Physiological response to whole-body vibration in athletes and sedentary subjects.

Whole-body vibration (WBV) is a new exercise method, with good acceptance among sedentary subjects. The metabolic response to WBV has not been well documented. Three groups of male subjects, inactive (SED), endurance (END) and strength trained (SPRINT) underwent a session of side-alternating WBV composed of three 3-min exercises (isometric half-squat, dynamic squat, dynamic squat with added load), and repeated at three frequencies (20, 26 and 32 Hz). VO(2), heart rate and Borg scale were monitored. Twenty-seven healthy young subjects (10 SED, 8 SPRINT and 9 END) were included. When expressed in % of their maximal value recorded in a treadmill test, both the peak oxygen consumption (VO(2)) and heart rate (HR) attained during WBV were greatest in the SED, compared to the other two groups (VO(2): 59.3 % in SED vs 50.8 % in SPRINT and 48.0 % in END, p<0.01; HR 82.7 % in SED vs 80.4 % in SPRINT and 72.4 % in END, p<0.05). In conclusions, the heart rate and metabolic response to WBV differs according to fitness level and type, exercise type and vibration frequency. In SED, WBV can elicit sufficient cardiovascular response to benefit overall fitness and thus be a potentially useful modality for the reduction of cardiovascular risk.

Dynamically tuned interferometers for the observation of gravitational waves from coalescing compact binaries

We propose a new method of operating laser interferometric gravitational-wave detectors when observing chirps of gravitational radiation from coalescing compact binary stars. This technique consists of the use of narrow-band dual recycling to increase the signal but with the tuning frequency of the detector arranged to follow the frequency of a chirp. We consider the response of such an instrument to chirps, including the effect of inevitable errors in tracking. Different possible tuning strategies are discussed. Both the final signal-to-noise ratio and timing accuracy are evaluated and are shown to be significantly improved by the use of dynamic tuning. This should allow an accurate and reliable measurement of Hubble's constant.

Extended treatment of treatment-naive patients with chronic hepatitis c virus (HCV) genotype 1-infection and slow response to pegylated interferon-alfa and ribavirin: a meta-analysis

Aims: Recently, several clinical trials analyzed if extended duration of treatment with pegylated interferon-alfa and ribavirin over 48 weeks can improve sustained virologic response (SVR) rates in HCV genotype 1-infected patients with slow virologic response. Because results of these clinical trials are conflicting, we performed a metaanalysis to determine the overall impact of extended treatment compared to standard treatment on virologic response rates in treatment-naive HCV genotype 1 slow responders. Methods: Literature search was performed independently by two observers using Pub Med, EMBASE, CENTRAL and abstracts presented in English at international liver and gastroenterology meetings. Randomized controlled clinical trials (RCTs; but studies that re-analyzed data retrospectively RCTs were also allowed) were considered if they included monoinfected treatment-naive HCV genotype 1 patients and compared treatment with pegIFN-alfa 2a or 2b in combination with ribavirin for 48 weeks versus extended treatment (up to 72 weeks) in slow responders. Primary and secondary end points were SVR rates and end-of-treatment (EOT) and relapse rates, respectively. In the present meta-analysis, study endpoints were summarized with a DerSimonian-Laird estimate for binary outcome basing on a random effects model. Results: Literature search yielded seven RTCs addressing the benefit of extended treatment with pegylated interferon-alfa and ribavirin in treatment-naive HCV genotype 1 slow responders. In total, 1330 slow responders were included in our meta-analysis. We show that extended treatment duration compared to the standard of care significantly improves SVR rates in HCV genotype 1 slow responders (12.4% improvement of overall SVR rate, 95% CI 0.055- 0.193, P = 0.0005). In addition, we show that rates of viral relapse were significantly reduced by extended treatment (24.1% reduction of relapse, 95% CI −0.3332 to −0.1487, P < 0.0001), whereas no significant impact of extended treatment on EOT response rates was found. Though extended treatment was burdened with an enhanced rate of premature treatment discontinuation due to interferonalfa- and ribavirin-related side effects, the frequency of serious adverse events was not increased. Conclusions: Treatment extension in HCV genotype 1 slow responders can improve SVR rates in difficult to treat patients and should be considered in patients who need to be treated before specific antivirals will be approved.

Evaluation of the caloric test by combining 3 response parameters.

The slow-phase velocity of nystagmus is one of the most sensitive parameters of vestibular function and is currently the standard for evaluating the caloric test. However, the assessment of this parameter requires recording the response by using nystagmography. The aim of this study was to evaluate whether frequency and duration of the caloric nystagmus, as measured by using a clinical test with Frenzel glasses, could predict the result of the recorded test. The retrospective analysis of 222 caloric test results recorded by means of electronystagmography has shown a good association between the 3 parameters for unilateral weakness. The asymmetry observed in the velocity can be predicted by a combination of frequency and duration. On the other hand, no relationship was observed between the parameters for directional preponderance. These results indicate that a clinical caloric test with frequency and duration as parameters can be used to predict the unilateral weakness, which would be obtained by use of nystagmography. We propose an evaluation of the caloric test on the basis of diagrams combining the 3 response parameters.

Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis

Epstein-Barr virus (EBV) has been associated with multiple sclerosis (MS), however, most studies examining the relationship between the virus and the disease have been based on serologies, and if EBV is linked to MS, CD8+ T cells are likely to be involved as they are important both in MS pathogenesis and in controlling viruses. We hypothesized that valuable information on the link between MS and EBV would be ascertained from the study of frequency and activation levels of EBV-specific CD8+ T cells in different categories of MS patients and control subjects. We investigated EBV-specific cellular immune responses using proliferation and enzyme linked immunospot assays, and humoral immune responses by analysis of anti-EBV antibodies, in a cohort of 164 subjects, including 108 patients with different stages of MS, 35 with other neurological diseases and 21 healthy control subjects. Additionally, the cohort were all tested against cytomegalovirus (CMV), another neurotropic herpes virus not convincingly associated with MS, nor thought to be deleterious to the disease. We corrected all data for age using linear regression analysis over the total cohorts of EBV- and CMV-infected subjects. In the whole cohort, the rate of EBV and CMV infections were 99% and 51%, respectively. The frequency of IFN-gamma secreting EBV-specific CD8+ T cells in patients with clinically isolated syndrome (CIS) was significantly higher than that found in patients with relapsing-remitting MS (RR-MS), secondary-progressive MS, primary-progressive MS, patients with other neurological diseases and healthy controls. The shorter the interval between MS onset and our assays, the more intense was the EBV-specific CD8+ T-cell response. Confirming the above results, we found that EBV-specific CD8+ T-cell responses decreased in 12/13 patients with CIS followed prospectively for 1.0 +/- 0.2 years. In contrast, there was no difference between categories for EBV-specific CD4+ T cell, or for CMV-specific CD4+ and CD8+ T-cell responses. Anti-EBV-encoded nuclear antigen-1 (EBNA-1)-specific antibodies correlated with EBV-specific CD8+ T cells in patients with CIS and RR-MS. However, whereas EBV-specific CD8+ T cells were increased the most in early MS, EBNA-1-specific antibodies were increased in early as well as in progressive forms of MS. Our data show high levels of CD8+ T-cell activation against EBV--but not CMV--early in the course of MS, which support the hypothesis that EBV might be associated with the onset of this disease.

Measurement of total estrone content in foods. Application to dairy products.

Estrone is a powerful growth-inducing hormone that is present in milk, mainly in the form of fatty acid esters, at concentrations that promote growth in experimental animals. We present here a method useful for the measurement of this natural hormone in foods and applied it to several common dairy products. Samples were frozen, finely powdered, and lyophilized then extracted with trichloromethane/methanol; the dry extract was saponified with potassium hydroxide. The free estrone evolved was extracted with ethyl acetate and was used for the estimation of total estrone content through radioimmunoassay. Application of the method to dairy products showed high relative levels of total estrone (essentially acyl-estrone) in milk, in the range of 1 ¿M, which were halved in skimmed milk. Free estrone levels were much lower, in the nanomolar range. A large proportion of estrone esters was present in all other dairy products, fairly correlated with their fat content. The amount of estrone carried by milk is well within the range, where its intake may exert a physiological response in the sucklings for which it is provided. These growth-inducing and energy expenditure-lowering effects may affect humans ingesting significant amounts of dairy products.

