Schizophrenia and birthplace of paternal and maternal grandfather in the Jerusalem perinatal cohort prospective study.

Some forms of epigenetic abnormalities transmitted to offspring are manifested in differences in disease incidence that depend on parent-of-origin. To explore whether such phenomena might operate in schizophrenia spectrum disorders, we estimated the relative incidence of these conditions in relation to parent-of-origin by considering the two grandfathers' countries of birth. In a prospective cohort of 88,829 offspring, born in Jerusalem in 1964-76 we identified 637 cases through Israel's psychiatric registry. Relative risks (RR) were estimated for paternal and maternal grandfathers' countries of birth using proportional hazards methods, controlling for parents' ages, low social class and duration of marriage. After adjusting for multiple observations, we found no significant differences between descendants of maternal or paternal grandfathers born in Iraq, Iran, Turkey, Syria, Yemen, Morocco, Algeria, Tunisia, Libya/Egypt, Poland, USSR, Czechoslovakia, Germany or the USA. Those with paternal grandfathers from Romania (RR=1.9, 95% CI=1.3-2.8) or Hungary (1.6, 1.0-2.6) showed an increased incidence; however, those with maternal grandfathers from these countries experienced reduced incidence (RR=0.5, 0.3-0.8 and 0.4, 0.2-0.8). In post-hoc analyses we found that results were similar whether the comparison groups were restricted to descendants of other Europeans or included those from Western Asia and North Africa; and effects of paternal grandfathers from Romania/Hungary were more pronounced in females, while effects of maternal grandfathers from these countries were similar in males and females. These post-hoc "hypothesis-generating" findings lead one to question whether some families with ancestors in Romania or Hungary might carry a variant or mutation at a parentally imprinted locus that is altering susceptibility to schizophrenia. Such a locus, if it exists, might involve the X chromosome.

Acute maternal stress in pregnancy and schizophrenia in offspring: a cohort prospective study.

UNLABELLED: Schizophrenia has been linked with intrauterine exposure to maternal stress due to bereavement, famine and major disasters. Recent evidence suggests that human vulnerability may be greatest in the first trimester of gestation and rodent experiments suggest sex specificity. We aimed to describe the consequence of an acute maternal stress, through a follow-up of offspring whose mothers were pregnant during the Arab-Israeli war of 1967. A priori, we focused on gestational month and offspring's sex. METHOD: In a pilot study linking birth records to Israel's Psychiatric Registry, we analyzed data from a cohort of 88,829 born in Jerusalem in 1964-76. Proportional hazards models were used to estimate the relative risk (RR) of schizophrenia, according to month of birth, gender and other variables, while controlling for father's age and other potential confounders. Other causes of hospitalized psychiatric morbidity (grouped together) were analyzed for comparison. RESULTS: There was a raised incidence of schizophrenia for those who were in the second month of fetal life in June 1967 (RR = 2.3, 1.1-4.7), seen more in females (4.3, 1.7-10.7) than in males (1.2, 0.4-3.8). Results were not explained by secular or seasonal variations, altered birth weight or gestational age. For other conditions, RRs were increased in offspring who had been in the third month of fetal life in June 1967 (2.5, 1.2-5.2), also seen more in females (3.6, 1.3-9.7) than males (1.8, 0.6-5.2). CONCLUSION: These findings add to a growing literature, in experimental animals and humans, attributing long term consequences for offspring of maternal gestational stress. They suggest both a sex-specificity and a relatively short gestational time-window for gestational effects on vulnerability to schizophrenia.

XAS study of iron and arsenic speciation during Fe(II) oxidation in the presence of As(III).

