New Insights for the Renewed Phytoplankton-Bacteria Coupling Concept: the Role of the Trophic Web.

It is widely accepted that in many aquatic ecosystems bacterioplankton is dependent on and regulated by organic carbon supplied by phytoplankton, leading to coupled algae-bacteria relationship. In this study, an in-depth analysis of this relationship has been carried out by combining two approaches: (i) a correlation analyses between heterotrophic bacterial production (BP) vs. primary production (PP) or algal excretion of organic carbon (EOC), (ii) the balance between bacterial carbon demands (BCD) and the supply of C as EOC, measured as BCD:EOC ratio. During the study period (2013-2016), the algae-bacteria relationship was constantly changing from a coupling in 2013, uncoupling in 2014 and 2015, and an incipient return to coupling (in 2016). Our results show that top-down control (bacterivory) by algal mixotrophy acts as a decoupling force since it provides a fresh C source different to algal EOC to satisfy bacterial carbon demands. Notably, a relationship between the BCD:EOC ratio and the ecosystem metabolic balance (Primary production (PP): respiration (R)) was found, suggesting that PP:R may be a good predictor of the algae-bacteria coupling. This analysis, including the comparison between basal and potential ecosystem metabolic balance, can be a tool to improve knowledge on the interaction between both biotics compartments, which the traditional analyses on coupling may not capture.

Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study).

OBJECTIVES: We evaluated whether maintenance therapy with atazanavir/ritonavir plus lamivudine (ATV/r + 3TC) was non-inferior to ATV/r plus two nucleosides (ATV/r + 2NUCs) at 96 weeks of follow-up. METHODS: SALT is a multicentre, open-label, non-inferiority clinical trial in HIV-1-infected virologically suppressed patients. Hepatitis B virus surface antigen-negative subjects with no previous treatment failure/resistance mutations and HIV-1-RNA <50 copies/mL for ≥6 months were randomized (1 : 1) to ATV/r + 3TC or ATV/r + 2NUCs. The primary endpoint was HIV-1-RNA <50 copies/mL in the PP population. Non-inferiority was demonstrated if the lower bound of the 95% CI for the difference was not below -12%. RESULTS: Some 286 patients were analysed. At week 96, 74.4% had HIV-1-RNA <50 copies/mL in the ATV/r + 3TC arm versus 73.9% in the ATV/r + 2NUCs arm (95% CI for the difference, -9.9%-11.0%). In both groups, similar values were observed for patients with confirmed virological failure in ATV/r + 3TC versus ATV/r + 2NUCs (9 versus 5), death (1 versus 0), discontinuation due to ART-related toxicity (7 versus 11), withdrawal from the study (7 versus 9) and loss to follow-up (6 versus 6). One patient taking ATV/r + 2NUCs developed resistance mutations (M184V and L63P). Similar values were obtained for change in mean CD4 count [19 versus 18 cells/mm3 (95% CI for the difference, -49.3-50.7), grade 3-4 adverse events (70.7% versus 70.2%) and changes in the global deficit score, -0.3 (95% CI, -0.5 to -0.1) for ATV/r + 3TC, versus -0.2 (95% CI, -0.4 to -0.1) for ATV/r + 2NUCs]. CONCLUSIONS: The long-term results of switching to ATV/r + 3TC show that this strategy is effective, safe and non-inferior to ATV + 2NUCs in virologically suppressed HIV-infected patients.

Very low level viraemia and risk of virological failure in treated HIV-1-infected patients.

OBJECTIVES: The aim of the study was to investigate whether very low level viraemia (VLLV) (20-50 HIV-1 RNA copies/mL) was associated with increased risk of virological failure (VF) as compared with persistent full suppression (< 20 copies/mL). METHODS: From the VACH Cohort database, we selected those patients who started antiretroviral therapy (ART) after January 1997 and who achieved effective viral suppression [two consecutive viral loads (VLs) < 50 copies/mL] followed by full suppression (at least one VL <20 copies/mL). We carried out survival analyses to investigate whether the occurrence of VLLV rather than maintaining full suppression at < 20 copies/mL was associated with virological failure (two consecutive VLs > 200 copies/mL or one VL > 200 copies/mL followed by a change of ART regimen, administrative censoring or loss to follow-up), adjusted for nadir CD4 cell count, sex, age, ethnicity, transmission group, type of ART and time on effective suppression at < 50 copies/mL. RESULTS: Of 21 480 patients who started ART, 13 674 (63.7%) achieved effective suppression at < 50 copies/mL, of whom 4289 (31.4%) further achieved full suppression at < 20 copies/mL after May 2009. A total of 2623 patients (61.1%) remained fully suppressed thereafter, while 1666 had one or more episodes of VL detection > 20 copies/mL (excluding virological failure). A total of 824 patients had VLLV after suppression at < 20 copies/mL. VLLV was not associated with virological failure as compared with persistent full suppression [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.44-1.00], independently of the number of blips recorded (from one to 18). CONCLUSIONS: In our population of HIV-infected patients on ART who achieved viral suppression at < 20 copies/mL, the risk of virological failure was no different for patients who remained fully suppressed compared with those who experienced subsequent episodes of VLLV.

The diversity of the human hair colour assessed by visual scales and instrumental measurements. A worldwide survey.

OBJECTIVES: To study (i) the diversity of the natural colour of the human hair through both visual assessment of hair tone levels and colorimetric measurements of hair strands collected from 2057 human male and female volunteers, from 23 regions of the world and (ii) the correlation between visual assessments and colorimetric measurements. METHODS: Hair strands were analysed by a spectrocolorimeter under the L*, a*, b* referential system and scored in vivo by experts before sampling, through standardized visual reference scales based on a 1-10 range. RESULTS: Results show that from a typological aspect, black or dark brown hairs largely predominate among studied ethnic groups, whereas Caucasian or derived populations exhibit the widest palette of medium to fair shades, partly explaining some past interbreeding among populations. Instrumental measurements clearly confirm that a given colour of a pigmented hair, at the exclusion of red hairs, is mostly governed by two components, L* and b*, from the L*, a*, b* reference system. CONCLUSION: The comparisons between visual assessments and instrumental data show that these appear closely linked. Darker hairs show close or subtle variations in L*, a*, b* parameters, making their individual colour differentiation calling for technical improvements in colorimetric measurements. The latter are likely governed by other physical factors such as shape, diameter and shine.

Percentage of ubiquitinated spermatozoa does not correlate with fertilizing capacity of thawed bovine semen.

In the spermatozoa of some species, the ubiquitin-proteasome system detects altered proteins and tags them for elimination by the proteasome. In some species' ejaculates, a high proportion of ubiquitinated spermatozoa (i.e. those having ubiquitin bound to the altered or damaged membrane proteins) has been related to infertility. The aim of this study was to assess whether the percentage of ubiquitinated spermatozoa relates to fertility of dairy bulls and whether ubiquitination increases during protein remodelling that occurs during in vitro spermatic capacitation. Thirty-two frozen semen straws from four high-fertility (ReproMax(®) ) and four normal-fertility (Normal) Holstein-Friesian sires were evaluated. Ubiquitinated and capacitated spermatozoa were quantified by sperm ubiquitin tag immunoassay and chlortetracycline stain, respectively. Fertilizing capacity of sires was assessed by in vitro fertilization. No differences were found between Normal and ReproMax(®) sires with regard to the observed percentage of ubiquitinated spermatozoa (42.97 ± 3.69% and 49.68 ± 9.27%, respectively; p > 0.05). Additionally, no differences were found in the percentage of ubiquitinated spermatozoa as a consequence of spermatic capacitation in either Normal (42.97 ± 3.69% before capacitation vs 44.67 ± 7.5% after; p > 0.05) or ReproMax(®) sires (49.68 ± 9.27% before vs 45.05 ± 7.51% after; p > 0.05). The percentage of ubiquitinated spermatozoa in a thawed sperm samples did not correlate with its in vitro fertilizing capacity; thus, this assay does not prove useful to detect in vivo fertility differences between sires. Additionally, protein degradation occurring during remodelling of the spermatozoon plasma membrane during the capacitation process does not seem to involve the ubiquitin-proteasome system.

