Changes in leg spring behaviour, plantar loading and foot mobility magnitude induced by an exhaustive treadmill run in adolescent middle-distance runners.

OBJECTIVES: This study aimed to determine adjustments in spring-mass model characteristics, plantar loading and foot mobility induced by an exhaustive run. DESIGN: Within-participants repeated measures. METHODS: Eleven highly-trained adolescent middle-distance runners ran to exhaustion on a treadmill at a constant velocity corresponding to 95% of velocity associated with VO₂max (17.8 ± 1.4 kmh(-1), time to exhaustion=8.8 ± 3.4 min). Contact time obtained from plantar pressure sensors was used to estimate spring-mass model characteristics, which were recorded (during 30 s) 1 min after the start and prior to exhaustion using pressure insoles. Foot mobility magnitude (a composite measure of vertical and medial-lateral mobility of the midfoot) was measured before and after the run. RESULTS: Mean contact area (foot to ground), contact time, peak vertical ground reaction force, centre of mass vertical displacement and leg compression increased significantly with fatigue, while flight time, leg stiffness and mean pressure decreased. Leg stiffness decreased because leg compression increased to a larger extent than peak vertical ground reaction forces. Step length, step frequency and foot mobility magnitude did not change at exhaustion. CONCLUSIONS: The stride pattern of adolescents when running on a treadmill at high constant velocity deteriorates near exhaustion, as evidenced by impaired leg-spring behaviour (leg stiffness) and altered plantar loading.

Is ultracision knife safe and efficient for breast capsulectomy? A preliminary study.

BACKGROUND: Silicone breast implants are used to a wide extent in the field of plastic surgery. However, capsular contracture remains a considerable concern. This study aimed to analyze the effectiveness and applicability of an ultracision knife for capsulectomy breast surgery. METHODS: A prospective, single-center, randomized study was performed in 2009. The inclusion criteria specified female patients 20-80 years of age with capsular contracture (Baker 3-4). Ventral capsulectomy was performed using an ultracision knife on one side and the conventional Metzenbaum-type scissors and surgical knife on the collateral side of the breast. Measurements of the resected capsular ventral fragment, operative time, remaining breast tissue, drainage time, seroma and hematoma formation, visual analog scale pain score, and sensory function of the nipple-areola complex were assessed. In addition, histologic analysis of the resected capsule was performed. RESULTS: Five patients (median age, 59.2 years) were included in this study with a mean follow-up period of 6 months. Three patients had Baker grade 3 capsular contracture, and two patients had Baker grade 4 capsular contracture. The ultracision knife was associated with a significantly lower pain score, shorter operative time, smaller drainage volume, and shorter drainage time and resulted in a larger amount of remaining breast tissue. Histologic analysis of the resected capsule showed no apoptotic cells in the study group or control group. CONCLUSIONS: The results suggest that ventral capsulectomy with Baker grade 3 or 4 contracture using the ultracision knife is feasible, safe, and more efficient than blunt dissection and monopolar cutting diathermy and has a short learning curve. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266 .

Low-dose valganciclovir is efficacious and safe for prophylaxis of cytomegalovirus infection in kidney transplantation

