Unfitness to Plead. Volume 1: Report.

This has been produced along with Volume 2: Draft Legislation as a combined document Presented to Parliament pursuant to section 3(2) of the Law Commissions Act 1965 Ordered by the House of Commons to be printed on 12 January 201

Microlaser-based contractility sensing in single cardiomyocytes and whole hearts

Microscopic whispering gallery mode lasers detect minute changes in cellular refractive index inside individual cardiac cells and in live zebrafish. We show that these signals encode cardiac contractility that can be used for intravital sensing.Postprin

Cardiac device implantation and device usage in Fabry and hypertrophic cardiomyopathy

Background: Fabry disease (FD) is a treatable X-linked condition leading to progressive cardiac disease, arrhythmia and premature death. We aimed to increase awareness of the arrhythmogenicity of Fabry cardiomyopathy, by comparing device usage in patients with Fabry cardiomyopathy and sarcomeric HCM. All Fabry patients with an implantable cardioverter defibrillator (ICD) implanted in the UK over a 17 year period were included. A comparator group of HCM patients, with primary prevention ICD implantation, were captured from a regional registry database. Results: Indications for ICD in FD varied with 72% implanted for primary prevention based on multiple potential risk factors. In FD and HCM primary prevention devices, arrhythmia occurred more frequently in FD over shorter follow-up (HR 4.2, p < 0.001). VT requiring therapy was more common in FD (HR 4.5, p = 0.002). Immediate shock therapy for sustained VT was also more common (HR 2.5, p < 0.001). There was a greater burden of AF needing anticoagulation and NSVT in FD (AF: HR 6.2, p = 0.004, NSVT: HR 3.1, p < 0.001). Conclusion: This study demonstrates arrhythmia burden and ICD usage in FD is high, suggesting that Fabry cardiomyopathy may be more ‘arrhythmogenic’ than previously thought. Existing risk models cannot be mutually applicable and further research is needed to provide clarity in managing Fabry patients with cardiac involvement

Exoplanetary Geophysics -- An Emerging Discipline

Thousands of extrasolar planets have been discovered, and it is clear that the galactic planetary census draws on a diversity greatly exceeding that exhibited by the solar system's planets. We review significant landmarks in the chronology of extrasolar planet detection, and we give an overview of the varied observational techniques that are brought to bear. We then discuss the properties of the currently known distribution, using the mass-period diagram as a guide to delineating hot Jupiters, eccentric giant planets, and a third, highly populous, category that we term "ungiants", planets having masses less than 30 Earth masses and orbital periods less than 100 days. We then move to a discussion of the bulk compositions of the extrasolar planets. We discuss the long-standing problem of radius anomalies among giant planets, as well as issues posed by the unexpectedly large range in sizes observed for planets with masses somewhat greater than Earth's. We discuss the use of transit observations to probe the atmospheres of extrasolar planets; various measurements taken during primary transit, secondary eclipse, and through the full orbital period, can give clues to the atmospheric compositions, structures, and meteorologies. The extrasolar planet catalog, along with the details of our solar system and observations of star-forming regions and protoplanetary disks, provide a backdrop for a discussion of planet formation in which we review the elements of the favored pictures for how the terrestrial and giant planets were assembled. We conclude by listing several research questions that are relevant to the next ten years and beyond.Comment: Review chapter to appear in Treatise on Geophysics, 2nd Editio

Renal outcome in adults with renal insufficiency and irregular asymmetric kidneys

BACKGROUND: The commonest cause of end-stage renal failure (ESRF) in children and young adults is congenital malformation of the kidney and urinary tract. In this retrospective review, we examine whether progression to ESRF can be predicted and whether treatment with angiotensin converting enzyme inhibitors (ACEI) can delay or prevent this. METHODS: We reviewed 78 patients with asymmetric irregular kidneys as a consequence of either primary vesico-ureteric reflux or renal dysplasia (Group 1, n = 44), or abnormal bladder function (Group 2, n = 34). Patients (median age 24 years) had an estimated GFR (eGFR) < 60 ml/min/1.73 m(2 )with at least 5 years of follow up (median 143 months). 48 patients received ACEI. We explored potential prognostic factors that affect the time to ESRF using Cox-regression analyses. RESULTS: At start, mean (SE) creatinine was 189 (8) μmol/l, mean eGFR 41 (1) ml/min 1.73 m(2), mean proteinuria 144 (14) mg/mmol creatinine (1.7 g/24 hrs). Of 78 patients, 36 (46%) developed ESRF, but none of 19 with proteinuria less than 50 mg/mmol and only two of 18 patients with eGFR above 50 ml/min did so. Renal outcome between Groups 1 and 2 appeared similar with no evidence for a difference. A benefit in favour of treatment with ACEI was observed above an eGFR of 40 ml/min (p = 0.024). CONCLUSION: The similar outcome of the two groups supports the nephrological nature of progressive renal failure in young men born with abnormal bladders. There is a watershed GFR of 40–50 ml/min at which ACEI treatment can be successful at improving renal outcome