Distressing Unusual Experiences, Childhood Adversity and Affect.

Background: Developing a better psychological understanding of unusual experiences (UEs) in a child and adolescent population has become an important area of research. Presently, much of our understanding of UEs has derived from psychological models of psychosis in adults. There is now a robust evidence-base supporting the relationship between childhood adversity (CA) and psychosis in adulthood, and researchers have begun to study the psychological processes involved in this relationship. Importantly, associated psychological processes appear to differ according to the type of experience, suggesting targeted approaches for therapy development. Research is needed to test these associations, and the potential applicability of theory and therapies, in children and young people. Aims: This study aimed to investigate specific associations between CA and distressing paranoia, voice-hearing, and visual experiences in a child and adolescent population, and consider the role of negative affect, schemas, and dissociative experiences as mediating components within this association. Method: A cross-sectional design, using secondary data analysis was adopted. A total sample of 249 participants, aged 8-18 years, from community and inpatient Child and Adolescent Mental Health Services (CAMHS) was comprised of three smaller, original studies which had also investigated alternative psycho-social correlates of UEs. Participants completed self-report questionnaires which measured UEs, previous experiences of adversity, negative affect, beliefs about oneself and others, and dissociative experiences. Hypothesised associations and mediating relationships were tested using correlational, between groups, and regression analyses. Results: The presence of more than one adverse experience was associated with severity of paranoia, negative affect, and negative self-evaluations. In line with hypotheses, negative affect and negative self-beliefs partially mediated the relationship between CA and distressing paranoia, and paranoia was not associated with dissociation. Contrary to hypotheses, CA was not independently associated with voice-hearing, visual experiences or dissociative experiences. Both voice-hearing and visual experiences were independently associated with negative affect, negative self-evaluations, and dissociative experiences. Discussion: The findings support the application of adult models of paranoia and interventions that target adverse experiences, negative affect and enhance positive self-beliefs in childhood. The application of adult models of voice-hearing and visual experiences was not supported and requires further investigation. Future directions for research and clinical implications for both services and broader social initiatives are discussed

Machine Learning and Machine Vision Accelerate 3D Printed Orodispersible Film Development

Orodispersible films (ODFs) are an attractive delivery system for a myriad of clinical applications and possess both large economical and clinical rewards. However, the manufacturing of ODFs does not adhere to contemporary paradigms of personalised, on-demand medicine, nor sustainable manufacturing. To address these shortcomings, both three-dimensional (3D) printing and machine learning (ML) were employed to provide on-demand manufacturing and quality control checks of ODFs. Direct ink writing (DIW) was able to fabricate complex ODF shapes, with thicknesses of less than 100 µm. ML algorithms were explored to classify the ODFs according to their active ingredient, by using their near-infrared (NIR) spectrums. A supervised model of linear discriminant analysis was found to provide 100% accuracy in classifying ODFs. A subsequent partial least square algorithm was applied to verify the dose, where a coefficient of determination of 0.96, 0.99 and 0.98 was obtained for ODFs of paracetamol, caffeine, and theophylline, respectively. Therefore, it was concluded that the combination of 3D printing, NIR and ML can result in a rapid production and verification of ODFs. Additionally, a machine vision tool was used to automate the in vitro testing. These collective digital technologies demonstrate the potential to automate the ODF workflow

An oral pH-responsive Streptococcus agalactiae vaccine formulation provides protective immunity to pathogen challenge in tilapia: A proof-of-concept study

Intensive tilapia farming has contributed significantly to food security as well as to the emergence of novel pathogens. This includes Streptococcus agalactiae or Group B Streptococcus (GBS) sequence type (ST) 283, which caused the first known outbreak of foodborne GBS illness in humans. An oral, easy-to-administer fish vaccine is needed to reduce losses in fish production and the risk of zoonotic transmission associated with GBS. We conducted a proof-of-concept study to develop an oral vaccine formulation that would only release its vaccine cargo at the site of action, i.e., in the fish gastrointestinal tract, and to evaluate whether it provided protection from experimental challenge with GBS. Formalin-inactivated S. agalactiae ST283, was entrapped within microparticles of Eudragit® E100 polymer using a double-emulsification solvent evaporation method. Exposure to an acidic medium simulating the environment in tilapia stomach showed that the size of the vaccine-loaded microparticles decreased rapidly, reflecting microparticle erosion and release of the vaccine cargo. In vivo studies in tilapia showed that oral administration of vaccine-loaded microparticles to fish provided significant protection from subsequent homologous pathogen challenge with GBS ST283 by immersion compared to the control groups which received blank microparticles or buffer, reducing mortality from 70% to 20%. The high efficacy shows the promise of the vaccine platform developed herein, which might be adapted for other bacterial pathogens and other fish species