Background: Optimal valganciclovir (VGC) dosage and duration for cytomegalovirus (CMV) prophylaxis in kidney transplant recipients remains controversial. This study aimed to determine GCV blood levels and efficacy/safety observed under low-dose oral VGC in kidney transplant recipients. Secondly, to quantify the variability of GCV blood levels, and its potential clinical impact. Methods: In this prospective study, each patient at risk for CMV undergoing kidney transplantation received low-dose VGC (450 mg qd) prophylaxis for 3 months, unless GFR was below 40 mL/min, in which case the dose was adapted to 450 mg every other day. GCV levels, at trough (Ctrough) and at peak (C3h) were measured monthly and CMV viremia was assessed during and after prophylaxis using real time quantitative Polymerase Chain Reaction. Adverse effects were recorded on each GCV sampling. Patients were followed up to one year after transplantation. Results: 38 kidney recipients (19 D+/R+, 11 D+/R-, 8 D-/R+) received 3-month VGC prophylaxis. Most patients (mean GFR of 59 mL/min) received 450 mg qd but the dose was reduced to 450 mg every other day in 6 patients with mean GFR of 22 mL/min. Average GCV C3h and Ctrough (regressed at 24h or 48h) were 3.9 mg/L (CV 33%, range: 1.3-8.2) and 0.4 mg/L (CV 111%, range 0.1-3.3). Population pharmacokinetic analysis showed a fair dispersion of the parameters mainly influenced by renal function. Despite this variability, patients remained aviremic during VGC prophylaxis. Neutropenia and thrombocytopenia (grade 2-4) were reported in 4% and 3% of patients respectively. During follow-up, asymptomatic CMV viremia was reported in 25% patients. One year after transplantation, 12% patients (all D+/R-) had developed a CMV disease, which was treated with a therapeutic 6-week course of oral VGC. Conclusion: Average GCV blood levels after oral administration of low-dose VGC in kidney transplant recipients were comparable to those previously reported with oral GCV prophylaxis, efficacious and well tolerated. Thus, a 3-month course of low-dose VGC is appropriate for the renal function of most kidney transplant recipients.

Development of a real-time PCR for the specific detection of Waddlia chondrophila in clinical samples.

Waddlia chondrophila is considered as an emerging human pathogen likely involved in miscarriage and lower respiratory tract infections. Given the low sensitivity of cell culture to recover such an obligate intracellular bacteria, molecular-based diagnostic approaches are warranted. We thus developed a real-time PCR that amplifies Waddlia chondrophila DNA. Specific primers and probe were selected to target the 16S rRNA gene. The PCR specifically amplified W. chondrophila but did not amplify other related-bacteria such as Parachlamydia acanthamoebae, Simkania negevensis and Chlamydia pneumoniae. The PCR exhibited a good intra-run and inter-run reproducibility and a sensitivity of less than ten copies of the positive control. This real-time PCR was then applied to 32 nasopharyngeal aspirates taken from children with bronchiolitis not due to respiratory syncytial virus (RSV). Three samples revealed to be Waddlia positive, suggesting a possible role of this Chlamydia-related bacteria in this setting.

Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic.

Each year, approximately five million people die worldwide from putatively vaccine-preventable mucosally transmitted diseases. With respect to mass vaccination campaigns, one strategy to cope with this formidable challenge is aerosol vaccine delivery, which offers potential safety, logistical, and cost-saving advantages over traditional vaccination routes. Additionally, aerosol vaccination may elicit pivotal mucosal immune responses that could contain or eliminate mucosally transmitted pathogens in a preventative or therapeutic vaccine context. In this current preclinical non-human primate investigation, we demonstrate the feasibility of aerosol vaccination with the recombinant poxvirus-based vaccine vectors NYVAC and MVA. Real-time in vivo scintigraphy experiments with radiolabeled, aerosol-administered NYVAC-C (Clade C, HIV-1 vaccine) and MVA-HPV vaccines revealed consistent mucosal delivery to the respiratory tract. Furthermore, aerosol delivery of the vaccines was safe, inducing no vaccine-associated pathology, in particular in the brain and lungs, and was immunogenic. Administration of a DNA-C/NYVAC-C prime/boost regime resulted in both systemic and anal-genital HIV-specific immune responses that were still detectable 5 months after immunization. Thus, aerosol vaccination with NYVAC and MVA vectored vaccines constitutes a tool for large-scale vaccine efforts against mucosally transmitted pathogens.

Adjustable Suture Removal: Increasing Aqueous Flow in "Safe" Trabeculectomy.

