On the dimensional control of 2D hybrid nanomaterials

Thermotropic smectic liquid crystalline polymers were used as a scaffold to create organic/inorganic hybrid layered nanomaterials. Different polymers were prepared by photopolymerizing blends of a hydrogen bonded carboxylic acid derivative and a 10 % cross-linker of variable length in their liquid crystalline phase. Nanopores with dimensions close to 1 nm were generated by breaking the hydrogen bonded dimers in a high pH solution. The pores were filled with positively charged silver (Ag) ions, resulting in a layered silver(I)-polymeric hybrid material. Subsequent exposure to a NaBH4 reducing solution allowed for the formation of supported hybrid metal/organic films. In the bulk of the film the dimension of the Ag nanoparticles (NPs) was regulated with subnanometer precision by the cross-linker length. Ag nanoparticles with an average size of 0.9, 1.3, and 1.8 nm were produced inside the nanopores thanks to the combined effect of spatially confined reduction and stabilization of the nanoparticles by the polymer carboxylic groups. At the same time, strong Ag migration occurred in the surface region, resulting in the formation of a nanostructured metallic top layer composed of large (10–20 nm) NPs.</p

Neonatal Safety of Elective Family-Centered Caesarean Sections: A Cohort Study

Developmen

Clinical evaluation of the clinicopathologic and gene expression profile (CP-GEP) in patients with melanoma eligible for sentinel lymph node biopsy: a multicenter prospective Dutch study

Sentinel lymph node biopsy (SLNB) is recommended for patients with >pT1b cutaneous melanoma, and should be considered and discussed with patients diagnosed with pT1b cutaneous melanoma for the purpose of staging, prognostication and determining eligibility for adjuvant therapy. Previously, the clinicopathologic and gene expression profile (CP-GEP, Merlin Assay (R)) model was developed to identify patients who can forgo SLNB because of a low risk for sentinel node metastasis. The aim of this study was to evaluate the clinical use and implementation of the CP-GEP model in a prospective multicenter study in the Netherlands. Both test performance and feasibility for clinical implementation were assessed in 260 patients with T1-T4 melanoma. The CPGEP model demonstrated an overall negative predictive value of 96.7% and positive predictive value of 23.7%, with a potential SLNB reduction rate of 42.2% in patients with T1-T3 melanoma. With a median time of 16 days from initiation to return of test results, there was sufficient time left before the SLNB was performed. Based on these outcomes, the model may support clinical decision-making to identify patients who can forgo SLNB in clinical practice.Surgical oncolog

Veneuze trombo-embolie : wanneer zijn laboratoriumtesten voor trombofilie zinvol?

Laboratoriumtesten voor trombofilieonderzoek worden vaak door de kliniek aangevraagd na het optreden van veneuze trombo-embolie. Indien afwijkingen worden gevonden leidt dit niet altijd tot klinische consequenties, zoals verlenging van antistollingstherapie. In de eind 2007 vastgestelde CBO-richtlijn ‘diagnostiek, preventie en behandeling van veneuze trombo-embolie en secundaire preventie arteriële trombose’ staan wetenschappelijk onderbouwde richtlijnen beschreven voor situaties waarbij het bepalen van trombofiliefactoren zinvol is en invloed heeft op het klinisch handelen. In dit artikel wordt de consequentie van deze richtlijn voor de laboratoria beschreven. Grofweg komt het erop neer dat voor de meeste patiënten met een eerste of recidief veneuze trombo-embolie het bepalen van trombofiliefactoren anders dan antifosfolipide-antistoffen geen therapeutische consequenties heeft en daarom wordt afgeraden. Slechts in uitzonderlijke gevallen wordt het bepalen van trombofiliefactoren wel overwogen. Daarbij is het van belang dat rekening gehouden wordt met preanalytische factoren die de uitslag van trombofilietesten kunnen beïnvloeden

Engineering cytokine therapeutics

Cytokines have pivotal roles in immunity, making them attractive as therapeutics for a variety of immune-related disorders. However, the widespread clinical use of cytokines has been limited by their short blood half-lives and severe side effects caused by low specificity and unfavourable biodistribution. Innovations in bioengineering have aided in advancing our knowledge of cytokine biology and yielded new technologies for cytokine engineering. In this Review, we discuss how the development of bioanalytical methods, such as sequencing and high-resolution imaging combined with genetic techniques, have facilitated a better understanding of cytokine biology. We then present an overview of therapeutics arising from cytokine re-engineering, targeting and delivery, mRNA therapeutics and cell therapy. We also highlight the application of these strategies to adjust the immunological imbalance in different immune-mediated disorders, including cancer, infection and autoimmune diseases. Finally, we look ahead to the hurdles that must be overcome before cytokine therapeutics can live up to their full potential

Acid ceramidase regulates innate immune memory

Innate immune memory, also called “trained immunity,” is a functional state of myeloid cells enabling enhanced immune responses. This phenomenon is important for host defense, but also plays a role in various immune-mediated conditions. We show that exogenously administered sphingolipids and inhibition of sphingolipid metabolizing enzymes modulate trained immunity. In particular, we reveal that acid ceramidase, an enzyme that converts ceramide to sphingosine, is a potent regulator of trained immunity. We show that acid ceramidase regulates the transcription of histone-modifying enzymes, resulting in profound changes in histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation. We confirm our findings by identifying single-nucleotide polymorphisms in the region of ASAH1, the gene encoding acid ceramidase, that are associated with the trained immunity cytokine response. Our findings reveal an immunomodulatory effect of sphingolipids and identify acid ceramidase as a relevant therapeutic target to modulate trained immunity responses in innate immune-driven disorders.</p

Acid ceramidase regulates innate immune memory

Innate immune memory, also called “trained immunity,” is a functional state of myeloid cells enabling enhanced immune responses. This phenomenon is important for host defense, but also plays a role in various immune-mediated conditions. We show that exogenously administered sphingolipids and inhibition of sphingolipid metabolizing enzymes modulate trained immunity. In particular, we reveal that acid ceramidase, an enzyme that converts ceramide to sphingosine, is a potent regulator of trained immunity. We show that acid ceramidase regulates the transcription of histone-modifying enzymes, resulting in profound changes in histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation. We confirm our findings by identifying single-nucleotide polymorphisms in the region of ASAH1, the gene encoding acid ceramidase, that are associated with the trained immunity cytokine response. Our findings reveal an immunomodulatory effect of sphingolipids and identify acid ceramidase as a relevant therapeutic target to modulate trained immunity responses in innate immune-driven disorders.</p

BB flavour tagging using charm decays at the LHCb experiment

An algorithm is described for tagging the flavour content at production of neutral $B$ mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a $B$ meson with the charge of a reconstructed secondary charm hadron from the decay of the other $b$ hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes $B^+ \to J/\psi \, K^+$ and $B^0 \to J/\psi \, K^{*0}$ using $3.0\mathrm{\,fb}^{-1}$ of data collected by the LHCb experiment at $pp$ centre-of-mass energies of $7\mathrm{\,TeV}$ and $8\mathrm{\,TeV}$. Its tagging power on these samples of $B \to J/\psi \, X$ decays is $(0.30 \pm 0.01 \pm 0.01) \%$.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm