Disarmament, Development and Security

SUMMARY Only action can make further discussion of the relationship between disarmament, development and security credible. Although the Brandt and Palme Commissions heightened public awareness, governments have largely ignored both such bodies and popular movements. The superpowers hold the key but alternative voices must be heard, including middle?country coalitions, the Commonwealth, and the smallest countries which feel special insecurity. Collective security would help developing countries cut arms spending. The Brandt Symposium in April 1985 urged governments to plan for conversion of resources from military to civilian use. The projected UN Conference on Disarmament and Development could make practical advances and reassert the centrality of the disarmament and development relationship. SOMMAIRE Désarmement, développement et sécurité Seul le fait d'agir peut restituer une certaine crédibilité à la discussion des rapports entre le désarmement, le développement et la sécurité. Quoique les commissions Brandt et Palme ont atteint la connaissance du public, les gouvernements ont grandement ignorés ces organisations ainsi que les mouvements populaires. Les grandes puissances tiennent les rênes mais d'autres doivent avoir droit à la parole, les pays moyens y compris, le Commonwealth, et les plus petits pays qui souffrent d'une certaine insécurité. Une sécurité collective aiderait les pays en voie de développement à freiner leurs dépenses en armement. Le Symposium de Brandt en avril 1985 pressait les gouvernements à mettre sur pied une stratégie pour convertir les ressources à but militaire à usage civil. La future Conférence des Nations Unies sur le Désarmement et le Développement pourrait avancer des idées pratiques et réaffirmer la centralisation des rapports du désarmement et du développement. RESUMEN Desarme, desarrollo y sequridad Cualquiera discusión futura acerca de la relación entre desarme, desarrollo y seguridad sólo tendrá credibilidad a través de la acción. Aunque las Comisiones. Brandt y Palme acrecentaron la conciencia pública sobre el problema, por lo general los gobiernos han ignorado tanto a esos organismos como a los movimientos populares. Las superpotencias tienen la última palabra pero las opiniones alternativas debieran hacerse oir incluyendo aquellas de coaliciones de países intermedios, del Commonwealth y los países más pequeños que sienten gran inseguridad. Los países en desarrollo podrían disminuir su gasto de armamentos mediante la creación de sistemas de seguridad colectivos. El symposium Brandt de abril de 1985 urgió a los gobiernos para que planificaran la conversión de recursos de uso militar a uso civil. La proyectada conferencia de las Naciones Unidas sobre Desarme y Desarrollo podría resultar en adelantos prácticos y reafirmar el carácter central de la relación entre desarme y desarrollo

Superconductivity in Ce- and U-based "122" heavy-fermion compounds

This review discusses the heavy-fermion superconductivity in Ce- and U-based compounds crystallizing in the body-centered tetragonal ThCr2Si2 structure. Special attention will be paid to the theoretical background of these systems which are located close to a magnetic instability.Comment: 12 pages, 9 figures. Invited topical review (special issue on "Recent Developments in Superconductivity") Metadata and references update

FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study

BACKGROUND The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2]). METHODS This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009. FINDINGS Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76–0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74–0·95, 0·85; 95% CI 0·83–0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0. INTERPRETATION The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

Background: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community. Methods and Results: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD. Conclusions: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases.Fil: Sun, Dan Qin. Jiangnan University Medical Center; China. Nantong University; ChinaFil: Targher, Giovanni. Azienda Ospedaliera Universitaria Integrata Verona; ItaliaFil: Byrne, Christopher D.. University of Southampton; Reino UnidoFil: Wheeler, David C.. University College London; Estados UnidosFil: Wong, Vincent Wai Sun. Chinese University of Hong Kong; ChinaFil: Fan, Jian Gao. Shanghai Jiao Tong University; ChinaFil: Tilg, Herbert. Medical University Innsbruck; AustriaFil: Yuan, Wei Jie. Shanghai Jiao Tong University; ChinaFil: Wanner, Christoph. Würzburg University Clinic; AlemaniaFil: Gao, Xin. Fudan University; ChinaFil: Long, Michelle T.. Boston University School of Medicine; Estados UnidosFil: Kanbay, Mehmet. Koc University School of Medicine; TurquíaFil: Nguyen, Mindie H.. Stanford University Medical Center; Estados UnidosFil: Navaneethan, Sankar D.. Baylor College of Medicine; Estados UnidosFil: Yilmaz, Yusuf. Marmara University; Turquía. Recep Tayyip Erdoğan University; TurquíaFil: Huang, Yuli. Southern Medical University; ChinaFil: Gani, Rino A.. Universitas Indonesia; IndonesiaFil: Marzuillo, Pierluigi. Università della Campania “Luigi Vanvitelli”; ItaliaFil: Boursier, Jérôme. Angers University; FranciaFil: Zhang, Huijie. Southern Medical University; ChinaFil: Jung, Chan Young. Yonsei University; Corea del SurFil: Chai, Jin. Army Medical University; ChinaFil: Valenti, Luca. Università degli Studi di Milano; ItaliaFil: Papatheodoridis, George. Kapodistrian University of Athens; GreciaFil: Sookoian, Silvia Cristina. Centro de Investigacion Traslacional En Salud (cenitres) ; Facultad de Cs. de la Salud ; Universidad Maimonides; . Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chunsun, Dai. Nanjing Medical University; ChinaFil: Eslam, Mohammed. University of Sydney; AustraliaFil: Wei, Lai. Tsinghua University; ChinaFil: George, Jacob. University of Sydney; AustraliaFil: Zheng, Ming Hua. Wenzhou Medical University; Chin

IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells

Objective Interleukin-26 (IL-26) is a member of the IL-10 cytokine family, first discovered based on its peculiar expression by virus-transformed T cells. IL-26 is overexpressed in chronic inflammation (rheumatoid arthritis and Crohn’s disease) and induces proinflammatory cytokines by myeloid cells and some epithelial cells. We thus investigated the expression and potential role of IL-26 in chronic HCV infection, a pathology associated with chronic inflammation.Design IL-26 was quantified in a cohort of chronically HCV-infected patients, naive of treatment and its expression in the liver biopsies investigated by immunohistochemistry. We also analysed the ability of IL-26 to modulate the activity of natural killer (NK) cells, which control HCV infection. Results The serum levels of IL-26 are enhanced in chronically HCV-infected patients, mainly in those with severe liver inflammation. Immunohistochemistry reveals an intense IL-26 staining in liver lesions, mainly in infiltrating CD3+ cells. We also show that NK cells from healthy subjects and from HCV-infected patients are sensitive to IL-26. IL-26 upregulates membrane tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression on CD16− CD56bright NK cells, enabling them to kill HCV-infected hepatoma cells, with the same efficacy as interferon (IFN)-α-treated NK cells. IL-26 also induces the expression of the antiviral cytokines IFN-β and IFN-γ, and of the proinflammatory cytokines IL-1β and TNF-α by NK cells. Conclusions This study highlights IL-26 as a new player in the inflammatory and antiviral immune responses associated with chronic HCV infection

IL-34 and macrophage colony-stimulating factor are overexpressed in hepatitis C virus fibrosis and induce profibrotic macrophages that promote collagen synthesis by hepatic stellate cells

Chronic hepatitis C virus (HCV) infection is characterized by progressive hepatic fibrosis, a process dependent on monocyte recruitment and accumulation into the liver. The mediators expressed in chronically injured liver that control the differentiation of human monocytes into profibrotic macrophages (Mφ) remain poorly defined. We report that chronically HCV-infected patients with high fibrosis stages have higher serum levels of macrophage colony-stimulating factor (M-CSF) and interleukin (IL)−34 than HCV-infected patients with lower fibrosis stages and healthy subjects. Immunohistochemistry reveals an intense expression of IL-34 and M-CSF by hepatocytes around liver lesions. In addition, HCV infection and inflammatory cytokines enhance the in vitro production of IL-34 and M-CSF by hepatocytes. We next analyzed the acquisition of profibrotic properties by Mφ generated with M-CSF (M-CSF-Mφ) or IL-34 (IL-34-Mφ). M-CSF and IL-34 up-regulate the expression, by differentiating monocytes, of chemokine (C-C motif) ligand (CCL)2, CCL4, C-C chemokine receptor (CCR)1, and CCR5, which are involved in monocyte recruitment/Mφ accumulation in liver lesions. M-CSF-Mφ and IL-34-Mφ also express the hepatic stellate cell (HSC) activators, platelet-derived growth factor, transforming growth factor beta, and galectin-3. IL-34-Mφ and M-CSF-Mφ induce type I collagen synthesis by HSCs, the main collagen-producing cells in liver fibrosis. IL-13, whose expression correlates with the fibrosis stage in HCV-infected patients, decreases the expression of the collagenase, matrix metalloproteinase 1, by IL-34-Mφ and M-CSF-Mφ, thereby enhancing collagen synthesis. By inhibiting the production of interferon-gamma (IFN-γ) by activated natural killer cells, IL-34-Mφ and M-CSF-Mφ prevent the IFN-γ-induced killing of HSCs. Conclusion: These results identify M-CSF and IL-34 as potent profibrotic factors in HCV liver fibrosis

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH—An individual participant data meta-analysis

\ua9 2024 The Authors. Liver International published by John Wiley & Sons Ltd.Background & Aims: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions. Methods: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported. Results: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were.78,.75,.68 and.57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were.73,.67,.60,.58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were.79,.84,.81,.76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of.7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%. Conclusions: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations

Polymerization-Induced Self-Assembly of Block Copolymer Nano-objects via RAFT Aqueous Dispersion Polymerization

In this Perspective, we discuss the recent development of polymerization-induced self-assembly mediated by reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization. This approach has quickly become a powerful and versatile technique for the synthesis of a wide range of bespoke organic diblock copolymer nano-objects of controllable size, morphology, and surface functionality. Given its potential scalability, such environmentally-friendly formulations are expected to offer many potential applications, such as novel Pickering emulsifiers, efficient microencapsulation vehicles, and sterilizable thermo-responsive hydrogels for the cost-effective long-term storage of mammalian cells