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Sustainable agriculture requires balancing crop yields with the effects of pesticides on non-target organisms, such as bees and other crop pollinators. Field studies demonstrated that agricultural use of neonicotinoid insecticides can negatively affect wild bee species1,2, leading to restrictions on these compounds3. However, besides neonicotinoids, field-based evidence of the effects of landscape pesticide exposure on wild bees is lacking. Bees encounter many pesticides in agricultural landscapes4–9and the effects of this landscape exposure on colony growth and development of any bee species remains unknown. Here we show that the many pesticides found in bumble bee-collected pollen are associated with reduced colony performance during crop bloom, especially in simplified landscapes with intensive agricultural practices. Our results from 316 Bombus terrestriscolonies at 106 agricultural sites across eight European countries confirm that the regulatory system fails to sufficiently prevent pesticide-related impacts on non-target organisms, even for a eusocial pollinator species in which colony size may buffer against such impacts10,11. These findings support the need for postapproval monitoring of both pesticide exposure and effects to confirm that the regulatory process is sufficiently protective in limiting the collateral environmental damage of agricultural pesticide use.

Radiation exposure to patient and surgeon during cardiac implantable electrical device (CIED) procedures remains a substantial health hazard to date. Advanced technical options for radiation dose reduction often pose considerable financial hurdles. We propose a near-zero cost, low-effort modification to a clinical x-ray system significantly reducing radiation dose during CIED implantation.

Cardiac autonomic dysfunction after myocardial infarction identifies patients at high risk despite only moderately reduced left ventricular ejection fraction. We aimed to show that telemedical monitoring with implantable cardiac monitors in these patients can improve early detection of subclinical but prognostically relevant arrhythmic events.

Lyme borreliosis, or Lyme disease, is caused by the spirochete Borrelia burgdorferi, which is transmitted by Ixodes ticks. The disease is endemic in wooded areas of the country with a moderate climate. Lyme borreliosis develops in three stages, which are characterized by different clinical symptoms. The early stages are associated with the development of skin lesions and nerve-related symptoms. However, the occurrence of all three stages is rare, and some patients can develop symptoms of the last stage without having any previous symptoms. Diagnosis of the chronic or later phase of Lyme disease is difficult, because symptoms are nonspecific and tests for identifying B. burgdorferi are difficult to interpret. The patient's immune response to B. burgdorferi may be useful in diagnosis. The cellular immune response to B. burgdorferi was assessed in 24 patients with Lyme disease, 30 patients with joint disease unrelated to B. burgdorferi infection, and 20 normal subjects. Exposure of blood to B. burgdorferi caused an increased proliferation of immune T cells. This response was greater in patients with Lyme disease than in normal subjects or patients with joint disease unrelated to Lyme disease. The rate of proliferation decreased after treatment with antibiotics. The T cells from patients with Lyme disease grew faster when exposed to B. burgdorferi than when exposed to Treponema phagedenis. T-cell proliferation was not correlated with the different stages of the disease. These findings suggest that the proliferation of lymphocytes, such T cells, may be useful is the diagnosis of Lyme disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Rheumatoid arthritis (RA) is a disease that causes inflammation and tissue damage in the joints. The changes that occur within the joints during RA are similar to those seen in autoimmune diseases. An autoimmune disease occurs when the body makes proteins, called antibodies, that attack and destroy the body's own tissues. Under normal circumstances, the immune system makes antibodies that attack and destroy only foreign substances or microorganisms that invade the body and cause infection. Patients with RA have abnormally large numbers of T lymphocytes (a type of white blood cell) in their affected joints. These cells are involved in the process of making antibodies that attack and destroy the tissue in the joint. Animal models of arthritis have been used to show that if T cells are taken from a joint with arthritis and injected into the joint of a healthy animal, the healthy joint will develop arthritis. Treatment for RA has focused on removing the T lymphocytes from the patient by using radiation treatments or by a form of plasmapheresis, where the blood is passed through a device that removes the white blood cells. These treatments have had modest success in improving the condition of patients with RA. In an attempt to develop a more effective method of treatment, monoclonal antibodies (called anti-CD4) were developed and used to remove the T lymphocytes. When patients with RA were injected with these antibodies, the numbers of T lymphocytes were drastically reduced within one hour and remained low for eight weeks. Treatment was performed for seven days, and five out of nine RA patients that were treated showed signs of improvement for up to six months following treatment. The remaining four patients were treated again and showed signs of improvement. The treatment reduced the number of swollen joints but did not reduce morning joint stiffness or improve grip strength. There were few side effects associated with this treatment. More studies are needed to determine the long-term effects of this treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

