Nonlinear analysis of human physical activity patterns in health and disease.

The reliable and objective assessment of chronic disease state has been and still is a very significant challenge in clinical medicine. An essential feature of human behavior related to the health status, the functional capacity, and the quality of life is the physical activity during daily life. A common way to assess physical activity is to measure the quantity of body movement. Since human activity is controlled by various factors both extrinsic and intrinsic to the body, quantitative parameters only provide a partial assessment and do not allow for a clear distinction between normal and abnormal activity. In this paper, we propose a methodology for the analysis of human activity pattern based on the definition of different physical activity time series with the appropriate analysis methods. The temporal pattern of postures, movements, and transitions between postures was quantified using fractal analysis and symbolic dynamics statistics. The derived nonlinear metrics were able to discriminate patterns of daily activity generated from healthy and chronic pain states.

CTLA-4 controls the thymic development of both conventional and regulatory T cells through modulation of the TCR repertoire.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is of pivotal importance for self-tolerance, with deficiency or unfavorable polymorphisms leading to autoimmune disease. Tolerance to self-antigens is achieved through thymic deletion of highly autoreactive conventional T (Tconv) cells and generation of FoxP3(+) regulatory T (Treg) cells. The main costimulatory molecule, CD28, augments the negative selection of Tconv cells and promotes the generation of FoxP3(+) Treg cells. The role of its antagonistic homolog CTLA-4, however, remains a topic of debate. To address this topic, we investigated the thymic development of T cells in the presence and absence of CTLA-4 in a T-cell receptor (TCR) transgenic mouse model specific for the myelin basic protein peptide Ac1-9. We reveal that CTLA-4 is expressed in the corticomedullary region of the thymus. Its absence alters the response of CD4(+)CD8(-) thymocytes to self-antigen recognition, which affects the quantity of the Treg cells generated and broadens the repertoire of peripheral Tconv cells. T-cell repertoire alteration after deletion of CTLA-4 results from changes in TCR Vα and Jα segment selection as well as CDR3α composition in Tconv and Treg cells. CTLA-4, therefore, regulates the early development of self-reactive T cells in the thymus and plays a key role in central tolerance.

A Variscan pressure-temperature-time path for the N-E Mont Blanc massif

The northeastern portion of the Mont Blanc massif in western Switzerland is predominantly comprised of the granitic rocks of the Mont Blanc intrusive suit, and the Mont Blanc basement gneisses. Within these metamorphic rocks are a variety of sub-economic Fe skarns. The mineral assemblages and fluid inclusions from these rocks have been used to derive age, pressure, temperature and fluid composition constraints for two Variscan events. Metamorphic hornblendes within the assemblages from the basement amphibolites and iron sk:lms have been dated using Ar-40/Ar-39, and indicate that these metamorphic events have a minimum age of approximately 334 Ma. Garnet-hornblende-plagioclase thermobarometry and stable isotope data obtained from the basement amphibolites are consistent with metamorphic temperatures in the range 515 to 580 degrees C, and pressures ranging from 5 to 8 kbar. Garnet-hornblende-magnetite thermobarometry and fluid inclusion studies indicate that the iron skarns formed at slightly lower temperatures, ranging from 400 to 500 degrees C in the presence of saline fluids at formational pressures similar to those experienced by the basement amphibolites. Late Paleozoic minimum uplift rates and geothermal gradients calculated using these data and the presence of Ladinien ichnofossils are on the order of 0.32 mm/year and 20 degrees C/km respectively. These uplift rates and geothermal gradients differ from those obtained from the neighbouring Aiguilles Rouges massif and indicate that these two massifs experienced different metamorphic conditions during the Carboniferous and Permian periods. During the early to late Carboniferous period the relative depths of the two massifs were reversed with the Aiguilles Rouges being initially unroofed at a much greater rate than the Mont Blanc, but experiencing relatively slower uplift rates near the termination of the Variscan orogeny.

Influence of ethanol dose and pigmentation on the incorporation of ethyl glucuronide into rat hair.

