Prevalence and Clinical Significance of DSM-5-Attenuated Psychosis Syndrome in Adolescents and Young Adults in the General Population: The Bern Epidemiological At-Risk (BEAR) Study

Objective: Section III of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lists attenuated psychosis syndrome as a condition for further study. One important question is its prevalence and clinical significance in the general population. Method: Analyses involved 1229 participants (age 16-40 years) from the general population of Canton Bern, Switzerland, enrolled from June 2011 to July 2012. "Symptom," "onset/worsening," "frequency," and "distress/disability" criteria of attenuated psychosis syndrome were assessed using the structured interview for psychosis-risk syndromes. Furthermore, help-seeking, psychosocial functioning, and current nonpsychotic axis I disorders were surveyed. Well-trained psychologists performed assessments using the computer-assisted telephone interviewing technique. Results: The symptom criterion was met by 12.9% of participants, onset/worsening by 1.1%, frequency by 3.8%, and distress/disability by 7.0%. Symptom, frequency, and distress/disability were met by 3.2%. Excluding trait-like attenuated psychotic symptoms (APS) decreased the prevalence to 2.6%, while adding onset/worsening reduced it to 0.3%. APS were associated with functional impairments, current mental disorders, and help-seeking although they were not a reason for help-seeking. These associations were weaker for attenuated psychosis syndrome. Conclusions: At the population level, only 0.3% met current attenuated psychosis syndrome criteria. Particularly, the onset/worsening criterion, originally included to increase the likelihood of progression to psychosis, lowered its prevalence. Because progression is not required for a self-contained syndrome, a revision of the restrictive onset criterion is proposed to avoid the exclusion of 2.3% of persons who experience and are distressed by APS from mental health care. Secondary analyses suggest that a revised syndrome would also possess higher clinical significance than the current syndrome.

Significance of telecoupling for exploration of land-use change

Land systems are increasingly influenced by distal connections: the externalities and unintended consequences of social and ecological processes which occur in distant locations, and the feedback mechanisms that lead to new institutional developments and governance arrangements. Economic globalization and urbanization accentuate these novel telecoupling relationships. The prevalence of telecoupling in land systems demands new approaches to research and analysis in land science. This chapter presents a working definition of a telecoupled system, emphasizing the role of governance and institutional change in telecoupled interactions. The social, institutional, and ecological processes and conditions through which telecoupling emerges are described. The analysis of these relationships in land science demands both integrative and diverse epistemological perspectives and methods. Such analyses require a focus on how the motivations and values of social actors relate to telecoupling processes, as well as on the mechanisms that produce unanticipated outcomes and feedback relationships among distal land systems.

Prognostic significance of multidetector CT in normotensive patients with pulmonary embolism: results of the protect study.

BACKGROUND In patients with acute pulmonary embolism (PE), rapid and accurate risk assessment is paramount in selecting the appropriate treatment strategy. The prognostic value of right ventricular dysfunction (RVD) assessed by multidetector CT (MDCT) in normotensive patients with PE has lacked adequate validation. METHODS The study defined MDCT-assessed RVD as a ratio of the RV to the left ventricle short axis diameter greater than 0.9. Outcomes assessed through 30 days after the diagnosis of PE included all-cause mortality and 'complicated course', which consisted of death from any cause, haemodynamic collapse or recurrent PE. RESULTS MDCT detected RVD in 533 (63%) of the 848 enrolled patients. Those with RVD on MDCT more frequently had echocardiographic RVD (31%) than those without RVD on MDCT (9.2%) (p<0.001). Patients with RVD on MDCT had significantly higher brain natriuretic peptide (269±447 vs 180±457 pg/ml, p<0.001) and troponin (0.10±0.43 vs 0.03±0.24 ng/ml, p=0.001) levels in comparison with those without RVD on MDCT. During follow-up, death occurred in 25 patients with and in 13 patients without RVD on MDCT (4.7% vs 4.3%; p=0.93). Those with and those without RVD on MDCT had a similar frequency of complicated course (3.9% vs 2.3%; p=0.30). CONCLUSIONS The PROgnosTic valuE of CT study showed a relationship between RVD assessed by MDCT and other markers of cardiac dysfunction around the time of PE diagnosis, but did not demonstrate an association between MDCT-RVD and prognosis.

Prevalence and prognostic significance of TMPRSS2-ERG gene fusion in lymph node positive prostate cancers.

BACKGROUND TMPRSS2-ERG gene fusion is the most frequent genetic alteration in prostate cancer. However, information about its distribution in lymph node positive prostate cancers and the prognostic significance in these advanced tumors is unknown. METHODS Gene fusion status was determined by fluorescence in situ hybridization on a tissue-microarray constructed from 119 hormone-naïve nodal positive, surgically treated prostate cancers containing samples from the primary tumors and corresponding lymph node metastases. Data were correlated with various tumor features (Gleason score, stage, cancer volume, nodal tumor burden) and biochemical recurrence-free, disease-specific, and overall survival. RESULTS TMPRSS2-ERG fusion was detected in 43.5% of the primary tumors. Conversely, only 29.9% of the metastasizing components showed the fusion. Concordance in TMPRSS2-ERG status between primary tumors and metastases was 70.9% (Kappa 0.39); 20.9% and 8.1% of the patients showed the mutation solely in their primary tumors and metastases, respectively. TMPRSS2-ERG fusion was not correlated with specific histopathological tumor features but predicted favorable biochemical recurrence-free, disease-specific and overall survival independently when present in the primary tumor (P < 0.05 each). CONCLUSION TMPRSS2-ERG fusion is more frequent in primary prostate cancer than in corresponding metastases suggesting no selection of fusion-positive cells in the metastatic process. The gene fusion in primary tumors independently predicts favorable outcome.