Synthesis, photo- and thermo-luminescent properties of Mg2P2O7:Tm3+ phosphors.

In this work, both undoped and Thulium (Tm3+) doped (0.3-10 mol%) magnesium pyrophosphate (Mg2P2O7) powders were synthesized by the solvent evaporation method to study their photo-and thermoluminescent properties. Two crystalline phases were observed in the powders by X-Ray diffraction (XRD), the main phase being Mg2P2O7 and the second one thulium phosphate (TmPO4). The superficial morphology was analyzed by scanning electron microscopy (SEM), which revealed that the powders are agglomerates with an undefined form and grains with non-uniform size distribution. The photoluminescence (PL) emission spectra of Tm3+ doped powders show the 1D2 → 3F4 transition, associated with Tm3+ ions, at 452 and 458 nm. The thermoluminescence (TL) properties were analyzed in the undoped and Tm3+ doped powders exposed to 90Sr beta source. The TL glow curve of Tm3+ doped powders exhibits three maxima at about ⁓64-66 °C, ⁓198-202 °C, and ⁓301 °C. The TL dose-response is sub-linear from 0.11 to 0.54 Gy, linear between 0.79 and 24.95 Gy, and supra-linear from 34.99 to 599.95 Gy. Acceptable repeatability with a coefficient of variation of ∼1% was obtained after ten cycles of irradiation and readout. At 63 d of storage, the powders show fading of 30%, and at 1.6 years (585 d), the integrated TL intensity decays by 47%. The kinetic parameters of activation energy and frequency factor were evaluated using the Initial Rise, Booth, Bohun, and Porfianovitch (BBP) and Hoogenstraaten methods and Glow Curve Deconvolution with a general order kinetic model.

Thermoluminescence properties and identification of irradiated cocoa beans during long-term storage.

This work reports on the thermoluminescence (TL) properties and detection of contaminating minerals isolated from Mexican cocoa beans irradiated with gamma radiation and stored for 4 years. Contaminating minerals isolated from cocoa beans consisting of quartz, diopside, plagioclase, albite, and iron oxide with irregular and rectangular grains and average length of 135 µm. Cocoa beans are detected as irradiated even after 4 years of storage using the shape and maximum temperature of the TL glow curve of contaminating minerals. The TL properties of dose-response, and fading of minerals were also analysed. The TL dose-response is linear from 5 to 100 Gy, supra-linear between 250 and 1000 Gy, and sub-linear above 1500 Gy. Based on the TL1/TL2 ratio the minerals are identified as irradiated from 250 Gy to 4500 Gy in the dose-response test and after different storage times in the darkness at room temperature. A continuum trap distribution can be associated with the TL glow curve of minerals using the Tm-Tstop method. First order kinetic peaks were used in the Glow Curve Deconvolution of natural and irradiated (1 and 10 kGy) TL curves.

Greying of the human hair: a worldwide survey, revisiting the '50' rule of thumb.

BACKGROUND: While numerous papers have reported on the biological mechanisms of human hair pigmentation and greying, epidemiological descriptions of both natural hair colour and the greying process, worldwide, remain scarce. OBJECTIVES: To assess hair colour and greying in a large world sample of human subjects, and to revisit the validity of the 50/50/50 rule of thumb, which states that 'at age 50 years, 50% of the population has at least 50% grey hair'. METHODS: The natural hair colour of 4192 healthy male and female volunteers was assessed using a sensorial expert evaluation through the comparison of each volunteer's hair with standard swatches. Hair colour was studied according to age, gender and ethnic or geographical origin. RESULTS: Overall we observed that between 45 and 65 years of age, 74% of people were affected by grey hair with a mean intensity of 27%. Men harboured significantly more grey hair than women. Both age at onset and rate of greying with age appeared to be clearly linked to ethnic/geographical origin. Subjects of Asian and African descent showed less grey hair than those of caucasian origin, at comparable ages, confirming previously reported data. CONCLUSIONS: Calculating the percentage of people showing at least 50% grey hair coverage at age 50 years leads to a global range of 6-23%, according to ethnic/geographical origin and natural hair colour: well below that expressed by the '50' rule of thumb.

Age-dependent changes in eumelanin composition in hairs of various ethnic origins.

