MCPH1 deletion in a newborn with severe microcephaly and premature chromosome condensation

A newborn with severe microcephaly and a history of parental consanguinity was referred for cytogenetic analysis and subsequently for genetic evaluation. While a 46,XY karyotype was eventually obtained, premature chromosome condensation was observed. A head MRI confirmed primary microcephaly. This combination of features focused clinical interest on the MCPH1 gene and directed genetic testing by sequence analysis and duplication/deletion studies disclosed a homozygous deletion of exons 1–11 of the MCPH1 gene. This case illustrates a strength of standard cytogenetic evaluation in directing molecular testing to a single target gene in this disorder, allowing much more rapid diagnosis at a substantial cost savings for this family.     

A case of an atypically large proximal 15q deletion as cause for Prader–Willi syndrome arising from a de novo unbalanced translocation

We describe an 11 month old female with Prader–Willi syndrome (PWS) resulting from an atypically large deletion of proximal 15q due to a de novo 3;15 unbalanced translocation. The 10.6 Mb deletion extends from the chromosome 15 short arm and is not situated in a region previously reported as a common distal breakpoint for unbalanced translocations. There was no deletion of the reciprocal chromosome 3q subtelomeric region detected by either chromosomal microarray or FISH. The patient has hypotonia, failure to thrive, and typical dysmorphic facial features for PWS. The patient also has profound global developmental delay consistent with an expanded, more severe, phenotype.     

Facilitators and Barriers to Teamworking and Patient Centeredness in Multidisciplinary Cancer Teams: Findings of a National Study

Background

Multidisciplinary teams (MDTs) are the standard means of making clinical decisions in surgical oncology. The aim of this study was to explore the views of MDT members regarding contribution to the MDT, representation of patients’ views, and dealing with disagreements in MDT meetings—issues that affect clinical decision making, but have not previously been addressed.

Methods

Responses to open questions from a 2009 national survey of MDT members about effective MDT working in the United Kingdom were analyzed for content. Emergent themes were identified and tabulated, and verbatim quotes were extracted to validate and illustrate themes.

Results

Free-text responses from 1,636 MDT members were analyzed. Key themes were: (1) the importance of nontechnical skills, organizational support, and good relationships between team members for effective teamworking; (2) recording of disagreements (potentially sharing them with patients) and the importance of patient-centered information in relation to team decision making; (3) the central role of clinical nurse specialists as the patient’s advocates, complementing the role of physicians in relation to patient centeredness.

Conclusions

Developing team members’ nontechnical skills and providing organizational support are necessary to help ensure that MDTs are delivering high-quality, patient-centered care. Recording dissent in decision making within the MDT is an important element, which should be defined further. The question of how best to represent the patient in MDT meetings also requires further exploration.     

A Modified AUGIS Delphi Process to Establish Future Research Priorities in Benign Upper Gastrointestinal Surgery

World Journal of Surgery - The aim of our study was to use a modified Delphi process to determine the research priorities amongst benign upper gastrointestinal (UGI) surgeons in the United Kingdom....     

The introduction of new critical care equipment into the aeromedical evacuation service of the Royal Air Force.

Changing world events over recent years and an increasingly complex patient casemix have led to a review of the equipment used by the Aeromedical Evacuation Squadron of the Royal Air Force. The initial special purpose aeromedical equipment (SPAME) project was completed in 2001 with the new equipment being brought into service in August of the same year. The project incorporated long term planning for replacing the equipment along with its rapidly developing technology, especially with that used for the care of the critically ill. An intensive training programme was simultaneously introduced to support the deployment of this new technology. Critical care teams comprise a consultant anaesthetist, a critical care nurse, a flight nurse attendant (paramedic) and a technician, all of whom attend courses designed specifically to accommodate their role within the team.A considerable amount of work has been undertaken by a dedicated team to ensure this project became a reality and which has resulted in the provision of care to meet the needs of any casualty, anywhere in the world, being achieved using the latest technology proportionate to any hospital-based ICU.     

Impact of Hypothermic Preservation on Tissue Yield and Viability in Pig Pancreata

Introduction

Chronic shortage of quality human cadaveric pancreata limits islet transplantation. Porcine islet xenotransplantation is being explored to increase the donor pool. For clinical-ready islets, centralized animal husbandry, Current Good Manufacturing Practice–regulated processing facilities, and organ transportation support are required. Amount of cold ischemia time (CIT) before isolation significantly affects transplantation. The goal of this study was to determine the maximum safe CIT of whole pancreata before islet isolation.

Materials and Methods

Pancreata were rapidly removed from Yorkshire pigs (age, 14–22 days) and stored in modified University of Wisconsin solution or in EuroCollins solution at 4^°C. Pancreata were processed with <1 hour CIT (control) or stored for 4 or 12 hours before isolation. Islet yield and percent purity and viability were determined after 7 days of in vitro tissue culture and maturation. Samples from nonprocessed pancreata were collected and snap-frozen in liquid nitrogen at 0, 3, 6, 9, 12, 15, and 24 hours of preservation, then analyzed for adenosine diphosphate/adenosine triphosphate ratio as a measure of tissue energetics.

Results

Up to 12 hours in cold storage had no significant impact on overall islet yield after 7 days of in vitro culture compared with controls; islet yield at the end of the maturation process was 28,700 ± 500 islet equivalents per pancreas (mean ± SEM control yield, 30,300 ± 900 islet equivalents per pancreas); islet purity was 75 ± 5% compared with 74 ± 5% in controls. Islet viability was significantly reduced at 12 hours compared with controls (80 ± 6% vs 96 ± 5%; P < .05). The tissue adenosine diphosphate/adenosine triphosphate ratio was maintained within the first 6 hours (1.6 ± 0.1 to 1.8 ± 0.2; P = NS) but was markedly increased during the 24-hour study (3.3 ± 0.1 at 24 hours), indicating a progressive loss of adenosine triphosphate tissue stores.

Conclusions

Young pig pancreata can be hypothermically stored for up to 12 hours without affecting islet yield and purity; however, islet viability is reduced. These data highlight the need for uniform shipping parameters to standardize islet quality, ideally with CIT <6 hours.     

Development and delivery of the BOOST (Better Outcomes for Older adults with Spinal Trouble) intervention for older adults with neurogenic claudication

Neurogenic claudication due to spinal stenosis is a common cause of disability in older adults. Conservative treatments are a favourable treatment option. This paper describes the development and delivery of the BOOST (Better Outcomes for Older adults with Spinal Trouble) intervention, a physiotherapist-delivered physical and psychological intervention for the management of neurogenic claudication in older adults. The BOOST intervention is being tested in a multi-centre, randomised controlled trial in UK National Health Service Trusts; delivered by physiotherapists registered with the Health and Care Professionals Council. Participants are aged 65 years or older, registered with a primary care practice, and report symptoms consistent with neurogenic claudication. Intervention content and delivery was initially informed by clinical and patient experts, research evidence, and behaviour change guidelines; and refined following an intervention development day attended by researchers, health professionals, and Patient and Public Involvement representatives. The BOOST intervention comprises 12 group sessions, promoting sustained adherence with a long term home and physical activity programme. Each session includes education and group discussion, individually tailored exercises, and walking. Initial exercise levels are set at a one-to-one assessment. Continued home exercise adherence and increased physical activity following completion of the sessions is facilitated through support telephone calls.
Trial registration ISRCTN12698674.