The rapid detection of trace gases is of great relevance for various spectroscopy applications. In this regard, the technology of external cavity diode lasers (ECDLs) has firmly established itself due to its excellent properties. Outside of the laboratory environment, however, these still have some restrictions, especially with regard to high acquisition rates for sensitive spectroscopy applications and mode-hop-free tuning. In this article, we present our innovative GaSb-based ECDL concept, in which a resonantly driven microelectromechanical system actuator is used. With this, a defined frequency range can be tuned extremely fast and without mode hops. Results of the characterization and its use for the rapid detection of trace gases are presented.

All-trans-retinoic acid (ATRA) is highly active in acute promyelocytic leukemia but not in other types of acute myeloid leukemia (AML). Previously, we showed that ATRA in combination with Lysine-specific demethylase 1 (LSD1) inhibition by tranylcypromine (TCP) can induce myeloid differentiation in AML blasts. This phase I/II clinical trial investigated the safety and efficacy of TCP/ATRA treatment as salvage therapy for relapsed/refractory (r/r) AML. The combination was evaluated in 18 patients, ineligible for intensive treatment. The overall response rate was 20%, including two complete remissions without hematological recovery and one partial response. We also observed myeloid differentiation upon TCP/ATRA treatment in patients who did not reach clinical remission. Median overall survival (OS) was 3.3 months, and one-year OS 22%. One patient developed an ATRA-induced differentiation syndrome. The most frequently reported adverse events were vertigo and hypotension. TCP plasma levels correlated with intracellular TCP concentration. Increased H3K4me1 and H3k4me2 levels were observed in AML blasts and white blood cells from some TCP/ATRA treated patients. Combined TCP/ATRA treatment can induce differentiation of AML blasts and lead to clinical response in heavily pretreated patients with r/r AML with acceptable toxicity. These findings emphasize the potential of LSD1 inhibition combined with ATRA for AML treatment.

Silver iodide (AgI) is an efficient blue emitter that is easily synthesized and nanostructured. We investigate the coupling of AgI to plasmon modes, choosing aluminum (Al) owing to its low damping in the blue spectral range, in contrast to silver or gold. We investigate, first, an extended Al thin film overcoated with a SiO2spacer layer and a AgI film. Spectroscopic surface plasmon resonance measurements confirm the anticrossing in the system’s dispersion diagram, with a large energy splitting of about 140 meV, indicative of the onset of strong coupling. Second, we probe Al nanodisks overcoated with SiO2and AgI, spectrally shifting the dipolar Al plasmon over the AgI absorption line by lithographically controlling the disk diameter. From extinction spectra, we again observe anticrossing, with an energy splitting of about 100 meV. Our results demonstrate that AgI is an easily fabricated and structured emitter, which in combination with Al forms an attractive platform to achieve an efficient plasmon–exciton coupling in the blue spectral range.