Effect of n-3 fatty acids on cerebral markers and the inflammatory response in sepsis

Introduction ICM+ software encapsulates our 20 years' experience in brain monitoring. It collects data from a variety of bedside monitors and produces time trends of parameters defi ned using confi gurable mathematical formulae. To date it is being used in nearly 40 clinical research centres worldwide. We present its application for continuous monitoring of cerebral autoregulation using near-infrared spectroscopy (NIRS). Methods Data from multiple bedside monitors are processed by ICM+ in real time using a large selection of signal processing methods. These include various time and frequency domain analysis functions as well as fully customisable digital fi lters. The fi nal results are displayed in a variety of ways including simple time trends, as well as time window based histograms, cross histograms, correlations, and so forth. All this allows complex information from bedside monitors to be summarized in a concise fashion and presented to medical and nursing staff in a simple way that alerts them to the development of various pathological processes. Results One hundred and fi fty patients monitored continuously with NIRS, arterial blood pressure (ABP) and intracranial pressure (ICP), where available, were included in this study. There were 40 severely headinjured adult patients, 27 SAH patients (NCCU, Cambridge); 60 patients undergoing cardiopulmonary bypass (John Hopkins Hospital, Baltimore) and 23 patients with sepsis (University Hospital, Basel). In addition, MCA fl ow velocity (FV) was monitored intermittently using transcranial Doppler. FV-derived and ICP-derived pressure reactivity indices (PRx, Mx), as well as NIRS-derived reactivity indices (Cox, Tox, Thx) were calculated and showed signifi cant correlation with each other in all cohorts. Errorbar charts showing reactivity index PRx versus CPP (optimal CPP chart) as well as similar curves for NIRS indices versus CPP and ABP were also demonstrated. Conclusions ICM+ software is proving to be a very useful tool for enhancing the battery of available means for monitoring cerebral vasoreactivity and potentially facilitating autoregulation guided therapy. Complexity of data analysis is also hidden inside loadable profi les, thus allowing investigators to take full advantage of validated protocols including advanced processing formulas.

Frequency, characterisation and therapies of fatigue after stroke.

Post-stroke objective or subjective fatigue occurs in around 50% of patients and is frequent (30%) even after minor strokes. It can last more than one year after the event, and is characterised by a different quality from usual fatigue and good response to rest. Associated risk factors include age, single patients, female, disability, depression, attentional impairment and sometimes posterior strokes, but also inactivity, overweight, alcohol and sleep apnoea syndrome. There are few therapy studies, but treatment may include low-intensity training, cognitive therapy, treatment of associated depression, wakefulness-promoting agents like modafinil, correction of risk factors and adaptation of activities.

Heated Optical Fiber for Distributed Soil-Moisture Measurements: A Lysimeter Experiment

An Actively Heated Fiber Optics (AHFO) method to estimate soil moisture is tested and the analysis technique improved on. The measurements were performed in a lysimeter uniformly packed with loam soil with variable water content profiles. In the first meter of the soil profi le, 30 m of fiber optic cable were installed in a 12 loops coil. The metal sheath armoring the fiber cable was used as an electrical resistance heater to generate a heat pulse, and the soil response was monitored with a Distributed Temperature Sensing (DTS) system. We study the cooling following three continuous heat pulses of 120 s at 36 W m(-1) by means of long-time approximation of radial heat conduction. The soil volumetric water contents were then inferred from the estimated thermal conductivities through a specifically calibrated model relating thermal conductivity and volumetric water content. To use the pre-asymptotic data we employed a time correction that allowed the volumetric water content to be estimated with a precision of 0.01-0.035 (m(3) m(-3)). A comparison of the AHFO measurements with soil-moisture measurements obtained with calibrated capacitance-based probes gave good agreement for wetter soils [discrepancy between the two methods was less than 0.04 (m(3) m(-3))]. In the shallow drier soils, the AHFO method underestimated the volumetric water content due to the longertime required for the temperature increment to become asymptotic in less thermally conductive media [discrepancy between the two methods was larger than 0.1 (m(3) m(-3))]. The present work suggests that future applications of the AHFO method should include longer heat pulses, that longer heating and cooling events are analyzed, and, temperature increments ideally be measured with higher frequency.

