Atomic configurations of dislocation core and twin boundaries in 3C-SiC studied by high-resolution electron microscopy

The defects in 3C-SiC film grown on (001) plane of Si substrate were studied using a 200 kV high-resolution electron microscope with point resolution of 0.2 nm. A posterior image processing technique, the image deconvolution, was utilized in combination with the image contrast analysis to distinguish atoms of Si from C distant from each other by 0.109 nm in the [110] projected image. The principle of the image processing technique utilized and the related image contrast theory is briefly presented. The procedures of transforming an experimental image that does not reflect the crystal structure intuitively into the structure map and of identifying Si and C atoms from the map are described. The atomic configurations for a 30 degrees partial dislocation and a microtwin have been derived at atomic level. It has been determined that the 30 degrees partial dislocation terminates in C atom and the segment of microtwin is sandwiched between two 180 degrees rotation twins. The corresponding stacking sequences are derived and atomic models are constructed according to the restored structure maps for both the 30 degrees partial dislocation and microtwin. Images were simulated based on the two models to affirm the above-mentioned results

Visualization of Genomic Changes by Segmented Smoothing Using an L0 Penalty

Copy number variations (CNV) and allelic imbalance in tumor tissue can show strong segmentation. Their graphical presentation can be enhanced by appropriate smoothing. Existing signal and scatterplot smoothers do not respect segmentation well. We present novel algorithms that use a penalty on the norm of differences of neighboring values. Visualization is our main goal, but we compare classification performance to that of VEGA

α-Synuclein in human cerebrospinal fluid is principally derived from neurons of the central nervous system

The source of Parkinson disease-linked α-synuclein (aSyn) in human cerebrospinal fluid (CSF) remains unknown. We decided to measure the concentration of aSyn and its gradient in human CSF specimens and compared it with serum to explore its origin. We correlated aSyn concentrations in CSF versus serum (QaSyn) to the albumin quotient (Qalbumin) to evaluate its relation to blood–CSF barrier function. We also compared aSyn with several other CSF constituents of either central or peripheral sources (or both) including albumin, neuron-specific enolase, β-trace protein and total protein content. Finally, we examined whether aSyn is present within the structures of the choroid plexus (CP). We observed that QaSyn did not rise or fall with Qalbumin values, a relative measure of blood–CSF barrier integrity. In our CSF gradient analyses, aSyn levels decreased slightly from rostral to caudal fractions, in parallel to the recorded changes for neuron-specific enolase; the opposite trend was recorded for total protein, albumin and β-trace protein. The latter showed higher concentrations in caudal CSF fractions due to the diffusion-mediated transfer of proteins from blood and leptomeninges into CSF in the lower regions of the spine. In postmortem sections of human brain, we detected highly variable aSyn reactivity within the epithelial cell layer of CP in patients diagnosed with a range of neurological diseases; however, in sections of mice that express only human SNCA alleles (and in those without any Snca gene expression), we detected no aSyn signal in the epithelial cells of the CP. We conclude from these complementary results that despite its higher levels in peripheral blood products, neurons of the brain and spinal cord represent the principal source of aSyn in human CSF

Testing density-functional approximations on a lattice and the applicability of the related Hohenberg-Kohn-like theorem

We present a metric-space approach to quantify the performance of approximations in lattice density-functional theory for interacting many-body systems and to explore the regimes where the Hohenberg-Kohn-type theorem on fermionic lattices is applicable. This theorem demonstrates the existence of one-to-one mappings between particle densities, wave functions and external potentials. We then focus on these quantities, and quantify how far apart in metric space the approximated and exact ones are. We apply our method to the one-dimensional Hubbard model for different types of external potentials, and assess the regimes where it is applicable to one of the most used approximations in density-functional theory, the local density approximation (LDA). We find that the potential distance may have a very different behaviour from the density and wave function distances, in some cases even providing the wrong assessments of the LDA performance trends. We attribute this to the systems reaching behaviours which are borderline for the applicability of the one-to-one correspondence between density and external potential. On the contrary the wave function and density distances behave similarly and are always sensitive to system variations. Our metric-based method correctly predicts the regimes where the LDA performs fairly well and the regimes where it fails. This suggests that our method could be a practical tool for testing the efficiency of density-functional approximations

A Cell-Based Optimised Approach for Rapid and Efficient Gene Editing of Human Pluripotent Stem Cells