The speciation of As and Fe was studied during the oxidation of Fe(II)-As(III) solutions by combining XAS analysis at both the Fe and As K-edges. Fe(II) and As(III) were first hydrolyzed to pH 7 under anoxic conditions; the precipitate was then allowed to oxidize in ambient air for 33 h under vigorous stirring. EXAFS analysis at the As K-edge shows clear evidence of formation of inner-sphere complexes between As(III) and Fe(II), i.e., before any oxidation. Inner-sphere complexes were also observed when Fe became sufficiently oxidized, in the form of edge-sharing and double-corner linkages between AsIIIO3 pyramids and FeIIIO6 octahedra. XAS analyses at the Fe K-edge reveal that the presence of As(III) in the solution limits the polymerization of Fe(II) and the formation of green rust and inhibits the formation of goethite and lepidocrocite. Indeed, As(III) accelerates the Fe(II) oxidation kinetics and leads to the formation of nanosized Fe-As subunits of amorphous aggregates. These observations, rather than a presumed weaker affinity of As(III) for iron oxyhydroxides, might explain why As(III) is more difficult to remove than As(V) by aerating reducing groundwater.

Cognitive performance of male adolescents is lower than controls across psychiatric disorders: a population-based study.

OBJECTIVE: Psychiatric patients, as well as humans or experimental animals with brain lesions, often concurrently manifest behavioral deviations and subtle cognitive impairments. This study tested the hypothesis that as a group, adolescents suffering from psychiatric disorders score worse on cognitive tests compared with controls. METHOD: As part of the assessment for eligibility to serve in the military, the entire, unselected population of 16-17-year old male Israelis undergo cognitive testing and screening for psychopathology by the Draft Board. We retrieved the cognitive test scores of 19 075 adolescents who were assigned any psychiatric diagnosis, and compared them with the scores of 243 507 adolescents without psychiatric diagnoses. RESULTS: Mean test scores of cases were significantly poorer then controls for all diagnostic groups, except for eating disorders. Effect sizes ranged from 0.3 to 1.6. CONCLUSION: As group, adolescent males with psychiatric disorders manifest at least subtle impairments in cognitive functioning.

Generalized cognitive impairment in male adolescents with schizotypal personality disorder.

Schizotypal Personality Disorder (SPD) shares common genetic and biological substrates with schizophrenia, and patients with SPD have been reported to suffer both from specific cognitive impairments, and from a generalized cognitive dysfunction, similar to those found in schizophrenia. The aim of this cross-sectional, population-based study was to assess general cognitive functioning in adolescents with SPD. The Israeli Draft Board systematically assesses cognitive functioning and administers psychiatric screening in all 16-17-year-old males in the population. Of 341,511 males assessed, the cognitive test scores of adolescents with SPD (N = 326) were retrieved, and compared to the scores of adolescents diagnosed as suffering from schizophrenia (N = 901), and adolescents with no neurological or psychiatric diagnosis (controls, N = 293,820). Male adolescents with SPD or with schizophrenia scored lower on all measures compared to healthy individuals (effect sizes ranging from 0.6-0.88, all P < 0.001). The SPD patients scored significantly higher than the schizophrenia patients on the sub-tests of similarities and Ravens Progressive Matrices, tests that reflect abstract reasoning. On the sub-tests of arithmetic and instruction comprehension, tests that rely on concentration, SPD and schizophrenia patients' scores did not differ significantly from each other. These results might be interpreted to imply that a generalized cognitive impairment, in the presence of schizotypal personality traits and in the absence of psychosis, might be conceptualized as being the core of the schizotaxia syndrome. The greater impairment in abstract reasoning in the schizophrenia patients might be correlated with the psychotic symptoms that differentiate schizophrenia from SPD.

Association between nonpsychotic psychiatric diagnoses in adolescent males and subsequent onset of schizophrenia.