We use cathodoluminescence (CL) spectroscopy in a transmission electron microscope to probe the radial breathing mode of plasmonic silver nanodisks. A two-mirror detection system sandwiching the sample collects the CL emission in both directions, that is, backward and forward with respect to the electron beam trajectory. We unambiguously identify a spectral shift of about 8 nm in the CL spectra acquired from both sides and show that this asymmetry is induced by the electron beam itself. By numerical simulations, we confirm the observations and identify the underlying physical effect due to the interference of the CL emission patterns of an electron-beam-induced dipole and the breathing mode. This effect can ultimately limit the achievable fidelity in CL measurements on any system involving multiple excitations and should therefore be considered with care in high-precision experiments.

Nanometric gaps in plasmonic structures can lead to huge optical near fields and, related, to strongly enhanced interaction of molecules and light. Nanocavities formed by sphere-on-film or cube-on-film systems were recently established as promising systems, eventually reaching the strong coupling regime. However, such structures are limited with respect to being bound to a surface and by having no means of adjusting the resonance wavelength to the requirements of arbitrary analytes, independent of the gap width. We suggest and investigate in this paper silver–gold compound nanocuboid dimers in colloidal solution as potential structures to mitigate both limitations. We analyze the dimers’ plasmonic properties by a combination of optical spectroscopy, electron energy loss spectroscopy, and numerical simulations, focusing on the longitudinal dimer geometry and the dominant light-coupled plasmon mode. We then calculate optical field enhancements under light and electron excitation to assess the cuboid dimer’s potential in sensing and spectroscopy applications.

Recent animal and human studies have shown antiarrhythmic effects inhibiting inducibility of atrial fibrillation through low-level transcutaneous electrical stimulation at the auricular branch of the vagus nerve (ABVN).

This work uses an open-source, data-driven, image-based modelling framework; OpenImpala. Lithium Iron Phosphate (LFP) electrode samples were imaged using micro-CT. Two scans were performed using the Zeiss 160 kVp Versa 510 at the University of Southampton. The two scans were both carried out on the same sample and using the same focal point, this is so they could be used as a direct comparison to see how porosity and tortuosity changed with spatial resolution. It is found that the Bruggeman correlation significantly underestimates the tortuosity compared to the OpenImpala calculated results. It is also found that there is a larger statistical variability in the 801 nm results, whereas the 400 nm results have a much smaller standard deviation. These results were compared to computer-generated images based on FIB/SEM tomographic data of a single Nickel Manganese Cobalt Oxide (NMC) porous active particle and found to have the same trends.

The discovery of Li-containing transition-metal (TM) oxides has attracted broad interest and triggered intensive studies on these oxides as cathodes for lithium-ion batteries over decades. Unfortunately, a clear picture of how Li/TM/O ions are transported and electrons are transferred during the synthesis of these compounds is still missing, especially when cubic close-packed (ccp) anion sublattices are involved, as it is the case for spinel, layered, or rock-salt systems. In the present study, a series of layered Li(Ni,Co,Mn)O2oxides were chosen as target materials to elucidate the underlying formation mechanism of these compounds during the high-temperature lithiation reaction. The consistent experimental results demonstrate that, as lithium ions are inserted from the surface to the bulk, some TM cations located within the bulk of crystallites are able to diffuse to the near-surface region. They create cation vacancies for the inserted lithium ions, and the mass transport behavior of these elements is driven by the chemical potential gradient. Concurrently, oxygen anions from lithium oxides and/or ambient oxygen are adsorbed and incorporated into the ccp oxygen lattice on the surface structure, connecting the relocated TM cations and the incorporated lithium ions by forming ionic bonds. This process is concomitant with crystal growth, surface reorganization caused by phase transformation, and occurrence and disappearance of pores.

