Swinging Atwood's Machine: Experimental and Theoretical Studies

A Swinging Atwood Machine (SAM) is built and some experimental results concerning its dynamic behaviour are presented. Experiments clearly show that pulleys play a role in the motion of the pendulum, since they can rotate and have non-negligible radii and masses. Equations of motion must therefore take into account the inertial momentum of the pulleys, as well as the winding of the rope around them. Their influence is compared to previous studies. A preliminary discussion of the role of dissipation is included. The theoretical behaviour of the system with pulleys is illustrated numerically, and the relevance of different parameters is highlighted. Finally, the integrability of the dynamic system is studied, the main result being that the Machine with pulleys is non-integrable. The status of the results on integrability of the pulley-less Machine is also recalled.Comment: 37 page

Sequential repeated tibial tubercle osteotomy in a two-stage exchange strategy : a superior approach to treating a chronically infected knee arthroplasty?

Surgical approach can impact the reliability of the debridement after a chronic total knee periprosthetic joint infection (PJI), a factor of utmost importance to eradicate the infection. The most adequate knee surgical approach in cases of PJI is a matter of debate. The purpose of this study was to determine the influence of performing a tibial tubercle osteotomy (TTO) in a two-stage exchange protocol for knee PJI treatment. Retrospective cohort study examining patients managed with two-stage arthroplasty due to chronic knee PJI (2010-2019). Performance and timing of the TTO were collected. Primary end-point was infection control with a minimum FU of 12 months and according to internationally accepted criteria. Correlation between TTO timing and reinfection rate was reviewed. Fifty-two cases were finally included. Overall success (average follow-up: 46.2 months) was 90.4%. Treatment success was significantly higher among cases addressed using TTO during the second stage (97.1% vs. 76.5%, pvalue 0.03). Only 4.8% of the patients relapsed after performing a sequential repeated TTO, that is, during both first and second stages, compared to 23.1% cases in which TTO was not done (p value 0.28). No complications were observed among patients in the TTO group with a significant decrease in soft tissue necrosis (p: 0.052). Sequential repeated tibial tubercle osteotomy during a two-stage strategy is a reasonable option and offers high rates of infection control in complex cases of knee PJI with a low rate of complications

Sequential repeated tibial tubercle osteotomy in a two-stage exchange strategy: a superior approach to treating a chronically infected knee arthroplasty?

Periprosthetic joint infection; Tibial tubercle osteotomy; Two-stage revision arthroplastyInfecció articular periprotèsica; Osteotomia del tubercle tibial; Artroplàstia de revisió en dues etapesInfección articular periprotésica; Osteotomía del tubérculo tibial; Artroplastia de revisión en dos tiemposPurpose Surgical approach can impact the reliability of the debridement after a chronic total knee periprosthetic joint infection (PJI), a factor of utmost importance to eradicate the infection. The most adequate knee surgical approach in cases of PJI is a matter of debate. The purpose of this study was to determine the influence of performing a tibial tubercle osteotomy (TTO) in a two-stage exchange protocol for knee PJI treatment. Methods Retrospective cohort study examining patients managed with two-stage arthroplasty due to chronic knee PJI (2010–2019). Performance and timing of the TTO were collected. Primary end-point was infection control with a minimum FU of 12 months and according to internationally accepted criteria. Correlation between TTO timing and reinfection rate was reviewed. Results Fifty-two cases were finally included. Overall success (average follow-up: 46.2 months) was 90.4%. Treatment success was significantly higher among cases addressed using TTO during the second stage (97.1% vs. 76.5%, p value 0.03). Only 4.8% of the patients relapsed after performing a sequential repeated TTO, that is, during both first and second stages, compared to 23.1% cases in which TTO was not done (p value 0.28). No complications were observed among patients in the TTO group with a significant decrease in soft tissue necrosis (p: 0.052). Conclusion Sequential repeated tibial tubercle osteotomy during a two-stage strategy is a reasonable option and offers high rates of infection control in complex cases of knee PJI with a low rate of complications.Open Access Funding provided by Universitat Autònoma de Barcelona

Reproductive ecology of Lophelia pertusa in Mingulay Reef and the Logachev mounds (North East Atlantic): a multi‐scale comparison

This paper presents the results of a multi-scale comparison in the reproductive stage of the cold-water coral Lophelia pertusa in two areas of the North-east Atlantic: The Mingulay Reef and the Logachev Mounds. The study was carried out during the Research cruise “Changing Oceans” on board of the RRV James Cook, conducted in May-June 2012. The comparative study between the two geographical areas revealed higher fecundity for the colonies analysed from Mingulay Reef compared to the colonies from the Logachev mounds. Moreover the development stage of the oocytes was more advanced in the colonies sampled from Mingulay than in the ones collected from Logachev. The comparison between single colonies and within the same colony from the Mingulay Reef did not show any differences in the maturity stage of the oocytes, nevertheless the analyses of the reproductive stage between mesenteries within the same polyps showed high variability, which indicates that the gametogenic development within each mesentery undergoes a prolonged period of oocyte production. This probably results in a protracted spawning period, which might improve the reproductive success of the species. This work has been developed under the framework of the UKOA program (United Kingdom Ocean Acidification program) and has been supported by the National Environmental Research Council (NERC, UK)