Hair pigmentation is one of the most conspicuous phenotypes of humans. From a chemical point of view, however, data remain scarce regarding human hair pigmentation characteristics. To determine melanin content and composition in human eumelanic hair from individuals of different ethnic origins and at different ages, we collected hair from 56 subjects with eumelanic hair from each group of African-American, East Asian, and Caucasian origin. The 56 subjects consist of 14, seven each of males and females, each from four age classes of younger than 11, between 12 and 19, between 20 and 45, and older than 46. We analysed hair colour scale, total melanin value, and contents of pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3-dicarboxylic acid (PDCA). We measured age-dependent increases in the relative quantity of eumelanin in pigmented human hairs in the three ethnic groups. Regarding melanin composition, we observed an increase in the PDCA/PTCA ratio with age in African-American and Caucasian hairs until approaching the quite constant level of the ratio in East Asian hairs in the elderly individuals. Our results evidence differences in the content and composition of eumelanin in human hair among African-American, Caucasian and East Asian individuals. Furthermore, we show evidence of age-dependent changes in the quantity and quality of eumelanin in pigmented human hairs. In particular, the age-dependent modification of the PDCA/PTCA ratio, a marker for 5,6-dihydroxyindole units in eumelanin, suggests a chronological evolution of hair follicle melanocyte phenotype (e.g. decrease in dopachrome tautomerase expression).

Continuous-wave optically stimulated luminescence properties of Guajillo chilli polyminerals exposed to gamma radiation.

In this investigation, the Continuous-Wave Optically Stimulated Luminescence (CW-OSL) properties of polyminerals extracted from Mexican and Peruvian Guajillo chilli were studied using a source of cesium-137 (Cs-137) gamma radiation. The Guajillo chilli polyminerals were stimulated with blue light for 120 s, and their luminescence was detected in the UV region. The General Order Kinetics (GOK) deconvolution analysis of the CW-OSL curves was carried out using three individual components. The CW-OSL dose response from 10 to 5000 Gy was analysed in Guajillo chilli polyminerals. After different storage periods, the polyminerals show an increase in the CW-OSL intensity. A strong and moderate effect of the sunlight (60 min) and artificial (6 h) light is observed on the CW-OSL response. Therefore, the CW-OSL properties of polyminerals could be used in the identification of Mexican and Peruvian Guajillo chilli exposed to Cs-137 gamma radiation.

Late initiation of HAART among HIV-infected patients in Spain is frequent and related to a higher rate of virological failure but not to immigrant status.

PURPOSE: To determine whether immigrant status is associated with late initiation of highly active antiretroviral treatment (HAART) and/or poor response to antiretrovirals. METHODS: GESIDA 5808 is a multicenter, retrospective cohort study (inclusion period January 2005 through December 2006) of treatment-naïve patients initiating HAART that compares HIV-infected patients who are immigrants with Spanish-born patients. A late starter (LS) was defined as any patient starting HAART with a CD4+ lymphocyte count <200 cells/µL and/or diagnosis of an AIDS-defining illness before or at the start of therapy. The primary endpoint was time to treatment failure (TTF), defined as virological failure (VF), death, opportunistic infection, treatment discontinuation/switch (D/S), or missing patient. Secondary endpoints were time to treatment failure as observed data (TTO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/S not due to VF). RESULTS: LS accounted for 56% of the patients. Lower educational and socioeconomic level and intravenous drug use (IVDU) were associated with categorization as LS, but immigrant status was not. Cox regression analysis (hazard ratio [HR]; 95% CI) between LS and non-LS patients showed no differences in TTF (0.97; 0.78-1.20) or TTO (1.18; 0.88-1.58), although it did reveal a difference in TVF (1.97; 1.18-3.29). CD4+ lymphocyte recovery was equivalent for both LS and non-LS patients (159 vs 173). CONCLUSIONS: In our cohort, immigrant status was not shown to be related to late initiation of HAART. Although LS patients did not have a longer TTF for any reason, TVF was significantly shorter. Despite universal free access to HAART in Spain, measures to ensure early diagnosis and treatment of HIV infection are necessary.

Improvements in beam's eye view fiducial tracking using a novel multilayer imager.