Ethyl glucuronide (EtG) is a minor and specific metabolite of ethanol. It is incorporated into growing hair, allowing a retrospective detection of alcohol consumption. However, the suitability of quantitative EtG measurements in hair to determine the quantity of alcohol consumed has not clearly been demonstrated yet. The purpose of this study was to evaluate the influence of ethanol dose and hair pigmentation on the incorporation of EtG into rat hair. Ethanol and EtG kinetics in blood were investigated after a single administration of ethanol. Eighteen rats were divided into four groups receiving 0 (control group), 1, 2, or 3g ethanol/kg body weight. Ethanol was administered on 4 consecutive days per week for 3 weeks by intragastric route. Twenty-eight days after the initial ethanol administration, newly grown hair was shaved. Pigmented and nonpigmented hair were analyzed separately by gas chromatography coupled to tandem mass spectrometry. Blood samples were collected within 12h after the ethanol administration. EtG and ethanol blood levels were measured by liquid chromatography coupled to tandem mass spectrometry and headspace gas chromatography-flame ionization detector, respectively. No statistically significant difference was observed in EtG concentrations between pigmented and nonpigmented hair (Spearman's rho=0.95). Thus, EtG incorporation into rat hair was not affected by hair pigmentation. Higher doses of ethanol resulted in greater blood ethanol area under the curve of concentration versus time (AUC) and in greater blood EtG AUC. A positive correlation was found between blood ethanol AUC and blood EtG AUC (Spearman's rho=0.84). Increased ethanol administration was associated with an increased EtG concentration in hair. Blood ethanol AUC was correlated with EtG concentration in hair (Pearson's r=0.89). EtG concentration in rat hair appeared to reflect the EtG concentration in blood. Ethanol was metabolized at a median rate of 0.22 g/kg/h, and the median elimination half-life of EtG was 1.21 h. This study supports that the bloodstream is likely to display a major role in the hair EtG incorporation.

Exposure to bioaerosols in poultry houses at different stages of fattening; use of real-time PCR for airborne bacterial quantification

Previous studies have demonstrated that poultry house workers are exposed to very high levels of organic dust and consequently have an increased prevalence of adverse respiratory symptoms. However, the influence of the age of broilers on bioaerosol concentrations has not been investigated. To evaluate the evolution of bioaerosol concentration during the fattening period, bioaerosol parameters (inhalable dust, endotoxin and bacteria) were measured in 12 poultry confinement buildings in Switzerland, at three different stages of the birds' growth; samples of air taken from within the breathing zones of individual poultry house employees as they caught the chickens ready to be transported for slaughter were also analysed. Quantitative polymerase chain reaction (Q-PCR) was used to assess the quantity of total airborne bacteria and total airborne Staphylococcus species. Bioaerosol levels increased significantly during the fattening period of the chickens. During the task of catching mature birds, the mean inhalable dust concentration for a worker was 26 +/- 1.9 mg m(-3) and endotoxin concentration was 6198 +/- 2.3 EU m(-3) air, >6-fold higher than the Swiss occupational recommended value (1000 EU m(-3)). The mean exposure level of bird catchers to total bacteria and Staphylococcus species measured by Q-PCR is also very high, respectively, reaching values of 53 (+/-2.6) x 10(7) cells m(-3) air and 62 (+/-1.9) x 10(6) m(-3) air. It was concluded that in the absence of wearing protective breathing apparatus, chicken catchers in Switzerland risk exposure beyond recommended limits for all measured bioaerosol parameters. Moreover, the use of Q-PCR to estimate total and specific numbers of airborne bacteria is a promising tool for evaluating any modifications intended to improve the safety of current working practices

Surgical treatment of lamellar macular hole associated with epimacular membrane.

BACKGROUND:: Although the surgical treatment of full-thickness macular hole is well established, the utility of pars plana vitrectomy in the treatment of lamellar macular hole (LMH) remains less clear. The purpose of the study is to report functional results of surgical treatment of LMH associated with epiretinal membrane. METHODS:: Retrospective chart review of patients undergoing pars plana vitrectomy and peeling of epiretinal membrane and internal limiting membrane, with or without air or gas tamponade, for symptomatic LMH associated with epimacular membrane. RESULTS:: Forty-five eyes of 44 patients were operated for LMH associated with epimacular membrane between May 2000 and July 2009. Pars plana vitrectomy and membrane peeling were combined with air or gas tamponade in 43 of 45 cases. Mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.4 preoperatively to 0.13 postoperatively (P < 0.0001). Improvement in visual acuity ranged from 0 Early Treatment Diabetic Retinopathy Study (ETDRS) lines to 8.9 ETDRS lines (mean, 2.65 ETDRS lines). Visual acuity improved by ≥1 ETDRS line(s) in 40 of 45 eyes (89%) and by ≥2 ETDRS lines in 26 of 45 eyes (58%) after the surgical procedure. No patient lost vision. CONCLUSION:: This small retrospective study suggests that surgical treatment of LMH associated with epimacular membrane may improve visual acuity in symptomatic patients.

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.