Endocan measurement for the postmortem diagnosis of sepsis

The vascular endothelium has been shown to play a pivotal role in the pathophysiology of sepsis through the expression of surface proteins and secretion of soluble mediators. Endocan (endothelial cell-specific molecule-1), a 50-kDa dermatan sulfate proteoglycan, is expressed by endothelial cells in lung and kidney and can be detected at low levels in the serum of healthy subjects. Increased concentrations were described in patients with sepsis, severe sepsis and septic shock compared to healthy individuals, with serum concentrations related to the severity of illness. In the present study, we investigated endocan, procalcitonin and C-reactive protein in postmortem serum from femoral blood in a series of sepsis-related fatalities and control individuals who underwent medicolegal investigations. Endocan was also measured in pericardial fluid. Two study groups were prospectively formed, a sepsis-related fatalities group and a control group. The sepsis-related fatalities group consisted of sixteen forensic autopsy cases with documented clinical diagnosis of sepsis in vivo. The control group consisted of sixteen forensic autopsy cases with various noninfectious causes of death. Postmortem serum endocan concentrations were significantly higher in the sepsis group, with values ranging from 0.519ng/ml to 6.756ng/ml. In the control group, endocan levels were undetectable in eleven out of sixteen cases. The results of the data analysis revealed similar endocan concentrations in the pericardial fluid of both studied groups. Endocan can be considered a suitable biological parameter for the detection of sepsis-related deaths in forensic pathology routine.

LiveCount Assay: concomitant measurement of cytolytic activity and phenotypic characterisation of CD8(+) T-cells by flow cytometry.

Tumour immunologists strive to develop efficient tumour vaccination and adoptive transfer therapies that enlarge the pool of tumour-specific and -reactive effector T-cells in vivo. To assess the efficiency of the various strategies, ex vivo assays are needed for the longitudinal monitoring of the patient's specific immune responses providing both quantitative and qualitative data. In particular, since tumour cell cytolysis is the end goal of tumour immunotherapy, routine immune monitoring protocols need to include a read-out for the cytolytic efficiency of Ag-specific cells. We propose to combine current immune monitoring techniques in a highly sensitive and reproducible multi-parametric flow cytometry based cytotoxicity assay that has been optimised to require low numbers of Ag-specific T-cells. The possibility of re-analysing those T-cells that have undergone lytic activity is illustrated by the concomitant detection of CD107a upregulation on the surface of degranulated T-cells. To date, the LiveCount Assay provides the only possibility of assessing the ex vivo cytolytic activity of low-frequency Ag-specific cytotoxic T-lymphocytes from patient material.

The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients.

BACKGROUND: Chronic hepatitis C infection is a major cause of end-stage liver disease. Therapy outcome is influenced by 25-OH vitamin D deficiency. To further address this observation, our study investigates the impact of the vitamin D receptor (NR1I1) haplotype and combined effects of plasma vitamin D levels in a well-described cohort of hepatitis C patients. METHODS: A total of 155 chronic hepatitis C patients were recruited from the Swiss Hepatitis C Cohort Study for NR1I1 genotyping and plasma 25-OH vitamin D level measurement. NR1I1 genotype data and combined effects of plasma 25-OH vitamin D level were analysed regarding therapy response (sustained virological response). RESULTS: A strong association was observed between therapy non-response and the NR1I1 CCA (bAt) haplotype consisting of rs1544410 (BsmI) C, rs7975232 (ApaI) C and rs731236 (TaqI) A alleles. Of the HCV patients carrying the CCA haplotype, 50.3% were non-responders (odds ratio [OR] 1.69, 95% CI 1.07, 2.67; P=0.028). A similar association was observed for the combinational CCCCAA genotype (OR 2.94, 95% CI 1.36, 6.37; P=0.007). The combinational CCCCAA genotype was confirmed as an independent risk factor for non-response in multivariate analysis (OR 2.50, 95% CI 1.07, 5.87; P=0.034). Analysing combined effects, a significant impact of low 25-OH vitamin D levels on sustained virological response were only seen in patients with the unfavourable NR1I1 CCA (bAt) haplotype (OR for non-SVR 3.55; 95% CI 1.005, 12.57; P=0.049). CONCLUSIONS: NR1I1 vitamin D receptor polymorphisms influence response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C and exert an additive genetic predisposition to previously described low 25-OH vitamin D serum levels.

