Regional Cerebral Oximetry as an Indicator of Acute Brain Injury in Adults Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation–A Prospective Pilot Study

Background: Regional cerebral oxygen saturation (rScO2) measured by near-infrared spectroscopy (NIRS) can be used to monitor brain oxygenation in extracorporeal membrane oxygenation (ECMO). ECMO patients that develop acute brain injuries (ABIs) are observed to have worse outcomes. We evaluated the association between rScO2 and ABI in venoarterial (VA) ECMO patients.Methods: We retrospectively reviewed prospectively-collected NIRS data from patients undergoing VA ECMO from April 2016 to October 2016. Baseline demographics, ECMO and clinical characteristics, cerebral oximetry data, neuroradiographic images, and functional outcomes were reviewed for each patient. rScO2 desaturations were defined as a >25% decline from baseline or an absolute value < 40% and quantified by frequency, duration, and area under the curve per hour of NIRS monitoring (AUC rate, rScO2*min/h). The primary outcome was ABI, defined as abnormalities noted on brain computerized tomography (CT) or magnetic resonance imaging (MRI) obtained during or after ECMO therapy.Results: Eighteen of Twenty patients who underwent NIRS monitoring while on VA ECMO were included in analysis. Eleven patients (61%) experienced rScO2 desaturations. Patients with desaturations were more frequently female (73 vs. 14%, p = 0.05), had acute liver dysfunction (64 vs. 14%, p = 0.05), and higher peak total bilirubin (5.2 mg/dL vs. 1.4 mg/dL, p = 0.02). Six (33%) patients exhibited ABI, and had lower pre-ECMO Glasgow Coma Scale (GCS) scores (5 vs. 10, p = 0.03) and higher peak total bilirubin levels (7.3 vs. 1.4, p = 0.009). All ABI patients experienced rScO2 desaturation while 42% of patients without ABI experienced desaturation (p = 0.04). ABI patients had higher AUC rates than non-ABI patients (right hemisphere: 5.7 vs. 0, p = 0.01, left hemisphere: 119 vs. 0, p = 0.06), more desaturation events (13 vs. 0, p = 0.05), longer desaturation duration (2:33 vs. 0, p = 0.002), and more severe desaturation events with rScO2 < 40 (9 vs. 0, p = 0.05). Patients with ABI had lower GCS scores (post-ECMO initiation) before care withdrawal or discharge than those without ABI (10 vs. 15, p = 0.02).Conclusions: The presence and burden of cerebral desaturations noted on NIRS cerebral oximetry are associated with secondary neurologic injury in adults undergoing VA ECMO

Two computational studies of a flatback airfoil using non-zonal and embedded scale-resolving turbulence modelling approaches

The contribution presents results from two computational studies conducted by Upstream CFD and ENERCON, which aim to evaluate their respective CFD methodologies for the aerodynamics and aeroacoustics prediction of a flatback airfoil with 35% relative thickness. The CFD is validated against data from two comprehensive experimental campaigns conducted in the NWB facility operated by the German-Dutch Wind Tunnels Foundation (DNW), which include measurements of mean force coefficients, static and total pressure distributions in the wake region, unsteady surface pressures and farfield sound emission. In both numerical studies, scale-resolving approaches based on detached-eddy simulation are utilised, where a comparison is drawn between a purely non-zonal use of the model in which attached boundary layers are fully modelled via RANS and a zonal use with synthetic turbulence being injected into the boundary layers upstream of the trailing edge. First, the aerodynamic flow fields are analysed, showing good agreement with the reference measurements. Farfield noise is then predicted from solid and permeable Ffowcs-Williams and Hawkings surfaces, where both the dominant shedding tone as well as broadband levels compare well with microphone array data

The Quiet Revolution and the Family: Gender Composition of Tertiary Education and Early Fertility Patterns

It is well known that highly 'female' fields of study in tertiary education are characterized by higher fertility. However, existing work does not disentangle the selection-causality nexus. We use variation in gender composition of fields of study implied by the recent expansion of tertiary education in 19 European countries and a difference-in-differences research design, to show that the share of women on study peer groups affects early fertility levels only little. Early fertility by endogamous couples, i.e., by tertiary graduates from the same field of study, declines for women and increases for men with the share of women in the group, but non-endogamous fertility almost fully compensates for these effects, consistent with higher early fertility in highly 'female' fields of study being driven by selection of family-oriented students into these fields. We also show that the EU-wide level of gender segregation across fields of study has not changed since 2000

Swarm Learning for decentralized and confidential clinical machine learning

Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine1,2. Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes3. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation4,5. Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning—a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine

Exchange rate dynamics, balance sheet effects, and capital flows. A Minskyan model of emerging market boom-bust cycles

