Role for positive schizotypy and hallucination proneness in semantic processing

Semantic processing underpins the organization of verbal information for both storage and retrieval. Deficits in semantic processing are associated with both the risk for and symptoms presented in schizophrenia. However, studies are mixed and could reflect the confounding effects of medication and symptom heterogeneity. Therefore, we considered whether two risk phenotypes, positive schizotypy and hallucinatory predisposition, present in the general population were associated with differential responding profiles for a semantic processing task. One hundred and eighty-three participants completed the Schizotypal Personality Questionnaire, Launay-Slade Hallucination Scale, National Adult Reading Test, a handedness measure, and a computerized semantic relatedness judgment task. Pairs of words were related through their dominant or subordinate meanings, or unrelated. Participants were divided into four groups using a mean split on cognitive-perceptual (positive) schizotypy and hallucination proneness. Significant differences between groups were found for reaction time on the semantic relatedness task, with the high cognitive-perceptual schizotypy groups responding significantly slower to all word pairs compared to their low scoring counterparts. There was some evidence that high hallucination proneness was associated with significantly faster reaction times which may reflect disinhibitive processes, however additional support is required. The results suggest that these two components of psychosis risk are associated with different patterns of responding to semantic processing. More diffuse activation of semantic information appeared to be associated with positive schizotypy, while those predisposed to hallucinations appeared to respond quicker. These results have significant implications in the re-conceptualization of hallucination proneness as distinct from positive schizotypy. Additional research is required to investigate the association between psychotic-like experiences separate from personality variables such as positive schizotypy and semantic processing

Bacterial culture underestimates lung pathogen detection and infection status in cystic fibrosis

Microbiological surveillance of airway secretions is central to clinical care in cystic fibrosis (CF). However, the efficacy of microbiological culture, the diagnostic gold standard for pathogen detection, has been increasingly questioned. Here we compared culture with targeted quantitative PCR (QPCR) for longitudinal detection of 2 key pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Prospectively collected respiratory samples taken from 20 pediatric and 20 adult CF patients over a period of 3-years were analyzed. Patients were eligible if considered free of chronic Pseudomonas infection within 12-months prior to start of study. QPCR revealed high levels of infection with both pathogens not apparent from culture alone. Pseudomonas and Staphylococcus were detected by culture on at least one sampling occasion in 12 and 29 of the patients, respectively. Conversely, both pathogens were detected in all 40 patients by QPCR. Classification of infection status also significantly altered in both pediatric and adult patients, where the number of patients deemed chronically infected with Pseudomonas and Staphylococcus increased from 1 to 28 and 9 to 34, respectively. Overall, Pseudomonas and Staphylococcus infection status classification changed respectively for 36 and 27 of all patients. In no cases did molecular identification lead to a patient being in a less clinically serious infection category. Pathogen detection and infection status classification significantly increased when assessed by QPCR in comparison to culture. This could have implications for clinical care of CF patients, including accuracy of infection diagnosis, relevant and timely antibiotic selection, antimicrobial resistance development, establishment of chronic infection, and cross-infection control. IMPORTANCE Chronic lung infection is the leading cause of morbidity and early mortality for people with cystic fibrosis (pwCF). Microbiological surveillance to detect lung pathogens is recommended as best practise in CF patient care. Here we studied pathogen detection in 40 pwCF over several years. We found that microbiological culture, the diagnostic gold standard, was significantly disparate to targeted culture-independent approaches for detection and determination of chronic infection status of two important pathogens in CF. Pathogen detection was significantly lower by culture and consequently infection status was also misclassified in most cases. In particular, the extent of chronic infection by both P. aeruginosa and S. aureus not realized with culture was striking. Our findings have implications for the development of infection and clinical care of pwCF. Future longitudinal studies with greater patient numbers will be needed to establish the full extent of the clinical implications indicated from this study

Effects of postage on recovery of pathogens from cystic fibrosis sputum samples

Background: Regular surveillance microbiology of sputum is used in cystic fibrosis (CF) to monitor for new pathogens and target treatments. A move to remote clinics has meant greater reliance on samples collected at home and posted back. The impact of delays and sample disruption caused by posting has not been systematically assessed but could have significant implications for CF microbiology. Methods: Sputum samples collected from adult CF patients were mixed, split, and either processed immediately or posted back to laboratory. Processing involved a further split into aliquots for culture-dependant and-independent microbiology (quantitative PCR [QPCR] and microbiota sequencing). We calculated retrieval by both approaches for five typical CF pathogens: Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter xylosoxidans, Staphylococcus aureus and Stenotrophomonas maltophilia. Results: 93 paired samples were collected from 73 CF patients. Median interval between sample posting and receipt was 5 days (range 1–10). For culture, overall concordance for posted and fresh samples was 86% across the five targeted pathogens (ranging from 57 to 100% for different organisms), with no bias towards either sample type. For QPCR, overall concordance was 62% (range 39–84%), again with no bias towards fresh or posted samples. There were no significant differences in culture or QPCR for samples with short (≤3days) versus extended (≥7days) postal delays. Posting had no significant impact on pathogen abundance nor on microbiota characteristics. Conclusions: Posted sputum samples reliably reproduced culture-based and molecular microbiology of freshly collected samples, even after prolonged delays at ambient conditions. This supports use of posted samples during remote monitoring

