Un programa de atención multidisciplinar al paciente con hepatitis crónica C mejora la eficacia del tratamiento con peginterferon alfa-2a y ribavirina

La adherencia al tratamiento antiviral de la hepatitis crónica C (HCC) es una variable importante en la obtención de la respuesta viral sostenida (RVS). El objetivo de este trabajo es evaluar el impacto de un programa de atención multidisciplinar (PAM) en la adherencia y eficacia del tratamiento de la HCC. Se incluyeron 447 pacientes tratados con peginterferón-alfa-2a y ribavirina y se clasificaron en tres grupos: grupo control (2003-2004, n=147), grupo PAM (2005-2006, n=131) y grupo Validación-PAM (2007-2009, n=169). La adherencia y los porcentajes de RVS fueron superiores en los pacientes incluidos en los grupos PAM (94.6% y 77.1%) y Validación-PAM (91.7% y 74.6%) en comparación con el grupo control (78.9% y 61.9%) (p 0.05 para todos los casos).L'adherència al tractament antiviral de la hepatitis crònica C (HCC) es una variable important en l'assoliment de la resposta viral sostinguda (RVS). L'objectiu d'aquest treball es avaluar l'impacte d'un programa d'atenció multidisciplinari (PAM) en l'adherència i eficàcia del tractament de la HCC. Es varen incloure 447 pacients tractats amb peginterferó-alfa-2a i ribavirina i es varen classificar en tres grups: grup control (2003-2004, n=147), grup PAM (2005-2006, n=131) o grup Validació-PAM (2007-2009, n=169). L'adherència i el percentatges de RVS varen ser superiors en els pacients inclosos en els grups PAM (94.6% i 77.1%) i Validació-PAM (91.7% i 74.6%) en comparació amb el grup control (78.9% i 61.9%) (p 0.05 per a tots els casos)

A multi-proxy approach to the palaecological reconstruction of the Orce Basin Archaeological Zone (Granada, Spain)

Comunicación oral presentada en XXI INQUA Congress. July 14th – 20th 2023, Rome (Italy)The Orce Basin Archaeological Zone (OZAB, Granada, Spain) extends over a surface area of some > 8.5 km2 and constitutes one of the richest Pleistocene vertebrate fossil records in western Europe including one of the oldest hominin presence in this part of Eurasia. Exceptionally rich collections of stone tools have been excavated from both of the Orce Oldowan sites: Barranco León (BL) (1.4 Ma) and Fuente Nueva 3 (FN3) (1.2 Ma), while BL has yielded a hominin deciduous lower molar. We present a multi-proxy approach to determine the palaeoeocological context of these first hominin settlements in Western Europe. By combining results from macrovertebrates, microvertebrates, as well as from pollen and stable isotopes from macrovertebrate tooth enamel, we determine whether the palaeo landscapes were dominated by savanna or open woodland. The results reveal the regional specificities of the OAZB, and also allow us to infer local features within the Orce sites. Overall, our data reveal the dominance of a typically Mediterranean climate and landscape since 1.8 Ma ago. The climatic conditions were generally more humid than at present, with warmer temperatures during the coldest months, indicating a higher net primary productivity (NPP). We find that precipitation and NPP appear to have been limiting factors for hominin presence in the OAZB. Thus, at the older palaeontological site of Venta Micena (1.6 Ma), climatic conditions appear to have been less compatible with hominin presence than during the BL and FN3 sequences, when early hominins inhabiting the OAZB were able to cope with changing climatic and environmental settings. Lastly, the comparison of the isotopic results of the Orce sites with those of the contemporaneous Shungura Formation (Ethiopia) reveals that the habitat in the westernmost part of Eurasia was distinctly unlike a typical African savanna

Not seen before. Unveiling depositional context and Mammuthus meridionalis exploitation at Fuente Nueva 3 (Orce, southern Iberia) through taphonomy and microstratigraphy

Meat consumption by early hominins is a hotly debated issue. A key question concerns their access to large mammal carcasses, including megafauna. Currently, the evidence of anthropic cut marks on proboscidean bones older than -or close to- 1.0 Ma are restricted to the archaeological sites of Dmanisi (Georgia), Olduvai (Tanzania), Gona (Ethiopia), Olorgesailie (Kenya) and La Boella (Spain). During an inspection of the almost complete carcass of Mammuthus meridionalis (FN3-5-MPS) from the Oldowan site of Fuente Nueva 3 (Orce, Spain, c. 1.2 Ma), a few traces compatible with human-made cut marks and carnivore tooth marks were found. From this finding and previous interpretations the following questions arise: When and under what conditions was FN3-5-MPS deposited? What is the nature of the marks found on the surface of the bones of this mammoth? To answer, we have conducted a high-resolution analysis of these remains, combining both taphonomic and microstratigraphic data. Our results, using microstratigraphic and micromorphological analyses of sediments based on thin-sections, show that this individual was deposited in a marshy environment. Subsequently, the carcass was exploited by hominins and large felids that left their marks on the surface of some of its bones. For this purpose, the identification and characterisation of both cut marks and tooth marks were performed using high-resolution 3D modelling, geometric morphometrics, and artificially intelligent algorithms. Based on the anatomical position of both the cut and tooth marks, we propose that both the hominins and the saber-toothed cats had early access to the animal. Finally, this paper shows how an interdisciplinary approach can shed detailed light on the particular story regarding the death and processing of the carcass of a female mammoth, deposited at Fuente Nueva 3.This research has been carried out thanks to projects PID 2021.125098NB.I00 funding by MCIN/AEI/10.13039/501100011033/FEDER Una manera de hacer Europa and ProyExcel_00274 funding by Dirección General de Planificación de la Investigación (Consejería de Universidad, Investigación e Innovación, Junta de Andalucía). In addition, this research has been supported by the following projects of the Spanish government: PID2021-122533NB-I00, PID2021-123092NB-C21, PID2022-136832NB-I00. We also acknowledge the support provided by the PALARQ Foundation through the project Ref: PR2004_19/01

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Can Microfluidics Improve Sperm Quality? A Prospective Functional Study

The same sperm selection techniques in assisted reproduction clinics have remained largely unchanged despite their weaknesses. Recently, microfluidic devices have emerged as a novel methodology that facilitates the sperm selection process with promising results. A prospective case-control study was conducted in two phases: 100 samples were used to compare the microfluidic device with Density Gradient, and another 100 samples were used to compare the device with the Swim-up. In the initial phase, a significant enhancement in progressive motility, total progressive motile sperm count, vitality, morphology, and sperm DNA fragmentation were obtained for the microfluidic group compared to Density Gradient. Nevertheless, no statistically significant differences were observed in sperm concentration and chromatin structure stability. In the subsequent phase, the microfluidic group exhibited significant increases in sperm concentration, total progressive motile sperm count, and vitality compared to Swim-up. However, non-significant differences were seen for progressive motility, morphology, DNA structure stability, and DNA fragmentation. Similar trends were observed when results were stratified into quartiles. In conclusion, in a comparison of microfluidics with standard techniques, an improvement in sperm quality parameters was observed for the microfluidic group. However, this improvement was not significant for all parameters