Introducing or correcting disease-causing mutations through genome editing in human pluripotent stem cells (hPSCs) followed by tissue-specific differentiation provide sustainable models of multiorgan diseases, such as cystic fibrosis (CF). However, low editing efficiency resulting in extended cell culture periods and the use of specialised equipment for fluorescence activated cell sorting (FACS) make hPSC genome editing still challenging. We aimed to investigate whether a combination of cell cycle synchronisation, single-stranded oligodeoxyribonucleotides, transient selection, manual clonal isolation, and rapid screening can improve the generation of correctly modified hPSCs. Here, we introduced the most common CF mutation, ΔF508, into the CFTR gene, using TALENs into hPSCs, and corrected the W1282X mutation using CRISPR-Cas9, in human-induced PSCs. This relatively simple method achieved up to 10% efficiency without the need for FACS, generating heterozygous and homozygous gene edited hPSCs within 3–6 weeks in order to understand genetic determinants of disease and precision medicine

Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation in manikins

<p>Abstract</p> <p>Background</p> <p>Paramedics are frequently required to perform tracheal intubation, a potentially life-saving manoeuvre in severely ill patients, in the prehospital setting. However, direct laryngoscopy is often more difficult in this environment, and failed tracheal intubation constitutes an important cause of morbidity. Novel indirect laryngoscopes, such as the Airtraq^®and Truview^®laryngoscopes may reduce this risk.</p> <p>Methods</p> <p>We compared the efficacy of these devices to the Macintosh laryngoscope when used by 21 Paramedics proficient in direct laryngoscopy, in a randomized, controlled, manikin study. Following brief didactic instruction with the Airtraq^®and Truview^®laryngoscopes, each participant took turns performing laryngoscopy and intubation with each device, in an easy intubation scenario and following placement of a hard cervical collar, in a SimMan^®manikin.</p> <p>Results</p> <p>The Airtraq^®reduced the number of optimization manoeuvres and reduced the potential for dental trauma when compared to the Macintosh, in both the normal and simulated difficult intubation scenarios. In contrast, the Truview^®increased the duration of intubation attempts, and required a greater number of optimization manoeuvres, compared to both the Macintosh and Airtraq^®devices.</p> <p>Conclusion</p> <p>The Airtraq^®laryngoscope performed more favourably than the Macintosh and Truview^®devices when used by Paramedics in this manikin study. Further studies are required to extend these findings to the clinical setting.</p

Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation in manikins

<p>Abstract</p> <p>Background</p> <p>Paramedics are frequently required to perform tracheal intubation, a potentially life-saving manoeuvre in severely ill patients, in the prehospital setting. However, direct laryngoscopy is often more difficult in this environment, and failed tracheal intubation constitutes an important cause of morbidity. Novel indirect laryngoscopes, such as the Airtraq^®and Truview^®laryngoscopes may reduce this risk.</p> <p>Methods</p> <p>We compared the efficacy of these devices to the Macintosh laryngoscope when used by 21 Paramedics proficient in direct laryngoscopy, in a randomized, controlled, manikin study. Following brief didactic instruction with the Airtraq^®and Truview^®laryngoscopes, each participant took turns performing laryngoscopy and intubation with each device, in an easy intubation scenario and following placement of a hard cervical collar, in a SimMan^®manikin.</p> <p>Results</p> <p>The Airtraq^®reduced the number of optimization manoeuvres and reduced the potential for dental trauma when compared to the Macintosh, in both the normal and simulated difficult intubation scenarios. In contrast, the Truview^®increased the duration of intubation attempts, and required a greater number of optimization manoeuvres, compared to both the Macintosh and Airtraq^®devices.</p> <p>Conclusion</p> <p>The Airtraq^®laryngoscope performed more favourably than the Macintosh and Truview^®devices when used by Paramedics in this manikin study. Further studies are required to extend these findings to the clinical setting.</p

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24&nbsp;h. In both studies, patients were followed for outcome until death, hospital discharge or for 60&nbsp;days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24&nbsp;h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (&gt; 29 cmH2O) and driving pressure (&gt; 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (&gt; 8&nbsp;ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure &gt; 29 cmH2O and driving pressure &gt; 14 cmH2O on the first day of mechanical ventilation but not tidal volume &gt; 8&nbsp;ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies

Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting

Multiple system atrophy (MSA) is a rare neurodegenerative disorder with substantial knowledge gaps despite recent gains in basic and clinical research. In order to make further advances, concerted international collaboration is vital. In 2014, an international meeting involving leaders in the field and MSA advocacy groups was convened in Las Vegas, Nevada, to identify critical research areas where consensus and progress was needed to improve understanding, diagnosis, and treatment of the disease. Eight topic areas were defined: pathogenesis, preclinical modeling, target identification, endophenotyping, clinical measures, imaging biomarkers, nonimaging biomarkers, treatments/trial designs, and patient advocacy. For each topic area, an expert served as a working group chair and each working group developed priority-ranked research recommendations with associated timelines and pathways to reach the intended goals. In this report, each groups' recommendations are provided