Development and validation of GLVS (Generic Laparoscopic Video Scoring System), a tool for assessment of laparoscopic skills in gynaecology using videotaped procedures: Are edited videos representative of their full-length version?

Background: Anonymized videotaped endoscopic procedures can be used for the assessment of surgical competence, but a reliable non-procedure-specific scoring system is needed for gynaecology. Objectives: To design and evaluate the validity of the Generic Laparoscopic Video Scoring System (GLVS), a novel tool in the assessment of various gynaecological laparoscopic procedures. Materials and Methods: Seventeen anonymized unedited video recordings of various gynaecological laparoscopic procedures and the 4-minute-long edited versions of the same videos were independently scored by two experts, twice, using GLVS. Main outcome measures: Internal consistency reliability, test-retest, and inter-rater reliability of GLVS. We also compared the scored achieved by edited videos with those of the full-length version of the same videos. Results: The mean score achieved by 4-minute-long edited videos was similar to that of the unedited version (p= 0.13 - 0.19). There was excellent correlation between the pooled scores for edited and unedited versions (intra-class correlation coefficient = 0.86). GLVS had excellent internal consistency reliability (Cronbach's alpha 0.92-0.97). Test-retest and inter-rater reliability were generally better for edited 4-minute-long videos compared to their full-length version. Test-retest reliability for edited videos was excellent for scorer 1 and good for scorer 2 with intra-class correlation coefficient (ICC) of 0.88 and 0.62 respectively. Inter-rater reliability was good for edited videos (ICC=0.64) but poor for full-length versions (ICC= -0.24). Conclusion: GLVS allows for objective surgical skills assessment using anonymized shortened self-edited videos of basic gynaecological laparoscopic procedures. Shortened video clips of procedures seem to be representative of their full-length version for the assessment of surgical skills. What's new?: We devised and undertook a validation study for a novel tool to assess surgical skills using surgical video clips. We believe this addition clearly delineates the unique contributions of our study.

Fire simulator exposure alters the innate epithelial response and inflammatory status in the airways of firefighters.

BACKGROUND: Firefighters are often exposed to high temperatures and by-products of combustion, which can compromise their health. We aimed to evaluate the effect of fire exposure in fire simulators on the airways of firefighters at different time-points. METHODOLOGY: Thirty-seven male firefighters exposed to fire simulators were evaluated in three phases: pre-exposure, at the end of the first week, and 4 weeks after. Pulmonary function by spirometry, nasal mucociliary clearance; peripheral oxygen saturation, inflammatory markers in the nasal lavage and CC16 in the sputum, nasal obstruction, and quality of life (using the questionnaires NOSE and SNOT-22) were assessed. RESULTS: Higher levels of IL-8, IL-10, and exhaled carbon monoxide were found more in phase 2 than in phase 1. Higher CC16 levels and lower peripheral oxygen saturation were observed in phase 3 as compared to phase 1. Lower levels of IL-2 and peripheral oxygen saturation were found in phase 3 than in phase 2. Higher nasal mucociliary clearance, as well as the worst quality of life and nasal obstruction, were observed in phases 2 and 3 as compared to phase 1. CONCLUSIONS: The firefighters’ exposures to high temperatures and by-products of combustion in the fire simulators elicit an inflammatory process in the airways with impairment in the innate epithelial response of the upper airway lining. Furthermore, changes in O2 transport affected the professionals’ quality of life negatively.

Risks factors and timing of genital human papillomavirus (HPV) infection in female stem cell transplant survivors: a longitudinal study.

This longitudinal single-center study describes the timing and risk factors for genital human papillomavirus (HPV) disease in women after allogeneic hematopoietic cell transplantation (HCT). Between 1994 and 2014, 109 females underwent HCT of whom 82 surviving transplant for >1 year had regular, comprehensive genital tract assessment and treatment of HPV disease. The cumulative proportions of any genital HPV infection at 1, 3, 5, 10 and 20 years were 4.8%, 14.9%, 28.1%, 36.7% and 40.9%, respectively. Demographic, disease-related factors, chronic GvHD (cGvHD) and its treatment were analyzed for their association with persistent, multifocal or severe genital HPV disease. Pre-transplant HPV disease was strongly associated with any posttransplant HPV (odds ratio (OR)=6.5, 95% confidence interval (CI)=1.65-25.85, P=0.008). Having either extensive or genital cGvHD was associated with increased risk of any HPV disease (OR=5.7, 95% CI=1.90-17.16, P=0.002) and a higher risk for severe genital dysplasia (CIN II-III/VIN II-III; OR=13.1, 95% CI=1.59-108.26, P=0.017), but no one developed HPV-related genital cancer. Persistent, multifocal or severe HPV disease occurred more frequently than in healthy populations. Women with extensive cGvHD, genital cGvHD or pre-transplant HPV are at greatest risk for post-transplant HPV disease. Early initiation of annual screening, comprehensive genital tract assessment and active management are cornerstones of their gynecology care.