Purpose.Electronic portal image devices (EPIDs) have been investigated previously for beams-eye view (BEV) applications such as tumor tracking but are limited by low contrast-to-noise ratio and detective quantum efficiency. A novel multilayer imager (MLI), consisting of four stacked flat-panels was used to measure improvements in fiducial tracking during liver stereotactic body radiation therapy (SBRT) procedures compared to a single layer EPID.Methods.The prototype MLI was installed on a clinical TrueBeam linac in place of the conventional DMI single-layer EPID. The panel was extended during volumetric modulated arc therapy SBRT treatments in order to passively acquire data during therapy. Images were acquired for six patients receiving SBRT to liver metastases over two fractions each, one with the MLI using all 4 layers and one with the MLI using the top layer only, representing a standard EPID. The acquired frames were processed by a previously published tracking algorithm modified to identify implanted radiopaque fiducials. Truth data was determined using respiratory traces combined with partial manual tracking. Results for 4- and 1-layer mode were compared against truth data for tracking accuracy and efficiency. Tracking and noise improvements as a function of gantry angle were determined.Results. Tracking efficiency with 4-layers improved to 82.8% versus 58.4% for the 1-layer mode, a relative improvement of 41.7%. Fiducial tracking with 1-layer returned a root mean square error (RMSE) of 2.1 mm compared to 4-layer RMSE of 1.5 mm, a statistically significant (p < 0.001) improvement of 0.6 mm. The reduction in noise correlated with an increase in successfully tracked frames (r = 0.913) and with increased tracking accuracy (0.927).Conclusion. Increases in MV photon detection efficiency by utilization of a MLI results in improved fiducial tracking for liver SBRT treatments. Future clinical applications utilizing BEV imaging may be enhanced by including similar noise reduction strategies.

The -383A>C TNFRI polymorphism is associated with soluble levels and clinical activity in rheumatoid arthritis.

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in inflammation, and it has been directly implicated in the pathogenesis of rheumatoid arthritis (RA). TNF-alpha activity is mediated through TNFRI and TNFRII cell surface receptors, which act as physiological attenuators of TNF-alpha activity. We recruited 190 RA patients and 190 healthy subjects (HS) in order to associate the -383A>C TNFRI polymorphism with sTNFRI levels and DAS28 score in RA. In results, sTNFRI levels were higher in RA patients than HS (P = 0.04). The -383A>C TNFRI polymorphism did not show significant differences in both studied groups. However, in the RA group the sTNFRI levels were significantly elevated (P = 0.004) in A/A genotype carriers. In addition, the A/A genotype carriers had the higher DAS28 score than A/C genotype (P = 0.02). These data suggest that -383A>C TNFRI polymorphism is not a susceptibility marker in RA, whereas the increased levels of sTNFRI could reflect the clinical activity in RA patients.

Automated MV markerless tumor tracking for VMAT.

Tumor tracking during radiotherapy treatment can improve dose accuracy, conformity and sparing of healthy tissue. Many methods have been introduced to tackle this challenge utilizing multiple imaging modalities, including a template matching based approach using the megavoltage (MV) on-board portal imager demonstrated on 3D conformal treatments. However, the complexity of treatments is evolving with the introduction of VMAT and IMRT, and successful motion management is becoming more important due to a trend towards hypofractionation. We have developed a markerless lung tumor tracking algorithm, utilizing the electronic portal imager (EPID) of the treatment machine. The algorithm has been specifically adapted to track during complex treatment deliveries with gantry and MLC motion. The core of the algorithm is an adaptive template matching method that relies on template stability metrics and local relative orientations to perform multiple feature tracking simultaneously. Only a single image is required to initialize the algorithm and features are automatically added, modified or removed in response to the input images. This algorithm was evaluated against images collected during VMAT arcs of a dynamic thorax phantom. Dynamic phantom images were collected during radiation delivery for multiple lung SBRT breathing traces and an example patient data set. The tracking error was 1.34 mm for the phantom data and 0.68 mm for the patient data. A multi-region, markerless tracking algorithm has been developed, capable of tracking multiple features simultaneously without requiring any other a priori information. This novel approach delivers robust target localization during complex treatment delivery. The reported tracking error is similar to previous reports for 3D conformal treatments.

