Identification and characterization of human KALRN mRNA and Kalirin protein isoforms.

Kalirin is a multidomain protein with important roles in neurite outgrowth, and synaptic spine formation and remodeling. Genetic and pathophysiological links with various neuropsychiatric disorders associated with synaptic dysfunction and cognitive impairment have sparked interest in its potential as a pharmacological target. Multiple Kalirin proteoforms are detected in the adult human brain, yet we know little about the diversity of the transcripts that encode them or their tissue profiles.

An Artificial Neural Network for Nasogastric Tube Position Decision Support.

Purpose: To develop and validate a deep learning model for detection of nasogastric tube (NGT) malposition on chest radiographs and assess model impact as a clinical decision support tool for junior physicians to help determine whether feeding can be safely performed in patients (feed/do not feed).

Materials And Methods: A neural network ensemble was pretrained on 1 132 142 retrospectively collected (June 2007-August 2019) frontal chest radiographs and further fine-tuned on 7081 chest radiographs labeled by three radiologists. Clinical relevance was assessed on an independent set of 335 images.

Providing care for children with tracheostomies: a qualitative interview study with parents and health professionals.

Objectives: To explore the experience of caring for children with tracheostomies from the perspectives of parents and health professional caregivers.

Design: Qualitative semistructured interview study.

Setting: One region in England covered by a tertiary care centre that includes urban and remote rural areas and has a high level of deprivation.

Two-way Automated Text Messaging Support From Community Pharmacies for Medication Taking in Multiple Long-term Conditions: Human-Centered Design With Nominal Group Technique Development Study.

Background: Reviews of digital communication technologies suggest that they can be effective in supporting medication use; however, their use alongside nondigital components is unclear. We also explored the delivery of a digital communication intervention in a relatively novel setting of community pharmacies and how such an intervention might be delivered to patients with multiple long-term conditions. This meant that despite the large number of intervention examples available in the literature, design questions remained, which we wanted to explore with key stakeholders.

CACNA1C (Ca1.2) and other L-type calcium channels in the pathophysiology and treatment of psychiatric disorders: Advances from functional genomics and pharmacoepidemiology.

A role for voltage-gated calcium channels (VGCCs) in psychiatric disorders has long been postulated as part of a broader involvement of intracellular calcium signalling. However, the data were inconclusive and hard to interpret. We review three areas of research that have markedly advanced the field.

Influencing medication taking behaviors using automated two-way digital communication: A narrative synthesis systematic review informed by the Behavior Change Wheel.

Purpose: Around half of prescribed medications for long-term conditions are not taken as directed. Automated two-way digital communication, such as text messaging and interactive voice response technology, could deliver interventions to improve medication adherence, and subsequently health. However, exploration of how such interventions may improve medication adherence is limited.

Exploration of prescribing error reporting across primary care: a qualitative study.

Objectives: To explore barriers and facilitators to prescribing error reporting across primary care.

Design: Qualitative semi-structured face-to-face and telephone interviews were conducted to explore facilitators and barriers to reporting prescribing errors. Data collection and thematic analysis were informed by the COM-B model of behaviour change.

Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes.

Background: Alternative splicing is a key mechanism underlying cellular differentiation and a driver of complexity in mammalian neuronal tissues. However, understanding of which isoforms are differentially used or expressed and how this affects cellular differentiation remains unclear. Long read sequencing allows full-length transcript recovery and quantification, enabling transcript-level analysis of alternative splicing processes and how these change with cell state.

Impact of COVID-19 on carers of children with tracheostomies.

Objectives: To explore the impact of the COVID-19 pandemic on the experiences of caregivers of children with tracheostomies.

Design: Qualitative semistructured interviews.

Setting: All participants were currently, or had previously cared for, a tracheostomised child who had attended a tertiary care centre in the North of England.

Neurological consultation with an autistic patient.

Autism is a neurodevelopmental condition with a very heterogeneous presentation. Autistic people are more likely to have unmet healthcare needs, making it essential that healthcare professionals are 'autism-aware'. In this article, we provide an overview of how autism presents and use case studies to illustrate how a neurological consultation in an outpatient clinic environment could prove challenging for a autistic person.

Targeting synaptic plasticity in schizophrenia: insights from genomic studies.

Patients with schizophrenia experience cognitive dysfunction and negative symptoms that do not respond to current drug treatments. Historical evidence is consistent with the hypothesis that these deficits are due, at least in part, to altered cortical synaptic plasticity (the ability of synapses to strengthen or weaken their activity), making this an attractive pathway for therapeutic intervention. However, while synaptic transmission and plasticity is well understood in model systems, it has been challenging to identify specific therapeutic targets for schizophrenia.