Grazing diffraction orders on metal gratings give rise to peculiar optical effects that were contemplated by Wood, Rayleigh, and Fano. With plasmonic nanoparticles as resonant grating elements, the phenomenology of such surface lattice resonances becomes quite rich, including spectrally narrow extinction peaks and optical band gap formation. It has been observed that at perpendicular incidence, either the higher- or lower-energy branch corresponding to the first grazing diffraction orders is bright, that is, couples strongly to light. Reviewing the literature, it appears that particle size is the factor determining which dispersion branch lights up. However, a consistent explanation for this effect is lacking. After revisiting the effect experimentally and by numerical simulation, we clarify the underlying physics by analyzing nanoparticle gratings in terms of, first, an oscillator model and, second, a photonic crystal description. Both approaches reveal the central role of a particle size-dependent phase shift in the back-scattering of grazing light fields by the particle grating. This phase shift determines the symmetry of the resulting field profiles corresponding to the dispersion branches and thus their ability to couple to the exciting light. This physical understanding could considerably simplify the dispersion engineering of plasmonic nanoparticle gratings for specific applications as sensing or lasing.

An innovative ceramic ink system for thin inkjet-printed dielectric layers is presented, with which it is possible to avoid undesired drying effects. This system contains surface-modified Ba0.6Sr0.4TiO3(BST) particles, a cross-linking agent, and a thermal radical initiator. The polymerization starts immediately after the ink drop contacts the heated substrate and therefore leads to very homogeneous topographies. Since an organic/inorganic composite ink is used, no sintering is needed after printing and thus printing on flexible substrates is possible. A comparison of the printing and drying behavior between modified and nonmodified BST with the described ink system is performed. The successful surface modification is confirmed via X-ray photoelectron spectroscopy (XPS). Topographies of different printed structures are compared by white light interferometry, the occurring polymerization is confirmed by measurements with an oscillatory rheometer, layer thicknesses are determined by scanning electron microscopy (SEM) images, and the capacitance of a printed capacitor is measured via impedance spectroscopy. It is successfully shown that the developed ink system enables the production of thin ceramic layers (<1 μm) with very homogeneous topographies since undesired drying effects can be avoided. The printed dielectric layers on flexible substrates have a high ceramic content and a high permittivity of 40.

Age is a relevant risk factor for the development of atrial fibrillation (AF) and is associated with increased recurrence rates in the setting of rhythm control. Catheter ablation is increasingly advocated in elderly despite conflicting data regarding its efficacy and safety in this patient cohort. Therefore, we aimed to analyse currently available evidence regarding catheter ablation for AF in patients ≥ 75 years old compared with younger patients.

Age is a major risk factor for development of atrial fibrillation (AF) and associated with increased recurrence rates in the setting of rhythm control. Current data tend to support catheter ablation in elderly patients but uncertainties exist regarding efficacy and safety of ablation in elderly patients.

Age is a major risk-factor for atrial fibrillation (AF) and associated hospitalizations. With increasing emphasis on rhythm-control, pulmonary-vein isolation (PVI) is often suggested, even to elderly patients (≥75 years). Efficacy of PVI aiming at rhythm-control is limited in persistent AF. Pacemaker implantation with atrioventricular-node ablation may represent a reasonable alternative, with the aim of controlling symptoms and improving quality-of-life in elderly patients. In this investigator-initiated, randomized, multicenter trial, we test the hypothesis that pacemaker-implantation and atrioventricular-node (AVN) ablation provides superior symptom-control over PVI in elderly patients with symptomatic persistent AF, without any increase in adverse-event profile.

Surface plasmon polaritons (SPPs) can confine and guide light in nanometer volumes and are ideal tools for achieving electric field enhancement and the construction of nanophotonic circuitry. The realization of the highest field strengths and fastest switching requires confinement also in the temporal domain. Here, we demonstrate a tapered plasmonic waveguide with an optimized grating structure that supports few-cycle surface plasmon polaritons with >70 THz bandwidth while achieving >50% light-field-to-plasmon coupling efficiency. This enables us to observe the─to our knowledge─shortest reported SPP wavepackets. Using time-resolved photoelectron microscopy with suboptical-wavelength spatial and sub-10 fs temporal resolution, we provide full spatiotemporal imaging of co- and counter-propagating few-cycle SPP wavepackets along tapered plasmonic waveguides. By comparing their propagation, we track the evolution of the laser-plasmon phase, which can be controlled via the coupling conditions.

