Effect of the Synthetic Bile Salt Analog CamSA on the Hamster Model of Clostridium difficile Infection

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and has gained worldwide notoriety due to emerging hypervirulent strains and the high incidence of recurrence. We previously reported protection of mice from CDI using the antigerminant bile salt analog CamSA. Here we describe the effects of CamSA in the hamster model of CDI. CamSA treatment of hamsters showed no toxicity and did not affect the richness or diversity of gut microbiota; however, minor changes in community composition were observed. Treatment of C. difficile-challenged hamsters with CamSA doubled the mean time to death, compared to control hamsters. However, CamSA alone was insufficient to prevent CDI in hamsters. CamSA in conjunction with suboptimal concentrations of vancomycin led to complete protection from CDI in 70% of animals. Protected animals remained disease-free at least 30 days postchallenge and showed no signs of colonic tissue damage. In a delayed-treatment model of hamster CDI, CamSA was unable to prevent infection signs and death. These data support a putative model in which CamSA reduces the number of germinating C. difficile spores but does not keep all of the spores from germinating. Vancomycin halts division of any vegetative cells that are able to grow from spores that escape CamSA

Select Biomarkers on the Day of Anterior Cruciate Ligament Reconstruction Predict Poor Patient-Reported Outcomes at 2-Year Follow-Up: A Pilot Study

Background. The majority of patients develop posttraumatic osteoarthritis within 15 years of anterior cruciate ligament (ACL) injury. Inflammatory and chondrodegenerative biomarkers have been associated with both pain and the progression of osteoarthritis; however, it remains unclear if preoperative biomarkers differ for patients with inferior postoperative outcomes. Hypothesis/Purpose. The purpose of this pilot study was to compare biomarkers collected on the day of ACL reconstruction between patients with good or poor 2-year postoperative outcomes. We hypothesized that inflammatory cytokines and chondrodegenerative biomarker concentrations would be significantly greater in patients with poorer outcomes. Study Design. Prospective cohort design. Methods. 22 patients (9 females, 13 males; age = 19.5 ± 4.1 years; BMI = 24.1 ± 3.6 kg/m2) previously enrolled in a randomized trial evaluating early anti-inflammatory treatment after ACL injury. Biomarkers of chondrodegeneration and inflammation were assessed from synovial fluid (sf) samples collected on the day of ACL reconstruction. Participants completed Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) questionnaires two years following surgery. Patients were then categorized based on whether their KOOS Quality of Life (QOL) score surpassed the Patient Acceptable Symptom State (PASS) threshold of 62.5 points or the IKDC PASS threshold of 75.9 points. Results. Patients that failed to reach the QOL PASS threshold after surgery (n = 6, 27%) had significantly greater sf interleukin-1 alpha (IL-1α; p = 0.004), IL-1 receptor antagonist (IL-1ra; p = 0.03), and matrix metalloproteinase-9 (MMP-9; p = 0.01) concentrations on the day of surgery. Patients that failed to reach the IKDC PASS threshold (n = 9, 41%) had significantly greater sf IL-1α (p = 0.02). Conclusion. These pilot data suggest that initial biochemical changes after injury may be an indicator of poor outcomes that are not mitigated by surgical stabilization alone. Biological adjuvant treatment in addition to ACL reconstruction may be beneficial; however, these data should be used for hypothesis generation and more definitive randomized clinical trials are necessary

Surgical aortic valve replacement in the era of transcatheter aortic valve implantation: a review of the UK national database

Objectives To date the reported outcomes of surgical aortic valve replacement (SAVR) are mainly in the settings of trials comparing it with evolving transcatheter aortic valve implantation. We set out to examine characteristics and outcomes in people who underwent SAVR reflecting a national cohort and therefore ‘real-world’ practice. Design Retrospective analysis of prospectively collected data of consecutive people who underwent SAVR with or without coronary artery bypass graft (CABG) surgery between April 2013 and March 2018 in the UK. This included elective, urgent and emergency operations. Participants’ demographics, preoperative risk factors, operative data, in-hospital mortality, postoperative complications and effect of the addition of CABG to SAVR were analysed. Setting 27 (90%) tertiary cardiac surgical centres in the UK submitted their data for analysis. Participants 31 277 people with AVR were identified. 19 670 (62.9%) had only SAVR and 11 607 (37.1%) had AVR+CABG. Results In-hospital mortality for isolated SAVR was 1.9% (95% CI 1.6% to 2.1%) and was 2.4% for AVR+CABG. Mortality by age category for SAVR only were: 75 years=2.2%. For SAVR+CABG these were; 2.2%, 1.8% and 3.1%. For different categories of EuroSCORE, mortality for SAVR in low risk people was 1.3%, in intermediate risk 1% and for high risk 3.9%. 74.3% of the operations were elective, 24% urgent and 1.7% emergency/salvage. The incidences of resternotomy for bleeding and stroke were 3.9% and 1.1%, respectively. Multivariable analyses provided no evidence that concomitant CABG influenced outcome. However, urgency of the operation, poor ventricular function, higher EuroSCORE and longer cross clamp and cardiopulmonary bypass times adversely affected outcomes. Conclusions Surgical SAVR±CABG has low mortality risk and a low level of complications in the UK in people of all ages and risk factors. These results should inform consideration of treatment options in people with aortic valve disease