BACKGROUND: Nonpsychotic psychiatric symptoms may occasionally herald the later development of schizophrenia. This study followed a population-based cohort of adolescents with nonpsychotic, non-major affective psychiatric disorders to ascertain future hospitalization for schizophrenia. METHODS: Results of the medical and mental health assessments on 124 24416- to 17-year-old males screened by the Israeli draft board were cross-linked with the National Psychiatric Hospitalization case registry, which contains data on all psychiatric hospitalizations in the country, during a 4- to 8-year-long follow-up through age 25 years. In the cohort, 9365 adolescents were assigned a nonpsychotic, non-major affective diagnosis by the draft board. RESULTS: After excluding 167 adolescents who were hospitalized before or up to 1 year after the draft board assessment, 1.03% of the adolescents assigned a nonpsychotic, non-major affective psychiatric diagnosis, compared with only 0.23% of the adolescents without any psychiatric diagnosis, were later hospitalized for schizophrenia. Of the patients with schizophrenia, 26.8%, compared with only 7.4% in the general population, had been assigned a nonpsychotic, non-major affective psychiatric diagnosis in adolescence (overall odds ratio [OR], 4.5; 95% confidence interval [CI], 3.6-5.6), ranging from OR, 21.5 (95% CI, 12.6-36.6) for schizophrenia spectrum personality disorders to OR, 3.6 (95% CI, 2.1-6.2) for neurosis. CONCLUSION: These results reflect the relatively common finding of impaired functioning in patients later hospitalized for schizophrenia and the relatively low power of these disorders in predicting schizophrenia.

Advancing paternal age and the risk of schizophrenia.

BACKGROUND: A major source of new mutations in humans is the male germ line, with mutation rates monotonically increasing as father's age at conception advances, possibly because of accumulating replication errors in spermatogonial cell lines. METHOD: We investigated whether the risk of schizophrenia was associated with advancing paternal age in a population-based birth cohort of 87 907 individuals born in Jerusalem from 1964 to 1976 by linking their records to the Israel Psychiatric Registry. RESULTS: Of 1337 offspring admitted to psychiatric units before 1998, 658 were diagnosed as having schizophrenia and related nonaffective psychoses. After controlling for maternal age and other confounding factors (sex, ethnicity, education [to reflect socioeconomic status], and duration of marriage) in proportional hazards regression, we found that paternal age was a strong and significant predictor of the schizophrenia diagnoses, but not of other psychiatric disorders. Compared with offspring of fathers younger than 25 years, the relative risk of schizophrenia increased monotonically in each 5-year age group, reaching 2.02 (95% confidence interval, 1.17-3.51) and 2.96 (95% confidence interval, 1.60-5.47) in offspring of men aged 45 to 49 and 50 years or more, respectively. Categories of mother's age showed no significant effects, after adjusting for paternal age. CONCLUSIONS: These findings support the hypothesis that schizophrenia may be associated, in part, with de novo mutations arising in paternal germ cells. If confirmed, they would entail a need for novel approaches to the identification of genes involved in schizophrenia.

Rehospitalization rates of chronically ill schizophrenic patients discharged on a regimen of risperidone, olanzapine, or conventional antipsychotics.

OBJECTIVE: The purpose of this study was to compare the rehospitalization rates of patients discharged from the hospital while being treated with risperidone, olanzapine, or conventional antipsychotics. METHOD: By using Israel's National Psychiatric Hospitalization Case Registry, rehospitalization status was monitored for all patients with schizophrenia who were discharged from any inpatient psychiatric facility in Israel while taking risperidone (N=268) or olanzapine (N=313) between Jan. 1, 1998, and Dec. 31, 1998, and a group of patients discharged during that time who were treated with conventional antipsychotics (N=458). Time to readmission over the course of 2 years was measured by the product-limit (Kaplan-Meier) formula. RESULTS: The readmission rate for patients discharged while taking conventional antipsychotics was higher than the rates for patients treated with either risperidone or olanzapine. At 24 months, 67% of the risperidone-treated patients and 69% of the olanzapine-treated patients remained in the community, as compared to 52% of the patients treated with conventional antipsychotics. CONCLUSIONS: This study suggests that the rehospitalization rates of patients taking the novel antipsychotics risperidone and olanzapine are not different from each other and are considerably lower than the rate for patients treated with conventional antipsychotics. The results confirm findings of previous studies suggesting that the levels of overall effectiveness of risperidone and olanzapine are not very different and offers evidence that these drugs are more effective in preventing rehospitalization than conventional antipsychotic drugs.

Gender differences in premorbid cognitive performance in a national cohort of schizophrenic patients.