Apport du CT-3D dans le diagnostic et le traitement des fractures des plateaux tibiaux [Value of 3D CT in diagnosis and treatment of fractures of the tibial plateau]

A precise classification and an optimal understanding of tibial plateau fractures are the basis of a conservative treatment or adequate surgery. The aim of this prospective study is to determine the contribution of 3D CT to the classification of fractures (comparison with standard X-rays) and as an aid to the surgeon in preoperative planning and surgical reconstruction. Between November 1994 and July 1996, 20 patients presenting 22 tibial plateau fractures were considered in this study. They all underwent surgical treatment. The fractures were classified according to the Müller AO classification. They were all investigated by means of standard X-rays (AP, profile, oblique) and the 3D CT. Analysis of the results has shown the superiority of 3D CT in the planning (easier and more acute), in the classification (more precise), and in the exact assessment of the lesions (quantity of fragments); thereby proving to be of undeniable value of the surgeon.

Routine use of intravascular ultrasound for endovascular aneurysm repair: angiography is not necessary.

INTRODUCTION: to assess the outcome of endovascular aortic aneurysm repair (EVAR) using intravascular ultrasound (IVUS) without angiography. MATERIALS/METHODS: eighty consecutive patients (median age 69 years (range 25-90): male 72 (90%), female 8 (10%)) underwent endovascular aneurysm repair (AAA 68 (85%), TAA 12 (15%)) using either angiography in 31/80 patients (39%) or IVUS in 49/80 patients (61%) in accordance to the surgeons preference. RESULTS: hospital mortality was 2/80 (3%), 1/68 for AAA (2%), 1/12 for TAA (8%), 2/31 for angiography (7%), and 0/49 for IVUS (0.0%: NS). Median quantity of contrast medium was 190 ml (range: 20-350) for angiography versus 0 ml for IVUS (p<0.01). Median X-ray exposure time 24 min (range 9-65 min) versus 8 min (range 0-60 min) for IVUS (p<0.05). No coverage of renal or suprarenal artery orifices occurred in either group. Conversion to open surgery was necessary in 4/80 patients (5%), 1/31 for angiography (3%) and 3/49 patients for IVUS (6%: NS). Early endoleaks were observed in 13/80 patients (16%): 8/31 patients for angiography (26%) versus 5/49 for IVUS (10%: p<0.05): 5/13 endoleaks resolved spontaneously (39%) whereas 8/13 (61%) required additional procedures. CONCLUSIONS: IVUS is a reliable tool for EVAR. In most cases, perprocedural angiography is not necessary.

A framework for hybrid simulations of two-phase flow in porous media

Rough a global coarse problem. Although these techniques are usually employed for problems in which the fine-scale processes are described by Darcy's law, they can also be applied to pore-scale simulations and used as a mathematical framework for hybrid methods that couples a Darcy and pore scales. In this work, we consider a pore-scale description of fine-scale processes. The Navier-Stokes equations are numerically solved in the pore geometry to compute the velocity field and obtain generalized permeabilities. In the case of two-phase flow, the dynamics of the phase interface is described by the volume of fluid method with the continuum surface force model. The MsFV method is employed to construct an algorithm that couples a Darcy macro-scale description with a pore-scale description at the fine scale. The hybrid simulations results presented are in good agreement with the fine-scale reference solutions. As the reconstruction of the fine-scale details can be done adaptively, the presented method offers a flexible framework for hybrid modeling.

Insight in the factors associated with the presence of protective antiviral T-cell response.