Spatial mapping of juxtacrine axo-glial interactions identifies novel molecules in peripheral myelination.

Cell-cell interactions promote juxtacrine signals in specific subcellular domains, which are difficult to capture in the complexity of the nervous system. For example, contact between axons and Schwann cells triggers signals required for radial sorting and myelination. Failure in this interaction causes dysmyelination and axonal degeneration. Despite its importance, few molecules at the axo-glial surface are known. To identify novel molecules in axo-glial interactions, we modified the 'pseudopodia' sub-fractionation system and isolated the projections that glia extend when they receive juxtacrine signals from axons. By proteomics we identified the signalling networks present at the glial-leading edge, and novel proteins, including members of the Prohibitin family. Glial-specific deletion of Prohibitin-2 in mice impairs axo-glial interactions and myelination. We thus validate a novel method to model morphogenesis and juxtacrine signalling, provide insights into the molecular organization of the axo-glial contact, and identify a novel class of molecules in myelination.

Early markers of Fabry disease revealed by proteomics.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal hydrolase α-galactosidase A (α-GalA) that leads to the intra-lysosomal accumulation of globotriaosylceramide (Gb3) in various organ systems. As a consequence, a multisystems disorder develops, culminating in stroke, progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though the monitoring of treatment is hindered by a lack of surrogate markers of response. Remarkably, due to the high heterogeneity of the Fabry phenotype, both diagnostic testing and treatment decisions are more challenging in females than in males; thus, reliable biomarkers for Fabry disease are needed, particularly for female patients. Here, we use a proteomic approach for the identification of disease-associated markers that can be used for the early diagnosis of FD as well as for monitoring the effectiveness of ERT. Our data show that the urinary proteome of Fabry naïve patients is different from that of normal subjects. In addition, biological pathways mainly affected by FD are related to immune response, inflammation, and energetic metabolism. In particular, the up-regulation of uromodulin, prostaglandin H2 d-isomerase and prosaposin in the urine of FD patients was demonstrated; these proteins might be involved in kidney damage at the tubular level, inflammation and immune response. Furthermore, comparing the expression of these proteins in Fabry patients before and after ERT treatment, a decrease of their concentration was observed, thus demonstrating the correlation between the identified markers and the effectiveness of the pharmacological treatment.

B-1 cells and concomitant immunity in Ehrlich tumour progression.

Concomitant immunity is a phenomenon in which a tumour-bearing host is resistant to the growth of an implanted secondary tumour. Metastases are considered to be secondary tumours that develop spontaneously during primary tumour growth, suggesting the involvement of concomitant immunity in controlling the rise of metastases. It has been demonstrated that B-1 cells, a subset of B-lymphocytes found predominantly in pleural and peritoneal cavities, not only increase the metastatic development of murine melanoma B16F10, but also are capable of differentiating into mononuclear phagocytes, modulating inflammatory responses in wound healing, in oral tolerance and in Paracoccidiose brasiliensis infections. Here, we studied B-1 cells' participation in concomitant immunity during Ehrlich tumour progression. Our results show that B-1 cells obtained from BALB/c mice previously injected with Ehrlich tumour in the footpad were able to protect BALB/c and BALB/Xid mice against Ehrlich tumour challenge. In addition, it was demonstrated that BALB/Xid show faster tumour growth and have lost concomitant immunity, and that this state can be partially restored by reconstituting these animals with B-1 cells. However, further researches are required to establish the mechanism involving B-1 cells in Ehrlich tumour growth.

Search for a dark matter annihilation signal from the galactic center halo with H.E.S.S.

A search for a very-high-energy (VHE; ≥100 GeV) γ-ray signal from self-annihilating particle dark matter (DM) is performed towards a region of projected distance r∼45-150 pc from the Galactic center. The background-subtracted γ-ray spectrum measured with the High Energy Stereoscopic System (H.E.S.S.) γ-ray instrument in the energy range between 300 GeV and 30 TeV shows no hint of a residual γ-ray flux. Assuming conventional Navarro-Frenk-White and Einasto density profiles, limits are derived on the velocity-weighted annihilation cross section (σv) as a function of the DM particle mass. These are among the best reported so far for this energy range and in particular differ only little between the chosen density profile parametrizations. In particular, for the DM particle mass of ∼1 TeV, values for (σv) above 3×10(-25) cm(3) s(-1) are excluded for the Einasto density profile.

