Basic symptoms and ultrahigh risk criteria: symptom development in the initial prodromal state

Symptom development during the prodromal phase of psychosis was explored retrospectively in first-episode psychosis patients with special emphasis on the assumed time-related syndromic sequence of "unspecific symptoms (UN)-predictive basic symptoms (BS)-attenuated psychotic symptoms (APS)-(transient) psychotic symptoms (PS)." Onset of syndromes was defined by first occurrence of any of their respective symptoms. Group means were inspected for time differences between syndromes and influence of sociodemographic and clinical characteristics on the recalled sequence. The sequence of "UN-BS/APS-PS" was clearly supported, and both BS and, though slightly less, APS were highly sensitive. However, onset of BS and APS did not show significant time difference in the whole sample (N = 126; 90% schizophrenia), although when each symptom is considered independently, APS tended to occur later than first predictive BS. On descriptive level, about one-third each recalled an earlier, equal and later onset of BS compared with APS. Level of education showed the greatest impact on the recall of the hypothesized sequence. Thereby, those with a higher school-leaving certificate supported the assumed sequence, whereas those of low educational background retrospectively dated APS before BS. These findings rather point out recognition and recall bias inherent to the retrospective design than true group characteristics. Future long-term prospective studies will have to explore this conclusively. However, as regards the criteria, the results support the notion of BS as at least a complementary approach to the ultrahigh risk criteria, which may also allow for an earlier detection of psychosis.

Intermittent spike-wave dynamics in a heterogeneous, spatially extended neural mass model

Generalised epileptic seizures are frequently accompanied by sudden, reversible transitions from low amplitude, irregular background activity to high amplitude, regular spike-wave discharges (SWD) in the EEG. The underlying mechanisms responsible for SWD generation and for the apparently spontaneous transitions to SWD and back again are still not fully understood. Specifically, the role of spatial cortico-cortical interactions in ictogenesis is not well studied. We present a macroscopic, neural mass model of a cortical column which includes two distinct time scales of inhibition. This model can produce both an oscillatory background and a pathological SWD rhythm. We demonstrate that coupling two of these cortical columns can lead to a bistability between out-of-phase, low amplitude background dynamics and in-phase, high amplitude SWD activity. Stimuli can cause state-dependent transitions from background into SWD. In an extended local area of cortex, spatial heterogeneities in a model parameter can lead to spontaneous reversible transitions from a desynchronised background to synchronous SWD due to intermittency. The deterministic model is therefore capable of producing absence seizure-like events without any time dependent adjustment of model parameters. The emergence of such mechanisms due to spatial coupling demonstrates the importance of spatial interactions in modelling ictal dynamics, and in the study of ictogenesis.

Tumor architecture exerts no bias on nuclear grading in breast cancer diagnosis

We recently reported that nuclear grading in prostate cancer is subject to a strong confirmation bias induced by the tumor architecture. We now wondered whether a similar bias governs nuclear grading in breast carcinoma. An unannounced test was performed at a pathology conference. Pathologists were asked to grade nuclei in a PowerPoint presentation. Circular high power fields of 27 invasive ductal carcinomas were shown, superimposed over low power background images of either tubule-rich or tubule-poor carcinomas. We found (a) that diagnostic reproducibility of nuclear grades was poor to moderate (weighed kappa values between 0.07 and 0.54, 27 cases, 44 graders), but (b) that nuclear grades were not affected by the tumor architecture. We speculate that the categorized grading in breast cancer, separating tubule formation, nuclear pleomorphism, and mitotic figure counts in a combined three tier score, prevents the bias that architecture exerts on nuclear grades in less well-controlled situations.

Evolution of gene expression changes in newborn rats after mechanical ventilation with reversible intubation