TOI-1416: A system with a super-Earth planet with a 1.07d period

TOI 1416 (BD+42 2504, HIP 70705) is a V=10 late G or early K-type dwarf star with transits detected by TESS. Radial velocities verify the presence of the transiting planet TOI-1416 b, with a period of 1.07d, a mass of $3.48 M_{Earth}$ and a radius of $1.62 R_{Earth}$, implying a slightly sub-Earth density of $4.50$ g cm$^{-3}$. The RV data also further indicate a tentative planet c with a period of 27.4 or 29.5 days, whose nature cannot be verified due to strong suspicions about contamination by a signal related to the Moon's synodic period of 29.53 days. The near-USP (Ultra Short Period) planet TOI-1416 b is a typical representative of a short-period and hot ($T_{eq} \approx$ 1570 K) super-Earth like planet. A planet model of an interior of molten magma containing a significant fraction of dissolved water provides a plausible explanation for its composition, and its atmosphere could be suitable for transmission spectroscopy with JWST. The position of TOI-1416 b within the radius-period distribution corroborates that USPs with periods of less than one day do not form any special group of planets. Rather, this implies that USPs belong to a continuous distribution of super-Earth like planets with periods ranging from the shortest known ones up to ~ 30 days, whose period-radius distribution is delimitated against larger radii by the Neptune desert and by the period-radius valley that separates super-Earths from sub-Neptune planets. In the abundance of small-short periodic planets against period, a plateau between periods of 0.6 to 1.4 days has however become notable that is compatible with the low-eccentricity formation channel. For the Neptune desert, its lower limits required a revision due to the increasing population of short period planets and new limits are provided. These limits are also given in terms of the planets' insolation and effective temperatures.Comment: 31 pages, 31 figures, 8 tables, accepted for publication in A&

Projeto SECCLASS: O desenvolvimento de um sistema de classificação da construção com componente de sustentabilidade adaptado ao BIM

O projeto SECClasS – Sustainability Enhanced Construction Classification System – financiado pelo EEA Grants – pretende facilitar a Economia Circular na Construção introduzindo um Sistema de Classificação de Informações sobre Construção otimizado para a Sustentabilidade. Este sistema será orientado para a metodologia BIM e servirá não só a componente de sustentabilidade, mas também os restantes usos BIM, como a gestão do processo BIM, extração de quantidades, compatibilização de especialidades ou planeamento de obra, e todas as fases do ciclo de vida. É objetivo do projeto que o sistema de classificação seja usado pelos profissionais do projeto, construção e responsáveis pela gestão e manutenção de edifícios e outras infraestruturas. Um sistema de classificação permite unificar a terminologia a todas as escalas, facilitando a comunicação, seleção de materiais e componentes, bem como uma avaliação precisa dos impactos dos edifícios ao longo do seu ciclo de vida, com o objetivo de melhorar o desempenho dos edifícios e redução dos resíduos através de ferramentas digitais de gestão e seleção informada dos elementos construtivos. Este trabalho apresenta os frutos do projeto até à data, que incluem a tradução do sistema Uniclass 2015, as primeiras implementações do sistema em pilotos e ambientes de produção, e o trabalho e resultados esperados até à sua conclusão no final de 2022.info:eu-repo/semantics/publishedVersio

Effects of a peer-led Walking In ScHools intervention (the WISH study) on physical activity levels of adolescent girls: a cluster randomised pilot study.

School-based interventions may be effective at increasing levels of physical activity (PA) among adolescents; however, there is a paucity of evidence on whether walking can be successfully promoted to increase PA in this age group. This pilot study aimed to assess the effects of a 12-week school-based peer-led brisk walking programme on levels of school-time PA post intervention