The special Sm core structure of the U7 snRNP: far-reaching significance of a small nuclear ribonucleoprotein

The polypeptide composition of the U7 small nuclear ribonucleoprotein (snRNP) involved in histone messenger RNA (mRNA) 3' end formation has recently been elucidated. In contrast to spliceosomal snRNPs, which contain a ring-shaped assembly of seven so-called Sm proteins, in the U7 snRNP the Sm proteins D1 and D2 are replaced by U7-specific Sm-like proteins, Lsm10 and Lsm11. This polypeptide composition and the unusual structure of Lsm11, which plays a role in histone RNA processing, represent new themes in the biology of Sm/Lsm proteins. Moreover this structure has important consequences for snRNP assembly that is mediated by two complexes containing the PRMT5 methyltransferase and the SMN (survival of motor neurons) protein, respectively. Finally, the ability to alter this polypeptide composition by a small mutation in U7 snRNA forms the basis for using modified U7 snRNA derivatives to alter specific pre-mRNA splicing events, thereby opening up a new way for antisense gene therapy.

Clinical significance of the CCR5delta32 allele in hepatitis C.

BACKGROUND The CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection. METHODS CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance. RESULTS Carriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35-0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99-1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4). CONCLUSIONS The CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.

Age matters in the prevalence and clinical significance of ultra-high-risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS-kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high-risk symptoms in children and adolescents as compared to adults. We examined ultra-high-risk (UHR) symptoms and criteria in a sample of individuals aged 8-40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non-perceptive APS were differentiated. Psychosocial functioning and current non-psychotic DSM-IV axis I disorders were also surveyed. Well-trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8-15-year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non-perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non-perceptive APS, and their interaction with age, also in terms of conversion to psychosis.

Comparison of the diagnostic significance of clinical, radiographic and ultrasonographic results after an experimental aerosol infection of pigs with Actinobacillus pleuropneumoniae

Scoring schemes for clinical, ultrasonographic and radiographic findings in pigs were developed based upon a standardized animal model for Actinobacillus pleuropneumoniae infection.The results of these methods were compared to each other as well as with the corresponding pathomorphological findings during necropsy. Altogether 69 pigs of different breeding lines (Hampshire, Pietrain and German Landrace were examined. Positive correlations were found between the results of all three methods as well as with the necropsy scores (p <0.0001). Different pathomorphological findings were detected either by radiographic or by ultrasonographic examination dependent upon the type of lung tissue alterations: Alterations of the pleura as well as sequestration of lung tissue on the lung surface could be clearly identified during the ultrasonographic examination while deep tissue alterations with no contact to the lung surface could be detected reliably by radiographic examination. Both methods complement each other, and the application of a combined ultrasonographic and radiographic examination of the thorax allows a comprehensive inspection of the lung condition. Particularly during the acute phase of the disease the extent of lung tissue damage can be estimated more precisely than by clinical examination alone.

The functional significance of EEG microstates-Associations with modalities of thinking

The momentary, global functional state of the brain is reflected by its electric field configuration. Cluster analytical approaches consistently extracted four head-surface brain electric field configurations that optimally explain the variance of their changes across time in spontaneous EEG recordings. These four configurations are referred to as EEG microstate classes A, B, C, and D and have been associated with verbal/phonological, visual, attention reorientation, and subjective interoceptive-autonomic processing, respectively. The present study tested these associations via an intra-individual and inter-individual analysis approach. The intra-individual approach tested the effect of task-induced increased modality-specific processing on EEG microstate parameters. The inter-individual approach tested the effect of personal modality-specific parameters on EEG microstate parameters. We obtained multichannel EEG from 61 healthy, right-handed, male students during four eyes-closed conditions: object-visualization, spatial-visualization, verbalization (6 runs each), and resting (7 runs). After each run, we assessed participants' degrees of object-visual, spatial-visual, and verbal thinking using subjective reports. Before and after the recording, we assessed modality-specific cognitive abilities and styles using nine cognitive tests and two questionnaires. The EEG of all participants, conditions, and runs was clustered into four classes of EEG microstates (A, B, C, and D). RMANOVAs, ANOVAs and post-hoc paired t-tests compared microstate parameters between conditions. TANOVAs compared microstate class topographies between conditions. Differences were localized using eLORETA. Pearson correlations assessed interrelationships between personal modality-specific parameters and EEG microstate parameters during no-task resting. As hypothesized, verbal as opposed to visual conditions consistently affected the duration, occurrence, and coverage of microstate classes A and B. Contrary to associations suggested by previous reports, parameters were increased for class A during visualization, and class B during verbalization. In line with previous reports, microstate D parameters were increased during no-task resting compared to the three internal, goal-directed tasks. Topographic differences between conditions concerned particular sub-regions of components of the metabolic default mode network. Modality-specific personal parameters did not consistently correlate with microstate parameters except verbal cognitive style which correlated negatively with microstate class A duration and positively with class C occurrence. This is the first study that aimed to induce EEG microstate class parameter changes based on their hypothesized functional significance. Beyond, the associations of microstate classes A and B with visual and verbal processing, respectively and microstate class D with interoceptive-autonomic processing, our results suggest that a finely-tuned interplay between all four EEG microstate classes is necessary for the continuous formation of visual and verbal thoughts, as well as interoceptive-autonomic processing. Our results point to the possibility that the EEG microstate classes may represent the head-surface measured activity of intra-cortical sources primarily exhibiting inhibitory functions. However, additional studies are needed to verify and elaborate on this hypothesis.