Exploring Predictors of Outcome in the Psychosis Prodrome: Implications for Early Identification and Intervention

Functional disability is a key component of many psychiatric illnesses, particularly schizophrenia. Impairments in social and role functioning are linked to cognitive deficits, a core feature of psychosis. Retrospective analyses demonstrate that substantial functional decline precedes the onset of psychosis. Recent investigations reveal that individuals at clinical-high-risk (CHR) for psychosis show impairments in social relationships, work/school functioning and daily living skills. CHR youth also demonstrate a pattern of impairment across a range of cognitive domains, including social cognition, which is qualitatively similar to that of individuals with schizophrenia. While many studies have sought to elucidate predictors of clinical deterioration, specifically the development of schizophrenia, in such CHR samples, few have investigated factors relevant to psychosocial outcome. This review integrates recent findings regarding cognitive and social-cognitive predictors of outcome in CHR individuals, and proposes potential directions for future research that will contribute to targeted interventions and improved outcome for at-risk youth

Personality predictors of cognitive dispersion: A coordinated analysis of data from seven international studies of older adults.

Objectives: Dispersion in cognitive test performance within a single testing session is proposed as an early marker of poor brain health. Existing research, however, has not investigated factors that may explain individual differences in cognitive dispersion. We investigate the extent to which the Big Five personality traits are associated with cognitive dispersion in older adulthood. Method: To promote transparency and reliability, we applied preregistration and conceptual replication via coordinated analysis. Drawing data from seven longitudinal studies of aging (Ntotal = 33,581; Mage range = 56.4–71.2), cognitive dispersion scores were derived from cognitive test results. Independent linear regression models were fit in each study to examine personality traits as predictors of dispersion scores, adjusting for mean cognitive performance and sociodemographics (age, sex, education). Results from individual studies were synthesized using random effects meta-analyses. Results: Synthesized results revealed that openness was positively associated with cognitive dispersion, 0.028, 95% CI [0.003, 0.054]. There was minimal evidence for associations between cognitive dispersion and the other personality traits in independent analyses or meta-analyses. Mean cognitive scores were negatively associated with cognitive dispersion across the majority of studies,while sociodemographic variables were not consistently associated with cognitive dispersion. Conclusion: Higher levels of openness were associated with greater cognitive dispersion across seven independent samples, indicating that individuals higher in openness had more dispersion across cognitive tests. Further research is needed to investigate mechanisms that may help to explain the link between openness and cognitive dispersion, as well as to identify additional individual factors, beyond personality traits, that may be associated with cognitive dispersion

High Affinity Humanized Antibodies without Making Hybridomas; Immunization Paired with Mammalian Cell Display and <em>In Vitro</em> Somatic Hypermutation

<div><p>A method has been developed for the rapid generation of high-affinity humanized antibodies from immunized animals without the need to make conventional hybridomas. Rearranged IgH D(J) regions were amplified from the spleen and lymph tissue of mice immunized with the human complement protein C5, fused with a limited repertoire of human germline heavy chain V-genes to form intact humanized heavy chains, and paired with a human light chain library. Completed heavy and light chains were assembled for mammalian cell surface display and transfected into HEK 293 cells co-expressing activation-induced cytidine deaminase (AID). Numerous clones were isolated by fluorescence-activated cell sorting, and affinity maturation, initiated by AID, resulted in the rapid evolution of high affinity, functional antibodies. This approach enables the efficient sampling of an immune repertoire and the direct selection and maturation of high-affinity, humanized IgGs.</p> </div

Effects of a classroom-based program on physical activity and on-task behavior

This study evaluated the effects of a classroom-based physical activity program on children's in-school physical activity levels and on-task behavior during academic instruction. Physical activity of 243 students was assessed during school hours. Intervention-group students (N = 135) received a classroom-based program (i.e., Energizers). The control group (N = 108) did not receive Energizers. On-task behavior during academic instruction time was observed for 62 third-grade (N = 37) and fourth-grade students (N = 25) before and after Energizers activities. An independent groups t-test compared in-school physical activity levels between intervention and control classes. A multiple-baseline across-classrooms design was used to evaluate the effectiveness of the Energizers on on-task behavior. Additionally, a two-way (time [pre- vs postobservation] x period [baseline vs intervention]) repeated-measures analysis of variance compared on-task behavior between observation periods. Magnitudes of mean differences were evaluated with Cohen's delta (ES). Students in the intervention group took significantly (P < 0.05) more in-school steps (5587 +/- 1633) than control-group students (4805 +/- 1543), and the size of this difference was moderate (ES = 0.49). The intervention was effective in improving on-task behavior; after the Energizers were systematically implemented, on-task behavior systematically improved. The improvement in on-task behavior of 8% between the pre-Energizers and post-Energizers observations was statistically significant (P < 0.017), and the difference was moderate (ES = 0.60). Likewise, the least on-task students improved on-task behavior by 20% after Energizers activities. This improvement was statistically significant (P < 0.001) and meaningful (ES = 2.20). A classroom-based physical activity program was effective for increasing daily in-school physical activity and improving on-task behavior during academic instruction