Purpose: Aqueous flow through trabeculectomy blebs has been suggested to influence filtration bleb survival. We investigated the relationship between the requirement to increase aqueous flow via adjustable suture removal and surgical outcomes following "safe trabeculectomy" with mitomycin C (MMC). Methods: 62 consecutive eyes of 53 patients underwent fornix based trabeculectomy with adjustable sutures, intraoperative MMC and intensive postoperative steroids. Subconjunctival antimetabolite injections and bleb needlings were administered according to bleb vascularity and IOP trends. Main outcome measures were: success rates (definition: IOP≤21mmHg and 20% IOP reduction); number of antimetabolite injections; bleb needlings; number of of eyes recommencing glaucoma medications and complications. Results: Mean age was 70.4±16.0 years (mean± SD); mean preoperative IOP was 24.5±9.1 mmHg and decreased to 12.3±8.9mmHg postoperatively. Mean number of sutures was 2.6 ± 0.7. Eyes were divided into 2 groups in relation to the number of sutures removed. The number of subconjunctival MMC injections required for those requiring 2 suture removals was significantly greater than those requiring 1 suture removal (p<0.05) The number of needlings and 5FU injections also increased but did not reach significance (p=0.09 and p=0.34 respectively). Least-squared linear regression analysis showed the number of needlings required had a statistically significant (p=0.05) trend with respect to time elapsed between surgery and first suture removal. No other interventions had significant trends. Mean time between surgery and suture removal was: 4.2±9.2 weeks (suture #1) and 5.7±9.7 weeks (suture#2). Antiglaucoma medication was restarted in only 5 eyes. Postoperative complications were infrequent: Seidel (3.2%), peripheral choroidal effusions at any time (3.2%), and shallow anterior chamber (1.6%). Conclusion: Eyes requiring a greater number of suture removals required a significantly greater number of antifibrosis interventions. The time elapsed before suture removal was inversely related to the number of postoperative needlings, suggesting these eyes may have decreased aqueous production and therefore require aggressive post-operative management to prevent bleb failure.

Prevalence and time course of acute mountain sickness in older children and adolescents after rapid ascent to 3450 meters

OBJECTIVE: Acute mountain sickness is a frequent and debilitating complication of high-altitude exposure, but there is little information on the prevalence and time course of acute mountain sickness in children and adolescents after rapid ascent by mechanical transportation to 3500 m, an altitude at which major tourist destinations are located throughout the world. METHODS: We performed serial assessments of acute mountain sickness (Lake Louise scores) in 48 healthy nonacclimatized children and adolescents (mean +/- SD age: 13.7 +/- 0.3 years; 20 girls and 28 boys), with no previous high-altitude experience, 6, 18, and 42 hours after arrival at the Jungfraujoch high-altitude research station (3450 m), which was reached through a 2.5-hour train ascent. RESULTS: We found that the overall prevalence of acute mountain sickness during the first 3 days at high altitude was 37.5%. Rates were similar for the 2 genders and decreased progressively during the stay (25% at 6 hours, 21% at 18 hours, and 8% at 42 hours). None of the subjects needed to be evacuated to lower altitude. Five subjects needed symptomatic treatment and responded well. CONCLUSION: After rapid ascent to high altitude, the prevalence of acute mountain sickness in children and adolescents was relatively low; the clinical manifestations were benign and resolved rapidly. These findings suggest that, for the majority of healthy nonacclimatized children and adolescents, travel to 3500 m is safe and pharmacologic prophylaxis for acute mountain sickness is not needed.

Regional income inequality in Italy in the long run (1871–2001). Patterns and determinants

The chapter presents up-to-date estimates of Italy’s regional GDP, with the present borders, in ten-year benchmarks from 1871 to 2001, and proposes a new interpretative hypothesis based on long-lasting socio-institutional differences. The inverted U-shape of income inequality is confirmed: rising divergence until the midtwentieth century, then convergence. However, the latter was limited to the centrenorth: Italy was divided into three parts by the time regional inequality peaked, in 1951, and appears to have been split into two halves by 2001. As a consequence of the falling back of the south, from 1871 to 2001 we record σ-divergence across Italy’s regions, i.e. an increase in dispersion, and sluggish β-convergence. Geographical factors and the market size played a minor role: against them are both the evidence that most of the differences in GDP are due to employment rather than to productivity and the observed GDP patterns of many regions. The gradual converging of regional GDPs towards two equilibria instead follows social and institutional differences − in the political and economic institutions and in the levels of human and social capital – which originated in pre-unification states and did not die (but in part even increased) in postunification Italy.

