Platelet-derived transforming growth factor-β1 promotes keratinocyte proliferation in cutaneous wound healing.

Platelets are a recognised potent source of transforming growth factor-β1 (TGFβ1), a cytokine known to promote wound healing and regeneration by stimulating dermal fibroblast proliferation and extracellular matrix deposition. Platelet lysate has been advocated as a novel personalised therapeutic to treat persistent wounds, although the precise platelet-derived growth factors responsible for these beneficial effects have not been fully elucidated. The aim of this study was to investigate the specific role of platelet-derived TGFβ1 in cutaneous wound healing. Using a transgenic mouse with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1fl/fl .PF4-Cre), we show for the first time that platelet-derived TGFβ1 contributes to epidermal and dermal thickening and cellular turnover after excisional skin wounding. In vitro studies demonstrate that human dermal fibroblasts stimulated with platelet lysate containing high levels of platelet-derived TGFβ1 did not exhibit enhanced collagen deposition or proliferation, suggesting that platelet-derived TGFβ1 is not a key promoter of these wound healing processes. Interestingly, human keratinocytes displayed enhanced TGFβ1-driven proliferation in response to platelet lysate, reminiscent of our in vivo findings. In summary, our novel findings define and emphasise an important role of platelet-derived TGFβ1 in epidermal remodelling and regeneration processes during cutaneous wound healing

Are tibial angles measured with inertial sensors useful surrogates for frontal plane projection angles using 2-dimensional video analysis during single leg squat tasks? A reliability and agreement analysis in elite football (soccer) players

During single leg squats (SLS), tibial angle (TA) quantification using inertial measurement units (IMU) may offer a practical alternative to frontal plane projection angle (FPPA) measurement using 2-dimensional (2D) video analysis. This study determined: (i) the reliability of IMUs and 2D video analysis for TA measurement, and 2D video analysis for FPPA measurement; (ii) the agreement between IMU TA and both 2D video TA and FPPA measurements during single leg squats in elite footballers. 18 players were tested on consecutive days. Absolute TA (ATA) and relative TA (RTA) were measured with IMUs. ATA and FPPA were measured concurrently using 2D video analysis. Within-session reliability for all measurements varied across days (intraclass correlation coefficient (ICC) range=0.27–0.83, standard error of measurement (SEM) range=2.12–6.23°, minimal detectable change (MDC) range=5.87–17.26°). Between-sessions, ATA reliability was good for both systems (ICCs=0.70–0.74, SEMs=1.64–7.53°, MDCs=4.55–7.01°), while IMU RTA and 2D FPPA reliability ranged from poor to good (ICCs=0.39–0.72, SEMs=2.60–5.99°, MDCs=7.20–16.61°). All limits of agreement exceeded a 5° acceptability threshold. Both systems were reliable for between-session ATA, although agreement was poor. IMU RTA and 2D video FPPA reliability was variable. For SLS assessment, IMU derived TAs are not useful surrogates for 2D video FPPA measures in this population

Numerical modelling of the effect of using multi-explosives on the explosive forming of steel cones

Modelling and analysis of underwater explosive forming process by using FEM and SPH formulation is presented in this work. The explosive forming of a steel cone is studied. The model setup includes a low carbon steel plate, plate holder, forming die as well as water and C4 explosive. The effect of multiple explosives on rate of targets deformation has been studied. Four different multi-explosives models have been developed and compared to the single explosive model. The formability of the steel plate based on forming limit failure criteria has been investigated. Aspects such as shape of plates deformation and thickness of the plate during the forming process have been examined. The model results indicate that a multi-explosives model does not always guarantee a faster rate of target deformation without central explosive. On the other hand the model results indicate that the multi-explosives setup is capable of preventing crack failure of the steel plate during the forming process which would occur if a single explosive model was used

A study of the effect of projectile orientation on the results of ballistic impact tests as described in the EASA CS-25 regulations for fuel tank access covers

This paper presents the results of an investigation of the ballistic limits and failure modes of AA2024-T351 sheets impacted with cubical projectiles. The experiment/test setup was based on EASA CS-25 regulations for fuel tank access covers. The effect of cube orientation on the ballistic limit and failure modes was considered in detail. A 25% variation in ballistic limit was observed with the lowest ballistic limit (202 m/s) observed for the cubical projectile edge impacted on the target. In the cube face impacts, the ballistic limit was higher (223 m/s), and the highest ballistic limit (254 m/s) was observed for the corner impact. The observed differences in the ballistic limit were due to differences in failure mechanism, which resulted in different localised deformations near the projectile impact point, but also led to differences in global dishing deformation

The fractal heart — embracing mathematics in the cardiology clinic

For clinicians grappling with quantifying the complex spatial and temporal patterns of cardiac structure and function (such as myocardial trabeculae, coronary microvascular anatomy, tissue perfusion, myocyte histology, electrical conduction, heart rate, and blood-pressure variability), fractal analysis is a powerful, but still underused, mathematical tool. In this Perspectives article, we explain some fundamental principles of fractal geometry and place it in a familiar medical setting. We summarize studies in the cardiovascular sciences in which fractal methods have successfully been used to investigate disease mechanisms, and suggest potential future clinical roles in cardiac imaging and time series measurements. We believe that clinical researchers can deploy innovative fractal solutions to common cardiac problems that might ultimately translate into advancements for patient care

FIC/FEM formulation with matrix stabilizing terms for incompressible flows at low and high Reynolds numbers