A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin

Signatura genètica; Biomarcadors predictius; TrabectedinaFirma genética; Biomarcadores predictivos; TrabectedinaGene signature; Predictive biomarkers; TrabectedinPredictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.This study was funded by the Spanish Group for Research on Sarcoma (GEIS) and partially by PharmaMar. The authors would like to thank the GEIS data center for data management. The authors also thank the donors and the Hospital Universitario Virgen del Rocío—Instituto de Biomedicina de Sevilla Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT17/0015/0041) for part of the human specimens used in this study. David S. Moura is recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155)

QTL mapping of melon fruit quality traits using a high-density GBS-based genetic map

Background Melon shows a broad diversity in fruit morphology and quality, which is still underexploited in breeding programs. The knowledge of the genetic basis of fruit quality traits is important for identifying new alleles that may be introduced in elite material by highly efficient molecular breeding tools. Results In order to identify QTLs controlling fruit quality, a recombinant inbred line population was developed using two commercial cultivars as parental lines: “Védrantais”, from the cantalupensis group, and “Piel de Sapo”, from the inodorus group. Both have desirable quality traits for the market, but their fruits differ in traits such as rind and flesh color, sugar content, ripening behavior, size and shape. We used a genotyping-by-sequencing strategy to construct a dense genetic map, which included around five thousand variants distributed in 824 bins. The RIL population was phenotyped for quality and morphology traits, and we mapped 33 stable QTLs involved in sugar and carotenoid content, fruit and seed morphology and major loci controlling external color of immature fruit and mottled rind. The median confidence interval of the QTLs was 942 kb, suggesting that the high density of the genetic map helped in increasing the mapping resolution. Some of these intervals contained less than a hundred annotated genes, and an integrative strategy combining gene expression and resequencing data enabled identification of candidate genes for some of these traits. Conclusion Several QTLs controlling fruit quality traits in melon were identified and delimited to narrow genomic intervals, using a RIL population and a GBS-based genetic map. Keywords Quantitative trait loci Melon Fruit quality Fruit morphology Genotyping-by-sequencing Genetic mapinfo:eu-repo/semantics/publishedVersio

Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (600 soluble proteins, our data highlight the importance of Th17 cells and Wnt/β-catenin signaling in HIV control and especially identify the IL-27/IL-27 receptor subunit alpha (IL-27RA) axis as a predictor of plasma viral load and proviral copy number in the peripheral blood. These data may provide important guidance to therapeutic approaches in the HIV cure agenda

Outcomes of off-label drug uses in hospitals : a multicentric prospective study

Altres ajuts: We would to thank the Spanish Ministry of Health, Social Affairs and Equality for their financial support given though a grant from the scholarship EC-206 in the public call for the promotion of independent clinical research (SAS/2370/2010 order of September 27)The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (33-62) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was €2,943.07 (541.9-5,872.54). There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed. The online version of this article (doi:10.1007/s00228-014-1746-2) contains supplementary material, which is available to authorized users

Identification of interleukin-27 (IL-27)/IL-27 receptor subunit alpha as a critical immune axis for in vivo hiv control

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (> 50,000) or low (<10,000 HIV RNA copies/ml) viral loads. Univariate and regression model analysis demonstrate that plasma levels of soluble interleukin-27 (IL-27) are significantly elevated in individuals with high plasma viremia (P < 0.0001) and are positively correlated with proviral HIV-DNA copy numbers in peripheral blood mononuclear cells (PBMC) (Rho = 0.4011; P = 0.0027). Moreover, soluble IL-27 plasma levels are negatively associated with the breadth and magnitude of the total virus-specific T-cell responses and directly with plasma levels of molecules involved in Wnt/beta-catenin signaling. In addition to IL-27, gene expression levels of the specific IL-27 receptor (IL27RA) in PBMC correlated directly with both plasma viral load (Rho = 0.3531; P = 0.0218) and the proviral copy number in the peripheral blood as an indirect measure of partial viral reservoir (Rho = 0.4580; P = 0.0030). These results were validated in unrelated cohorts of early infected subjects as well as subjects before and after initiation of antiretroviral treatment, and they identify IL-27 and its specific receptor as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in PBMC. IMPORTANCE The detailed knowledge of immune mechanisms that contribute to HIV control is a prerequisite for the design of effective treatment strategies to achieve HIV cure. Cells communicate with each other by secreting signaling proteins, and the blood is a key conduit for transporting such factors. Investigating the communication factors promoting effective immune responses and having potentially antiviral functions against HIV using a novel focused omics approach (Peer ReviewedPostprint (published version