Immune responses induced by Pelargonium sidoides extract in serum and nasal mucosa of athletes after exhaustive exercise: modulation of secretory IgA, IL-6 and IL-15.

The evidence that exhaustive exercise may compromise the immune response is mainly confirmed by upper respiratory tract infections which are probably related to the decrease in secretory immunoglobulin A in the upper airway mucosa and/or profile changes of systemic cytokines as well as local cytokines of the upper respiratory tract. An extract from Pelargonium sidoides roots is currently used to treat infections in the upper airways. The aim of the present study was to evaluate the action of this herbal medicine on the immune response of athletes submitted to an intense running session by analyzing the production of immunoglobulin A in their saliva and of cytokines both locally and systemically, using a placebo as control. The results show that Pelargonium sidoides extract modulates the production of secretory immunoglobulin A in saliva, both interleukin-15 and interleukin-6 in serum, and interleukin-15 in the nasal mucosa. Secretory immunoglobulin A levels were increased, while levels of IL-15 and IL-6 were decreased. Based on this evidence, we suggest that this herbal medicine can exert a strong modulating influence on the immune response associated with the upper airway mucosa in athletes submitted to intense physical activity.

B-1 cells modulate the kinetics of wound-healing process in mice.

Wound healing is a complex phenomenon whose mechanisms are not fully understood. Although inflammatory cells are recruited to the site of the lesion there are no reports concerning the participation of B lymphocytes in tissue repair. As demonstrated in our laboratory, B-1 cells migrate to a non-specific inflammatory focus and differentiate into a phagocyte. It has been reported that BALB/Xid mice are deficient in B-1 cells. Using this model, here we report that BALB/Xid mice have an increased inflammatory response, a delayed wound-healing process, a prominent neutrophilic infiltration of the lesion, and an increased neovascularization of the lesion as compared with BALB/c and BALB/Xid reconstituted with B-1 cells. The infiltration of B-1 cells into the wound was demonstrated. As B-1 cells secret and use interleukin 10 (IL-10) as an autocrine growth factor, the possible participation of this interleukin in the kinetics of wound healing was investigated. Results show that C57/BL6 IL-10 KO mice had an increased inflammatory response when compared with C57/BL6 and C57/BL6 IL-10 KO mice reconstituted with B-1 cells, thus suggesting that the observed effects of B-1 cells in the healing process is mediated by this interleukin. However, the mechanisms by which IL-10 influence these phenomena remain to be uncovered.

Detection of gamma rays from a starburst galaxy.

Starburst galaxies exhibit in their central regions a highly increased rate of supernovae, the remnants of which are thought to accelerate energetic cosmic rays up to energies of approximately 10(15) electron volts. We report the detection of gamma rays--tracers of such cosmic rays--from the starburst galaxy NGC 253 using the High Energy Stereoscopic System (H.E.S.S.) array of imaging atmospheric Cherenkov telescopes. The gamma-ray flux above 220 billion electron volts is F = (5.5 +/- 1.0(stat) +/- 2.8(sys)) x 10(-13) cm(-2) s(-1), implying a cosmic-ray density about three orders of magnitude larger than that in the center of the Milky Way. The fraction of cosmic-ray energy channeled into gamma rays in this starburst environment is five times as large as that in our Galaxy.

Limits on an energy dependence of the speed of light from a flare of the active galaxy PKS 2155-304.

In the past few decades, several models have predicted an energy dependence of the speed of light in the context of quantum gravity. For cosmological sources such as active galaxies, this minuscule effect can add up to measurable photon-energy dependent time lags. In this Letter a search for such time lags during the High Energy Stereoscopic System observations of the exceptional very high energy flare of the active galaxy PKS 2155-304 on 28 July 2006 is presented. Since no significant time lag is found, lower limits on the energy scale of speed of light modifications are derived.

Energy spectrum of cosmic-ray electrons at TeV energies.

The very large collection area of ground-based gamma-ray telescopes gives them a substantial advantage over balloon or satellite based instruments in the detection of very-high-energy (>600 GeV) cosmic-ray electrons. Here we present the electron spectrum derived from data taken with the High Energy Stereoscopic System (H.E.S.S.) of imaging atmospheric Cherenkov telescopes. In this measurement, the first of this type, we are able to extend the measurement of the electron spectrum beyond the range accessible to direct measurements. We find evidence for a substantial steepening in the energy spectrum above 600 GeV compared to lower energies.

HESS observations of the galactic center region and their possible dark matter interpretation.