Changes in intraocular pressure in study and fellow eyes in the IVAN trial

PURPOSE: To describe changes in intraocular pressure (IOP) in the 'alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)' trial (registered as ISRCTN92166560). DESIGN: Randomised controlled clinical trial with factorial design. PARTICIPANTS: Patients (n=610) with treatment naïve neovascular age-related macular degeneration were enrolled and randomly assigned to receive either ranibizumab or bevacizumab and to two regimens, namely monthly (continuous) or as needed (discontinuous) treatment. METHODS: At monthly visits, IOP was measured preinjection in both eyes, and postinjection in the study eye. OUTCOME MEASURES: The effects of 10 prespecified covariates on preinjection IOP, change in IOP (postinjection minus preinjection) and the difference in preinjection IOP between the two eyes were examined. RESULTS: For every month in trial, there was a statistically significant rise in both the preinjection IOP and the change in IOP postinjection during the time in the trial (estimate 0.02 mm Hg, 95% CI 0.01 to 0.03, p<0.001 and 0.03 mm Hg, 95% CI 0.01 to 0.04, p=0.002, respectively). There was also a small but significant increase during the time in trial in the difference in IOP between the two eyes (estimate 0.01 mm Hg, 95% CI 0.005 to 0.02, p<0.001). There were no differences between bevacizumab and ranibizumab for any of the three outcomes (p=0.93, p=0.22 and p=0.87, respectively). CONCLUSIONS: Anti-vascular endothelial growth factor agents induce increases in IOP of small and uncertain clinical significance

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Role for Positive Schizotypy and Hallucination Proneness in Semantic Processing

© Copyright © 2020 de Leede-Smith, Roodenrys, Horsley, Matrini, Mison and Barkus. Semantic processing underpins the organization of verbal information for both storage and retrieval. Deficits in semantic processing are associated with both the risk for and symptoms presented in schizophrenia. However, studies are mixed and could reflect the confounding effects of medication and symptom heterogeneity. Therefore, we considered whether two risk phenotypes, positive schizotypy and hallucinatory predisposition, present in the general population were associated with differential responding profiles for a semantic processing task. One hundred and eighty-three participants completed the Schizotypal Personality Questionnaire, Launay-Slade Hallucination Scale, National Adult Reading Test, a handedness measure, and a computerized semantic relatedness judgment task. Pairs of words were related through their dominant or subordinate meanings, or unrelated. Participants were divided into four groups using a mean split on cognitive-perceptual (positive) schizotypy and hallucination proneness. Significant differences between groups were found for reaction time on the semantic relatedness task, with the high cognitive-perceptual schizotypy groups responding significantly slower to all word pairs compared to their low scoring counterparts. There was some evidence that high hallucination proneness was associated with significantly faster reaction times which may reflect disinhibitive processes, however additional support is required. The results suggest that these two components of psychosis risk are associated with different patterns of responding to semantic processing. More diffuse activation of semantic information appeared to be associated with positive schizotypy, while those predisposed to hallucinations appeared to respond quicker. These results have significant implications in the re-conceptualization of hallucination proneness as distinct from positive schizotypy. Additional research is required to investigate the association between psychotic-like experiences separate from personality variables such as positive schizotypy and semantic processing

Neurological soft signs: Effects of trait schizotypy, psychological distress and auditory hallucination predisposition

Schizotypy is regarded as a trait vulnerability for psychotic disorders, yet alone is insufficient for development of a diagnosable disorder. Additional symptoms and psychological distress are necessary for help seeking and transition from an at risk mental state to a clinical diagnosis. The present study investigated the interaction between trait schizotypy, state auditory verbal hallucination (AVH) predisposition, distress and handedness for the expression of neurological soft signs (NSS), a neurodevelopmental vulnerability factor for psychosis. Cluster analysis formed schizotypy groups statistically across the dimensions captured by the SPQ. It was hypothesized that schizotypy and AVH predisposition would interact, resulting in significantly greater NSS. Psychological distress and handedness were hypothesized to be significant covariates, accounting for some variance in the expression of NSS between the groups. A sample of University students (n = 327) completed the Schizotypal Personality Questionnaire, Launay-Slade Hallucination Scale, General Health Questionnaire and the Neurological Evaluation Scale (NES). Cluster Analysis revealed four schizotypy groups. Distress was not a significant covariate in any analysis. As expected, those with high overall schizotypy and high AVH predisposition expressed significantly greater Motor-Coordination NSS compared to those with high schizotypy and low AVH predisposition. Within the Mixed Interpersonal and Cognitive-Perceptual Schizotypy cluster, those with low AVH predisposition expressed significantly more Motor-Coordination NSS than those with high AVH predisposition. These findings suggest motor coordination NSS are detectable in schizotypy, and AVH predisposition appears to interact with these traits. This study highlights the importance of considering both trait and subclinical state risk factors when investigating risk for psychosis