Investigating whether adverse prenatal and perinatal events are associated with non-clinical psychotic symptoms at age 12 years in the ALSPAC birth cohort

Background. Non-clinical psychosis-like symptoms (PLIKS) occur in about 15% of the population. It is not clear whether adverse events during early development alter the risk of developing PLIKS. We aimed to examine whether maternal infection, diabetes or pre-eclampsia during pregnancy, gestational age, perinatal cardiopulmonary resuscitation or 5-min Apgar score were associated with development of psychotic symptoms during early adolescence. Method. A longitudinal study of 6356 12-year-old adolescents who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Prenatal and perinatal data were obtained from obstetric records and maternal questionnaires completed during pregnancy. Results. The presence of definite psychotic symptoms was associated with maternal infection during pregnancy [adjusted odds ratio (OR) 1.44, 95% confidence interval (CI) 1.11–1.86, p=0.006], maternal diabetes (adjusted OR 3.43, 95% CI 1.14–10.36, p=0.029), need for resuscitation (adjusted OR 1.50, 95% CI 0.97–2.31, p=0.065) and 5-min Apgar score (adjusted OR per unit decrease 1.30, 95% CI 1.12–1.50, p<0.001). None of these associations were mediated by childhood IQ score. Most associations persisted, but were less strong, when including suspected symptoms as part of the outcome. There was no association between PLIKS and gestational age or pre-eclampsia. Conclusions. Adverse events during early development may lead to an increased risk of developing PLIKS. Although the status of PLIKS in relation to clinical disorders such as schizophrenia is not clear, the similarity between these results and findings reported for schizophrenia indicates that future studies of PLIKS may help us to understand how psychotic experiences and clinical disorders develop throughout the life-course

How computation can facilitate sensemaking about physics: A case study

We present a case study featuring a first-year bio-science university student using computation to solve a radioactive decay problem and interpret the results. In a semi-structured cognitive interview, we use this case to examine the process of sensemaking in a computational science context. We observe the student entering the sensemaking process by inspecting and comparing computational outputs. She then makes several attempts to resolve the perceived inconsistency, foregrounding knowledge from different domains. The key to making sense of the model for this student proves to be thinking about how to implement a better model computationally. This demonstrates that integrating computation in physics activities may provide students with opportunities to engage in sensemaking and critical thinking. We finally discuss some implications for instruction.Comment: 4 pages. Updated after peer review to be ready for inclusion in the PERC 2018 proceeding

Short-term sequence evolution and vertical inheritance of the Naegleria twin-ribozyme group I intron

Background Ribosomal DNA of several species of the free-living Naegleria amoeba harbors an optional group I intron within the nuclear small subunit ribosomal RNA gene. The intron (Nae.S516) has a complex organization of two ribozyme domains (NaGIR1 and NaGIR2) and a homing endonuclease gene (NaHEG). NaGIR2 is responsible for intron excision, exon ligation, and full-length intron RNA circularization, reactions typical for nuclear group I intron ribozymes. NaGIR1, however, is essential for NaHEG expression by generating the 5' end of the homing endonuclease messenger RNA. Interestingly, this unusual class of ribozyme adds a lariat-cap at the mRNA. Results To elucidate the evolutionary history of the Nae.S516 twin-ribozyme introns we have analyzed 13 natural variants present in distinct Naegleria isolates. Structural variabilities were noted within both the ribozyme domains and provide strong comparative support to the intron secondary structure. One of the introns, present in N. martinezi NG872, contains hallmarks of a degenerated NaHEG. Phylogenetic analyses performed on separate data sets representing NaGIR1, NaGIR2, NaHEG, and ITS1-5.8S-ITS2 ribosomal DNA are consistent with an overall vertical inheritance pattern of the intron within the Naegleria genus. Conclusion The Nae.S516 twin-ribozyme intron was gained early in the Naegleria evolution with subsequent vertical inheritance. The intron was lost in the majority of isolates (70%), leaving a widespread but scattered distribution pattern. Why the apparent asexual Naegleria amoebae harbors active intron homing endonucleases, dependent on sexual reproduction for its function, remains a puzzle