Induced Pluripotent Stem Cells in Psychiatry: An Overview and Critical Perspective.

A key challenge in psychiatry research is the development of high-fidelity model systems that can be experimentally manipulated to explore and test pathophysiological mechanisms of illness. In this respect, the emerging capacity to derive neural cells and circuits from human induced pluripotent stem cells (iPSCs) has generated significant excitement. This review aims to provide a critical appraisal of the potential for iPSCs in illuminating pathophysiological mechanisms in the context of other available technical approaches.

Long read transcript profiling of ion channel splice isoforms.

Alternative splicing of RNA transcripts allows a single gene to generate multiple products and is a key means of generating functionally diverse voltage-gated ion channels. Splicing can be regulated according to cell type, cell state, and stage of development to produce a bespoke complement of protein isoforms. Characterizing the identities of full-length transcript isoforms is essential in order to fully understand a gene's expression and function.

Factors shaping the implementation and use of Clinical Cancer Decision Tools by GPs in primary care: a qualitative framework synthesis.

Objective: Clinical Cancer Decision Tools (CCDTs) aim to alert general practitioners (GPs) to signs and symptoms of cancer, supporting prompt investigation and onward referral. CCDTs are available in primary care in the UK but are not widely utilised. Qualitative research has highlighted the complexities and mechanisms surrounding their implementation and use; this has focused on specific cancer types, formats, systems or settings.

Prescribing error reporting in primary care: a narrative synthesis systematic review.

Prescribing errors can cause avoidable harm to patients. Most prescriptions originate in primary care, where medications tend to be self-administered and errors have the most potential to cause harm. Reporting prescribing errors can identify trends and reduce the risk of the reoccurrence of incidents; however, under-reporting is common.

Long-read sequencing reveals the complex splicing profile of the psychiatric risk gene CACNA1C in human brain.

RNA splicing is a key mechanism linking genetic variation with psychiatric disorders. Splicing profiles are particularly diverse in brain and difficult to accurately identify and quantify. We developed a new approach to address this challenge, combining long-range PCR and nanopore sequencing with a novel bioinformatics pipeline.

Internet-based pharmacy and centralised dispensing: an exploratory mixed-methods study of the views of family practice staff.

Objectives: Over the last decade, technological advances, market competition and increasing pressures for efficiencies across healthcare systems have resulted in changes to the processes and policies involved in medicines prescribing and dispensing. The aim of this study was to explore the views of family practice staff, including GPs, on the perceived impact of changes associated with remote dispensing and the increasing availability of distance-selling pharmacies.

Methods: Exploratory mixed-methods study using qualitative focus groups and an online cross-sectional survey distributed to a non-probability sample of staff from family practices across England.

Extending alcohol brief advice into non-clinical community settings: a qualitative study of experiences and perceptions of delivery staff.

Background: At a population level, the majority of alcohol-related harm is attributable to drinkers whose consumption exceeds recommended drinking levels, rather than those with severe alcohol dependency. Identification and Brief Advice (IBA) interventions offer a cost-effective approach for reducing this harm. Traditionally, IBA interventions have been delivered in healthcare settings and therefore contextual influences on their use in non-clinical settings are not well understood.

The researchers' role in knowledge translation: a realist evaluation of the development and implementation of diagnostic pathways for cancer in two United Kingdom localities.

Background: In examining an initiative to develop and implement new cancer diagnostic pathways in two English localities, this paper evaluates 'what works' and examines the role of researchers in facilitating knowledge translation amongst teams of local clinicians and policy-makers.

Methods: Using realist evaluation with a mixed methods case study approach, we conducted documentary analysis of meeting minutes and pathway iterations to map pathway development. We interviewed 14 participants to identify the contexts, mechanisms and outcomes (CMOs) that led to successful pathway development and implementation.

Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study.

Objective: Pancreatic cancer has poor survival rates due to non-specific symptoms leading to later diagnosis. Understanding how patients interpret their symptoms could inform approaches to earlier diagnosis. This study sought to explore symptom appraisal and help-seeking among patients referred to secondary care for symptoms suggestive of pancreatic cancer.

The rise of inventory management in operating theatre departments.

The procurement and inventory management challenges within our healthcare sector have been the subject of debate for some time, but with new government initiatives recently introduced, procurement and inventory management have become the new areas of focus behind muchneeded change within the NHS back-office.