Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Alpha entrainment is responsible for the attentional blink phenomenon

AbstractThe attentional blink phenomenon is the reduced ability to report a second target (T2) after identifying a first target (T1) in a rapid serial visual presentation (RSVP) of stimuli (e.g., letters), which are presented at approximately 10 items per second. Several explanations have been proposed, which focus primarily on cognitive aspects, such as attentional filter-, capacity limitation- and retrieval failure‐processes.Here, we focus on the hypothesis that an entrainment of alpha oscillations (with a frequency of about 10Hz) is a critical factor for the attentional blink phenomenon. Our hypothesis is based on the fact that item presentation rate in the RSVP typically lies in the alpha frequency range and is motivated by theories assuming an inhibitory function for alpha. We predict that entrainment – during the time window of T2 presentation – is larger for attentional blink (AB) items (when T2 cannot be reported) than for NoAB trials (when T2 cannot be reported).The results support our hypothesis and show that alpha entrainment as measured by the amplitude of the alpha evoked response and the extent of alpha phase concentration is larger for AB than for NoAB trials. Together with the lack of differences in alpha power these findings demonstrate that the differences between AB and NoAB trials – during presentation onset of T2 – are due to an entrainment of alpha phase and not due to an amplitude modulation. Thus, we conclude that alpha entrainment may be considered the critical factor underlying the attentional blink phenomenon

The mechanism of Li2S activation in lithium-sulfur batteries: Can we avoid the polysulfide formation?

International audienceElectrochemical reactions in the Lisingle bondS batteries are considered as a multistep reaction process with at least 2–3 equilibrium states. Here we report a possibility of having a conversion of Li2S into sulfur without detectible formation of polysulfides. That was confirmed by using a novel material system consisting of carbon coated Li2S particles prepared by carbothermal reduction of Li2SO4. Two independent in operando measurements showed direct oxidation of Li2S into sulfur for this system, with almost negligible formation of polysulfides at potentials above 2.5 V vs. Li/Li+. Our results link the diversity of first charge profiles in the literature to the Li2S oxidation mechanism and show the importance of ionic wiring within the material. Furthermore, we demonstrate that the Li2S oxidation mechanism depends on the relative amount of soluble sulfur in the electrolyte. By controlling the type and the amount of electrolyte within the encapsulating carbon shell, it is thereby possible to control the reaction mechanism of Li2S activation

Armoring of the Wendelstein 7-X divertor-observation immersion-tubes based on NBI fast-ion simulations

The first neutral beam injector (NBI) experiments of the Wendelstein 7-X stellarator took place in summer 2018. The modelling of the fast ion production and slowing down processes predicts losses of the NBI fast ions to the first wall on the order of 15%. One location receiving a high load (possibly peaking at several M W/m 2 ) is the immersion tube for optical and infrared monitoring of the divertor targets. The stainless steel face of the tube has three vacuum windows, which are sensitive to temperature gradients and overheating. To protect the windows from damage caused by the fast ions, different heat load mitigation techniques were investigated. Given the available time and resources until the first NBI experiments, a protective stainless steel collar mounted at the front of the immersion tubes was regarded the most realistic solution. This contribution describes the fast ion modelling of the loads, the new design, thermal modelling of the design, and finally experimental experience with the protective collar showing heat loads in excess of 1.5 M W/m 2 . The fast ion heat loads have been assessed computationally with the ASCOT code and experimentally with thermal imaging

Evoked traveling alpha waves predict visual-semantic categorization-speed

In the present study we have tested the hypothesis that evoked traveling alpha waves are behaviorally significant. The results of a visual-semantic categorization task show that three early ERP components including the P1–N1 complex had a dominant frequency characteristic in the alpha range and behaved like traveling waves do. They exhibited a traveling direction from midline occipital to right lateral parietal sites. Phase analyses revealed that this traveling behavior of ERP components could be explained by phase-delays in the alpha but not theta and beta frequency range. Most importantly, we found that the speed of the traveling alpha wave was significantly and negatively correlated with reaction time indicating that slow traveling speed was associated with fast picture-categorization. We conclude that evoked alpha oscillations are functionally associated with early access to visual-semantic information and generate – or at least modulate – the early waveforms of the visual ERP