Mechanical ventilation (MV) is life-saving but potentially harmful for lungs of premature infants. So far, animal models dealt with the acute impact of MV on immature lungs, but less with its delayed effects. We used a newborn rodent model including non-surgical and therefore reversible intubation with moderate ventilation and hypothesized that there might be distinct gene expression patterns after a ventilation-free recovery period compared to acute effects directly after MV. Newborn rat pups were subjected to 8 hr of MV with 60% oxygen (O(2)), 24 hr after injection of lipopolysaccharide (LPS), intended to create a low inflammatory background as often recognized in preterm infants. Animals were separated in controls (CTRL), LPS injection (LPS), or full intervention with LPS and MV with 60% O(2) (LPS + MV + O(2)). Lungs were recovered either directly following (T:0 hr) or 48 hr after MV (T:48 hr). Histologically, signs of ventilator-induced lung injury (VILI) were observed in LPS + MV + O(2) lungs at T:0 hr, while changes appeared similar to those known from patients with chronic lung disease (CLD) with fewer albeit larger gas exchange units, at T:48 hr. At T:0 hr, LPS + MV + O(2) increased gene expression of pro-inflammatory MIP-2. In parallel anti-inflammatory IL-1Ra gene expression was increased in LPS and LPS + MV + O(2) groups. At T:48 hr, pro- and anti-inflammatory genes had returned to their basal expression. MMP-2 gene expression was decreased in LPS and LPS + MV + O(2) groups at T:0 hr, but no longer at T:48 hr. MMP-9 gene expression levels were unchanged directly after MV. However, at T:48 hr, gene and protein expression increased in LPS + MV + O(2) group. In conclusion, this study demonstrates the feasibility of delayed outcome measurements after a ventilation-free period in newborn rats and may help to further understand the time-course of molecular changes following MV. The differences obtained from the two time points could be interpreted as an initial transitory increase of inflammation and a delayed impact of the intervention on structure-related genes.

Visual and quantitative electroencephalographic analysis of healthy young and adult cats under medetomidine sedation

A study was designed to investigate the effect of medetomidine sedation on quantitative electroencephalography (q-EEG) in healthy young and adult cats to determine objective guidelines for diagnostic EEG recordings and interpretation. Preliminary visual examination of EEG recordings revealed high-voltage low-frequency background activity. Spindles, k-complexes and vertex sharp transients characteristic of sleep or sedation were superimposed on a low background activity. Neither paroxysmal activity nor EEG burst-suppression were observed. The spectral analysis of q-EEG included four parameters, namely, relative power (%), and mean, median and peak frequency (Hz) of all four frequency bands (delta, theta, alpha and beta). The findings showed a prevalence of slow delta and theta rhythms as opposed to fast alpha and beta rhythms in both young (group A) and adult (group B) cats. A posterior gradient was reported for the theta band and an anterior gradient for the alpha and beta bands in both groups, respectively. The relative power value in group B compared to group A was significantly higher for theta, alpha and beta bands, and lower for the delta band. The mean and median frequency values in group B was significantly higher for delta, theta and beta bands and lower for the alpha band. The study has shown that a medetomidine sedation protocol for feline EEG may offer a method for investigating bio-electrical cortical activity. The use of q-EEG analysis showed a decrease in high frequency bands and increased activity of the low frequency band in healthy cats under medetomidine sedation.

Hidden school dropout among immigrant students: a cross-sectional study

Actual school dropout among immigrant youth has been addressed in a number of studies, but research on hidden school dropout among immigrant students is rare. Thus, the objective of this paper is to analyze hidden school dropout among primary school students with an immigrant background. The analyses were performed using survey data of 1186 immigrant students in Swiss primary schools. Our results show that immigrant students’ academic achievement, their attitudes towards school-related values, and the quality of their relationships with classmates and teachers were significant predictors of their disengagement during classes. Moreover, our findings strongly suggest that those predictors that are important for actual school dropout are crucial for hidden school dropout as well. We conclude that low-achieving immigrant youth who do not value school and who have poor relationships with teachers and peers are especially at risk of hidden and, eventually, of actual school dropout.

GeMSE: A new low-background facility for meteorite and material screening

We are currently setting up a facility for low-background gamma-ray spectrometry based on a HPGe detector. It is dedicated to material screening for the XENON and DARWIN dark matter projects as well as to the characterization of meteorites. The detector will be installed in a medium depth (∼620 m.w.e.) underground laboratory in Switzerland with several layers of shielding and an active muon-veto. The GeMSE facility will be operational by fall 2015 with an expected background rate of ∼250 counts/day (100-2700 keV).