The paper provides a Minskyan open economy model of endogenous boom-bust cycles in emerging market economies, which explains the empirically observed procyclicality of exchange rates and the countercyclicality of the trade balance. It highlights the interaction of flexible exchange rate dynamics with balance sheets. Currency appreciation improves the net worth of firms with foreign currency debt, giving a boost to investment. Throughout the boom phase, the trade balance worsens. Pressures on the domestic exchange rate mount until the currency depreciates. Contractionary balance sheet effects then set in as domestic firms face a drop in their net worth. If capital inflows are driven by exogenous risk appetite, fluctuations can assume the form of shock-independent endogenous cycles. An increase in risk appetite raises the volatility of the cycle. Financial account regulation can reduce macroeconomic volatility, but the larger the risk appetite, the more financial account regulation is required to achieve this

The khmer software package: enabling efficient nucleotide sequence analysis

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

Physcomitrella patens DCL3 Is Required for 22–24 nt siRNA Accumulation, Suppression of Retrotransposon-Derived Transcripts, and Normal Development

Endogenous 24 nt short interfering RNAs (siRNAs), derived mostly from intergenic and repetitive genomic regions, constitute a major class of endogenous small RNAs in flowering plants. Accumulation of Arabidopsis thaliana 24 nt siRNAs requires the Dicer family member DCL3, and clear homologs of DCL3 exist in both flowering and non-flowering plants. However, the absence of a conspicuous 24 nt peak in the total RNA populations of several non-flowering plants has raised the question of whether this class of siRNAs might, in contrast to the ancient 21 nt microRNAs (miRNAs) and 21–22 nt trans-acting siRNAs (tasiRNAs), be an angiosperm-specific innovation. Analysis of non-miRNA, non-tasiRNA hotspots of small RNA production within the genome of the moss Physcomitrella patens revealed multiple loci that consistently produced a mixture of 21–24 nt siRNAs with a peak at 23 nt. These Pp23SR loci were significantly enriched in transposon content, depleted in overlap with annotated genes, and typified by dense concentrations of the 5-methyl cytosine (5 mC) DNA modification. Deep sequencing of small RNAs from two independent Ppdcl3 mutants showed that the P. patens DCL3 homolog is required for the accumulation of 22–24 nt siRNAs, but not 21 nt siRNAs, at Pp23SR loci. The 21 nt component of Pp23SR-derived siRNAs was also unaffected by a mutation in the RNA-dependent RNA polymerase mutant Pprdr6. Transcriptome-wide, Ppdcl3 mutants failed to accumulate 22–24 nt small RNAs from repetitive regions while transcripts from two abundant families of long terminal repeat (LTR) retrotransposon-associated reverse transcriptases were up-regulated. Ppdcl3 mutants also displayed an acceleration of leafy gametophore production, suggesting that repetitive siRNAs may play a role in the development of P. patens. We conclude that intergenic/repeat-derived siRNAs are indeed a broadly conserved, distinct class of small regulatory RNAs within land plants

The khmer software package: enabling efficient nucleotide sequence analysis [version 1; referees: 2 approved, 1 approved with reservations]

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

Identification of calcium-binding proteins associated with the human sperm plasma membrane

<p>Abstract</p> <p>Background</p> <p>The precise composition of the human sperm plasma membrane, the molecular interactions that define domain specific functions, and the regulation of membrane associated proteins during the capacitation process, still remain to be fully understood. Here, we investigated the repertoire of calcium-regulated proteins associated with the human sperm plasma membrane.</p> <p>Methods</p> <p>Surface specific radioiodination was combined with two-dimensional gel electrophoresis, a 45Ca-overlay assay, computer assisted image analysis and mass spectrometry to identify calcium-binding proteins exposed on the human sperm surface.</p> <p>Results</p> <p>Nine acidic 45Ca-binding sperm proteins were excised from stained preparative 2D gels and identified by mass spectrometry. Five of the calcium binding proteins; HSPA2 (HSP70-1), HSPA5 (Bip), HYOU1 (ORP150), serum amyloid P-component (SAP) and protein kinase C substrate 80K-H (80K-H) were found to be accessible to Iodo-Bead catalyzed 125I-labelling on the surface of intact human sperm. Agglutination and immunofluorescence analysis confirmed that SAP is situated on the plasma membrane of intact, motile sperm as well as permeabilized cells. Western blot analysis showed increased phosphorylation of human sperm 80K-H protein following in vitro capacitation. This is the first demonstration of the 80K-H protein in a mammalian sperm.</p> <p>Conclusion</p> <p>The presence of SAP on the surface of mature sperm implies that SAP has a physiological role in reproduction, which is thought to be in the removal of spermatozoa from the female genital tract via phagocytosis. Since 80K-H is a Ca2+-sensor recently implicated in the regulation of both inositol 1,4,5-trisphosphate receptor and transient receptor potential (TRP) cation channel activities, its detection in sperm represents the first direct signaling link between PKC and store-operated calcium channels identified in human sperm.</p