An efficient algorithm to perform multiple testing in epistasis screening

Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. Gene-gene interaction studies will require a memory proportional to the squared number of SNPs. A genome-wide epistasis search would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MBMDR-3.0.3. We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn’s disease. Results: In the case of a binary (affected/unaffected) trait, the parallel workflow of MBMDR-3.0.3 analyzes all gene-gene interactions with a dataset of 100,000 SNPs typed on 1000 individuals within 4 days and 9 hours, using 999 permutations of the trait to assess statistical significance, on a cluster composed of 10 blades, containing each four Quad-Core AMD Opteron(tm) Processor 2352 2.1 GHz. In the case of a continuous trait, a similar run takes 9 days. Our program found 14 SNP-SNP interactions with a multiple-testing corrected p-value of less than 0.05 on real-life Crohn’s disease (CD) data. Conclusions: Our software is the first implementation of the MB-MDR methodology able to solve large-scale SNP-SNP interactions problems within a few days, without using much memory, while adequately controlling the type I error rates. A new implementation to reach genome-wide epistasis screening is under construction. In the context of Crohn’s disease, MBMDR-3.0.3 could identify epistasis involving regions that are well known in the field and could be explained from a biological point of view. This demonstrates the power of our software to find relevant phenotype-genotype higher-order associations.

First detection of Waddlia chondrophila in Africa using SYBR Green real-time PCR on veterinary samples.

Waddlia chondrophila is a strict intracellular microorganism belonging to the order Chlamydiales that has been isolated twice from aborted bovine fetuses, once in USA and once in Germany. This bacterium is now considered as an abortigenic agent in cattle. However, no information is available regarding the presence of this bacterium in Africa. Given the low sensitivity of cell culture to recover such an obligate intracellular bacterium, molecular-based diagnostic approaches are warranted. This report describes the development of a quantitative SYBR Green real-time PCR assay targeting the recA gene of W. chondrophila. Analytical sensitivity was 10 copies of control plasmid DNA per reaction. No cross-amplification was observed when testing pathogens that can cause abortion in cattle. The PCR exhibited a good intra-run and inter-run reproducibility. This real-time PCR was then applied to 150 vaginal swabs taken from Tunisian cows that have aborted. Twelve samples revealed to be Waddlia positive, suggesting a possible role of this bacterium in this setting. This new real-time PCR assay represents a diagnostic tool that may be used to further study the prevalence of Waddlia infection.

Changes in running mechanics and spring-mass behaviour during a 5-km time trial.

Research into the biomechanical manifestation of fatigue during exhaustive runs is increasingly popular but additional understanding of the adaptation of the spring-mass behaviour during the course of strenuous, self-paced exercises continues to be a challenge in order to develop optimized training and injury prevention programs. This study investigated continuous changes in running mechanics and spring-mass behaviour during a 5-km run. 12 competitive triathletes performed a 5-km running time trial (mean performance: ̴17 min 30 s) on a 200 m indoor track. Vertical and anterior-posterior ground reaction forces were measured every 200 m by a 5-m long force platform system, and used to determine spring-mass model characteristics. After a fast start, running velocity progressively decreased (- 11.6%; P<0.001) in the middle part of the race before an end spurt in the final 400-600 m. Stride length (- 7.4%; P<0.001) and frequency (- 4.1%; P=0.001) decreased over the 25 laps, while contact time (+ 8.9%; P<0.001) and total stride duration (+ 4.1%; P<0.001) progressively lengthened. Peak vertical forces (- 2.0%; P<0.01) and leg compression (- 4.3%; P<0.05), but not centre of mass vertical displacement (+ 3.2%; P>0.05), decreased with time. As a result, vertical stiffness decreased (- 6.0%; P<0.001) during the run, whereas leg stiffness changes were not significant (+ 1.3%; P>0.05). Spring-mass behaviour progressively changes during a 5-km time trial towards deteriorated vertical stiffness, which alters impact and force production characteristics.

