A crack closure system for cementitious composite materials using knotted shape memory polymer (k-SMP) fibres

YesFormation of cracks represents one of the major causes of concrete deterioration, which can lead to durability and safety issues. In this work, a novel crack closure system is developed, using polyethylene terephthalate (PET) polymer fibres embedded in a mortar mix. The PET polymer has shape memory properties and shrinks upon thermal activation, if free to do so, or otherwise exerts shrinkage restraint forces. A single knot was manufactured at each end of the PET fibres to provide mechanical anchorage into the mortar matrix. Mortar samples with embedded knotted fibres were pre-cracked and subsequently placed in an oven to thermally activate the polymers and induce the shrinkage mechanism into the fibres. Crack closure was measured in the range 45–100%, depending on the geometry, dimension and distribution of the fibres, and the size of the initial crack.This work is supported by UKRI-EPSRC (Grant No. EP/P02081X/1, Resilient Materials 4 Life, RM4L)

Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment

[EN] The intrinsic characteristics of the tumor microenvironment (TME), including acidic pH and overexpression of hydrolytic enzymes, offer an exciting opportunity for the rational design of TME-drug delivery systems (DDS). We developed and characterized a pH-responsive biodegradable poly-L-glutamic acid (PGA)-based combination conjugate family with the aim of optimizing anticancer effects. We obtained combination conjugates bearing Doxorubicin (Dox) and aminoglutethimide (AGM) with two Dox loadings and two different hydrazone pH sensitive linkers that promote the specific release of Dox from the polymeric backbone within the TME. Low Dox loading coupled with a short hydrazone linker yielded optimal effects on primary tumor growth, lung metastasis (-90% reduction), and toxicological profile in a preclinical metastatic triple-negative breast cancer (TNBC) murine model. The use of transcriptomic analysis helped us to identify the molecular mechanisms responsible for such results including a differential immunomodulation and cell death pathways among the conjugates. This data highlights the advantages of targeting the TME, the therapeutic value of polymer-based combination approaches, and the utility of -omits-based analysis to accelerate anticancer DDS.The authors would like to thank Dr. Stuart P. Atkinson for his collaboration in manuscript preparation and English revision, and Irene Borreda for essential immunohistological support. This work has been supported by the European Research Council (grant ERC-CoG-2014-648831 "MyNano") and the Spanish Ministry of Science and Innovation (CTQ2010-18195, SAF2013-44848-R, BES-2008-006801, IPT-2012-0712-010000, Programa I3, and BIO2015-71658-R). LBN is funded through a University of South Florida-Helmsley Foundation award. FHL is funded through NIH grant. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with FEDER funds (PO FEDER of Comunitat Valenciana 2014-2020).Arroyo-Crespo, JJ.; Armiñán, A.; Charbonnier, D.; Balzano-Nogueira, L.; Huertas-López, F.; Martí, C.; Tarazona Campos, S.... (2018). Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment. Biomaterials. 186:8-21. https://doi.org/10.1016/j.biomaterials.2018.09.02382118

Applications and life cycle assessment of shape memory polyethylene terephthalate in concrete for crack closure

YesShape memory polymer (SMP) products have been developed for application as crack closure de-vices in concrete. They have been made from PET in the form of both fibres and hollow tubes. Here, manufacturing methods using die-drawing and mandrel-drawing to induce shape memory are reported. The fibre-based devices are incorporated into concrete and, upon triggering, exert shrinkage restraint forces that close cracks in the concrete. The evolution of shrinkage restraint force in the fibres as manufactured was measured as a function of temperature, showing stresses in excess of 35 MPa. Tendons consisting of fibre bundles are incorporated into concreate beams subjected to controlled cracking. When activated, the tendons reduce the crack widths by 80%. The same fibres are used to produce another class of device known as knotted fibres, which have knotted ends that act as anchor points when they incorporated directly into concrete. Upon acti-vation within the cracked concrete, these devices are shown to completely close cracks. The tubes are used to enclose and restrain prestressed Kevlar fibres. When the tubes are triggered, they shrink and release the prestress force in the Kevlar, which is transferred to the surrounding con-crete in the form of a compressive force, thereby closing cracks. The Kevlar fibres also provide substantial reinforcement after activation. The devices are shown to be able to partially and fully close cracks that have been opened to 0.3 mm and achieve post-activation flexural strengths com-parable to those of conventional reinforced and prestressed structural elements. Finally, a pre-liminary life cycle assessment study was used to assess the carbon footprint a nominal unit of concrete made with SMPs fibres compared to conventional concrete.This research was funded by the UKRI-EPSRC Resilient Materials 4 Life (RM4L), grant number EP/P02081X/1 and the support of ARUP via the UKIMEA research funding

