Citations

Mr Justice Baker delivered the Oxford Shrieval Lecture ‘A Matter of Life and Death’ on 11 October 2016. The lecture created public controversies about who can authorise withdrawal of assisted nutrition and hydration (ANH) in disorders of consciousness (DOC). The law requires court permission in ‘best interests’ decisions before ANH withdrawal only in permanent vegetative state and minimally conscious state. Some clinicians favour abandoning the need for court approval on the basis that clinicians are already empowered to withdraw ANH in other common conditions of DOC (e.g. coma, neurological disorders, etc.) based on their best interests assessment without court oversight. We set out a rationale in support of court oversight of best interests decisions in ANH withdrawal intended to end life in any person with DOC (who will lack relevant decision-making capacity). This ensures the safety of the general public and the protection of vulnerable disabled persons in society.

Abstract Posterolateral rotatory instability (PLRI) is the most commonly encountered pattern of elbow instability. It is the result of disruption of the lateral collateral ligament complex leading to a posterolateral rotatory subluxation of the ulna and radial head. A number of examination maneuvers have been described to assist in clinical identification of PLRI. Despite this, some inconsistency in the description of these techniques remains in the orthopaedic literature. This Technical Note details the mechanism of injury and patient presentation, and emphasizes the primacy of the posterolateral rotatory drawer test in the assessment of PLRI while providing video instruction on how it should be performed. Technique Video video See video under supplementary data.

Abstract Currently, a number of examination and imaging techniques exist for diagnosing posterolateral rotatory instability of the elbow. Although the posterolateral rotatory drawer is the primary examination maneuver, other special tests include the lateral pivot‐shift test, prone push‐up test, chair push‐up test, and tabletop push‐up test. In addition, posterolateral rotatory instability can be evaluated using radiography, magnetic resonance imaging, dynamic fluoroscopy, or dynamic ultrasound. In this Technical Note, each of these tests is described in detail. Video instruction is also provided to further explain the techniques and provide examples of positive tests. Technique Video video See video under supplementary data.

Abstract Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. In this Perspective, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity – basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposis (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape. Emerging genetic and pharmacologic (metformin) disruption of mitochondrial (mt) respiration increased autophagy to prevent cancer in a Li-Fraumeni mouse model (biology reproduced in clinical pilot) and revealed profound influences of subtle changes in mt DNA background variation on obesity, aging, and cancer risk. The elaborate communication between the immune system and neoplasia includes an increasingly complex cellular microenvironment and dynamic interactions between host genetics, environmental factors, and microbes in shaping the immune response. Cancer vaccines are in early murine and clinical precancer studies, building on the recent successes of immunotherapy and HPV vaccine immune prevention. Molecular monitoring in Barrett's esophagus to avoid overdiagnosis/treatment highlights an important PCA theme. Next generation sequencing (NGS) discovered age-related clonal hematopoiesis of indeterminate potential (CHIP). Ultra-deep NGS reports over the past year have redefined the premalignant landscape remarkably identifying tiny clones in the blood of up to 95% of women in their 50s, suggesting that potentially premalignant clones are ubiquitous. Similar data from eyelid skin and peritoneal and uterine lavage fluid provide unprecedented opportunities to dissect the earliest phases of stem/progenitor clonal (and microenvironment) evolution/diversity with new single-cell and liquid biopsy technologies. Cancer mutational signatures reflect exogenous or endogenous processes imprinted over time in precursors. Accelerating the prevention of cancer will require a large-scale, longitudinal effort, leveraging diverse disciplines (from genetics, biochemistry, and immunology to mathematics, computational biology, and engineering), initiatives, technologies, and models in developing an integrated multi-omics and immunity PCA – an immense national resource to interrogate, target, and intercept events that drive oncogenesis. Cancer Res; 77(7); 1510–41. ©2017 AACR.

Abstract Aims/Hypothesis: We sought to establish whether the increased incidence of diabetes associated with Down syndrome was due to a congenital deficit in β cells. Methods: The pancreas was obtained at autopsy from nondiabetic subjects with Down syndrome (n = 29) and age-matched nondiabetic control subjects without Down syndrome (n = 28). The pancreas sections were evaluated for the fractional β-cell area. Results: No difference was found in the fractional β-cell area between the subjects with Down syndrome and the control subjects. Conclusions/Interpretations: The increased incidence and prevalence of diabetes in individuals with Down syndrome is not due to an underlying congenital deficiency of β cells.