight-cell stage and the fully expanded blastocyst stage. These stages were chosen for their ease in identification of multiple synchronous embryos. Synchronous cohorts of 30-50 embryos were labelled with L-[35S]methionine for 2 hr. The embryos were then lysed in 30 microliters hot SDS sample buffer, and the lysates were stored at -80 degrees C until the gels were run. Five replicates were run for eight-cell embryos, and four for blastocyst-stage embryos. The samples were processed for 2D gel electrophoresis and fluorography; multiple exposures were made. Gel images were analyzed using the PDQUEST system, and databases were constructed. Analysis of the databases for both developmental stages showed high reproducibility of protein spots in multiple gel images. Of 1,674 total spots in eight-cell embryo standards, > 79% of spots had a percentage error (S.E.M./average) < 50%, and > 45% had a percentage error < 30%. Similarly, of 1,653 total spots in blastocyst-stage embryo standards, 74% of spots had a percentage error < 50%, and approximately 47% of spots had a percentage error < 30%. Forty-three spots (approximately 3% of the total spots) were found to be detected only in the eight-cell stage, while 75 spots were detected solely in the blastocyst stage. Sixty-nine proteins showed a greater than threefold increase in isotope incorporation from the eight-cell to the blastocyst stage, with a percentage error < 50% in both the eight-cell and the blastocyst stages. In contrast, 41 of the proteins showed a decrease during this period. Analysis of the protein databases described in this study has allowed us to document the overall quantitative changes in proteins from the compacted eight-cell stage to the blastocyst stage of mouse preimplantation development. These data-bases provide a valuable tool for further detailed quantitative analysis of specific proteins associated with developmental events. In addition they will permit analysis of the effects of environmental factors, such as growth factors, on early embryo development.

Animals↗

Sleep electroencephalographic coherence abnormalities in individuals at high risk for depression: a pilot study.

BACKGROUND: Sleep electroencephalographic (EEG) studies of individuals with major depressive disorder have identified several microarchitectural features associated with the illness. These abnormalities are also found in clinically remitted individuals, raising the question of whether they are vulnerability markers of depression. This study evaluated the sleep EEG in high-risk individuals to see if abnormalities are present in the sleep EEG prior to the onset of illness. METHODS: A total of 26 subjects (13 males and 13 females) were recruited for study on the basis of 1) having a parent or grandparent treated for major depressive or bipolar affective disorder and 2) having no history of personal psychiatric illness. Polysomnographic data were collected and compared with gender- and age-matched healthy control subjects with no personal or family history of psychiatric illness. The primary outcome measures were interhemispheric and intrahemispheric coherence. RESULTS: Period analysis of the sleep EEG showed that beta-delta coherence was lower bilaterally in male high-risk subjects. Right-hemispheric theta-delta coherence was also lower in male high-risk subjects, with female high-risk subjects evidencing lower beta coherence. CONCLUSIONS: Sleep-EEG abnormalities associated with major depressive disorder are present in never mentally ill individuals at high risk for the illness. These markers may be useful in the prediction of illness and in family genetic studies of mood disorders.

Adolescent↗

3alpha-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period.

Allopregnanolone (ALLO) and pregnanolone (PREG), the 3alpha-reduced metabolites of progesterone (PROG), are potent modulators of gamma-aminobutyric acid type A receptors that may function as endogenous anxiolytics. They are purported to be involved in the etiology or expression of clinical depression. In the present study we quantified ALLO and PREG, as well as PROG, 5alpha-dihydroprogesterone (5alpha-DHP), 5beta-dihydroprogesterone (5beta-DHP), epiallopregnanolone and pregnenolone (PREGNEN), in plasma from healthy women at five time points during pregnancy and the postpartum period. Analysis was by gas chromatography/electron capture - negative chemical ionization - mass spectrometry. Neuroactive steroids increased significantly from 10 to 36 weeks of pregnancy, except for 5beta-DHP and PREGNEN which did not change significantly. PROG was the most abundant steroid throughout pregnancy, followed by 5alpha-DHP and ALLO. Metabolite to precursor ratios differed depending on the enzyme and substrate: the turnover of PROG to 5alpha-DHP (catalyzed by 5alpha-reductase) was stable while the conversion of PROG to 5beta-DHP (catalyzed by 5beta-reductase) decreased later in pregnancy. 3alpha-Hydroxysteroid oxidoreductase-mediated turnover of 5alpha- and 5beta-DHP to their metabolites ALLO and PREG, respectively, rose during pregnancy, but the turnover of 5alpha-DHP to ALLO dropped at the late prenatal visit. At 6 weeks postpartum all steroids were significantly reduced compared with late prenatal values, with 5alpha-DHP being the most abundant postpartum steroid. These results provide the basis for further study of neuroactive steroids in psychiatric conditions of pregnancy and the postpartum period.

5-alpha-Dihydroprogesterone↗

Evaluation of the ABX Cobas Vega automated hematology analyzer and comparison with the Coulter STKS.

An evaluation of the new automated hematology analyzer was performed in comparison with the Coulter STKS on 1,694 blood samples coming from the different departments of Nice University Hospital. The Cobas Vega showed very satisfactory results in terms of repeatability, reproducibility and linearity. Correlation with the STKS was excellent with the exception of the following parameters: red blood cell distribution index and the absolute values for eosinophils and basophils. Two qualities were particularly appreciable: absence of leukocyte carryover, and stability of the complete blood count and leukocyte differential count over a long period. Analysis of qualitative flags showed that the overall blood smear review rate was 47% for the Cobas Vega, not forgetting that optical microscopy detects 37% of all abnormalities. The STKS's review rate was 49.5%. Flags commonly concerned the granulocytic lineage, 61% for the STKS and 48% for the Vega, with a false positive rate of 43.4% for the STKS compared with 22% for the Vega. The opposite phenomenon was observed with the flag for atypical lymphocytes which represented 11% of flags for the STKS and 25.6% for the Vega, with a false positive rate of 25.5% for the STKS and 34% for the Cobas Vega. This may be explained by the fact that lymphocyte abnormalities sometimes generated "granulocytic" flags on the STKS. Studies of the false negative rate carried out using light microscopy on 505 blood samples without flags on either system, detected the presence of a slight myelemia, and a few hyperbasophilic lymphocytes or plasmocytes in 18.6% of all cases. Finally, the Cobas Vega's practicality was greatly appreciated and there was no trouble with breakdowns throughout the whole period of its use.

Autoanalysis↗

Treatment options in moderate and severe depression: decision analysis supporting a clinical guideline.

BACKGROUND: Treatment options for depression include antidepressants, psychological therapy and a combination of the two. AIMS: To develop cost-effective clinical guidelines. METHOD: Systematic literature reviews were used to identify clinical, utility and cost data. A decision analysis was then conducted to compare the benefits and costs of antidepressants with combination therapy for moderate and severe depression in secondary care in the UK. RESULTS: Over the 15-month analysis period, combination therapy resulted in higher costs and an expected 0.16 increase per person in the probability of remission and no relapse compared with antidepressants. The cost per additional successfully treated patient was 4056 UK pounds (95% CI1400-18300); the cost per quality-adjusted life year gained was 5777 UK pounds (95% CI1900-33 800) for severe depression and 14 540 UK pounds (95% CI 4800-79 400) for moderate depression. CONCLUSIONS: Combination therapy is likely to be a cost-effective first-line secondary care treatment for severe depression. Its cost-effectiveness for moderate depression is more uncertain from current evidence. Targeted combination therapy could improve resource utilisation.

Antidepressive Agents↗