Fossil biomass preserved as graphitic carbon in a late paleoproterozoic banded iron formation metamorphosed at more than 550°C

Metamorphism is thought to destroy microfossils, partly through devolatilization and graphitization of biogenic organic matter. However, the extent to which there is a loss of molecular, elemental and isotope signatures from biomass during high-temperature metamorphism is not clearly established. We report on graphitic structures inside and coating apatite grains from the c. 1850 Ma Michigamme silicate banded iron formation from Michigan, metamorphosed above 550°C. Traces of N, S, O, H, Ca and Fe are preserved in this graphitic carbon and X-ray spectra show traces of aliphatic groups. Graphitic carbon has an expanded lattice around 3.6 Å, forms microscopic concentrically-layered and radiating polygonal flakes and has homogeneous δ13C values around −22‰, identical to bulk analyses. Graphitic carbon inside apatite is associated with nanometre-size ammoniated phyllosilicate. Precursors of these metamorphic minerals and graphitic carbon originated from ferruginous clayrich sediments with biomass. We conclude that graphite coatings and inclusions in apatite grains indicate fluid remobilization during amphibolite-facies metamorphism of precursor biomass. This new evidence fills in observational gaps of metamorphosed biomass into graphite and supports the existence of biosignatures in the highly metamorphosed iron formation from the Eoarchean Akilia Association, which dates from the beginning of the sedimentary rock record

Biomartr: genomic data retrieval with R

$\textbf{MOTIVATION}$: Retrieval and reproducible functional annotation of genomic data are crucial in biology. However, the current poor usability and transparency of retrieval methods hinders reproducibility. Here we present an open source R package, $\textit{biomartr}$, which provides a comprehensive easy-to-use framework for automating data retrieval and functional annotation for meta-genomic approaches. The functions of biomartr achieve a high degree of clarity, transparency and reproducibility of analyses. $\textbf{RESULTS}$: The $\textit{biomartr}$ package implements straightforward functions for bulk retrieval of all genomic data or data for selected genomes, proteomes, coding sequences and annotation files present in databases hosted by the National Center for Biotechnology Information (NCBI) and European Bioinformatics Institute (EMBL-EBI). In addition, $\textit{biomartr}$ communicates with the BioMartr database for functional annotation of retrieved sequences. Comprehensive documentation of $\textit{biomartr}$ functions and five tutorial vignettes provide step-by-step instructions on how to use the package in a reproducible manner. $\textbf{AVAILABILITY AND IMPLEMENTATION}$: The open source $\textit{biomartr}$ package is available at https://github.com/HajkD/biomartr and https://cran.r-project.org/web/packages/biomartr/index.htmlThis work was supported by an European Research Council grant named EVOBREED [grant number 322621] (to JP) and a Gatsby Fellowship [grant number AT3273/GLE] (to JP)

Pore-size dependence of the thermal conductivity of porous silicon : a phonon hydrodynamic approach

Phononhydrodynamics is used to analyze the influence of porosity and of pore size on reduction in thermal conductivity in porous silicon, with respect to crystalline silicon. The expressions predict that the thermal conductivity is lower for higher porosity and for smaller pore radius, as a consequence of phononballisticeffects. The theoretical results describe experimental data better than the assumption that they only depend on porosity

A Systematic Review of the Effects of Hyperoxia in Acutely Ill Patients:Should We Aim for Less?

Introduction. Despite widespread and liberal use of oxygen supplementation, guidelines about rational use of oxygen are scarce. Recent data demonstrates that current protocols lead to hyperoxemia in the majority of the patients and most health care professionals are not aware of the negative effects of hyperoxemia. Method. To investigate the effects of hyperoxemia in acutely ill patients on clinically relevant outcomes, such as neurological and functional status as well as mortality, we performed a literature review using Medline (PubMed) and Embase. We used the following terms: hyperoxemia OR hyperoxemia OR [“oxygen inhalation therapy” AND (mortality OR death OR outcome OR survival)] OR [oxygen AND (mortality OR death OR outcome OR survival)]. Original studies about the clinical effects of hyperoxemia in adult patients suffering from acute or emergency illnesses were included. Results. 37 articles were included, of which 31 could be divided into four large groups: cardiac arrest, traumatic brain injury (TBI), stroke, and sepsis. Although a single study demonstrated a transient protective effect of hyperoxemia after TBI, other studies revealed higher mortality rates after cardiac arrest, stroke, and TBI treated with oxygen supplementation leading to hyperoxemia. Approximately half of the studies showed no association between hyperoxemia and clinically relevant outcomes. Conclusion. Liberal oxygen therapy leads to hyperoxemia in a majority of patients and hyperoxemia may negatively affect survival after acute illness. As a clinical consequence, aiming for normoxemia may limit negative effects of hyperoxemia in patients with acute illness