Distribution of arm velocity and frequency of arm usage during daily activity: objective outcome evaluation after shoulder surgery.

In clinical settings, functional evaluation of shoulder movement is primarily based on what the patient thinks he/she is able to do rather than what he/she is actually performing. We proposed a new approach for shoulder assessment based on inertial sensors to monitor arm movement in the daily routine. The detection of movement of the humerus relative to the trunk was first validated in a laboratory setting (sensitivity>95%, specificity>97%). Then, 41 control subjects and 21 patients suffering from a rotator cuff tear were evaluated (before and after surgery) using clinical questionnaires and a one-day measurement of arm movement. The quantity of movement was estimated with the movement frequency and its symmetry index (SIFr). The quality of movement was assessed using the Kolmogorov-Smirnov distance (KS) between the cumulative distribution of the arm velocity for controls and the same distribution for each patient. SIFr presented differences between patients and controls at 3 month follow-up (p<0.05) while KS showed differences also after 6 months (p<0.01). SIFr illustrated a change in dominance due to the disorder whereas KS, which appeared independent of the dominance and occupation, showed a change in movement velocity. Both parameters were correlated to clinical scores (R(2) reaching 0.5). This approach provides clinicians with new objective parameters for evaluating the functional ability of the shoulder in daily conditions, which could be useful for outcome assessment after surgery.

Evaluation of a computer model to simulate water table response to subirrigation

The objective of this work was to evaluate the water flow computer model, WATABLE, using experimental field observations on water table management plots from a site located near Hastings, FL, USA. The experimental field had scale drainage systems with provisions for subirrigation with buried microirrigation and conventional seepage irrigation systems. Potato (Solanum tuberosum L.) growing seasons from years 1996 and 1997 were used to simulate the hydrology of the area. Water table levels, precipitation, irrigation and runoff volumes were continuously monitored. The model simulated the water movement from a buried microirrigation line source and the response of the water table to irrigation, precipitation, evapotranspiration, and deep percolation. The model was calibrated and verified by comparing simulated results with experimental field observations. The model performed very well in simulating seasonal runoff, irrigation volumes, and water table levels during crop growth. The two-dimensional model can be used to investigate different irrigation strategies involving water table management control. Applications of the model include optimization of the water table depth for each growth stage, and duration, frequency, and rate of irrigation.

Measurement of the mechanical power of walking by satellite positioning system (GPS).

PURPOSE: This descriptive article illustrates the application of Global Positioning System (GPS) professional receivers in the field of locomotion studies. The technological challenge was to assess the external mechanical work in outdoor walking. METHODS: Five subjects walked five times during 5 min on an athletic track at different imposed stride frequency (from 70-130 steps x min(-1)). A differential GPS system (carrier phase analysis) measured the variation of the position of the trunk at 5 Hz. A portable indirect calorimeter recorded breath-by-breath energy expenditure. RESULTS: For a walking speed of 1.05 +/- 0.11 m x s(-1), the vertical lift of the trunk (43 +/- 14 mm) induced a power of 46.0 +/- 20.4 W. The average speed variation per step (0.15 +/- 0.03 m x s(-1)) produced a kinetic power of 16.9 +/- 7.2 W. As compared with commonly admitted values, the energy exchange (recovery) between the two energy components was low (39.1 +/- 10.0%), which induced an overestimated mechanical power (38.9 +/- 18.3 W or 0.60 W x kg(-1) body mass) and a high net mechanical efficiency (26.9 +/- 5.8%). CONCLUSION: We assumed that the cause of the overestimation was an unwanted oscillation of the GPS antenna. It is concluded that GPS (in phase mode) is now able to record small body movements during human locomotion, and constitutes a promising tool for gait analysis of outdoor unrestrained walking. However, the design of the receiver and the antenna must be adapted to human experiments and a thorough validation study remains to be conducted.