T cells play a primordial role in antiviral immunity. Virus-specific T-cell responses can be characterized by a number of independent variables. These include the magnitude of the response; the functional quality of the response, i.e. the types of cytokines secreted after stimulation and the proliferative or lytic potential; the tissue distribution of the T cells; the breadth of the response; and the avidity of the response. All of these together constitute the T-cell response to antigen (Ag) and comprise potential variables that may correlate with antiviral protective immunity. Substantial advances have recently been obtained in the characterization of virus-specific T-cell responses. These studies have shown that the quality (in term of functional profile) rather than the quantity of Ag-specific T cells was associated with protection. Recently, the term polyfunctional has been used to define T-cell responses that, in addition to typical effector functions such as secretion of IFN-g, TNF-a and MIP-1b and cytotoxic activity, comprise distinct T-cell populations, also able to secrete IL-2 and retaining Ag-specific proliferation capacity. The term \only effector" defines T-cell responses/ populations able to secrete cytokines such as IFN-g, TNF-a and MIP-1b and endowed with cytotoxic activity but lacking IL-2 and proliferation capacity. Several models of virus infections (HIV-1, cytomegalovirus [CMV], Epstein Barr virus [EBV], influenza [Flu] and Herpes Simplex virus) exclusively differentiated on the basis of Ag exposure and persistence, were investigated: 1) antigen clearance, 2) protracted Ag exposure and persistence and low Ag levels, 3) Ag persistence and high Ag levels, and 4) acute Ag exposure/re-exposure. These analyses have demonstrated that polyfunctional and not \only effector" T-cell responses were associated with protective antiviral immunity. However, the factors and mechanisms governing the generation of functionally distinct T-cell populations remain to be elucidated. Recently, several studies have shown a major influence of HLA genotype in the evolution of HIV and the progression of HIV-associated disease. In particular, certain HLA-B alleles were most closely associated with non-progressive disease and low viral load or disease and had a dominant involvement on the clinical course of HIV-associated diseases. In this study, we have investigated the relationship between HLA restriction and the functional profile of Tcell responses in order to determine whether HLA-B influenced the generation of polyfunctional CD8 T-cell responses. To be able to address this issue, we studied CD8 T-cell responses against HIV-1, CMV, EBV and Flu in 128 subjects. These analyses enabled us to demonstrate that HLA-Arestricted epitopes were mostly associated with \only effector" T-cell responses while, in contrast, polyfunctional CD8 T-cell responses were predominantly driven by virus epitopes restricted by HLA-B alleles. We then characterized eventual differences in the responsiveness of CD8 T-cell populations restricted by different HLA-A and HLA-B alleles. For this purpose, we investigated the T-cell receptor (TCR) avidity for the cognate epitope of polyfunctional and \only effector" CD8 T-cell populations. Our results indicated that overall virus-specific CD8 T-cell populations recognizing virus epitopes restricted by HLA-B alleles were equipped with lower avidity TCR for the cognate epitopes when compared to those recognizing epitopes restricted by HLA-A alleles. In conclusion, these results provide the rationale for the observed protective role of HLA-B genotypes in HIV-1- infection and new insights into the relationship between TCR avidity and functional profile of virus-specific CD8 Tcells.

Quantification of thermotolerant campylobacter in Swiss water treatment plants, by real-time quantitative polymerase chain reaction

A total of 49 wastewater samples from 23 different wastewater treatment plants (WWTPs) were analyzed using real-time quantitative polymerase chain reaction for the presence and quantity of thermotolerant campylobacters. Thermotolerant campylobacters were detected in 87.5% (21/24) and 64% (16/25) of untreated and treated wastewater samples, respectively. Their concentration was sufficiently high to be quantified in 20.4% (10/49) of the samples. In these samples, the concentration ranged from 68 000 to 2292 000 cells/L in untreated wastewater and from 10 800 to 28 000 cells/L in treated water. We conclude that thermotolerant campylobacters present a health hazard for workers at WWTPs in Switzerland. [Authors]

Magmatic fluids in the Breccia-hosted epithermal Au-Ag deposit of Rosia Montana, Romania