The detection of gamma rays from the source HESS J1745-290 in the Galactic Center (GC) region with the High Energy Spectroscopic System (HESS) array of Cherenkov telescopes in 2004 is presented. After subtraction of the diffuse gamma-ray emission from the GC ridge, the source is compatible with a point source with spatial extent less than 1.2;{'}(stat) (95% C.L.). The measured energy spectrum above 160 GeV is compatible with a power law with photon index of 2.25+/-0.04(stat)+/-0.10(syst) and no significant flux variation is detected. It is finally found that the bulk of the very high energy emission must have non-dark-matter origin.

Fast variability of tera-electron volt gamma rays from the radio galaxy M87.

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.

A low level of extragalactic background light as revealed by gamma-rays from blazars.

The diffuse extragalactic background light consists of the sum of the starlight emitted by galaxies through the history of the Universe, and it could also have an important contribution from the 'first stars', which may have formed before galaxy formation began. Direct measurements are difficult and not yet conclusive, owing to the large uncertainties caused by the bright foreground emission associated with zodiacal light. An alternative approach is to study the absorption features imprinted on the gamma-ray spectra of distant extragalactic objects by interactions of those photons with the background light photons. Here we report the discovery of gamma-ray emission from the blazars H 2356 - 309 and 1ES 1101 - 232, at redshifts z = 0.165 and z = 0.186, respectively. Their unexpectedly hard spectra provide an upper limit on the background light at optical/near-infrared wavelengths that appears to be very close to the lower limit given by the integrated light of resolved galaxies. The background flux at these wavelengths accordingly seems to be strongly dominated by the direct starlight from galaxies, thus excluding a large contribution from other sources-in particular from the first stars formed. This result also indicates that intergalactic space is more transparent to gamma-rays than previously thought.

Discovery of very-high-energy gamma-rays from the Galactic Centre ridge.

The source of Galactic cosmic rays (with energies up to 10(15) eV) remains unclear, although it is widely believed that they originate in the shock waves of expanding supernova remnants. At present the best way to investigate their acceleration and propagation is by observing the gamma-rays produced when cosmic rays interact with interstellar gas. Here we report observations of an extended region of very-high-energy (> 10(11) eV) gamma-ray emission correlated spatially with a complex of giant molecular clouds in the central 200 parsecs of the Milky Way. The hardness of the gamma-ray spectrum and the conditions in those molecular clouds indicate that the cosmic rays giving rise to the gamma-rays are likely to be protons and nuclei rather than electrons. The energy associated with the cosmic rays could have come from a single supernova explosion around 10(4) years ago.

Discovery of very high energy gamma rays associated with an x-ray binary.

X-ray binaries are composed of a normal star in orbit around a neutron star or stellar-mass black hole. Radio and x-ray observations have led to the presumption that some x-ray binaries called microquasars behave as scaled-down active galactic nuclei. Microquasars have resolved radio emission that is thought to arise from a relativistic outflow akin to active galactic nuclei jets, in which particles can be accelerated to large energies. Very high energy gamma-rays produced by the interactions of these particles have been observed from several active galactic nuclei. Using the High Energy Stereoscopic System, we find evidence for gamma-ray emission of >100 gigaelectron volts from a candidate microquasar, LS 5039, showing that particles are also accelerated to very high energies in these systems.

A new population of very high energy gamma-ray sources in the Milky Way.

Very high energy gamma-rays probe the long-standing mystery of the origin of cosmic rays. Produced in the interactions of accelerated particles in astrophysical objects, they can be used to image cosmic particle accelerators. A first sensitive survey of the inner part of the Milky Way with the High Energy Stereoscopic System (HESS) reveals a population of eight previously unknown firmly detected sources of very high energy gamma-rays. At least two have no known radio or x-ray counterpart and may be representative of a new class of "dark" nucleonic cosmic ray sources.

High-energy particle acceleration in the shell of a supernova remnant.

A significant fraction of the energy density of the interstellar medium is in the form of high-energy charged particles (cosmic rays). The origin of these particles remains uncertain. Although it is generally accepted that the only sources capable of supplying the energy required to accelerate the bulk of Galactic cosmic rays are supernova explosions, and even though the mechanism of particle acceleration in expanding supernova remnant (SNR) shocks is thought to be well understood theoretically, unequivocal evidence for the production of high-energy particles in supernova shells has proven remarkably hard to find. Here we report on observations of the SNR RX J1713.7 - 3946 (G347.3 - 0.5), which was discovered by ROSAT in the X-ray spectrum and later claimed as a source of high-energy gamma-rays of TeV energies (1 TeV = 10(12) eV). We present a TeV gamma-ray image of the SNR: the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there. The energy spectrum indicates efficient acceleration of charged particles to energies beyond 100 TeV, consistent with current ideas of particle acceleration in young SNR shocks.