Clinical translation of a new flat-panel detector for beam's-eye-view imaging.

Electronic portal imaging devices (EPIDs) lend themselves to beams-eye view clinical applications, such as tumor tracking, but are limited by low contrast and detective quantum efficiency (DQE). We characterize a novel EPID prototype consisting of multiple layers and investigate its suitability for use under clinical conditions. A prototype multi-layer imager (MLI) was constructed utilizing four conventional EPID layers, each consisting of a copper plate, a Gd2O2S:Tb phosphor scintillator, and an amorphous silicon flat panel array detector. We measured the detector's response to a 6 MV photon beam with regards to modulation transfer function, noise power spectrum, DQE, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and the linearity of the detector's response to dose. Additionally, we compared MLI performance to the single top layer of the MLI and the standard Varian AS-1200 detector. Pre-clinical imaging was done on an anthropomorphic phantom, and the detector's CNR, SNR and spatial resolution were assessed in a clinical environment. Images obtained from spine and liver patient treatment deliveries were analyzed to verify CNR and SNR improvements. The MLI has a DQE(0) of 9.7%, about 5.7 times the reference AS-1200 detector. Improved noise performance largely drives the increase. CNR and SNR of clinical images improved three-fold compared to reference. A novel MLI was characterized and prepared for clinical translation. The MLI substantially improved DQE and CNR performance while maintaining the same resolution. Pre-clinical tests on an anthropomorphic phantom demonstrated improved performance as predicted theoretically. Preliminary patient data were analyzed, confirming improved CNR and SNR. Clinical applications are anticipated to include more accurate soft tissue tracking.

Risk of cardiovascular disease in patients with HIV infection undergoing antiretroviral therapy. / Riesgo de enfermedad cardiovascular en pacientes con infección VIH en tratamiento antirretroviral.

BACKGROUND: The increased survival of patients with HIV infection thanks to antiretroviral therapy (ART) is accompanied by a higher rate of cardiovascular disease (CVD). We analysed the prevalence of the cardiovascular risk factors (CRFs) and estimated the risk of CVD in a cohort of patients with HIV in Spain. METHODS: We conducted a cross-sectional, observational study of CRFs in the Spanish VACH cohort of patients with HIV who undergo ART. RESULTS: The study assessed 15,559 patients with HIV (76% men; mean age, 46 years). Some 3.7% had experienced at least 1 CVD event. The prevalence of CRFs was high (hyperlipidaemia, 64%; tobacco use, 47%; arterial hypertension, 22%; and diabetes, 16%). According to the Framingham scale, 10.9% of the patients presented a high CVD risk, and 28.8% presented a moderate risk. Of the patients with a high CVD risk, 49% took protease inhibitors and 43% took abacavir. Fifty-three percent of the patients diagnosed with arterial hypertension took antihypertensive drugs, and 2.6% of the patients with diabetes took antidiabetic agents. CONCLUSIONS: Classical CRFs are common in patients with HIV undergoing ART in Spain, and a large proportion of them have a moderate-high risk of CVD. Therefore, controlling the modifiable CRFs in patients with HIV should be improved, and the use of drugs with a better cardiovascular risk profile should be assessed.

Reproducibility of manual choroidal thickness measurements using optical coherence tomography. / Reproducibilidad de la medición manual del grosor coroideo utilizando la tomografía de coherencia óptica.

PURPOSE: Spectral-domain optical coherence tomography (SD-OCT) is the most useful tool to measure choroidal thickness (CT). CT may be increased in ocular and systemic diseases. However, there are concerns relating reproducibility and external validity of OCT. The aim of this study was to assess the inter-observer and intra-observer variability of manual OCT measurements. METHODS: CT was manually measured in the central choroid of 40 eyes from 21 subjects (11 healthy and 10 with ankylosing spondylitis) using RTVue-100 OCT (Optovue Inc., Fremont, CA, EE.UU.). Measurements were performed by 9 independent ophthalmologists from 6 different centers. To assess the inter-observer variability, the intra-class correlation coefficient (ICC) method was calculated. Also, intra-observer variability was assessed in 2 of the ophthalmologists. RESULTS: The mean subfoveal CT was 364.9±85.1µm (range, 170 to 572). The inter-observer ICC was 0.823 (CI 95%, 0.749 to 0.888, p<0.001). The intra-observer ICCs were 0.885 (CI 95%, 0.783 to 0.939, p<0.001) and 0.925 (CI 95%, 0.859 to 0.960. p<0.001). CONCLUSIONS: In this study, manual measurements of CT with OCT showed a good concordance. These results suggest that manual OCT is a valid tool for multicenter studies.

