Evidence for distinct polymer chain orientations in KC60 and RbC60

The KC60 and RbC60 polymer phases exhibit contrasting electronic properties while powder diffraction studies have revealed no definite structural difference. We have performed single crystal X-ray diffraction and diffuse scattering studies of these compounds. It is found that KC60 and RbC60 possess different chain orientations about their axes, which are described by distinct space groups Pmnn and I2/m, respectively. Such a structural difference will be of great importance to a complete understanding of the physical properties.Comment: To be published in Phys. Rev. Let

Absence of Myocardial Thyroid Hormone Inactivating Deiodinase Results in Restrictive Cardiomyopathy in Mice

Cardiac injury induces myocardial expression of the thyroid hormone inactivating type 3 deiodinase (D3), which in turn dampens local thyroid hormone signaling. Here, we show that the D3 gene (Dio3) is a tissue-specific imprinted gene in the heart, and thus, heterozygous D3 knockout (HtzD3KO) mice constitute a model of cardiac D3 inactivation in an otherwise systemically euthyroid animal. HtzD3KO newborns have normal hearts but later develop restrictive cardiomyopathy due to cardiac-specific increase in thyroid hormone signaling, including myocardial fibrosis, impaired myocardial contractility, and diastolic dysfunction. In wild-type littermates, treatment with isoproterenol-induced myocardial D3 activity and an increase in the left ventricular volumes, typical of cardiac remodeling and dilatation. Remarkably, isoproterenol-treated HtzD3KO mice experienced a further decrease in left ventricular volumes with worsening of the diastolic dysfunction and the restrictive cardiomyopathy, resulting in congestive heart failure and increased mortality. These findings reveal crucial roles for Dio3 in heart function and remodeling, which may have pathophysiologic implications for human restrictive cardiomyopathy

The use of remote monitoring of cardiac implantable devices during the COVID-19 pandemic: an EHRA physician survey

It is unclear to what extent the COVID-19 pandemic has influenced the use of remote monitoring (RM) of cardiac implantable electronic devices (CIEDs). The present physician-based European Heart Rhythm Association (EHRA) survey aimed to assess the influence of the COVID-19 pandemic on RM of CIEDs among EHRA members and how it changed the current practice. The survey comprised 27 questions focusing on RM use before and during the pandemic. Questions focused on the impact of COVID-19 on the frequency of in-office visits, data filtering, reasons for initiating in-person visits, underutilization of RM during COVID-19, and RM reimbursement. A total of 160 participants from 28 countries completed the survey. Compared to the pre-pandemic period, there was a significant increase in the use of RM in patients with pacemakers (PMs) and implantable loop recorders (ILRs) during the COVID-19 pandemic (PM 24.2 vs. 39.9%, P = 0.002; ILRs 61.5 vs. 73.5%, P = 0.028), while there was a trend towards higher utilization of RM for cardiac resynchronization therapy-pacemaker (CRT-P) devices during the pandemic (44.5 vs. 55%, P = 0.063). The use of RM with implantable cardioverter-defibrillators (ICDs) and CRT-defibrillator (CRT-D) did not significantly change during the pandemic (ICD 65.2 vs. 69.6%, P = 0.408; CRT-D 65.2 vs. 68.8%, P = 0.513). The frequency of in-office visits was significantly lower during the pandemic (P < 0.001). Nearly two-thirds of participants (57 out of 87 respondents), established new RM connections for CIEDs implanted before the pandemic with 33.3% (n = 29) delivering RM transmitters to the patient's home address, and the remaining 32.1% (n = 28) activating RM connections during an in-office visit. The results of this survey suggest that the crisis caused by COVID-19 has led to a significant increase in the use of RM of CIEDs

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Case report: Synergetic effect of ischaemia and increased vagal tone inducing ventricular fibrillation in a patient with Brugada syndrome

Background Brugada syndrome (BS) is a hereditary channelopathy associated with syncope, malignant ventricular arrhythmia, and sudden cardiac death. Right ventricular ischaemia and BS have similar underlying substrates precipitating ventricular tachycardia or fibrillation (VF). ................................................................................................................................................................................................... Case summary A 72-year-old woman with BS and a stenosis on the proximal right coronary artery received several subsequent implantable cardioverter-defibrillator shocks due to VF during an episode of extreme nausea with vomiting. ................................................................................................................................................................................................... Discussion This case report emphasizes on the synergetic effect of mild ischaemia and increased vagal tone on the substrate responsible for BS to create pathophysiological changes precipitating VF