The final publication is available at Springer via http://dx.doi.org/10.1007/s00466-006-0060-yWe present a general formulation for incompressible fluid flow analysis using the finite element method. The necessary stabilization for dealing with convective effects and the incompressibility condition are introduced via the Finite Calculus method using a matrix form of the stabilization parameters. This allows to model a wide range of fluid flow problems for low and high Reynolds numbers flows without introducing a turbulence model. Examples of application to the analysis of incompressible flows with moderate and large Reynolds numbers are presented.Peer ReviewedPostprint (author's final draft

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

BACKGROUND: Insertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use. METHODS/DESIGN: Overall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted. DISCUSSION: The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN49474281

Improved Exercise-Related Skeletal Muscle Oxygen Consumption Following Uptake of Endurance Training Measured Using Near-Infrared Spectroscopy

Skeletal muscle metabolic function is known to respond positively to exercise interventions. Developing non-invasive techniques that quantify metabolic adaptations and identifying interventions that impart successful response are ongoing challenges for research. Healthy non-athletic adults (18–35 years old) were enrolled in a study investigating physiological adaptations to a minimum of 16 weeks endurance training prior to undertaking their first marathon. Before beginning training, participants underwent measurements of skeletal muscle oxygen consumption using near-infrared spectroscopy (NIRS) at rest (resting muscleV˙O2) and immediately following a maximal exercise test (post-exercise muscleV˙O2). Exercise-related increase in muscleV˙O2 (ΔmV˙O2) was derived from these measurements and cardio-pulmonary peakV˙O2 measured by analysis of expired gases. All measurements were repeated within 3 weeks of participants completing following the marathon and marathon completion time recorded. MuscleV˙O2 was positively correlated with cardio-pulmonary peakV˙O2 (r = 0.63, p < 0.001). MuscleV˙O2 increased at follow-up (48% increase; p = 0.004) despite no change in cardio-pulmonary peakV˙O2 (0% change; p = 0.97). Faster marathon completion time correlated with higher cardio-pulmonary peakV˙O2 (rpartial = −0.58, p = 0.002) but not muscleV˙O2 (rpartial = 0.16, p = 0.44) after adjustment for age and sex [and adipose tissue thickness (ATT) for muscleV˙O2 measurements]. Skeletal muscle metabolic adaptions occur following training and completion of a first-time marathon; these can be identified non-invasively using NIRS. Although the cardio-pulmonary system is limiting for running performance, skeletal muscle changes can be detected despite minimal improvement in cardio-pulmonary function

Sex Dimorphism in the Myocardial Response to Aortic Stenosis

OBJECTIVES: The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. BACKGROUND: AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. METHODS: This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. RESULTS: In 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro-brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001). CONCLUSIONS: CMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471.)

Magnetic Resonance Imaging-Based Assessment of Breast Cancer-Related Lymphoedema Tissue Composition.

OBJECTIVES: The aim of this study was to propose a magnetic resonance imaging acquisition and analysis protocol that uses image segmentation to measure and depict fluid, fat, and muscle volumes in breast cancer-related lymphoedema (BCRL). This study also aims to compare affected and control (unaffected) arms of patients with diagnosed BCRL, providing an analysis of both the volume and the distribution of the different tissue components. MATERIALS AND METHODS: The entire arm was imaged with a fluid-sensitive STIR and a 2-point 3-dimensional T1W gradient-echo-based Dixon sequences, acquired in sagittal orientation and covering the same imaging volume. An automated image postprocessing procedure was developed to simultaneously (1) contour the external volume of the arm and the muscle fascia, allowing separation of the epifacial and subfascial volumes; and to (2) separate the voxels belonging to the muscle, fat, and fluid components. The total, subfascial, epifascial, muscle (subfascial), fluid (epifascial), and fat (epifascial) volumes were measured in 13 patients with unilateral BCRL. Affected versus unaffected volumes were compared using a 2-tailed paired t test; a value of P < 0.05 was considered to be significant. Pearson correlation was used to investigate the linear relationship between fat and fluid excess volumes. The distribution of fluid, fat, and epifascial excess volumes (affected minus unaffected) along the arm was also evaluated using dedicated tissue composition maps. RESULTS: Total arm, epifascial, epifascial fluid, and epifascial fat volumes were significantly different (P < 0.0005), with greater volume in the affected arms. The increase in epifascial volume (globally, 94% of the excess volume) constituted the bulk of the lymphoedematous swelling, with fat comprising the main component. The total fat excess volume summed over all patients was 2.1 times that of fluid. Furthermore, fat and fluid excess volumes were linearly correlated (Pearson r = 0.75), with the fat excess volume being greater than the fluid in 11 subjects. Differences in muscle compartment volume between affected and unaffected arms were not statistically significant, and contributed only 6% to the total excess volume. Considering the distribution of the different tissue excess volumes, fluid accumulated prevalently around the elbow, with substantial involvement of the upper arm in only 3 cases. Fat excess volume was generally greater in the upper arm; however, the relative increase in epifascial volume, which considers the total swelling relative to the original size of the arm, was in 9 cases maximal within the forearm. CONCLUSIONS: Our measurements indicate that excess of fat within the epifascial layer was the main contributor to the swelling, even when a substantial accumulation of fluid was present. The proposed approach could be used to monitor how the internal components of BCRL evolve after presentation, to stratify patients for treatment, and to objectively assess treatment response. This methodology provides quantitative metrics not currently available during the standard clinical assessment of BCRL and shows potential for implementation in clinical practice