Interventional Radiological Management and Prevention of Complications after Pancreatic Surgery: Drainage, Embolization and Islet Auto-Transplantation

Pancreatic surgery still remains burdened by high levels of morbidity and mortality with a relevant incidence of complications, even in high volume centers. This review highlights the interventional radiological management of complications after pancreatic surgery. The current literature regarding the percutaneous drainage of fluid collections due to pancreatic fistulas, percutaneous transhepatic biliary drainage due to biliary leaks and transcatheter embolization (or stent–graft) due to arterial bleeding is analyzed. Moreover, also, percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also examined. Moreover, a topic not usually treated in other similar reviewsas percutaneous intra-portal islet autotransplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also one of our areas of focus. In islet auto-transplantation, the patient is simultaneously donor and recipient. Differently from islet allo-transplantation, it does not require immunosuppression, has no risk of rejection and is usually efficient with a small number of transplanted islets

Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Bez danych nie ma polityki równościowej: Podejście MINDtheGEPs do opartej na dowodach polityki na rzecz równości płci

<p>Fakty i liczby wzmacniają naszą zdolność do podejmowania działań kulturowych i strukturalnych na rzecz równości płci. Wierzymy, że dzielenie się wiedzą na temat nierówności płci zdobytą w ramach projektu MINDtheGEPs może przyczynić się do trwałej zmiany. Wychodząc z założenia, że wszelkie polityki muszą opierać się na danych, niniejsze opracowanie zawiera zalecenia jak zbudować solidne podstawy planów równości płci w organizacjach.</p> <p>Potrzebujemy kilku rodzajów danych, aby móc uchwycić różne czynniki zachęcające i zniechęcające, które (de)konstruują nierówności płci w różnych fazach kariery naukowej (wczesnej, środkowej, późnej) i na różnych poziomach (indywidualnym, organizacyjnym, krajowym). Dlaczego? Ponieważ płeć jest konstruktem społecznym, który charakteryzuje się wieloma zazębiającymi się barierami, wymagającymi wielu krzyżujących się działań, aby je usunąć.</p>Przetłumaczył z angielskiego ks Jakub Gogol

Lopinavir/ritonavir, a new galenic oral formulation from commercial solid form, fine-tuned by NMR spectroscopy.

Objectives The lopinavir/ritonavir combination is one of the first antiretroviral drugs to be used in the treatment of COVID-19. In incapacitated patients, such as those in intensive care, an oral liquid formulation is needed. In Italy a marketed formulation is available, but only by importing it from other European countries. A galenic oral formulation prepared in the hospital pharmacy from lopinavir/ritonavir tablets was fine-tuned, evaluating the content of the active pharmaceutical ingredient (API) and stability of the formulation by using nuclear magnetic resonance (NMR) spectroscopy. Methods To overcome the insolubility of lopinavir/ ritonavir in water, ethanol and glycerol have been used as additional excipients. To define the best excipient proportion and best preparation method, three different formulations (ethanol 7.1–7.5%, glycerol 6–15%,and water) and two different preparation procedures (two step vs one step) have been studied. Each formulation has been compared with Kaletra oral solution (lopinavir 80 mg/mL, ritonavir 20 mg/mL) by NMR spectroscopy. API content and stability were measured. Results The presence of ethanol and glycerol as co- solvents is crucial both to improve solubilisation and promote the stability of the oral form. In the two-step preparation method, when crushed tablets were first dispersed in the ethanol/glycerol mixture and then in water, the content of solubilised active ingredients was equal or only slightly lower than the standard Kaletra (range 89–100%). The one-step method provided a comparable API content (65%) to that obtained by using water as the sole dispersing medium. Conclusions The two-step setup method with final 7.1% ethanol and 11% glycerol concentration is an efficient procedure for extemporaneous preparation of lopinavir/ritonavir liquid formulations from crushed tablets. The method combines simplicity of preparation and reconstitution in the hospital ward with good solubilisation, comparable to the commercial solution, and stability of active ingredients over time