American Foulbrood (AFB) is a particularly pernicious bacterial disease of honey bees due to the extreme persistence of endospores of the causative agent Paenibacillus larvae. These spores are resistant to harsh environmental conditions, unaffected by antimicrobial agents and can remain viable for decades. The germination of the endospore in the larval midgut is the crucial first step leading to infection, followed by vegetative growth, tissue invasion and disease, culminating in spore formation when the host´s nutrients have been exhausted. Therefore, inhibiting spore germination or impeding early vegetative growth would be a highly effective strategy for limiting the impact of AFB. We previously showed that honey bee-specific lactic acid bacteria (hbs–LAB) had a major inhibitory effect on P. larvaeboth in culture and in larval bioassays. The present study documents the progress towards characterization of compounds, processes and interactions between P. larvaeand the hbs–LAB responsible for this inhibitory effect. Firstly, we used an agar diffusion assay and larval infection bioassay to show that most, if not all, of the inhibitory effect was associated with the extracellular fraction (secretome). Secondly, we employed a turbidimetric growth assay to demonstrate that the hbs–LAB secretome strongly inhibited P. larvaevegetative growth, however, probably not by reducing spore germination. The inhibition was similarly effective against both major P. larvaegenotypes (ERIC-I and II) in all experiments. The implications of our results for characterization of the secretome and for the management and treatment of AFB and P. larvaeare further discussed.

During the last decades we see a many-faceted picture in industry and retail trade, which has been strongly influenced by an increasing digitalization and commercial liberalization in a globalized economy. Linked to these changes there are some fundamental areas which are discussed, especially the use of additive manufacturing (or 3D-printing). In this contribution some technological basics of additive manufacturing and practical applications are sketched. Following, the structural and organizational effects on logistics processes within selected supply chains are analyzed and evaluated. Moreover, the consequences of these developments are considered, not only from an operational point of view, but also under legal and social aspects, especially with regard to labor markets. It is also made clear, that we have not a theoretical discussion about a far-off future, but that these presented technologies is an integrated part of our today’s world with a growing importance.

In view of the requirements for high-energy lithium ion batteries (LIBs), hierarchically layered LiNi1/3Co1/3Mn1/3O2 (NCM111) cathode materials have been prepared using a hydroxide coprecipitation method and subsequent high-temperature solid-state reaction. The diffraction results show that the synthesized NCM111 has a well-defined layered hexagonal structure. The initial specific discharge capacity of a Li/NCM111 cell is 204.5 mAh g[?]1 at a current density of 28 mA g[?]1 between 2.7 and 4.8 V. However, the cell suffers from poor capacity retention over extended charge-discharge cycles. The structural evolution of NCM111 electrode during electrochemical cycling is carefully investigated by in situ high-resolution synchrotron radiation diffraction. It is found that the nanodomain formation of a layered hexagonal phase H3 and a cubic spinel phase after charging to voltages above 4.6 V is the main source for the structural collapse in c direction and the poor cycling performance. This process is accompanied by the removal of oxygen, the transition metal (TM) migration and the crack generation in the nanodomains of the primary particles. These results may help to better understand the structural degradation of layered cathodes in order to develop high energy density LIBs.

The ultimate goal in the treatment of ET is to eliminate mutant cells with the capacity to both proliferate and self-renew. Lysine-specific demethylase-1, LSD1, is an enzyme critical for regulating the proliferation of hematopoietic stem cells and the maturation of progenitors (Sprussel et al.2012). Bomedemstat is an orally active LSD1 inhibitor that reduces platelets, inflammatory cytokines, and the mutant cell burden in mouse models of myeloproliferative neoplasms (Jutzi et. al., 2019). All current treatments - hydroxyurea, interferon, or anagrelide - have their limitations and do not substantially affect the natural history of ET.