The breccia-hosted epithermal Au-Ag deposit of Rosia Montana is located 7 kin northeast of Abrud, in the northern part of the South Apuseni Mountains, Romania. Estimated total reserves of 214.91 million metric toils (Mt) of ore at 1.46 g/t An and 6.9 g/t Ag (10.1 Moz of An and 47.6 Moz of Ag) make Rosia Montana one of the largest gold deposits in Europe. At this location, Miocene calc-alkaline magmatic and hydrothermal activity was associated with local extensional tectonics within a strike-slip regime related to the indentation of the Adriatic microplate into the European plate during the Carpathian orogenesis. The host rocks of the magmatic complex consist of pre-Mesozoic metamorphosed continental crust covered by Cretaceous turbiditic sediment (flysch). Magmatic activity at Rosia Montana and its surroundings occurred in several pulses and lasted about 7 m.y, Rosia Montana is a breccia-hosted epithermal system related to strong phreatomagmatic activity due to the shallow emplacement of the Montana dacite. The Montana dacite intruded Miocene volcaniclastic material (volcaniclastic breccias) and crops out at Cetate and Carnic Hills. Current mining is focused primarily on the Cetate open pit, which was mapped in detail, leading to the recognition of three distinct breccia bodies: the dacite breccia with a dominantly hydrothermal matrix, the gray polymict breccia with a greater proportion of sand-sized matrix support, and the black polymict breccia, which reached to the surface, contains carbonized tree trunks and has a dominantly barren elastic matrix. The hydrothermal alteration is pervasive. Adularia alteration with a phyllic overprint is ubiquitous; silicification and argillic alteration occur locally. Mineralization consists of quartz, adularia, carbonates (commonly Mn-rich), pyrite, Fe-poor sphalerite, galena, chalcopyrite, tetrahedrite, and native gold and occurs as disseminations, as well as in veins and filling vugs within the Montana dacite and the different breccias. The age of mineralization (12.85 +/- 0.07 Ma) was determined by Ar-40- Ar-39 dating on hydrothermal adularia crystals from vugs in the dacite breccia in the Cetate open pit. Microthermometric measurements of fluid inclusions in quartz phenocrysts from the Montana dacite revealed two fluid types that are absent from the hydrothermal breccia and must have been trapped at depth prior to dacite dome emplacement: brine inclusions (32-55 -wt % NaCl equiv, homogenizing at T-h > 460 degrees C) and intermediate density fluids (4.9-15.6 wt % NaCl equiv, T, between 345 degrees-430 degrees C). Secondary aqueous fluid inclusion assemblages in the phenocrysts have salinities of 0.2 to 2.2 wt percent NaCl equiv and T-h of 200 degrees to 280 degrees C. Fluid inclusion assemblages in hydrothermal quartz from breccias and veins have salinities of 0.2 to 3.4 wt percent NaCl equiv and T-h, from 200 degrees to 270 degrees C. The oxygen isotope composition of several zones of an ore-related epithermal quartz crystal indicate a very constant delta O-18 of 4.5 to 5.0 per mil for the mineralizing fluid, despite significant salinity and temperature variation over time. Following microthermometry, selected fluid inclusion assemblages were analyzed by laser ablation-inductively coupled-plasma mass spectrometry (LA-ICMS). Despite systematic differences in salinity between phenocryst-hosted fluids trapped at depth and fluids from quartz in the epithermal breccias, all fluids have overlapping major and trace cation ratios, including identical Na/K/Rb/Sr/Cs/Ba. Consistent with the constant near-magmatic oxygen isotope composition of the hydrothermal fluids, these data strongly indicate a common magmatic component of these chemically conservative solutes in all fluids. Cu, Pb, Zn, and Mn show variations in concentration relative to the relatively non-reactive alkalis, reflecting the precipitation of sulfide minerals together with An in the epithermal breccia, and possibly of Cu in an inferred subjacent porphyry environment. The magmatic-hydrothermal processes responsible for epithermal Au-Ag mineralization at Rosia Montana are, however, not directly related to the formation of the spatially associated porphyry Cu-Au deposit of Rosia Poieni, which occurred lout 3 m.y. later.

A murine genital-challenge model is a sensitive measure of protective antibodies against human papillomavirus infection.

The available virus-like particle (VLP)-based prophylactic vaccines against specific human papillomavirus (HPV) types afford close to 100% protection against the type-associated lesions and disease. Based on papillomavirus animal models, it is likely that protection against genital lesions in humans is mediated by HPV type-restricted neutralizing antibodies that transudate or exudate at the sites of genital infection. However, a correlate of protection was not established in the clinical trials because few disease cases occurred, and true incident infection could not be reliably distinguished from the emergence or reactivation of prevalent infection. In addition, the current assays for measuring vaccine-induced antibodies, even the gold standard HPV pseudovirion (PsV) in vitro neutralization assay, may not be sensitive enough to measure the minimum level of antibodies needed for protection. Here, we characterize the recently developed model of genital challenge with HPV PsV and determine the minimal amounts of VLP-induced neutralizing antibodies that can afford protection from genital infection in vivo after transfer into recipient mice. Our data show that serum antibody levels >100-fold lower than those detectable by in vitro PsV neutralization assays are sufficient to confer protection against an HPV PsV genital infection in this model. The results clearly demonstrate that, remarkably, the in vivo assay is substantially more sensitive than in vitro PsV neutralization and thus may be better suited for studies to establish correlates of protection.

Loss of mating flight and shift in the pattern of carbohydrate storage in sexuals of ants (Hymenoptera; Formicidae)

In ants, energy for flying is derived from carbohydrates (glycogen and free sugars). The amount of these substrates was compared in sexuals participating or not participating in mating flights. Results show that in participating females (Lasius niger, L. flavus, Myrmica scabrinodis, Formica rufa, F. polyctena, F. lugubris), the amount of carbohydrates, especially glycogen, was higher than in non-participating females (Cataglyphis cursor, Iridomyrmex humilis). Similarly, male C. cursor and I. humilis which fly, exhibit a much higher carbohydrate content than do the non-flying females of these species. Furthermore, the quantity of carbohydrates stored was generally higher in males than in females for each species. These results are discussed with regard to the loss of the nuptial flight by some species of ants.