TOI-1416: A system with a super-Earth planet with a 1.07 d period

TOI-1416 (BD+42 2504, HIP 70705) is a V =10 late G- or early K-type dwarf star. TESS detected transits in its Sectors 16, 23, and 50 with a depth of about 455 ppm and a period of 1.07 days. Radial velocities (RVs) confirm the presence of the transiting planet TOI-1416 b, which has a mass of 3.48 ± 0.47 M• and a radius of 1.62 ± 0.08 R•, implying a slightly sub-Earth density of 4.500.83+0.99 g cm3. The RV data also further indicate a tentative planet, c, with a period of 27.4 or 29.5 days, whose nature cannot be verified due to strong suspicions of contamination by a signal related to the Moon s synodic period of 29.53 days. The nearly ultra-short-period planet TOI-1416 b is a typical representative of a short-period and hot (Teq ≈ 1570 K) super-Earth-like planet. A planet model of an interior of molten magma containing a significant fraction of dissolved water provides a plausible explanation for its composition, and its atmosphere could be suitable for transmission spectroscopy with JWST. The position of TOI-1416 b within the radius-period distribution corroborates the idea that planets with periods of less than one day do not form any special group. It instead implies that ultra-short-period planets belong to a continuous distribution of super-Earth-like planets with periods ranging from the shortest known ones up to ≈ 30 days; their period-radius distribution is delimited against larger radii by the Neptune Desert and by the period-radius valley that separates super-Earths from sub-Neptune planets. In the abundance of small, short-periodic planets, a notable plateau has emerged between periods of 0.6- 1.4 days, which is compatible with the low-eccentricity formation channel. For the Neptune Desert, its lower limits required a revision due to the increasing population of short-period planets; for periods shorter then 2 days, we establish a radius of 1.6 R• and a mass of 0.028 Mjup (corresponding to 8.9 M•) as the desert s lower limits. We also provide corresponding limits to the Neptune Desert against the planets insolation and effective temperatures

Validating AU Microscopii d with Transit Timing Variations

AU Mic is a young (22 Myr) nearby exoplanetary system that exhibits excess TTVs that cannot be accounted for by the two known transiting planets nor stellar activity. We present the statistical "validation" of the tentative planet AU Mic d (even though there are examples of "confirmed" planets with ambiguous orbital periods). We add 18 new transits and nine midpoint times in an updated TTV analysis to prior work. We perform the joint modeling of transit light curves using EXOFASTv2 and extract the transit midpoint times. Next, we construct an O-C diagram and use Exo-Striker to model the TTVs. We generate TTV log-likelihood periodograms to explore possible solutions for the period of planet d and then follow those up with detailed TTV and RV MCMC modeling and stability tests. We find several candidate periods for AU Mic d, all of which are near resonances with AU Mic b and c of varying order. Based on our model comparisons, the most-favored orbital period of AU Mic d is 12.73596+/-0.00793 days (T_{C,d}=2458340.55781+/-0.11641 BJD), which puts the three planets near a 4:6:9 mean-motion orbital resonance. The mass for d is 1.053+/-0.511 M_E, making this planet Earth-like in mass. If confirmed, AU Mic d would be the first known Earth-mass planet orbiting a young star and would provide a valuable opportunity in probing a young terrestrial planet's atmosphere. Additional TTV observation of the AU Mic system are needed to further constrain the planetary masses, search for possible transits of AU Mic d, and detect possible additional planets beyond AU Mic c.Comment: 89 pages, 35 figures, 34 tables. Redid EXOFASTv2 transit modeling to recover more reasonable stellar posteriors, so redid Exo-Striker TTV modeling for consistency. Despite these changes, the overall results remain unchanged: the 12-7-day case is still the most favored. Submitted to AAS Journals on 2023 Feb 9t

Validating AU Microscopii d with Transit Timing Variations

AU Mic is a young (22 Myr), nearby exoplanetary system that exhibits excess transit timing variations (TTVs) that cannot be accounted for by the two known transiting planets nor stellar activity. We present the statistical “validation” of the tentative planet AU Mic d (even though there are examples of “confirmed” planets with ambiguous orbital periods). We add 18 new transits and nine midpoint times in an updated TTV analysis to prior work. We perform the joint modeling of transit light curves using EXOFASTv2 and extract the transit midpoint times. Next, we construct an O − C diagram and use Exo-Striker to model the TTVs. We generate TTV log-likelihood periodograms to explore possible solutions for d’s period, then follow those up with detailed TTV and radial velocity Markov Chain Monte Carlo modeling and stability tests. We find several candidate periods for AU Mic d, all of which are near resonances with AU Mic b and c of varying order. Based on our model comparisons, the most-favored orbital period of AU Mic d is 12.73596 ± 0.00793 days ( T _C _,d = 2458340.55781 ± 0.11641 BJD), which puts the three planets near 4:6:9 mean-motion resonance. The mass for d is 1.053 ± 0.511 M _⊕ , making this planet Earth-like in mass. If confirmed, AU Mic d would be the first known Earth-mass planet orbiting a young star and would provide a valuable opportunity in probing a young terrestrial planet’s atmosphere. Additional TTV observations of the AU Mic system are needed to further constrain the planetary masses, search for possible transits of AU Mic d, and detect possible additional planets beyond AU Mic c