Effects of coastal submarine canyons on tsunami propagation and impact

We analyse the variations produced on tsunami propagation and impact over a straight coastline because of the presence of a submarine canyon incised in the continental margin. For ease of calculation we assume that the shoreline and the shelf edge are parallel and that the incident wave approaches them normally. A total of 512 synthetic scenarios have been computed by combining the bathymetry of a continental margin incised by a parameterised single canyon and the incident tsunami waves. The margin bathymetry, the canyon and the tsunami waves have been generated using mathematical functions (e.g. Gaussian). Canyon parameters analysed are: (i) incision length into the continental shelf, which for a constant shelf width relates directly to the distance from the canyon head to the coast, (ii) canyon width, and (iii) canyon orientation with respect to the shoreline. Tsunami wave parameters considered are period and sign. The COMCOT tsunami model from Cornell University was applied to propagate the waves across the synthetic bathymetric surfaces. Five simulations of tsunami propagation over a non-canyoned margin were also performed for reference. The analysis of the results reveals a strong variation of tsunami arrival times and amplitudes reaching the coastline when a tsunami wave travels over a submarine canyon, with changing maximum height location and alongshore extension. In general, the presence of a submarine canyon lowers the arrival time to the shoreline but prevents wave build-up just over the canyon axis. This leads to a decrease in tsunami amplitude at the coastal stretch located just shoreward of the canyon head, which results in a lower run-up in comparison with a non-canyoned margin. Contrarily, an increased wave build-up occurs on both sides of the canyon head, generating two coastal stretches with an enhanced run-up. These aggravated or reduced tsunami effects are modified with (i) proximity of the canyon tip to the coast, amplifying the wave height, (ii) canyon width, enlarging the areas with lower and higher maximum height wave along the coastline, and (iii) canyon obliquity with respect to the shoreline and shelf edge, increasing wave height shoreward of the leeward flank of the canyon. Moreover, the presence of a submarine canyon near the coast produces a variation of wave energy along the shore, eventually resulting in edge waves shoreward of the canyon head. Edge waves subsequently spread out alongshore reaching significant amplitudes especially when coupling with tsunami secondary waves occurs. Model results have been groundtruthed using the actual bathymetry of Blanes Canyon area in the North Catalan margin. This paper underlines the effects of the presence, morphology and orientation of submarine canyons as a determining factor on tsunami propagation and impact, which could prevail over other effects deriving from coastal configuration.

In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence.

Time-resolved measurements of tissue autofluorescence (AF) excited at 405 nm were carried out with an optical-fiber-based spectrometer in the bronchi of 11 patients. The objectives consisted of assessing the lifetime as a new tumor/normal (T/N) tissue contrast parameter and trying to explain the origin of the contrasts observed when using AF-based cancer detection imaging systems. No significant change in the AF lifetimes was found. AF bronchoscopy performed in parallel with an imaging device revealed both intensity and spectral contrasts. Our results suggest that the spectral contrast might be due to an enhanced blood concentration just below the epithelial layers of the lesion. The intensity contrast probably results from the thickening of the epithelium in the lesions. The absence of T/N lifetime contrast indicates that the quenching is not at the origin of the fluorescence intensity and spectral contrasts. These lifetimes (6.9 ns, 2.0 ns, and 0.2 ns) were consistent for all the examined sites. The fact that these lifetimes are the same for different emission domains ranging between 430 and 680 nm indicates that there is probably only one dominant fluorophore involved. The measured lifetimes suggest that this fluorophore is elastin.