Effect of light-emitting diodes (LEDs) on snow crab catch rates in the Barents Sea pot fishery

Snow crab (Chionoecetes opilio) has become an important species for the Norwegian seafood industry since its first commercial harvest in 2012. However, periodically catch rates can be low, causing a financial strain on the fishery. Thus, improving the catch rate of existing pot designs has the potential to significantly improve the profitability of fishing enterprises. In this study, we investigated whether the addition of low-powered purple and white light-emitting diode (LED) fishing lights inside the pots could improve catch rates of snow crab in the Barents Sea. Results showed that pots with purple lights harvested a 12.8% higher catch per unit effort (CPUE; number of crab per pot) of legal-sized crab, which was significantly more than the control pots (p = 0.035); pots with white lights did not catch significantly more crab (p > 0.05). Pots equipped with only light (no bait) caught very few crabs and were not considered a viable alternative. Although purple LEDs increased snow crab capture, the economic benefits of using underwater lights in pots remains unclear given the high capital investment required.publishedVersio

Child suicide rates during the COVID-19 pandemic in England

BACKGROUND: There is concern about the impact of COVID-19, and the control measures to prevent the spread, on children's mental health. The aim of this work was to identify if there had been a rise of childhood suicide during the COVID pandemic. METHOD: Using data from England's National Child Mortality Database (NCMD) the characteristics and rates of children dying of suicide between April to December 2020 were compared with those in 2019. In a subset (1(st) January to 17(th) May 2020) further characteristics and possible contributing factors were obtained. RESULTS: A total of 193 likely childhood deaths by suicide were reported. There was no evidence overall suicide deaths were higher in 2020 than 2019 (RR 1.09 (0.80-1.48), p=0.584) but weak evidence that the rate in the first lockdown period (April to May 2020) was higher than the corresponding period in 2019 (RR 1.56 (0.86-2.81), p=0.144). Characteristics of individuals were similar between periods. Social restrictions (e.g. to education), disruption to care and support services, tensions at home and isolation appeared to be contributing factors. LIMITATIONS: As child suicides are fortunately rare, the analysis is based on small numbers of deaths with limited statistical power to detect anything but major increases in incidence. CONCLUSION: We found no consistent evidence that child suicide deaths increased during the COVID-19 pandemic although there was a possibility that they may have increased during the first UK lockdown. A similar peak was not seen during the following months, or the second lockdown

Site-specific reverse splicing of a HEG-containing group I intron in ribosomal RNA

The wide, but scattered distribution of group I introns in nature is a result of two processes; the vertical inheritance of introns with or without losses, and the occasional transfer of introns across species barriers. Reversal of the group I intron self-splicing reaction, termed reverse splicing, coupled with reverse transcription and genomic integration potentially mediate an RNA-based intron mobility pathway. Compared to the well characterized endonuclease-mediated intron homing, reverse splicing is less specific and represents a likely explanation for many intron transpositions into new genomic sites. However, the frequency and general role of an RNA-based mobility pathway in the spread of natural group I introns is still unclear. We have used the twin-ribozyme intron (Dir.S956-1) from the myxomycete Didymium iridis to test how a mobile group I intron containing a homing endonuclease gene (HEG) selects between potential insertion sites in the small subunit (SSU) rRNA in vitro, in Escherichia coli and in yeast. Surprisingly, the results show a site-specific RNA-based targeting of Dir.S956-1 into its natural (S956) SSU rRNA site. Our results suggest that reverse splicing, in addition to the established endonuclease-mediated homing mechanism, potentially accounts for group I intron spread into the homologous sites of different strains and species

Application of Luminescent Netting in Traps to Improve the Catchability of the Snow Crab Chionoecetes opilio

