Social functioning and subclinical psychosis in adolescence: a longitudinal general adolescent population study.

OBJECTIVES: To investigate the longitudinal relationship between subclinical psychotic symptoms and social functioning in a representative general population sample of adolescents. METHOD: Data were derived from a routine general health screening of 1909 adolescents in a circumscribed region. Baseline measurement was in the second grade of secondary school (T0), and follow-up occurred approximately 2 years later (T1). Social functioning and subclinical psychotic symptoms of hallucinations and delusions were assessed at both time points. RESULTS: Baseline (T0) social problems preceded follow-up (T1) subclinical delusions, but not T1 subclinical hallucinations. Similarly, T0 delusions preceded social problems at T1, but T0 hallucinations did not. CONCLUSION: This longitudinal general population study demonstrated a bidirectional association between social problems and delusions, but found no link between social problems and hallucinations. This may reflect a downward negative spiral where delusional thoughts and social problems reinforce each other.

Childhood trauma is associated with a specific admixture of affective, anxiety, and psychosis symptoms cutting across traditional diagnostic boundaries.

BACKGROUND: Meta-analyses link childhood trauma to depression, mania, anxiety disorders, and psychosis. It is unclear, however, whether these outcomes truly represent distinct disorders following childhood trauma, or that childhood trauma is associated with admixtures of affective, psychotic, anxiety and manic psychopathology throughout life. METHOD: We used data from a representative general population sample (NEMESIS-2, n = 6646), of whom respectively 1577 and 1120 had a lifetime diagnosis of mood or anxiety disorder, as well as from a sample of patients with a diagnosis of schizophrenia (GROUP, n = 825). Multinomial logistic regression was used to assess whether childhood trauma was more strongly associated with isolated affective/psychotic/anxiety/manic symptoms than with their admixture. RESULTS: In NEMESIS-2, largely comparable associations were found between childhood trauma and depression, mania, anxiety and psychosis. However, childhood trauma was considerably more strongly associated with their lifetime admixture. These results were confirmed in the patient samples, in which it was consistently found that patients with a history of childhood trauma were more likely to have a combination of multiple symptom domains compared to their non-traumatized counterparts. This pattern was also found in exposed individuals who did not meet criteria for a psychotic, affective or anxiety disorder and who did not seek help for subclinical psychopathology. CONCLUSIONS: Childhood trauma increases the likelihood of a specific admixture of affective, anxiety and psychotic symptoms cutting across traditional diagnostic boundaries, and this admixture may already be present in the earliest stages of psychopathology. These findings may have significant aetiological, pathophysiological, diagnostic and clinical repercussions.

Does social defeat mediate the association between childhood trauma and psychosis? Evidence from the NEMESIS-2 Study.

OBJECTIVE: Based on theoretical considerations and animal studies, mediation of 'social defeat' (SD) in the association between childhood trauma (CT) and psychosis was investigated. METHOD: Trained interviewers administered a structured interview assessing CT, psychotic experiences and other psychopathology in 6646 participants in the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). RESULTS: Childhood trauma was associated with psychotic experiences making up the extended psychosis phenotype (EPP), as well as with a diagnosis of psychotic disorder (PD). Similarly, CT was associated with a priori selected items indexing SD (discouraged, hopeless, worthless, loss of self-confidence, low self-esteem, better off dead, suicidal thoughts) and with a measure of affective dysregulation (AD), which in turn were also associated with psychosis. While SD and AD individually acted as mediators in the association between CT and EPP, only SD acted as a mediator in the association between CT and PD. Cannabis use did not mediate the association between CT and EPP or PD. CONCLUSION: The present results suggest a developmental model implicating SD as an important mediator in the link between childhood adverse experiences and later development of psychotic experiences. The combined mediation by SD and AD is compatible with an 'affective pathway' to early psychosis.

On the application of a monolithic array for detecting intensity-correlated photons emitted by different source types.

It is not widely appreciated that many subtleties are involved in the accurate measurement of intensity-correlated photons; even for the original experiments of Hanbury Brown and Twiss (HBT). Using a monolithic 4 x 4 array of single-photon avalanche diodes (SPADs), together with an off-chip algorithm for processing streaming data, we investigate the difficulties of measuring second-order photon correlations g((2))(x(iota), t(iota),x, t) in a wide variety of light fields that exhibit dramatically different correlation statistics: a multimode He-Ne laser, an incoherent intensity-modulated lamp-light source and a thermal light source. Our off-chip algorithm treats multiple photon-arrivals at pixel-array pairs, in any observation interval, with photon fluxes limited by detector saturation, in such a way that a correctly normalized g((2)) function is guaranteed. The impact of detector background correlations between SPAD pixels and afterpulsing effects on second-order coherence measurements is discussed. These results demonstrate that our monolithic SPAD array enables access to effects that are otherwise impossible to measure with stand-alone detectors.