A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates.

Coxsackievirus B (CVB) enteroviruses are common human pathogens known to cause severe diseases including myocarditis, chronic dilated cardiomyopathy, and aseptic meningitis. CVBs are also hypothesized to be a causal factor in type 1 diabetes. Vaccines against CVBs are not currently available, and here we describe the generation and preclinical testing of a novel hexavalent vaccine targeting the six known CVB serotypes. We show that the vaccine has an excellent safety profile in murine models and nonhuman primates and that it induces strong neutralizing antibody responses to the six serotypes in both species without an adjuvant. We also demonstrate that the vaccine provides immunity against acute CVB infections in mice, including CVB infections known to cause virus-induced myocarditis. In addition, it blocks CVB-induced diabetes in a genetically permissive mouse model. Our preclinical proof-of-concept studies demonstrate the successful generation of a promising hexavalent CVB vaccine with high immunogenicity capable of preventing CVB-induced diseases.

The relationship between antiretroviral prescription patterns and treatment guidelines in treatment-naïve HIV-1-infected patients.

BACKGROUND: Reports have shown that the publication of practice guidelines does not guarantee their use in clinical practice. The objective of this study was to evaluate the agreement between antiretroviral treatments (ARTs) prescribed in clinical practice and the recommendations in published guidelines. METHODS: A retrospective cohort study was carried out in ART-naïve adults of the Spanish Asociacion Medica Vach de Estudios Multicentricos (VACH) Cohort for the period from 2003 to 2006. RESULTS: A total of 945 patients initiated ART. Of these patients, 12.3% had a CD4 cell count above 350 cells/microL. A 'nonrecommended' antiretroviral regimen was prescribed to 5.3, 5.1 and 7.8% of patients with CD4 counts <200, 200-350 and >350 cells/microL, respectively. Multivariate analyses demonstrated that only a higher viral load was associated with the selection of a combination treatment that was recommended by the guidelines. CONCLUSIONS: Most patients were prescribed initial treatments in agreement with the recommendations. Appropriate routine data collection in databases can be used to evaluate the level of antiretroviral guideline compliance. We propose that routine evaluations of the guidelines must be part of quality assessment to improve medical care.

Circulating TNFRI and TNFRII levels correlated with the disease activity score (DAS28) in rheumatoid arthritis.

OBJECTIVE: To measure levels of soluble tumour necrosis factor alpha (TNFalpha) receptor type I (sTNFRI) and type II (sTNFRII) in order to correlate them with C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and disease activity score (DAS28) in RA patients. METHODS: We recruited 41 RA patients classified according to American College of Rheumatology (ACR) criteria and 38 healthy subjects (HS). sTNFRI and sTNFRII were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Clinical activity in RA patients was evaluated using the Disease Activity Score using 28 joint counts (DAS28). The statistical analysis was realized using SPSS version 10.0. RESULTS: Soluble TNFRI and TNFRII levels were higher in RA patients (p = 0.04 and 0.001, respectively) than HS. Serum levels of sTNFRI correlated with sTNFRII (r = 0.699, p < 0.0001). sTNFRII correlated with DAS28 (r = 0.375, p = 0.017), RF (r = 0.505, p = 0.004), and ESR (r = 0.323, p = 0.042). CONCLUSION: The increased levels of both sTNFRI and sTNFRII suggest a secondary event related to the inflammatory state observed in RA, whereas the correlation of sTNFRII with RF, ESR, and DAS28 reflects the preferential TNFRII shedding induced by TNFalpha. sTNFRII may be useful as an additional inflammatory marker in RA.