In this study, we investigated luminescent netting as a means to improve the catch rates of snow crabs Chionoecetes opilio. A laboratory experiment was conducted to investigate the intensity and duration of luminescence using time‐lapse photography. We exposed experimental traps to five different treatments of UV light to excite the luminescent fibers in the netting. Our results showed that luminescent netting can be effectively activated to emit light, and that the resulting intensity and duration of luminescence emitted over time depends on the initial duration of UV exposure and the source of light. A fishing experiment was subsequently conducted in eastern Canada to compare the catch rate of traditional and luminescent traps, and to determine how soak time affected catch rate. Results indicate that the effect of luminescent traps on the CPUE (measured as number of crab per trap) depended on the soak time. The CPUE was significantly higher (a 55% increase) in luminescent traps that underwent relatively short soak times (~1 d), but when soak times were longer (~8 d), the CPUE was not significantly different.publishedVersio

Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease

OBJECTIVE: To use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside. METHODS: Rasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurocognitive examinations collected as part of the prospective National Prion Monitoring Cohort study, October 2008-December 2016.A longitudinal clinical examination dataset constructed from 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores over 130 patient-years of study, was used to demonstrate scale utility. RESULTS: The Rasch-derived Motor Scale consists of 8 items, including assessments reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform independently of age or gender and have excellent inter-rater reliability. They can be completed in minutes at the bedside, as part of a normal neurocognitive examination. A composite Examination Scale can be derived by averaging both scores. Several scale uses, in measuring longitudinal change, prognosis and phenotypic heterogeneity are illustrated. CONCLUSIONS: These two novel sCJD Motor and Cognitive Scales and the composite Examination Scale should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly progressive, multisystem conditions with limited longitudinal follow-up

Feasibility and design of a trial regarding the optimal mode of delivery for preterm birth: the CASSAVA multiple methods study

BACKGROUND: Around 60,000 babies are born preterm (prior to 37 weeks' gestation) each year in the UK. There is little evidence on the optimal birth mode (vaginal or caesarean section). OBJECTIVE: The overall aim of the CASSAVA project was to determine if a trial to define the optimal mode of preterm birth could be carried out and, if so, determine what sort of trial could be conducted and how it could best be performed. We aimed to determine the specific groups of preterm women and babies for whom there are uncertainties about the best planned mode of birth, and if there would be willingness to recruit to, and participate in, a randomised trial to address some, but not all, of these uncertainties. This project was conducted in response to a Heath Technology Assessment programme commissioning call (17/22 'Mode of delivery for preterm infants'). METHODS: We conducted clinician and patient surveys (n = 224 and n = 379, respectively) to identify current practice and opinion, and a consensus survey and Delphi workshop (n = 76 and n = 22 participants, respectively) to inform the design of a hypothetical clinical trial. The protocol for this clinical trial/vignette was used in telephone interviews with clinicians (n = 24) and in focus groups with potential participants (n = 13). RESULTS: Planned sample size and data saturation was achieved for all groups except for focus groups with participants, as this had to be curtailed because of the COVID-19 pandemic and data saturation was not achieved. There was broad agreement from parents and health-care professionals that a trial is needed. The clinician survey demonstrated a variety of practice and opinion. The parent survey suggested that women and their families generally preferred vaginal birth at later gestations and caesarean section for preterm infants. The interactive workshop and Delphi consensus process confirmed the need for more evidence (hence the case for a trial) and provided rich information on what a future trial should entail. It was agreed that any trial should address the areas with most uncertainty, including the management of women at 26-32 weeks' gestation, with either spontaneous preterm labour (cephalic presentation) or where preterm birth was medically indicated. Clear themes around the challenges inherent in conducting any trial emerged, including the concept of equipoise itself. Specific issues were as follows: different clinicians and participants would be in equipoise for each clinical scenario, effective conduct of the trial would require appropriate resources and expertise within the hospital conducting the trial, potential participants would welcome information on the trial well before the onset of labour and minority ethnic groups would require tailored approaches. CONCLUSION: Given the lack of evidence and the variation of practice and opinion in this area, and having listened to clinicians and potential participants, we conclude that a trial should be conducted and the outlined challenges resolved. FUTURE WORK: The CASSAVA project could be used to inform the design of a randomised trial and indicates how such a trial could be carried out. Any future trial would benefit from a pilot with qualitative input and a study within a trial to inform optimal recruitment. LIMITATIONS: Certainty that a trial could be conducted can be determined only when it is attempted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12295730. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 61. See the NIHR Journals Library website for further project information