Model-based comparison of two ways to enhance WWTP capacity under stormwater conditions.

Two different approaches to increase the fraction of combined water treated in the wastewater treatment plant (WWTP) which would otherwise contribute to combined sewer overflows (CSO) are presented and compared based on modelling results with regard to their efficiencies during various rain events. The first option is to generally increase the WWTP inflow according to its actual capacity rather than pre-setting a maximum that applies to worst case loading. In the second option the WWTP inflow is also increased, however, the extra inflow of combined water is bypassing the activated sludge tank and directly discharged to the secondary clarifier. Both approaches have their advantages. For the simulated time series with various rain events, the reduction of total COD load from CSOs and WWTP effluent discharged to the receiving water was up to 20% for both approaches. The total ammonia load reduction was between 6% for the bypass and 11% for inflow increase. A combination of both approaches minimises the adverse effects and the overall emission to the receiving water.

Modelling of enhanced CSO treatment in secondary clarifiers with a modified Activated Sludge Model no. 3.

An alternative approach for combined water treatment as opposed to its CSO discharge into receiving water is its bypass to the inlet of secondary clarifiers (SC). To analyse the processes and to evaluate the performance of this approach, experiments and numerical modelling were carried out. In batch and pilot scale experiments major effects were identified and quantified. The Activated Sludge Model No. 3 (ASM3) was modified to simulate the batch and pilot scale experiments for implementation of the bypass-specific processes and thus to set up an overall balance of the relevant compounds. With some modifications of ASM3, good agreement of the modelling results with measurements of COD, nitrogen and phosphorus were achieved.

Utilization of activated sludge plants for enhanced treatment of combined sewage.

A process is introduced which utilizes secondary clarifiers for the treatment of combined sewage. Under storm water conditions, surplus sewage bypasses the aeration tanks after primary treatment and is directly introduced into the secondary clarifiers. The hydraulic capacity of existing activated sludge plants can be increased without additional tank volume. Particulate matter as well as dissolved compounds are removed to a high extent. Investigations on a full scale treatment plant (100,000 p.e.) show that the effluent quality is comparable with full biological treatment, even if the hydraulic loading is increased by 50%.

[Problem-based learning for surgery. Increased motivation with less teaching personnel?]. / Problemorientiertes Lernen in der Chirurgie. Erhöhte Lernmotivation bei geringerem Personalaufwand?

BACKGROUND: Traditional teacher-centred education strategies often do not meet the needs and student abilities of adult learning. The introduction of small learning groups requires considerable increases in staff. Problem-based learning could increase the motivation to acquire knowledge but without being as staff-intensive. METHODS: Medical students (n=98) in their fourth clinical semester were randomly assigned to either a structured course (SC) or problem-based learning (PBL) for surgery. Their motivation and acceptance of the courses were recorded at the end of term in anonymous questionnaires using Likert scales, with scores ranging from 1 (very good) to 6 (unsatisfactory). RESULTS: Both course structure and the teachers received much better ratings from the PBL students (P<0.01 each). The motivation of students to deal with surgical problems beyond the course material was significantly higher after PBL, with 1.8 (0.7), than after the structured course with 3.1 (1.2) (P<0.01). The overall rating was substantially worse for the structured course, with 3.1 (1.2) than for PBL at 1.4 (0.6) (P<0.01). CONCLUSIONS: Problem-based learning in the surgical curriculum increases student acceptance and motivation with little demand on staff. It should be increasingly implemented.

Characteristics of early- and late-diagnosed schizophrenia: implications for first-episode studies.

First-episode studies of schizophrenia are being carried out in many places. However, previous work has suggested that only half of the patients with schizophrenia receive the diagnosis in the initial stages of the illness. We examined whether cases of early- and late-diagnosed schizophrenia differed with respect to key sociodemographic characteristics and indicators of service use that might bias first-episode studies. Individuals who (i) presented for the first time between 1983 and 1993 to psychiatric services in a defined urban area with a cumulative mental health case register; and (ii) received a diagnosis of schizophrenia at least once during their mental health career were identified (n = 186). This sample was divided into those who received the diagnosis of schizophrenia for the first time within the first year of service contact (early-diagnosed schizophrenia; EDS), and those who received it for the first time after the first year of service contact (late-diagnosed schizophrenia; LDS). The 10-year incidence of EDS and LDS were 10.4 and 7.0 per 100,000 person-years, respectively. EDS and LDS did not differ in their pattern of association with sex, single marital status and higher levels of neighbourhood socioeconomic deprivation. However, EDS was more incident in the higher age groups, and the level of service use was higher for EDS cases in the first years of contact with mental health services, with LDS cases gradually catching up and exceeding EDS service use later in the illness course. Although differences between EDS and LDS were few, studies of patients with schizophrenia in the 'first' episode are likely to be most representative if patients who receive the diagnosis for the first time after previous episodes of care for non-schizophrenic episodes are also included.