A wearable system to time gate crossing during alpine skiing slalom

INTRODUCTION: In alpine skiing, chronometry analysis is currently the most common tool to assess performance. It is widely used to rank competitors during races, as well as to manage athletes training and to evaluate material. Usually, this measurement is accurately realized using timing cells. Nevertheless, these devices are too complex and expensive to allow chronometry of every gates crossing. On the other side, differential GPS can be used for measuring gate crossing time (Waegli et al). However, this is complex (e.g. recording gate position with GPS) and mainly used in research applications. The aim of the study was to propose a wearable system to time gates crossing during alpine skiing slalom (SL), which is suitable for routine uses. METHODS: The proposed system was composed of a 3D accelerometer (ADXL320®, Analog Device, USA) placed at the sacrum of the athlete, a matrix of force sensors (Flexiforce®, Tekscan, USA) fixed on the right shin guard and a data logger (Physilog®, BioAGM, Switzerland). The sensors were sampled at 500 Hz. The crossing time were calculated in two phases. First, the accelerometer was used to detect the curves by considering the maximum of the mediolateral peak acceleration. Then, the force sensors were used to detect the impacts with the gates by considering maximum force variation. In case of non impact, the detection was realized based on the acceleration and features measured at the other gates. In order to assess the efficiency of the system, two different SL were monitored twice for two world cup level skiers, a male SL expert and a female downhill expert. RESULTS AND DISCUSSION: The combination of the accelerometer and force sensors allowed to clearly identify the gate crossing times. When comparing the runs of the SL expert and the downhill expert, we noticed that the SL expert was faster. For example for the first SL, the overall difference between the best run of each athlete was of 5.47s. At each gate, the SL expert increased the time difference slower at the beginning (0.27s/gate) than at the end (0.34s/gate). Furthermore, when comparing the runs of the SL expert, a maximum time difference of 20ms at each gate was noticed. This showed high repeatability skills of the SL expert. In opposite, the downhill expert with a maximum difference time of 1s at each gate was clearly less repeatable. Both skiers were not disturbed by the system. CONCLUSION: This study proposed a new wearable system to automatically time gates crossing during alpine skiing slalom combining force and accelerometer sensors. The system was evaluated with two professional world cup skiers and showed a high potential. This system could be extended to time other parameters. REFERENCES Waegli A, Skaloud J (2007). Inside GNSS, Spring, 24-34.

Coordination and collaboration in European research towards healthy and safe nanomaterials

Nanotechnology is becoming part of our daily life in a wide range of products such as computers, bicycles, sunscreens or nanomedicines. While these applications already become reality, considerable work awaits scientists, engineers, and policy makers, who want such nanotechnological products to yield a maximum of benefit at a minimum of social, environmental, economic and (occupational) health cost. Considerable efforts for coordination and collaboration in research are needed if one wants to reach these goals in a reasonable time frame and an affordable price tag. This is recognized in Europe by the European Commission which funds not only research projects but also supports the coordination of research efforts. One of these coordination efforts is NanoImpactNet, a researcher-operated network, which started in 2008 promote scientific cross-talk across all disciplines on the health and environmental impact of nanomaterials. Stakeholders contribute to these activities, notably the definition of research and knowledge needs. Initial discussions in this domain focused on finding an agreement on common metrics, and which elements are needed for standardized approaches for hazard and exposure identification. There are many nanomaterial properties that may play a role. Hence, to gain the time needed to study this complex matter full of uncertainties, researchers and stakeholders unanimously called for simple, easy and fast risk assessment tools that can support decision making in this rapidly moving and growing domain. Today, several projects are starting or already running that will develop such assessment tools. At the same time, other projects investigate in depth which factors and material properties can lead to unwanted toxicity or exposure, what mechanisms are involved and how such responses can be predicted and modelled. A vision for the future is that once these factors, properties and mechanisms are understood, they can and will be accounted for in the development of new products and production processes following the idea of "Safety by Design". The promise of all these efforts is a future with nanomaterials where most of their risks are recognized and addressed before they even reach the market.