Despite significant research, there are still inconsistent findings regarding gender differences in cognitive performance in individuals already diagnosed with schizophrenia; studies have found that males suffering from schizophrenia are more, less or equally impaired compared with females. Gender differences in cognitive performance in individuals suffering from schizophrenia may be influenced by gender differences in premorbid cognitive performance; the very few and very small N studies published indicated that males have a poorer pre-morbid cognitive performance than females. This study examined the gender differences in premorbid cognition, utilizing cognitive assessments performed on female and male adolescents before induction into military service. The Israeli Draft Board Registry, which contains cognitive assessments equivalent to IQ scores on 16-18 year old Israeli adolescents, was linked with the Israeli National Psychiatric Hospitalization Case Registry, which records all psychiatric hospitalizations in the country. Scores on premorbid cognitive performance in schizophrenia were examined in 90 female-male case pairs matched for school attended as a proxy for socio-economic status. The mean age of first hospitalization was 20. 1+/-1.8 years of age for males and 19.6+/-1.8 years of age for females. A repeated-measures ANCOVA with age of first hospitalization and years of formal education as covariates, and controlling for gender differences in cognitive performance in healthy adolescents, revealed a significant difference in pre-morbid cognitive performance between males and females on all four cognitive measures [F(1,87)=8.07, P=0.006] with females scoring lower (worse) than males. In this national cohort, pre-morbid cognition was poorer in female, compared with male, adolescents who will suffer from schizophrenia in the future, a result consistent with some, but not all, similar studies. These results may be valid only for patients with first hospitalization around age 20. Hence, gender differences in premorbid cognition should be taken into account when assessing gender differences in cognition in schizophrenia.

Modeling flavor release from aqueous sucrose solutions, using mass transfer and partition coefficients.

The penetration theory of interfacial mass transfer was used to model flavor release from aqueous solutions containing different concentrations of sucrose. The mass transfer coefficient and the gas/solution partition coefficient are the main factors of the model influencing the release in time. Parameters governing the isolation by a purge and trap method at mouth conditions (volume, temperature, and artificial saliva) were used in the model description of the flavor release. Viscosities of the different sucrose solutions (0-60 w/v %) at 37 degrees C were estimated, and their influence on the mass transfer coefficients was determined. The gas/solution partition coefficients for ethyl acetate, methyl butanoate, ethyl butanoate, hexanal, and octanal were measured for the different sucrose concentrations at 37 degrees C. At lower sucrose concentrations the partition coefficient primarily controls flavor release during a purge time of 10 min, whereas at higher sucrose concentrations the influence of the mass transfer coefficient is more important.

The goals and limitations of Israel's psychiatric case register.

The Israeli Ministry of Health maintains a psychiatric case register that includes basic demographic and clinical information for all psychiatric hospital admissions since 1950. Currently, the case register includes information about some 130,000 people who have been hospitalized. The case register is an important tool in many aspects of mental health care planning, such as delineating problem populations, developing interventions, assessing the ramifications of policies, enacting programs for quality control, and conducting research. In certain situations stipulated by law, some information in the case register is shared with other authorities. Although the full potential of the psychiatric case register has not been exploited so far, creation of additional linkages with other databases and increased application of case register data in field studies could enhance its usefulness.

Sensory evaluation of mixtures of maltitol or aspartame, sucrose and an orange aroma.

The suitability of Beidler's mixture equation for mixtures of sucrose and maltitol as well as for mixtures of sucrose and aspartame was examined in the presence of an orange aroma. The mean scores for the attribute sweet remained constant for each combination of sucrose and maltitol and for each combination of sucrose and aspartame. Therefore, Beidler's mixture equation can be used to choose combinations of sucrose and maltitol and of sucrose and aspartame giving the same sweetness. Quantitative descriptive analysis of different solutions indicated that the flavour profiles of sucrose and maltitol did not differ significantly at a constant concentration of orange aroma. However, flavour profiles of solutions with increasing aspartame concentrations (but constant aroma levels) showed significantly higher scores for the attributes sour, chemical and aftertaste. Addition of orange aroma provided the different solutions with a more distinct flavour. The mean scores for the attributes orange, sour, fruity and aftertaste increased significantly for most of the sucrose-maltitol mixtures. This effect of orange aroma was even more pronounced in solutions containing combinations of sucrose and aspartame. Further comments on the attribute aftertaste showed similar terms for the different solutions, the most often mentioned being orange, sour, fruity and chemical for solutions containing the orange aroma. The aftertaste of solutions containing relatively more aspartame was mainly described as sweet and chemical.