Protein microheterogeneity and crystal habits: the case of epidermal growth factor receptor isoforms as isolated in a multicompartment electrolyzer with isoelectric membranes.

A purified, soluble form of the epidermal growth factor receptor (sEGFR) was found, by isoelectric focusing in immobilized pH gradients, to consist of three major isoforms (with pI values 6.45, 6.71 and 6.96, respectively) and ca. a dozen minor components. This wild-type sEGFR, while producing crystals, has so far defied any attempt at decoding the structure, due to the very poor diffraction pattern. When the wild-type sEGFR was purified in a multicompartment electrolyzer with isoelectric Immobiline membranes, it yielded the three major isoforms as single-pI components, collected in three separate chambers of the recycling electrolyzer. The pI 6.71 and the pI 6.96 isoforms produced large crystals of apparent good quality. However, while the former produced a high-quality diffraction pattern, which may lead to decoding of three-dimensional structure, the pI 6.96 produced crystals which did not diffract at all. It is concluded that, in the case of "tough" proteins (large size, heterogeneous glycosylation, high water content of crystals), purification to single-charge components might be an essential step for growing proper crystals. The unique advantage of purification via isoelectric membranes is that the protein is collected both isoelectric and isoionic, i.e. uncontaminated by soluble buffers (such as the carrier ampholytes used in conventional focusing).

Serva collagenase NB1: a new enzyme preparation for human islet isolation.

INTRODUCTION: Advances in the rate of success of human islet isolation are due in part to the availability of new purified enzyme blends. In this study we evaluated a new enzyme preparation composed of a highly purified collagenase that can be reproducibly blended with predetermined amounts of separately packaged neutral protease. METHODS: Nine human islet isolations were performed with collagenase NB1 supplemented with neutral protease (Serva Electrophoresis GMbH, group I). Yields, purity, morphology, in vitro function and islet cell apoptosis were assessed. The results were compared to those of nine human islet isolations performed with Liberase (Roche, group II) and matched for donor age, BMI, and circumstances of death. RESULTS: Islet yields were similar in both groups. However, islet equivalents (IE) per gram of pancreas and IE number to islet number were higher in group I (P <.05). Stimulation indices after insulin response to glucose (static incubation) were similar in both groups. Islet cell apoptosis rate was statistically significantly lower in group I. Islet morphology was significantly improved in group I with a higher proportion of intact islets. CONCLUSION: This new enzyme preparation (collagenase NB1 with neutral protease adjunct) was as effective as Liberase in terms of islet yields and function. Islet morphology was improved and rate of islet cell apoptosis was lower with this new collagenase. The absence of lot-to-lot variability in terms of neutral protease to collagenase ratio makes collagenase NB1 a promising enzyme for human islet isolation.

Optimization of neutral protease to collagenase activity ratio for islet of Langerhans isolation.

AIM: The optimal neutral protease to collagenase activity ratio has not been determined for islet isolation. We evaluated a new highly purified collagenase that can be blended with predetermined amounts of neutral protease (NP). METHODS: Islets were isolated from 7 groups of Sprague-Dawley rats. In group I, collagenase type XI (Sigma) at 2 mg/mL, and, in group II, Liberase at 0.6 mg/mL (2.4 PZ- U/mL; Roche) were used as controls. In groups III to VII, collagenase NB1 0.6 mg/mL (2.4 PZ-U/mL; Serva Electrophoresis) was used with increasing amounts of added NP. The NP to collagenase activity ratio (DMC-U/PZ-U) increased from 0.5% in group III to 2.0% in group VII. RESULTS: Mean islet equivalent (IE) yields per rat were 1367, 1755, 597, 895, 1712, 1043, and 905 in groups I to VII. IE yields were maximal at DMC-U/PZ-U = 1.2%. Islet morphology was influenced by NP concentration with decreasing numbers of trapped islets and increasing numbers of fragmented islets as NP contents increased. Cytokine release, islet cell apoptosis, and in vitro function were significantly better in groups III to VII as compared with groups I and II. CONCLUSION: NP is a crucial additive to collagenase for islet isolation. Optimization of the NP to collagenase activity ratio (1.2% in this model) improves yields and morphology after islet isolation.