Can active surveillance really reduce the harms of overdiagnosing prostate cancer? A reflection of real life clinical practice in the PRIAS study

Background: Active surveillance (AS) for low-risk prostate cancer (PCa) appears to provide excellent long-term PCa-specific and overall survival. The choice for AS as initial treatment is mainly based on avoiding side effects from invasive treatment; but AS entails regular check-ups and the possibility of still having to switch or deciding to switch to invasive treatment. Here, we assessed the long-term follow-up data from AS in real life clinical practices. Methods: Data from the first 500 men, enrolled in PRIAS before July 2008 by 30 centers across 8 countries, were analyzed to provide long-term follow-up results. Men were advised to be regularly examined with prostate-specific antigen (PSA) tests, digital rectal examinations, and prostate biopsies. Men were advised to switch to invasive treatment if they had disease reclassification [Gleason score (GS) >= 3+ 4 on biopsy, more than two positive biopsy cores, a stage higher than cT2] or a PSA-doubling time of 0-3 years. We assessed time on AS, outcomes and reasons for discontinuing AS, and rates of potential unnecessary biopsies and treatments. Results: The median follow-up time was 6.5 years. During this period, 325 (65%) men discontinued after a median of 2.3 years and 121 (24%) men had no recent (> 1 year) data-update after a median of 7.3 years. The remaining 54 (11%) men were confirmed to be still on AS. Most men discontinued based on protocol advice; 38% had other reasons. During follow-up, 838 biopsy sessions were performed of which 79% to 90% did not lead to reclassification, depending on the criteria. Of the 325 discontinued men, 112 subsequently underwent radical prostatectomy (RP), 126 underwent radiotherapy, 57 switched to watchful waiting (WW) or died, and 30 had another or unknown treatment. RP results were available of 99 men: 34% to 68%, depending on definition, had favorable outcomes; 50% of unfavorable the outcomes occurred in the first 2 years. Of the 30 (6%) men who died, 1 man died due to PCa. Conclusions: These data, reflecting real life clinical practice, show that more than half of men switched to invasive treatment within 2.3 years, indicating limitations to the extent in which AS is able to reduce the adverse effects of overdiagnosis. Therefore, despite guidelines stating that PCa diagnosis must be uncoupled from treatment, it remains important to avoid overdiagnosing PCa as much as possible.Peer reviewe

Intraoperative neurophysiological monitoring during scoliosis surgery in patients with Duchenne muscular dystrophy

PURPOSE: Little is known about the reliability and value of intraoperative neurophysiological monitoring (IONM) in patients with Duchenne muscular dystrophy (DMD) undergoing scoliosis correction surgery. The aim of this study was to investigate the feasibility of IONM and the cortical excitability in these patients. METHODS: Fifteen patients with DMD and scoliosis and 15 patients with adolescent idiopathic scoliosis (AIS) underwent scoliosis correction surgery with the use of IONM. IONM consisted of transcranial electrical stimulation motor evoked potential (Tc-MEP) and somatosensory evoked potential (SSEP) monitoring. The highest Tc-MEP amplitudes were collected to test the feasibility. Preoperative compound muscle action potentials (CMAPs) and transcranial magnetic stimulation (TMS)-MEPs were recorded to test the cortical excitability. SSEPs were scored as elicitable or not elicitable. RESULTS: Tc-MEP amplitudes were significantly lower in the DMD group for both the gastrocnemius and tibialis anterior muscles. However, the abductor hallucis muscle had similar amplitudes in both the DMD as the AIS group. TMS/CMAP and Tc-MEP/CMAP ratios were similar in the DMD and AIS group (P = 0.126 and P = 0.792 respectively). CONCLUSIONS: Tc-MEP and SSEP monitoring is feasible, particularly when Tc-MEPs are recorded from the abductor hallucis muscle in patients with DMD. Similar TMS/CMAP and Tc-MEP/CMAP ratios show that there were no differences observed in cortical excitability between the groups. IONM seems a feasible and valuable neurophysiological tool to signal possible surgically induced damage to the spinal cord during scoliosis correction surgery in patients with DMD

Isolated eyelid closure myotonia in two families with sodium channel myotonia

Sodium channelopathies (NaCh), as part of the non-dystrophic myotonic syndromes (NDMs), reflect a heterogeneous group of clinical phenotypes accompanied by a generalized myotonia. Because of recent availability of diagnostic genetic testing in NDM, there is a need for identification of clear clinical genotype–phenotype correlations. This will enable clinicians to distinguish NDMs from myotonic dystrophy, thus allowing them to inform patients promptly about the disease, perform genetic counseling, and orient therapy (Vicart et al. Neurol Sci 26:194–202, 2005). We describe the first distinctive clinical genotype–phenotype correlation within NaCh: a strictly isolated eyelid closure myotonia associated with the L250P mutation in SCN4A. Using clinical assessment and needle EMG, we identified this genotype–phenotype correlation in six L250P patients from one NaCh family and confirmed this finding in another, unrelated NaCh family with three L250P patients