Should I Stay or Should I Go? Career Choice Intentions of Students with Family Business Background

Personal and motivational patterns of intentional founders have been researched in great depth; however, antecedents to career choices of intentional successors have been conspicuously missing in entrepreneurship research. By drawing on theory of planned behavior, we investigate how intentional founders, successors, and employees differ in terms of locus of control and entrepreneurial self-efficacy as well as independence and innovation motives. We find that transitive likelihood of career intent depends on degree of entrepreneurial self-efficacy and the independence motive. Unexpectedly, we see that high levels of internal locus of control lead to a preference of employment, which challenges traditional entrepreneurship research and suggests that the feasibility of an entrepreneurial career path does not automatically make it desirable. Our findings suggest that students with family business background are pessimistic about being in control in an entrepreneurial career, but optimistic about their efficacy to pursue an entrepreneurial career.

Contribution of Genetic Background and Clinical Risk Factors to Low-Trauma Fractures in Human Immunodeficiency Virus (HIV)-Positive Persons: The Swiss HIV Cohort Study.

Background.  The impact of human genetic background on low-trauma fracture (LTF) risk has not been evaluated in the context of human immunodeficiency virus (HIV) and clinical LTF risk factors. Methods.  In the general population, 6 common single-nucleotide polymorphisms (SNPs) associate with LTF through genome-wide association study. Using genome-wide SNP arrays and imputation, we genotyped these SNPs in HIV-positive, white Swiss HIV Cohort Study participants. We included 103 individuals with a first, physician-validated LTF and 206 controls matched on gender, whose duration of observation and whose antiretroviral therapy start dates were similar using incidence density sampling. Analyses of nongenetic LTF risk factors were based on 158 cases and 788 controls. Results.  A genetic risk score built from the 6 LTF-associated SNPs did not associate with LTF risk, in both models including and not including parental hip fracture history. The contribution of clinical LTF risk factors was limited in our dataset. Conclusions.  Genetic LTF markers with a modest effect size in the general population do not improve fracture prediction in persons with HIV, in whom clinical LTF risk factors are prevalent in both cases and controls.

Predicting the transition from acute to persistent low back pain

BACKGROUND: Most people experience low back pain (LBP) at least once in their lifetime. Only a minority of them go on to develop persistent LBP. However, the socioeconomic costs of persistent LBP significantly exceed the costs of the initial acute LBP episode. AIMS: To identify factors that influence the progression of acute LBP to the persistent state at an early stage. METHODS: Prospective inception cohort study of patients attending a health practitioner for their first episode of acute LBP or recurrent LBP after a pain free period of at least 6 months. Patients were assessed at baseline addressing occupational and psychological factors as well as pain, disability, quality of life and physical activity and followed up at 3, 6, 12 weeks and 6 months. Variables were combined to the three indices 'working condition', 'depression and maladaptive cognitions' and 'pain and quality of life'. RESULTS: The index 'depression and maladaptive cognitions' was found to be a significant baseline predictor for persistent LBP up to 6 months (OR 5.1; 95% CI: 1.04-25.1). Overall predictive accuracy of the model was 81%. CONCLUSIONS: In this study of patients with acute LBP in a primary care setting psychological factors at baseline correlated with a progression to persistent LBP up to 6 months. The benefit of including factors such as 'depression and maladaptive cognition' in screening tools is that these factors can be addressed in primary and secondary prevention.

Predicting the transition from acute to persistent low back pain

BACKGROUND: Most people experience low back pain (LBP) at least once in their lifetime. Only a minority of them go on to develop persistent LBP. However, the socioeconomic costs of persistent LBP significantly exceed the costs of the initial acute LBP episode. AIMS: To identify factors that influence the progression of acute LBP to the persistent state at an early stage. METHODS: Prospective inception cohort study of patients attending a health practitioner for their first episode of acute LBP or recurrent LBP after a pain free period of at least 6 months. Patients were assessed at baseline addressing occupational and psychological factors as well as pain, disability, quality of life and physical activity and followed up at 3, 6, 12 weeks and 6 months. Variables were combined to the three indices 'working condition', 'depression and maladaptive cognitions' and 'pain and quality of life'. RESULTS: The index 'depression and maladaptive cognitions' was found to be a significant baseline predictor for persistent LBP up to 6 months (OR 5.1; 95% CI: 1.04-25.1). Overall predictive accuracy of the model was 81%. CONCLUSIONS: In this study of patients with acute LBP in a primary care setting psychological factors at baseline correlated with a progression to persistent LBP up to 6 months. The benefit of including factors such as 'depression and maladaptive cognition' in screening tools is that these factors can be addressed in primary and secondary prevention.