Introduction:Polycythemia vera (PV) is characterized by trilineage blood cell expansion, PV-associated symptoms, and the risk of thromboembolic complications, progression to post-PV myelofibrosis, and acute leukemia. Cytoreductive treatment with hydroxyurea (HU) or ropeginterferon-alpha is approved in EU for the treatment of high-risk patients (pts) with PV. In addition, ruxolitinib (RUX) is approved for HU-intolerant/-resistant PV. However, RUX vs. best available therapy (BAT) has not been investigated as first-line treatment of pts with untreated PV. We hypothesized that RUX may have higher efficacy in such early-line PV pts.

This group of rheumatologists gathered in Vienna out of concern about the absence of a uniform view and guidance on the introduction of tumour necrosis factor (TNF)-blocking therapies in our [...]

Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. Since this discovery, additional VHL mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHL is a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHL cryptic exon (termed E1′) deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1′ in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1′ in addition to a mutation in VHL coding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHL exons. In this study, we show that the mutations induced a dysregulation of VHL splicing with excessive retention of E1′ and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHL exon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHL alterations and reveals a novel complex splicing regulation of the VHL gene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway.

Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. Since this discovery, additional VHLmutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHLis a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHLcryptic exon (termed E1′) deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1′ in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1′ in addition to a mutation in VHLcoding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHLexons. In this study, we show that the mutations induced a dysregulation of VHLsplicing with excessive retention of E1′ and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHLexon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHLalterations and reveals a novel complex splicing regulation of the VHLgene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway.

The paper focuses on the performance and aging behavior of lithium nickel cobalt manganese oxide commercial standard material (NCM-111) which is improved with a post synthesis process in order to enhance the cathode active material of lithium-ion pouch cells regarding their capacity and cyclic stability. The aging behavior of the cells is analyzed with electrochemical impedance spectroscopy (EIS) during long-term electrochemical load cycling tests based on the Common Artemis Driving Cycle (CADC). Additionally, post-mortem investigations using scanning electron microscopy (SEM) and X-ray diffraction (XRD) were performed. The results demonstrate that post-processing of electrode active material is an effective tool to improve the properties of lithium-ion electrode materials, especially regarding high energy applications and lifetime optimization. The paper bridges the gap between lithium-ion battery electrode material development and the necessary cell testing under automotive relevant conditions which is important for the evaluation of new lithium-ion battery materials for automotive applications.

The availability of monoclonal antibodies has revolutionized the treatment of an increasingly broad spectrum of diseases. Inflammatory diseases are among those most widely treated with protein-based therapeutics, termed biologics. Following the first large-scale clinical trials with monoclonal antibodies performed in the 1990s by rheumatologists and clinical immunologists, the approval of these agents for use in daily clinical practice led to substantial progress in the treatment of rheumatic diseases. Despite this progress, however, only a proportion of patients achieve a long-term clinical response. Data on the use of agents blocking TNF, which were among the first biologics introduced into clinical practice, provide ample evidence of primary and secondary treatment inefficacy in patients with rheumatoid arthritis (RA). Important issues relevant to primary and secondary failure of these agents in RA include immunogenicity, methodological problems for the detection of antidrug antibodies and trough drug levels, and the implications for treatment strategies. Although there is no strong evidence to support the routine estimation of antidrug antibodies or serum trough levels during anti-TNF therapy, these assessments might be helpful in a few clinical situations; in particular, they might guide decisions on switching the therapeutic biologic in certain instances of secondary clinical failure.