Crystallization of the EGF receptor ectodomain on US space mission STS-47.

Although biochemists working in the field of biological signal transduction have characterized cell surface receptors for numerous growth factors within the past ten years, none of the three-dimensional structures could be obtained for these important proteins which represent major components of the cells' growth control system. Now, the extracellular ligand binding domain of the EGF receptor was crystallized in the presence of EGF under microgravity on US Shuttle mission STS-47. In 8 out of 9 experiments prepared under different conditions crystal growth was observed. One of these space-grown crystals showed higher diffraction quality than all crystals previously obtained in the laboratory. It allowed, for the first time, evaluation of the real space group by partial data collection.

"Fast-track" rehabilitation for elective colonic surgery in Germany--prospective observational data from a multi-centre quality assurance programme.

BACKGROUND: The results of "Fast-track" colonic surgery in an unselected population outside of specialised units has been unknown yet. MATERIALS AND METHODS: Data from 24 German hospitals performing "Fast-track" rehabilitation as the standard peri-operative care for patients undergoing elective colonic resection were collected in a prospective multi-centre study conducted between April 2005 and September 2006 to evaluate local and general morbidity. RESULTS: One thousand and forty-seven patients undergoing elective "fast-track" colonic resection were included. Compliance to essential parts of "fast-track" rehabilitation was high (epidural analgesia 86,6%, early oral feeding and mobilisation on the day of surgery 85.5 and 85.4%). Surgical morbidity was observed in 148 patients (14.1%) and general morbidity in 95 patients (9.1%), while mortality was 0.8%. Predefined discharge criteria were met within 5 (1-83) days after surgery, but because of economical restraints in the German DRG system, patients were discharged only after 8 (3-83) days. Re-admission rate was 3.9%. CONCLUSION: "Fast-track" rehabilitation for elective colonic resection was safe and feasible in German hospitals of all sizes and yielded a low general morbidity and re-admission rate. Post-operative recovery was enhanced, but discharge from hospital was delayed because of economical reasons.

The combination of shared family environment and individual-specific developmental deviance as a cause for treated psychiatric morbidity in children.

OBJECTIVE: There is an incomplete understanding of why some children growing up in the same family are in need of treatment for psychiatric morbidity whilst their siblings are not. The present paper examined the possible role of individual-specific developmental risk factors. METHOD: Three case-control analyses were conducted: i) 80 children referred to the Community Mental Health Centre (cases) and 320 population controls, ii) 68 healthy siblings of cases and 272 population controls, and iii) 80 children and 68 healthy siblings. Measures of development and psychosocial circumstances were obtained from routine, longitudinal, standardized child medical records. RESULTS: Given shared family environments, additional presence of delays in speech and motor development contributed most to differential sibling mental health outcomes. In addition, cases displayed both earlier expression and more severe levels of developmental behavioural deviance than their healthy siblings, who in turn had higher levels of behavioural deviance than population controls. CONCLUSION: In siblings sharing a familial risk environment, development of psychiatric morbidity may be canalized through additional individual-specific developmental exposures.

The secreted form of the epidermal growth factor receptor. Characterization and crystallization of the receptor-ligand complex.

A protein composed of the external domain of the epidermal growth factor (EGF) receptor is secreted by A431 human tumor cells. The soluble receptor protein was isolated in bulk quantities from cell culture supernatants. It has an intact ligand binding site, exists in a 93-kDa monomeric form, and does not undergo oligomerization upon ligand binding; thus the receptor dimerization reported for the EGF holoreceptor appears not to be a function of its external domain. The unique system of a physiological soluble receptor was utilized for a crystallization study. Crystals were obtained but only in the presence of the ligand. They contained (in equimolar amounts) receptor as well as EGF. The crystals belong to the tetragonal space group P4(3)2(1)2 or P4(1)2(1)2 with unit cell dimensions a = b = 118 A, c = 202 A. The packing density parameter was 3.55 A3/dalton, indicating the asymmetric unit to consist of one receptor-ligand complex.

spo0J is required for normal chromosome segregation as well as the initiation of sporulation in Bacillus subtilis.