The influence of depth of anesthesia and blood pressure on muscle recorded motor evoked potentials in spinal surgery. A prospective observational study protocol

For high-risk spinal surgeries, intraoperative neurophysiological monitoring (IONM) is used to detect and prevent intraoperative neurological injury. The motor tracts are monitored by recording and analyzing muscle transcranial electrical stimulation motor evoked potentials (mTc-MEPs). A mTc-MEP amplitude decrease of 50-80% is the most common warning criterion for possible neurological injury. However, these warning criteria often result in false positive warnings. False positives may be caused by inadequate depth of anesthesia and blood pressure on mTc-MEP amplitudes. The aim of this paper is to validate the study protocol in which the goal is to investigate the effects of depth of anesthesia (part 1) and blood pressure (part 2) on mTc-MEPs. Per part, 25 patients will be included. In order to investigate the effects of depth of anesthesia, a processed electroencephalogram (pEEG) monitor will be used. At pEEG values of 30, 40 and 50, mTc-MEP measurements will be performed. To examine the effect of blood pressure on mTc-MEPs the mean arterial pressure will be elevated from 60 to 100 mmHg during which mTc-MEP measurements will be performed. We hypothesize that by understanding the effects of depth of anesthesia and blood pressure on mTc-MEPs, the mTc-MEP monitoring can be interpreted more reliably. This may contribute to fewer false positive warnings. By performing this study after induction and prior to incision, this protocol provides a unique opportunity to study the effects of depths of anesthesia and blood pressure on mTc-MEPs alone with as little confounders as possible. Trial registration number NL7772

Ground State Vortex Lattice Structures in d-wave Superconductors

We show in a realistic $d_{x^{2}-y^{2}}$ symmetry gap model for a cuprate superconductor that the clean vortex lattice has discontinuous structural transitions (at and near T=0), as a function of the magnetic field $B$ along the c-axis. The transitions arise from the singular nonlocal and anisotropic susceptibility of the $d_{x^{2}-y^{2}}$ superconductor to the perturbation caused by supercurrents associated with vortices. The susceptibility, due to virtual Dirac quasiparticle-hole excitation, is calculated carefully, and leads to a ground state transition for the triangular lattice from an orientation along one of the crystal axis to one at 45$^o$ to them, i.e, along the gap zero direction. The field scale is seen to be 5 Tesla $\sim (\Delta_{0}/ta)^{2}\Phi_{0}$, where $\Delta_{0}$ is the gap maximum, $t$ is the nearest neighbour hopping, $a$ is the lattice constant, and $\Phi_{0}$ is the flux quantum. At much higher fields ($\sim 28T$) there is a discontinuous transition to a centred square structure. The source of the differences from existing calculations, and experimental observability are discussed, the latter especially in view of the very small (a few degrees $K$ per vortex) differences in the ground state energy.Comment: To be published in Phys. Rev.

Sex Proportionality in Pre-clinical and Clinical Trials: An Evaluation of 22 Marketing Authorization Application Dossiers Submitted to the European Medicines Agency

This study assessed to what extent women were included in all phases of drug development; whether the clinical studies in the marketing authorization application dossiers include information per sex; and explored whether there are differences between women and men in the drugs' efficacy and safety. Data were extracted from dossiers submitted to the European Medicines Agency. Twenty-two dossiers of drugs approved between 2011 and 2015 for the treatment of various diseases were included. Female animals were included in only 9% of the pharmacodynamics studies, but female and male animals were included in all toxicology studies. Although fewer women than men were included in the clinical studies used to evaluate pharmacokinetics (PK) (29 to 40% women), all dossiers contained sex-specific PK parameter estimations. In the phase III trials, inclusion of women was proportional to disease prevalence for depression, epilepsy, thrombosis, and diabetes [participation to prevalence ratio (PPR) range: 0.91–1.04], but women were considered underrepresented for schizophrenia, hepatitis C, hypercholesterolemia, HIV, and heart failure (PPR range: 0.49-0.74). All dossiers contained sex-specific subgroup analyses of efficacy and safety. There seemed to be higher efficacy for women in one dossier and a trend toward lower efficacy in another dossier. More women had adverse events in both treatment (73.0 vs. 70.6%, p < 0.001) and placebo groups (69.5 vs. 65.5%, p < 0.001). In conclusion, women were included throughout all phases of clinical drug research, and sex-specific information was available in the evaluated dossiers. The included number of women was, however, not always proportional to disease prevalence rates