Polycaprolactone-Based 3D-Printed Scaffolds as Potential Implant Materials for Tendon-Defect Repair

Chronic tendon ruptures are common disorders in orthopedics. The conventional surgical methods used to treat them often require the support of implants. Due to the non-availability of suitable materials, 3D-printed polycaprolactone (PCL) scaffolds were designed from two different starting materials as suitable candidates for tendon-implant applications. For the characterization, mechanical testing was performed. To increase their biocompatibility, the PCL-scaffolds were plasma-treated and coated with fibronectin and collagen I. Cytocompatibility testing was performed using L929 mouse fibroblasts and human-bone-marrow-derived mesenchymal stem cells. The mechanical testing showed that the design adaptions enhanced the mechanical stability. Cell attachment was increased in the plasma-treated specimens compared to the control specimens, although not significantly, in the viability tests. Coating with fibronectin significantly increased the cellular viability compared to the untreated controls. Collagen I treatment showed an increasing trend. The desired cell alignment and spread between the pores of the construct was most prominent on the collagen-I-coated specimens. In conclusion, 3D-printed scaffolds are possible candidates for the development of tendon implants. Enhanced cytocompatibility was achieved through surface modifications. Although adaptions in mechanical strength still require alterations in order to be applied to human-tendon ruptures, we are optimistic that a suitable implant can be designed

The barrel DIRC of PANDA

Cooled antiproton beams of unprecedented intensities in the momentum range of 1.5-15 GeV/c will be used for the PANDA experiment at FAIR to perform high precision experiments in the charmed quark sector. The PANDA detector will investigate antiproton annihilations with beams in the momentum range of 1.5 GeV/c to 15 GeV/c on a fixed target. An almost 4π acceptance double spectrometer is divided in a forward spectrometer and a target spectrometer. The charged particle identification in the latter is performed by ring imaging Cherenkov counters employing the DIRC principle

The barrel DIRC of PANDA

Cooled antiproton beams of unprecedented intensities in the momentum range of 1.5-15 GeV/c will be used for the PANDA experiment at FAIR to perform high precision experiments in the charmed quark sector. The PANDA detector will investigate antiproton annihilations with beams in the momentum range of 1.5 GeV/c to 15 GeV/c on a fixed target. An almost 4π acceptance double spectrometer is divided in a forward spectrometer and a target spectrometer. The charged particle identification in the latter is performed by ring imaging Cherenkov counters employing the DIRC principle

Challenges facing the Family Farm - proceedings of a seminar

The papers put forward should be valuable reference to all farmers in the wheatbelt. to bridge the gap between experts and farmers. My aim in organising this seminar was an attempt to bridge the gap between experts and farmers

Light Sterile Neutrinos: A White Paper

This white paper addresses the hypothesis of light sterile neutrinos based on recent anomalies observed in neutrino experiments and the latest astrophysical data

Assessing the impact of COVID-19 on liver cancer management (CERO-19)

Background & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. Results: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%,17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). Conclusions: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. Lay summary: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL)

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Assessing the impact of Ocean Alkalinity Enhancement on the zooplankton community

Ocean alkalinity enhancement (OAE) can help mitigate climate change impacts by increasing the carbon storage capacity of the ocean. The technique involves addition of alkaline substances to the seawater to accelerate the natural rock weathering process. However, this will lead to sudden seawater chemistry changes, such as increased pH that might directly and/or indirectly (through trophic pathways) affect zooplankton, an important trophic link, by altering its metabolic state and community composition. In addition, varying dilution times of alkaline substances might impact organisms differently. To date, the possible influences of OAE on zooplankton communities are largely unexplored. To bridge the knowledge gap, we conducted mesocosm and laboratory experiments in simulated non-equilibrated, calcium-based (Ca(OH)2) OAE setups. An incrementally enhanced alkalinity gradient from 0 to 1250 &amp;#181;mol kg-1 in steps of 250 &amp;#181;mol kg-1 was used in all experiments. The wide-ranging enhanced total alkalinity (&amp;#8710;TA) was selected to assess the safety threshold. In addition, we compared immediate versus delayed dilution scenarios in our mesocosm study, where each scenario ended up with the same &amp;#8710;TA gradient after mixing. We examined the multitrophic community response by monitoring twelve mesocosms for 39 days including the natural spring bloom community of Helgoland roads waters in the North Sea. Subsequently, the direct effect of alkalinity enhancement on the physiology (i.e., respiration and grazing) of Temora longicornis (predominant copepod in the mesocosms) was evaluated in the laboratory. The species-specific bottom-up effect was examined by culturing Rhodomonas salina in aforementioned &amp;#8710;TA gradient and feeding them to the T. longicornis. We observed relatively lower zooplankton abundance, and growth rate in mesocosms with &amp;#8710;TA1000 and 1250 &amp;#181;mol kg-1, which might be a bottom-up effect. In our lab experiments, though, we observed a negative impact on R. salina growth rate and nutritional quality from &amp;#8710;TA750 &amp;#181;mol kg-1, we did not detect any substantial direct or indirect impact on the physiological performance of T. longicornis. Overall, our laboratory study provided a preliminary understanding of the direct and indirect effects of OAE on a key copepod species, and the mesocosm study gave insight into the zooplankton community response.</jats:p