Impact of Peptide Structure on Colonic Stability and Tissue Permeability

Most marketed peptide drugs are administered parenterally due to their inherent gastrointestinal (GI) instability and poor permeability across the GI epithelium. Several molecular design techniques, such as cyclisation and D-amino acid (D-AA) substitution, have been proposed to improve oral peptide drug bioavailability. However, very few of these techniques have been translated to the clinic. In addition, little is known about how synthetic peptide design may improve stability and permeability in the colon, a key site for the treatment of inflammatory bowel disease and colorectal cancer. In this study, we investigated the impact of various cyclisation modifications and D-AA substitutions on the enzymatic stability and colonic tissue permeability of native oxytocin and 11 oxytocin-based peptides. Results showed that the disulfide bond cyclisation present in native oxytocin provided an improved stability in a human colon model compared to a linear oxytocin derivative. Chloroacetyl cyclisation increased native oxytocin stability in the colonic model at 1.5 h by 30.0%, whereas thioether and N-terminal acetylated cyclisations offered no additional protection at 1.5 h. The site and number of D-AA substitutions were found to be critical for stability, with three D-AAs at Tyr, Ile and Leu, improving native oxytocin stability at 1.5 h in both linear and cyclic structures by 58.2% and 79.1%, respectively. Substitution of three D-AAs into native cyclic oxytocin significantly increased peptide permeability across rat colonic tissue; this may be because D-AA substitution favourably altered the peptide’s secondary structure. This study is the first to show how the strategic design of peptide therapeutics could enable their delivery to the colon via the oral route

Rites of passage in initial teacher training: ritual, performance, ordeal and numeracy skills test

'Transition' was identified by cultural anthropologists in the early twentieth century as the liminal stage of a 'rite of passage'. Contemporary anthropology challenges the structural nature of these classic interpretations of ritual and analyses them as 'performance theory': 'social drama' (Turner), 'dramatism' (Burke), 'interaction rituals' (Goffman), and 'ritualisation' (Bell). In applying a contemporary anthropological lens to initial teacher training, we identify the transition not as a linear progression but as a complex process of extended and ambiguous 'in-betweenness' that involves play, performance and ordeal. We depict pre-service teachers enmeshed in the performance of symbolic acts and the undertaking of 'ritual ordeals'; and report how they narrate their passage as a complex 'game' of 'being' and 'becoming', and portray the holistic experience metaphorically in terms of 'play'. We explore, in particular, students' perceptions of the Numeracy Skills Test, the most recently imposed 'ritual ordeal': a 'rite of intensification' characterised by government as a device to police the boundaries of the teaching profession

Gastrointestinal Tracking and Gastric Emptying of Coated Capsules in Rats with or without Sedation Using CT imaging

Following oral administration, gastric emptying is often a rate-limiting step in the absorption of drugs and is dependent on both physiological and pharmaceutical factors. To guide translation into humans, small animal imaging during pre-clinical studies has been increasingly used to localise the gastrointestinal transit of solid dosage forms. In contrast to humans, however, anaesthesia is usually required for effective imaging in animals which may have unintended effects on intestinal physiology. This study evaluated the effect of anaesthesia and capsule size on the gastric emptying rate of coated capsules in rats. Computed tomography (CT) imaging was used to track and locate the capsules through the gastrointestinal tract. Two commercial gelatine mini-capsules (size 9 and 9h) were filled with barium sulphate (contrast agent) and coated using Eudragit L. Under the effect of anaesthesia, none of the capsules emptied from the stomach. In non-anaesthetised rats, most of the size 9 capsules did not empty from the stomach, whereas the majority of the smaller size 9h capsules successfully emptied from the stomach and moved into the intestine. This study demonstrates that even with capsules designed to empty from the stomach in rats, the gastric emptying of such solid oral dosage forms is not guaranteed. In addition, the use of anaesthesia was found to abolish gastric emptying of both capsule sizes. The work herein further highlights the utility of CT imaging for the effective visualisation and location of solid dosage forms in the intestinal tract of rats without the use of anaesthesia