Flavour release from rehydrated french beans (Phaseolus vulgaris) influenced by composition and volume of artificial saliva.

Influence of saliva composition and volume on flavour release from rehydrated French beans (Phaseolus vulgaris) was studied in three types of mouth model systems; dynamic headspace (DH), dynamic headspace and mastication (DHM) and a purge-and-trap (PT) model system. Volatile compounds were analysed by gas chromatography, using flame ionization detection (FID), mass spectrometry and sniffing port detection. Areas of FID peaks were largest in the PT system, followed by those of the DHM and DH systems, respectively. Saliva composition as well as volume influenced the release of volatile compounds from rehydrated French beans. Generally, FID data showed a decrease in release by the saliva component mucin, because of interactions between volatile compounds and protein, and in increase in release by its alpha-amylase, probably due to degradation of inclusion complexes of starch. The decrease in flavour release by the enlarged saliva volume was evaluated by a model study. Sniffing patterns of odour active compounds were barely influenced by either saliva composition or volume.

The relation between biological activity of the rain forest and mineral composition of soils.

In most soils of the humid tropics, kaolinitic topsoil horizons overlie more gibbsitic horizons. This arrangement cannot be produced simply by leaching. Quantitative measurement of the turnover of chemical elements in the litterfall in an Amazonian ecosystem indicates that the forest cycles a significant amount of elements, particularly silicon. As a result, fluids that percolate through topsoil horizons already contain dissolved silicon. This effect keeps silicon from being leached down and may account for the stability of kaolinite in the soil upper horizons. The soil mineral composition is thus maintained by biological activity.

Critical anatomic dimensions for intrathoracic circulatory assist devices.

The design of totally implantable circulatory support devices must account for the anatomical constraints of the body cavity. To aid development of an implantable electrohydraulic ventricular assist device (EVAD), thoracic anatomical measurements and fit trials were performed. Various dimensions of the thoracic cavity were measured in 19 preserved and fresh cadavers. The mean left ventricle apex to chest wall distance was 2.7 +/- 0.2 cm. The mean sagittal radius of curvature at the fifth rib was 11.1 +/- 0.4 cm, and the transverse radius at the fifth rib was 9.4 +/- 0.3 cm. The mean sternal length was 18.9 +/- 1.2 cm. Using these measurements a model measuring 17.5 x 10.5 x 3.8 cm was designed. This model was placed in the chest of 11 patients undergoing open heart surgery. In one patient there was significant lung compression and in another hypotension suggesting great vessel compression. Finally, 1 of 11 patients had a short sternum and a small thorax, and the device did not fit. In conclusion, thoracic measurements may be used in the design of circulatory support devices. The model fit adequately in 73% of patient trials.

Electrohydraulic ventricular assist device development.

A 64 ml (effective stroke volume) in vitro electrohydraulic ventricular assist device (VAD) prototype has been built. The energy converter is an axial flow pump driven by a brushless direct current (DC) motor. Systole begins as silicone oil is pumped from the volume displacement chamber (VDC) into the ventricle, displacing the flexing diaphragm separating the oil and the blood. In diastole, the motor reverses, providing active filling by pumping oil from the ventricle into the VDC. The surface mount electronic internal controller provides motor commutator, energy management, telemetry, and physiologic control functions. Energy is supplied externally by either a 12 V DC power supply or a 12 V DC rechargeable battery and is transmitted through the skin by a transcutaneous energy transformer (TET). Energy can also be supplied by a 12 V DC rechargeable internal battery. Bidirectional infrared telemetry is used to transmit information between the internal and external controllers.