Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention.

Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression.

Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis.

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms' Tumour (WT1) and tyrosinase).

Analogue peptides for the immunotherapy of human acute myeloid leukemia.

The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction.

Exploring inter-subject anatomic variability using a population of patient-specific femurs and a statistical shape and intensity model.

This paper is motivated by the need to accurately and efficiently measure key periosteal and endosteal parameters of the femur, known to critically influence hip biomechanics following arthroplasty. The proposed approach uses statistical shape and intensity models (SSIMs) to represent the variability across a wide range of patients, in terms of femoral shape and bone density. The approach feasibility is demonstrated by using a training dataset of computer tomography scans from British subjects aged 25-106 years (75 male and 34 female).

Suture Autotransplantation and Dural Stripping for Craniosynostosis: A Long-Term Growth Study in Humans.

Objective: Craniosynostosis treatment by suture autotransplantation and dura stripping has proven to be successful in animals. When applied clinically, it may reduce operative morbidity and postoperative growth disturbances known to occur after radical remodeling. It may prevent resynostosis, which is known to occur after simple synostostectomy.

Effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral artery disease: a systematic review.

Symptoms or signs of peripheral artery disease (PAD) can be observed in up to 50% of the patients with a diabetic foot ulcer and is a risk factor for poor healing and amputation. In 2012, a multidisciplinary working group of the International Working Group on the Diabetic Foot published a systematic review on the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. This publication is an update of this review and now includes the results of a systematic search for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980 to June 2014.

Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: a systematic review.

Non-invasive tests for the detection of peripheral artery disease (PAD) among individuals with diabetes mellitus are important to estimate the risk of amputation, ulceration, wound healing and the presence of cardiovascular disease, yet there are no consensus recommendations to support a particular diagnostic modality over another and to evaluate the performance of index non-invasive diagnostic tests against reference standard imaging techniques (magnetic resonance angiography, computed tomography angiography, digital subtraction angiography and colour duplex ultrasound) for the detection of PAD among patients with diabetes. Two reviewers independently screened potential studies for inclusion and extracted study data. Eligible studies evaluated an index test for PAD against a reference test.

Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review.

Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion.

Republished: Respiratory microbiota: addressing clinical questions, informing clinical practice.

Over the last decade, technological advances have revolutionised efforts to understand the role played by microbes in airways disease. With the application of ever more sophisticated techniques, the literature has become increasingly inaccessible to the non-specialist reader, potentially hampering the translation of these gains into improvements in patient care. In this article, we set out the key principles underpinning microbiota research in respiratory contexts and provide practical guidance on how best such studies can be designed, executed and interpreted.

Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial.

Background: Cisplatin and gemcitabine is the standard first-line chemotherapy regimen for patients with advanced biliary tract cancer; expression of VEGF and its receptors is associated with adverse outcomes. We aimed to assess the effect of the addition of cediranib (an oral inhibitor of VEGF receptor 1, 2, and 3) to cisplatin and gemcitabine on progression-free survival.

Methods: In this multicentre, placebo-controlled, randomised phase 2 study, we recruited patients aged 18 years or older with histologically confirmed or cytologically confirmed advanced biliary tract cancer from hepatobiliary oncology referral centres in the UK.

Sensitivity and specificity of the subcutaneous implantable cardioverter defibrillator pre-implant screening tool.

Background: The sensitivity and specificity of the subcutaneous implantable cardioverter defibrillator (S-ICD) pre-implant screening tool required clinical evaluation.

Methods: Bipolar vectors were derived from electrodes positioned at locations similar to those employed for S-ICD sensing and pre-implant screening electrodes, and recordings collected through 80-electrode PRIME®-ECGs, in six different postures, from 40 subjects (10 healthy controls, and 30 patients with complex congenital heart disease (CCHD); 10 with Tetralogy of Fallot (TOF), 10 with single ventricle physiology (SVP), and 10 with transposition of great arteries (TGA)). The resulting vectors were analysed using the S-ICD pre-implant screening tool (Boston Scientific) and processed through the sensing algorithm of S-ICD (Boston Scientific).

A quantitative analysis of the prevalence of clinical depression and anxiety in patients with prostate cancer undergoing active surveillance.