Baseline Surface Radiation Network (BSRN): structure and data description (1992-2017)

Small changes in the radiation budget at the earth's surface can lead to large climatological responses when persistent over time. With the increasing debate on anthropogenic influences on climatic processes during the 1980s the need for accurate radiometric measurements with higher temporal resolution was identified, and it was determined that the existing measurement networks did not have the resolution or accuracy required to meet this need. In 1988 the WMO therefore proposed the establishment of a new international Baseline Surface Radiation Network (BSRN), which should collect and centrally archive high-quality ground-based radiation measurements in 1min resolution. BSRN began its work in 1992 with 9 stations; currently (status 2018-01-01), the network comprises 59 stations (delivering data to the archive) and 9 candidates (stations recently accepted into the network with data forthcoming to the archive) distributed over all continents and oceanic environments. The BSRN database is the World Radiation Monitoring Center (WRMC). It is hosted at the Alfred Wegener Institute (AWI) in Bremerhaven, Germany, and now offers more than 10300 months of data from the years 1992 to 2017.ISSN:1866-3516ISSN:1866-350

Discovery and affinity maturation of C5-C345C-specific antibodies.

<p>(<i>A</i>) FACS scattergrams depicting isolation of a C5-C345C-specific population from the sub-library pool containing IGHV3-30-3 and IGHV4-34 (panels I–III), and subsequent affinity maturation of APE777 in strategy B (panels IV–VI). Approximately 5×10⁷ cells were sorted per round. IgG expression is shown on the y-axis and C5-C345C binding on the x-axis. (I) The first sort round (5 µM C5-C345C-Myc) showed little detectable binding; (II) round 4 (100 nM C5-C345C-Myc); and (III) round 9 (3 nM C5-C345C-Myc) which included a room-temperature incubation to increase stringency. Affinity maturation FACS scattergrams of isolated C5-C345C-specific antibody, APE777, are shown for strategy B starting with (IV) round 1 (20 nM C5-C345C-Myc), (V) round 5 (1.5 nM C5-C345C-Dyl-650), and (VI) round 8 (100 pM C5-C345C-Dyl-650). Each sort round consisted of AID-induced SHM and selection of highest antigen binding and antibody expressing cells by FACS. Note emergence of new cell populations that exhibited increased antigen binding relative to the original population over time, and which were able to recognize sequentially decreasing antigen concentrations. (<i>B</i>) Plot comparing stability late (value corresponds to amount of antibody-bound antigen) versus binding late (value corresponds to off-rate, k_d) capture-adjusted report points for Biacore 4000 screen of single cell clone supernatants. Higher values correspond to more antigen bound per unit antibody (binding late) and slower off-rates (stability late). Highlighted points indicate highest affinity C5-C345C binding clones further characterized by Biacore T200 and sequencing. (<i>C</i>) Full kinetic analysis of APE777 binding to C5-C345C (first panel) with a K_D of 200 nM (k_a = 1.4×10⁵ M⁻¹ s⁻¹, k_d = 2.4×10⁻² s⁻¹). Binding to C5 and C5b6 complement proteins was detectible (second and third panels), while APE777 shows no significant binding to the C7 negative control.</p

Summary of observed enriching mutations.

<p>Table of HC and LC point mutation, insertion, and deletion events observed during affinity maturation of APE777. The first column indicates the amino acid mutation, listed with Kabat numbering. The second column indicates whether the mutation is in the HC or LC. Columns three and four show the starting and ending nucleotide sequence surrounding the site of mutation, with the mutated nucleotides underlined. Columns five and six indicate the starting and ending nucleotide for point mutations. The last two columns indicate which strategy the mutation was observed in, and at which round it was enriched. Ten of the 11 point mutations were initiated at G or C nucleotides; one of the 11 was initiated at a T. Seven of the point mutations, the deletion, and one of the insertions occurred at known AID hotspots (WRCH, highlighted in <b>bold</b>) located within CDRs 1, 2, or 3. Seven of the 11 point mutations were nucleotide transitions, and four were nucleotide transversions.</p>1<p>Enrichment observed by Sanger sequencing of 40 HC and LC variable regions post-sort round.</p