The spo0J gene of Bacillus subtilis is required for the initiation of sporulation. We show that the sporulation defect caused by null mutations in spo0J is suppressed by a null mutation in the gene located directly upstream from spo0J, soj (suppressor of spo0J). These results indicate that Soj inhibits the initiation of sporulation and that Spo0J antagonizes that inhibition. Further genetic experiments indicated that Soj ultimately affects sporulation by inhibiting the activation (phosphorylation) of the developmental transcription factor encoded by spo0A. In addition, the temperature-sensitive sporulation phenotype caused by the ftsA279 (spoIIN279) mutation was partly suppressed by the soj null mutation, indicating that FtsA might also affect the activity of Soj. Soj and Spo0J are known to be similar in sequence to a family of proteins involved in plasmid partitioning, including ParA and ParB of prophage P1, SopA and SopB of F, and IncC and KorB of RK2, spo0J was found to be required for normal chromosome partitioning as well as for sporulation. spo0J null mutants produced a significant proportion of anucleate cells during vegetative growth. The dual functions of Spo0J could provide a mechanism for regulating the initiation of sporulation in response to activity of the chromosome partition machinery.

Shared social environment and psychiatric disorder: a multilevel analysis of individual and ecological effects.

We examined associations, in terms of relative and population-attributable risks, between shared social environment at the neighbourhood level and (1) treated incidence of non-psychotic, non-organic disorders, and (2) subsequent level of service consumption. The multilevel analysis used linked records of all individuals in contact for the first time with any catchment area mental health service for non-psychotic, non-organic disorder over various specified time periods between 1981 and 1995. Socioeconomic indicators of 36 neighbourhoods in the city of Maastricht yielded a multivariately defined neighbourhood deprivation score. There were significant linear trends in the association between level of deprivation and treated incidence, especially in the population under 35 years of age (adjusted rate ratio for linear trend 1.17, 95% confident interval 1.11-1.23), who constituted around half of the patient population. The fraction of the incidence of psychiatric disorder attributable to deprivation was 17.8%. Multilevel analyses of rates of a second cohort, with cases divided according to level of service use over a standardised follow-up of 5 years after first contact with psychiatric services, revealed that the effect of deprivation scores on rates declined with intensity of out-patient service use, but increased with level of in-patient use. Up to 50% of in-patient episodes in this group could be attributed to neighbourhood level of deprivation. The increase in risk conferred by neighbourhood deprivation remained after adjustment for the individual-level equivalent. The findings therefore suggest that elements in the shared social environment influence both incidence and severity of non-psychotic, non-organic disorders, over and above any individual-level effect.

Neighbourhood variation in incidence of schizophrenia. Evidence for person-environment interaction.

BACKGROUND: Neighbourhood characteristics may influence the risk of psychosis, independently of their individual-level equivalents. AIMS: To examine these issues in a multi-level model of schizophrenia incidence. METHOD: Cases of schizophrenia, incident between 1986 and 1997, were identified from the Maastricht Mental Health Case Register. A multi-level analysis was conducted to examine the independent effects of individual-level and neighbourhood-level variables in 35 neighbourhoods. RESULTS: Independent of individual-level single and divorced marital status, an effect of the proportion of single persons and proportion of divorced persons in a neighbourhood was apparent (per 1% increase respectively: RR = 1.02; 95% CI 1.00-1.03; and RR = 1.12, 95% CI 1.04-1.21). Single marital status interacted with the neighbourhood proportion of single persons, the effect being stronger in neighbourhoods with fewer single-person households. CONCLUSIONS: The neighbourhood environment modifies the individual risk for schizophrenia. Premorbid vulnerability resulting in single marital status may be more likely to progress to overt disease in an environment with a higher perceived level of social isolation.

Analysis of antibiotic stability in a parenteral nutrition solution.

In children receiving multiple antibiotics and total parenteral nutrition (TPN), the amount of nutrition received can be less than optimal if the central venous line is used for administration of blood products, antibiotics and other medications. The purpose of this study was to evaluate the compatibility of commonly used antibiotics in our standard hyperalimentation solution to determine whether these drugs could be administered in a "piggyback" fashion with parenteral nutrition. If there were no incompatibility this could allow significantly more TPN to be delivered without need for extra fluid in patients receiving antibiotics several times daily. We found 13 antibiotics (amikacin, azlocillin, cefamandole, cephalothin, gentamicin, mezlocillin, moxalactam, nafcillin, oxacillin, penicillin, piperacillin, ticarcillin and tobramycin) to be stable for 6 hours and compatible with the TPN solution. They could be safely given in the presence of the hyperalimentation preparation (1.5% amino acid, 15% dextrose, vitamins, calcium (300 mg/liter) and standard electrolyte concentrations).