The prognostic significance of adenosine-mediated dormant pulmonary vein conduction, and whether such dormant conduction should be eliminated, remains controversial. We sought to perform a meta-analysis of data from eligible studies to delineate the prognostic impact of adenosine-guided radiofrequency catheter ablation of atrial fibrillation. A systematic literature search was performed using online databases in order to identify relevant studies from January 2004 to September 2016. Ten studies [six observational and four randomized control trials (RCTs)] were included in the analysis. Five studies (two observational and three RCTs) compared the efficacy of adenosine-mediated elimination of dormant conduction versus no adenosine test. Overall, the adenosine-guided ablation strategy displayed better long-term outcomes as compared with no adenosine testing (RR 1.08, 95% CI 1.01–1.14, p=0.02; Heterogeneity: I2=42%, p: 0.14). The meta-analysis of only RCTs failed to show any differences between the two strategies (RR 1.03, 95% CI 0.96–1.11, p=0.37; Heterogeneity: I20%, p: 0.41). Eight studies (five observational and three RCTs) addressed the efficacy of adenosine-induced dormant conduction and additional ablation versus no dormant conduction during adenosine challenge. Overall, a trend towards a better outcome in those without dormant conduction during drug challenge was noted (RR 0.89, 95% CI 0.77–1.03, p=0.11; Heterogeneity: I265% p: 0.006). The pooled analysis of RCTs failed to show any differences between the two arms (RR 0.90, 95% CI 0.62–1.30, p= 0.57; Heterogeneity: I288%, p: 0.0002). Adenosine-guided radiofrequency catheter ablation of atrial fibrillation does not provide additional benefit in terms of freedom of arrhythmia recurrence.

The high voltage LiNi0.5Mn1.5O4 spinel suffers from severe capacity fade when cycled against a graphitic anode as well as a relatively low theoretical capacity. Using metallic lithium as counter electrode, the stability is improved and the ability of the spinel structure to host 2 Li eq. can be used to improve the capacity. This leads to a theoretical specific energy of [?]1000 Wh kg[?]1. Unfortunately, the cycling of 2 Li eq. involves a phase transition from cubic to tetragonal associated with material degradation. In this work doping is used to improve capacity retention when cycling between 2.0 and 5.0 V. Initial capacities and stabilities are directly dependent on synthesis conditions and doping elements. Therefore, Fe- and Ti-doped spinels are compared with Ru- and Ti-doped spinels and tested at different cycling conditions. The cycling stability can be improved significantly by using reannealed material and by changing the discharge cutoff criteria. Thus a capacity of 190 mAh g[?]1 is achieved at a rate of C/2 with a capacity retention of [?]92% after 100 cycles. Furthermore, differences in the discharge behavior between the differently treated Ru- and Ti- doped materials are discussed based on the electrochemical behavior, the particle morphology and in-situ XRD analysis.

Metabolic changes drive monocyte differentiation and fate. Although abnormal mitochondria metabolism and innate immune responses participate in the pathogenesis of many inflammatory disorders, molecular events regulating mitochondrial activity to control life and death in monocytes remain poorly understood. We show here that, in human monocytes, microRNA-125b (miR-125b) attenuates the mitochondrial respiration through the silencing of the BH3-only proapoptotic protein BIK and promotes the elongation of the mitochondrial network through the targeting of the mitochondrial fission process 1 protein MTP18, leading to apoptosis. Proinflammatory activation of monocyte-derived macrophages is associated with a concomitant increase in miR-125b expression and decrease in BIK and MTP18 expression, which lead to reduced oxidative phosphorylation and enhanced mitochondrial fusion. In a chronic inflammatory systemic disorder, CD14+ blood monocytes display reduced miR-125b expression as compared with healthy controls, inversely correlated with BIK and MTP18 messenger RNA expression. Our findings not only identify BIK and MTP18 as novel targets for miR-125b that control mitochondrial metabolism and dynamics, respectively, but also reveal a novel function for miR-125b in regulating metabolic adaptation of monocytes to inflammation. Together, these data unravel new molecular mechanisms for a proapoptotic role of miR-125b in monocytes and identify potential targets for interfering with excessive inflammatory activation of monocytes in inflammatory disorders.