Classification accuracy and compatibility across devices of a new Rapid-E+ flow cytometer

The study evaluated a new model of a Plair SA airflow cytometer, Rapid-E+, and assessed its suitability for airborne pollen monitoring within operational networks. Key features of the new model are compared with the previous one, Rapid-E. A machine learning algorithm is constructed and evaluated for (i) classification of reference pollen types in laboratory conditions and (ii) monitoring in real-life field campaigns. The second goal of the study was to evaluate the device usability in forthcoming monitoring networks, which would require similarity and reproducibility of the measurement signal across devices. We employed three devices and analysed (dis-)similarities of their measurements in laboratory conditions. The lab evaluation showed similar recognition performance to that of Rapid-E, but field measurements in conditions when several pollen types were present in the air simultaneously showed notably lower agreement of Rapid-E+ with manual Hirst-type observations than those of the older model. An exception was the total-pollen measurements. Comparison across the Rapid-E+ devices revealed noticeable differences in fluorescence measurements between the three devices tested. As a result, application of the recognition algorithm trained on the data from one device to another led to large errors. The study confirmed the potential of the fluorescence measurements for discrimination between different pollen classes, but each instrument needed to be trained individually to achieve acceptable skills. The large uncertainty of fluorescence measurements and their variability between different devices need to be addressed to improve the device usability.</p

Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures

Cancer genomes harbor a broad spectrum of structural variants (SVs) driving tumorigenesis, a relevant subset of which escape discovery using short-read sequencing. We employed Oxford Nanopore Technologies (ONT) long-read sequencing in a paired diagnostic and post-therapy medulloblastoma to unravel the haplotype-resolved somatic genetic and epigenetic landscape. We assembled complex rearrangements, including a 1.55-Mbp chromothripsis event, and we uncover a complex SV pattern termed templated insertion (TI) thread, characterized by short (mostly <1 kb) insertions showing prevalent self-concatenation into highly amplified structures of up to 50 kbp in size. TI threads occur in 3% of cancers, with a prevalence up to 74% in liposarcoma, and frequent colocalization with chromothripsis. We also perform long-read-based methylome profiling and discover allele-specific methylation (ASM) effects, complex rearrangements exhibiting differential methylation, and differential promoter methylation in cancer-driver genes. Our study shows the advantage of long-read sequencing in the discovery and characterization of complex somatic rearrangements

Dynamical Mean Field Theory for Self-Generated Quantum Glasses

We present a many body approach for non-equilibrium behavior and self-generated glassiness in strongly correlated quantum systems. It combines the dynamical mean field theory of equilibrium systems with the replica theory for classical glasses without quenched disorder. We apply this approach to study a quantized version of the Brazovskii model and find a self-generated quantum glass that remains in a quantum mechanically mixed state as T -> 0. This quantum glass is formed by a large number of competing states spread over an energy region which is determined within our theory.Comment: 10 pages, 4 figure

What is the future for nuclear fission technology? A technical opinion from the Guest Editors of VSI NFT series and the Editor of the Journal Nuclear Engineering and Design

The Nuclear Fission Technology (NFT) series of Virtual Special Issues (VSIs) for the Journal Nuclear Engineering and Design (J NED) was proposed in 2023, including the request to potential authors of manuscript to address the following questions: o For how long will (water-cooling based) large size nuclear reactor survive? o Will water-technology based SMRs displace large reactors? o Will non-water-cooling technology SMRs and micro-reactors have an industrial deployment? o Will breeding technology, including thorium exploitation, have due relevance? o Will ‘nuclear infrastructure’ (fuel supply, financial framework, competence by regulators for new designs, waste management, etc.) remain or be sufficiently robust? Several dozen Guest Editors (GEs), i.e., the authors of the present document, managed the activity together with the Editor-in-Chief (EiC) of the journal. More than one thousand scientists contributed 470+ manuscripts, not evenly distributed among the geographical regions of the world and not necessarily addressing directly the bullet-questions, but certainly providing a view of current research being done. Key conclusions are as follows: (a) Large size reactors are necessary for a sustainable and safe exploitation of nuclear fission technology; (b) The burning of 233U (from thorium) and 239Pu (from uranium) is unavoidable, as well as recycling residual uranium currently part of waste; (c) Nuclear infrastructures in countries that currently use, or are entering the use of, fission energy for electricity production need a century planning; (d) The adoption of small reactors for commercial naval propulsion, hydrogen production and desalination is highly recommended