Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States

The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects that channel noise can have on neural dynamics are generally studied using numerical simulations of stochastic models. Algorithms based on discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but even optimized algorithms come with a non-negligible computational cost. Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE) to approximate the behavior of a number of MCs, considerably speeding up simulation times. However, model comparisons have suggested that DA methods did not lead to the same results as in MC modeling in terms of channel noise statistics and effects on excitability. Recently, it was shown that the difference arose because MCs were modeled with coupled activation subunits, while the DA was modeled using uncoupled activation subunits. Implementations of DA with coupled subunits, in the context of a specific kinetic scheme, yielded similar results to MC. However, it remained unclear how to generalize these implementations to different kinetic schemes, or whether they were faster than MC algorithms. Additionally, a steady state approximation was used for the stochastic terms, which, as we show here, can introduce significant inaccuracies. We derived the SDE explicitly for any given ion channel kinetic scheme. The resulting generic equations were surprisingly simple and interpretable - allowing an easy and efficient DA implementation. The algorithm was tested in a voltage clamp simulation and in two different current clamp simulations, yielding the same results as MC modeling. Also, the simulation efficiency of this DA method demonstrated considerable superiority over MC methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur

Antarctic climate, Southern Ocean circulation patterns, and deep water formation during the Eocene

We assess early-to-middle Eocene seawater neodymium (Nd) isotope records from seven Southern Ocean deep-sea drill sites to evaluate the role of Southern Ocean circulation in long-term Cenozoic climate change. Our study sites are strategically located on either side of the Tasman Gateway and are positioned at a range of shallow (Nd(t) = −9.3 ± 1.5). IODP Site U1356 off the coast of Adélie Land, a locus of modern-day Antarctic Bottom Water production, is identified as a site of persistent deep water formation from the early Eocene to the Oligocene. East of the Tasman Gateway an additional local source of intermediate/deep water formation is inferred at ODP Site 277 in the SW Pacific Ocean (εNd(t) = −8.7 ± 1.5). Antarctic-proximal shelf sites (ODP Site 1171 and Site U1356) reveal a pronounced erosional event between 49 and 48 Ma, manifested by ~2 εNd unit negative excursions in seawater chemistry toward the composition of bulk sediments at these sites. This erosional event coincides with the termination of peak global warmth following the Early Eocene Climatic Optimum and is associated with documented cooling across the study region and increased export of Antarctic deep waters, highlighting the complexity and importance of Southern Ocean circulation in the greenhouse climate of the Eocene

Supracricoid partial laryngectomy in the management of t3 laryngeal cancer

Objective. To evaluate the oncologic results only in T3 glottic and supraglottic cancers regarding supracricoid partial laryngectomy (SCPL) not requiring total laryngectomy and to assess functional results by self-evaluation by the patient. Study Design. Case series with medical record review. Setting. Single tertiary care center. Subjects and Methods. Thirty-two patients with laryngeal squamous cell carcinoma, previously untreated, who underwent SCPL with cricohyoidopexy or cricohyoidoepiglottopexy were reviewed. Results. At 1, 3, and 5 years, the disease-free survival rates were 96.9%, 89.4%, and 78.2%; overall survival rates were 96.9%, 93.2%, and 87.3%; local control and locoregional control rates were 100%, 96.2%, and 96.2%; and distant metastasis-free survival rates were 100%, 100%, and 88.2%, respectively. Aspiration pneumonia was the most common complication observed. The 3 laryngeal functions (speech, swallowing, and breathing) were spared in 83.9% of patients. Conclusion. Supracricoid partial laryngectomy for selected glottic and supraglottic T3 tumors has excellent oncologic and functional results

The controversy of patellar resurfacing in total knee arthroplasty: Ibisne in medio tutissimus?

Early arthroplasty designs were associated with a high level of anterior knee pain as they failed to cater for the patello-femoral joint. Patellar resurfacing was heralded as the saviour safeguarding patient satisfaction and success but opinion on its necessity has since deeply divided the scientific community and has become synonymous to topics of religion or politics. Opponents of resurfacing contend that the native patella provides better patellar tracking, improved clinical function, and avoids implant-related complications, whilst proponents argue that patients have less pain, are overall more satisfied, and avert the need for secondary resurfacing. The question remains whether complications associated with patellar resurfacing including those arising from future component revision outweigh the somewhat increased incidence of anterior knee pain recorded in unresurfaced patients. The current scientific literature, which is often affected by methodological limitations and observer bias, remains confusing as it provides evidence in support of both sides of the argument, whilst blinded satisfaction studies comparing resurfaced and non-resurfaced knees generally reveal equivalent results. Even national arthroplasty register data show wide variations in the proportion of patellar resurfacing between countries that cannot be explained by cultural differences alone. Advocates who always resurface or never resurface indiscriminately expose the patella to a random choice. Selective resurfacing offers a compromise by providing a decision algorithm based on a propensity for improved clinical success, whilst avoiding potential complications associated with unnecessary resurfacing. Evidence regarding the validity of selection criteria, however, is missing, and the decision when to resurface is often based on intuitive reasoning. Our lack of understanding why, irrespective of pre-operative symptoms and patellar resurfacing, some patients may suffer pain following TKA and others may not have so far stifled our efforts to make the strategy of selective resurfacing succeed. We should hence devote our efforts in defining predictive criteria and indicators that will enable us to reliably identify those individuals who might benefit from a resurfacing procedure. Level of evidence V

ICAR: endoscopic skull‐base surgery

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Dutch modality exclusivity norms : Simulating perceptual modality in space

Perceptual information is important for the meaning of nouns. We present modality exclusivity norms for 485 Dutch nouns rated on visual, auditory, haptic, gustatory, and olfactory associations. We found these nouns are highly multimodal. They were rated most dominant in vision, and least in olfaction. A factor analysis identified two main dimensions: one loaded strongly on olfaction and gustation (reflecting joint involvement in flavor), and a second loaded strongly on vision and touch (reflecting joint involvement in manipulable objects). In a second study, we validated the ratings with similarity judgments. As expected, words from the same dominant modality were rated more similar than words from different dominant modalities; but - more importantly - this effect was enhanced when word pairs had high modality strength ratings. We further demonstrated the utility of our ratings by investigating whether perceptual modalities are differentially experienced in space, in a third study. Nouns were categorized into their dominant modality and used in a lexical decision experiment where the spatial position of words was either in proximal or distal space. We found words dominant in olfaction were processed faster in proximal than distal space compared to the other modalities, suggesting olfactory information is mentally simulated as "close" to the body. Finally, we collected ratings of emotion (valence, dominance, and arousal) to assess its role in perceptual space simulation, but the valence did not explain the data. So, words are processed differently depending on their perceptual associations, and strength of association is captured by modality exclusivity ratings

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS