Novel pathways for headache via neurology same day emergency care: admission avoidance, prevention of lumbar punctures and reduced length of stay in hospital.

There are various models for acute neurology services in the UK, with considerable variation in practice. Patients are often admitted unnecessarily for neurology review, leading to delay in diagnosis and treatment. Alternative models, such as the Neurology Same Day Emergency Care service (Neuro-SDEC) at University College London Hospital provide a pathway that can prevent admissions and streamline patient care.

Investigating innovations in outpatient services: a mixed-methods rapid evaluation.

Background: Within outpatient services, a broad range of innovations are being pursued to better manage care and reduce unnecessary appointments. One of the least-studied innovations is Patient-Initiated Follow-Up, which allows patients to book appointments if and when they need them, rather than follow a standard schedule.

Objectives: To use routine national hospital data to identify innovations in outpatient services implemented, in recent years, within the National Health Service in England.

A role for vessel-associated extracellular matrix proteins in multiple sclerosis pathology.

Multiple sclerosis (MS) is unsurpassed for its clinical and pathological hetherogeneity, but the biological determinants of this variability are unknown. HLA-DRB1*15, the main genetic risk factor for MS, influences the severity and distribution of MS pathology. This study set out to unravel the molecular determinants of the heterogeneity of MS pathology in relation to HLA-DRB1*15 status.

Rapid evaluation of the Special Measures for Quality and challenged provider regimes: a mixed-methods study.

Background: Health-care organisations in England that are rated as inadequate for leadership and one other domain enter the Special Measures for Quality regime to receive support and oversight. A 'watch list' of challenged providers that are at risk of entering Special Measures for Quality also receive support. Knowledge is limited about whether or not the support interventions drive improvements in quality, the costs of the support interventions and whether or not the support interventions strike the right balance between support and scrutiny.

Identification and Optimization of RNA-Splicing Modulators as Huntingtin Protein-Lowering Agents for the Treatment of Huntington's Disease.

Huntington's disease (HD) is caused by an expanded CAG trinucleotide repeat in exon 1 of the huntingtin () gene. We report the design of a series of pre-mRNA splicing modulators that lower huntingtin (HTT) protein, including the toxic mutant huntingtin (mHTT), by promoting insertion of a pseudoexon containing a premature termination codon at the exon 49-50 junction. The resulting transcript undergoes nonsense-mediated decay, leading to a reduction of mRNA transcripts and protein levels.

Tuberous sclerosis complex-1 (TSC1) contributes to selective neuronal vulnerability in Alzheimer's disease.

Aims: Selective neuronal vulnerability of hippocampal Cornu Ammonis (CA)-1 neurons is a pathological hallmark of Alzheimer's disease (AD) with an unknown underlying mechanism. We interrogated the expression of tuberous sclerosis complex-1 (TSC1; hamartin) and mTOR-related proteins in hippocampal CA1 and CA3 subfields.

Methods: A human post-mortem cohort of mild (n = 7) and severe (n = 10) AD and non-neurological controls (n = 9) was used for quantitative and semi-quantitative analyses.

The Special Measures for Quality and Challenged Provider Regimes in the English NHS: A Rapid Evaluation of a National Improvement Initiative for Failing Healthcare Organisations.

Background: There is limited knowledge about interventions used for the improvement of low-performing healthcare organisations and their unintended consequences. Our evaluation sought to understand how healthcare organisations in the National Health Service (NHS) in England responded to a national improvement initiative (the Special Measures for Quality [SMQ] and challenged provider [CP] regimes) and its perceived impact on achieving quality improvements (QIs).

Methods: Our evaluation included national-level interviews with key stakeholders involved in the delivery of SMQ (n=6); documentary analysis (n=20); and a qualitative study based on interviews (n=60), observations (n=8) and documentary analysis (n=291) in eight NHS case study sites.

Out with the old, in with the new: Could plasma exchange be used to fill a therapeutic gap in neurology?

The global tally of neurological disorders is exponentially rising and yet effective therapies for most remain evasive. There is a great deal of research into novel small molecules, immunotherapies and gene therapies to fill this therapeutic gap. We believe greater focus on plasma exchange as a research and clinical tool may provide useful insight into pathological mechanisms and effective treatment strategies.

The bicipital groove as a landmark for humeral version reference during shoulder arthroplasty: a computed tomography study of normal humeral rotation.

Background: Accurate reproduction of humeral version is important in shoulder arthroplasty. Traditional referencing relative to the transepicondylar axis (TEA) is prone to error as it is absent on preoperative imaging and inaccurately reproduced intraoperatively. The bicipital groove is present on preoperative imaging and in the operative field and thus may be a useful landmark for accurate reproduction of humeral version.

Design and Development of a Macrocyclic Series Targeting Phosphoinositide 3-Kinase δ.

A macrocyclization approach has been explored on a series of benzoxazine phosphoinositide 3-kinase δ inhibitors, resulting in compounds with improved potency, permeability, and clearance while maintaining good solubility. The thermodynamics of binding was explored via surface plasmon resonance, and the binding of lead macrocycle was found to be almost exclusively entropically driven compared with progenitor , which demonstrated both enthalpic and entropic contributions. The pharmacokinetics of macrocycle was also explored , where it showed reduced clearance when compared with the progenitor .

A contingency management intervention to reduce cannabis use and time to relapse in early psychosis: the CIRCLE RCT.

Background: Cannabis is the most prevalent illicit substance among people with psychosis, and its use is associated with poorer clinical and social outcomes. However, so far, there has been limited evidence that any treatment is effective for reducing use. Contingency management (CM) is an incentive-based intervention for substance misuse that has a substantial evidence base across a range of substances and cohorts.

Clinical and cost-effectiveness of contingency management for cannabis use in early psychosis: the CIRCLE randomised clinical trial.

Background: Cannabis is the most commonly used illicit substance amongst people with psychosis. Continued cannabis use following the onset of psychosis is associated with poorer functional and clinical outcomes. However, finding effective ways of intervening has been very challenging.

A high-throughput and rapid method for accurate identification of emerging multidrug-resistant Candida auris.

Candida auris is an emerging multidrug-resistant yeast associated with invasive infection in healthcare settings. Recently, C auris cases in the United States have been detected in 11 states with the majority of cases in New York, New Jersey and Illinois. Rapid and accurate identification of C auris is critical for patient care and the implementation of public health measures to control the spread of infection.

Are Psychologic Factors Associated With Shoulder Scores After Rotator Cuff Surgery?

Background: Psychologic factors are associated with pain and disability in patients with chronic shoulder pain. Recent research regarding the association of affective psychologic factors (emotions) with patients' pain and disability outcome after surgery disagrees; and the relationship between cognitive psychologic factors (thoughts and beliefs) and outcome after surgery is unknown.

Questions/purposes: (1) Are there identifiable clusters (based on psychologic functioning measures) in patients undergoing shoulder surgery? (2) Is poorer psychologic functioning associated with worse outcome (American Shoulder and Elbow Surgeons [ASES] score) after shoulder surgery?

Methods: This prospective cohort study investigated patients undergoing shoulder surgery for rotator cuff-related shoulder pain or rotator cuff tear by one of six surgeons between January 2014 and July 2015.

Physical Activity Preferences Among Older Adults: A Systematic Review.

The objective of this study was to identify preferences for physical activity among adults aged 65 years and over. A systematic review was conducted. A search strategy without language and date restriction (up until March 31, 2017) was developed for PubMed, CINAHL, PsycINFO, ERIC, and SPORTDiscus.

Tailored online cognitive behavioural therapy with or without therapist support calls to target psychological distress in adults receiving haemodialysis: A feasibility randomised controlled trial.

Background: Psychological distress is prevalent in haemodialysis (HD) patients yet access to psychotherapy remains limited. This study assessed the feasibility and acceptability of online cognitive-behavioural therapy (CBT) tailored for HD patients, with or without therapist support, for managing psychological distress.

Methods: This feasibility randomised controlled trial recruited patients from a UK HD centre.

Vascular pathology in multiple sclerosis: reframing pathogenesis around the blood-brain barrier.

Blood-brain barrier (BBB) disruption has long been recognised as an important early feature of multiple sclerosis (MS) pathology. Traditionally, this has been seen as a by-product of the myelin-specific immune response. Here, we consider whether vascular changes instead play a central role in disease pathogenesis, rather than representing a secondary effect of neuroinflammation or neurodegeneration.

One-Pot, Three-Step Synthesis of Cyclopropylboronic Acid Pinacol Esters from Synthetically Tractable Propargylic Silyl Ethers.

Simple propargylic silyl ethers can be converted to complex cyclopropylboronic acid pinacol esters in an efficient one-pot procedure. Terminal acetylenes undergo a Schwartz's reagent catalyzed hydroboration; subsequent addition of further Schwartz's reagent and Lewis acid-mediated activation of neighboring silyl ether allows cyclization to access a range of cyclopropylboronic acid pinacol esters. The scope includes aromatic, aliphatic, quaternary, and spiro substituted cyclopropyl rings, which can be transformed via Suzuki coupling into a range of lead-like substituted cyclopropyl aryl products.

Target-distractor synchrony affects performance in a novel motor task for studying action selection.

The study of action selection in humans can present challenges of task design since our actions are usually defined by many degrees of freedom and therefore occupy a large action-space. While saccadic eye-movement offers a more constrained paradigm for investigating action selection, the study of reach-and-grasp in upper limbs has often been defined by more complex scenarios, not easily interpretable in terms of such selection. Here we present a novel motor behaviour task which addresses this by limiting the action space to a single degree of freedom in which subjects have to track (using a stylus) a vertical coloured target line displayed on a tablet computer, whilst ignoring a similarly oriented distractor line in a different colour.