Objective: To quantitatively determine the prevalence of anxiety and depression in men on active surveillance (AS).

Design: Cross-sectional questionnaire survey.

Setting: Secondary care prostate cancer (PCa) clinics across South, Central and Western England.

White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

Background And Purpose: Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation.

Methods: A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury.

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers.

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production.

Splenic Switch-off: A Tool to Assess Stress Adequacy in Adenosine Perfusion Cardiac MR Imaging.

Purpose: To investigate the pharmacology and potential clinical utility of splenic switch-off to identify understress in adenosine perfusion cardiac magnetic resonance (MR) imaging.

Materials And Methods: Splenic switch-off was assessed in perfusion cardiac MR examinations from 100 patients (mean age, 62 years [age range, 18-87 years]) by using three stress agents (adenosine, dobutamine, and regadenoson) in three different institutions, with appropriate ethical permissions. In addition, 100 negative adenosine images from the Clinical Evaluation of MR Imaging in Coronary Heart Disease (CE-MARC) trial (35 false and 65 true negative; mean age, 59 years [age range, 40-73 years]) were assessed to ascertain the clinical utility of the sign to detect likely pharmacologic understress.

Clinical proteomics and breast cancer.

Background: Breast cancer is a heterogeneous disease. Yet, many molecular players and mechanisms behind the complexity of its clinical behaviour remain unknown, and advances in biomedical research are expected to unravel novel molecular discoveries in breast and other cancers. Clinical proteomics is currently experiencing rapid advances in technology that promise new means to improve breast cancer early diagnosis, stratification, and treatment response.

Inter-subject variability effects on the primary stability of a short cementless femoral stem.

This paper is concerned with the primary stability of the Furlong Evolution(®) cementless short stem across a spectrum of patient morphology. A computational tool is developed that automatically selects and positions the most suitable stem from an implant system made of a total of 48 collarless stems to best match a 3D model based on a library of CT femur scans (75 males and 34 females). Finite Element contact models of reconstructed hips, subjected to physiologically-based boundary constraints and peak loads of walking mode, were simulated using a coefficient of friction of 0.

Genetic factors in susceptibility to contact sensitivity.

There are clear differences in individual susceptibility to the development of contact allergies; some individuals readily become allergic to many chemicals, and others remain clinically tolerant of everything that they come into contact with. A great number of molecules and pathways can contribute to the perturbation by xenobiotics and the subsequent possible immune response. It is necessary to consider susceptibility in two ways: as allergen-specific and as non-allergen-specific.

Potential eligibility of congenital heart disease patients for subcutaneous implantable cardioverter-defibrillator based on surface electrocardiogram mapping.

Aims: The eligibility of complex congenital heart disease (C-CHD) patients for subcutaneous implantable cardioverter-defibrillator (S-ICD) has yet to be determined. The aim of this study was to determine in C-CHD patients: (i) the S-ICD eligibility, (ii) the most effective sensing vector, (iii) the impact of posture change on screening eligibility, and (iv) the impact of using two vs. six postures for screening.

Modifiable early-life risk factors for childhood adiposity and overweight: an analysis of their combined impact and potential for prevention.

Background: Early life may be a "critical period" when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects.

Objective: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey).

The incidence of stress fracture following peri-acetabular osteotomy: an under-reported complication.

Stress fractures occurring in the pubis and ischium after peri-acetabular osteotomy (PAO) are not well recognised, with a reported incidence of 2% to 3%. The purpose of this study was to analyse the incidence of stress fracture after Bernese PAO under the care of two high-volume surgeons. The study included 359 patients (48 men, 311 women) operated on at a mean age of 31.

RYR1-related malignant hyperthermia with marked cerebellar involvement - a paradigm of heat-induced CNS injury?

Heat-induced CNS injury has been recognized for more than 50 years but the biological basis for the marked selectivity of CNS damage is currently uncertain. We present clinical, imaging, autopsy and genetic findings of a 14-year-old male who developed fatal cerebellar swelling in the course of a malignant hyperthermia (MH) episode caused by triggering anaesthetics. Unaccustomed intense exercise in the days prior to general anaesthesia was a probable confounding factor for the MH reaction.