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Spiking Neural Network (SNN) is a promising energy-efficient neural architecture when implemented on neuromorphic hardware. The Artificial Neural Network (ANN) to SNN conversion method, which is the most effective SNN training method, has successfully converted moderately deep ANNs to SNNs with satisfactory performance. However, this method requires a large number of time-steps, which hurts the energy efficiency of SNNs. How to effectively covert a very deep ANN (e.g., more than 100 layers) to an SNN with a small number of time-steps remains a difficult task. To tackle this challenge, this paper makes the first attempt to propose a novel error analysis framework that takes both the "quantization error" and the "deviation error" into account, which comes from the discretization of SNN dynamicsthe neuron's coding scheme and the inconstant input currents at intermediate layers, respectively. Particularly, our theories reveal that the "deviation error" depends on both the spike threshold and the input variance. Based on our theoretical analysis, we further propose the Threshold Tuning and Residual Block Restructuring (TTRBR) method that can convert very deep ANNs (>100 layers) to SNNs with negligible accuracy degradation while requiring only a small number of time-steps. With very deep networks, our TTRBR method achieves state-of-the-art (SOTA) performance on the CIFAR-10, CIFAR-100, and ImageNet classification tasks.
Observational studies have highlighted that where individuals live is far more important for risk of dying with COVID-19, than for dying of other causes. Deprivation is commonly proposed as explaining such differences. During the period of localised restrictions in late 2020, areas with higher restrictions tended to be more deprived. We explore how this impacted the relationship between deprivation and mortality and see whether local or regional deprivation matters more for inequalities in COVID-19 mortality.
We use publicly available population data on deaths due to COVID-19 and all-cause mortality between March 2020 and April 2021 to investigate the scale of spatial inequalities. We use a multiscale approach to simultaneously consider three spatial scales through which processes driving inequalities may act. We go on to explore whether deprivation explains such inequalities.
Adjusting for population age structure and number of care homes, we find highest regional inequality in October 2020, with a COVl inequalities are greatest in periods of lowest overall mortality, implying that as mortality declines it does not do so equally. During the prolonged period of low restrictions and low mortality in summer 2020, spatial inequalities strongly increased. Contrary to previous months, we show that the strong spatial patterning during autumn 2020 is almost entirely explained by deprivation. As overall mortality declines, policymakers must be proactive in detecting areas where this is not happening, or risk worsening already strong health inequalities.
There is scarce evidence of effective treatments for the chronic phase of Febrile infection-related epilepsy syndrome (FIRES). This study aimed to analyze the outcomes of treatment with anakinra and tocilizumab.
Retrospective study including patients receiving either anti-interleukin-1 (anti-IL-1, anakinra) or anti-IL-6 (tocilizumab) during the chronic phase of FIRES. We evaluated seizure outcomes, non-seizure comorbidities, and adverse events. Additionally, an indirect control group including patients during the chronic phase of FIRES non-treated with-IL therapies was evaluated.
Five patients were included; three females. Median age at FIRES 8 years (IQR 6-10). Five patients received anakinra; one patient switched to tocilizumab after ineffectiveness. Median treatment duration was 9months (IQR 7-20). While no patients became seizure-free, 20-50% reduction in seizure frequency was reported in 3/5 patients after 6 months with anakinra. Retention rate was 100% at 6 months and 40% at 12months. Three patients reported reduced seizure intensity and rescue medication needed, and better behavior/communication. Similar improvement was reported for the patient switching to tocilizumab. Patients with the best response received anti-IL a median of 9 years after acute phase. All discontinuations were due to ineffectiveness. There were none relevant adverse events apart from one patient presenting transient seizure aggravation. Nine patients were included in the control group; none of them showed relevant improvement in seizure outcomes or cognitive/behavioral comorbidities. Only one presented mild improvement in seizure frequency during the 6-months follow-up.
This study provides promising data on effectiveness/safety of anakinra and tocilizumab in the chronic phase of FIRES. These findings warrant prospective/larger studies.
This study provides promising data on effectiveness/safety of anakinra and tocilizumab in the chronic phase of FIRES. These findings warrant prospective/larger studies.Diversiform okra dry powders were prepared and controlled-temperature ultrasonic-assisted extraction (CTUAE) was then utilized to obtain okra pectin (OP) from the preparative powders. During processing of hybrid techniques, 6 types of dry powders were prepared through different drying technologies (hot air drying, HD; freeze-drying, FD) and meshes (60, 80, 120 meshes) at first. Next, the extraction yield, physicochemical and function characteristics, and molecular structure of OP were analyzed with or without CTUAE technique. Meanwhile, the time-frequency domains of acoustic fields during extraction process of OP were monitored to analyze the effects of ultrasonic fields. Results showed that OP main chains with less cracking by FD than that by HD; the yield, GalA, esterification degree (DE), Mw and viscosity of OP increased, but its particle size decreased. Water holding capacity (WHC) and oil holding capacity (OHC) of OP by HD were more prominent. Secondly, HD OP had dendritic rigid chains, while FD OP had flexible chains with multiple branches. For HD OP, as meshes of okra dry powders decreased, GalA, viscosity and emulsification ability decreased; while gel strength and thermal stability increased. For FD OP, the reduction of meshes improved thermal stability. Above all, CTUAE technique increased the yield and GalA, and decreased DE, Mw and particle size of OP. In terms of functional characteristics, the technique also improved gel strength, resilience and viscoelasticity, enhanced emulsifying stability, WHC and thermal stability, and reduced viscosity. Finally, the correlation between functional and structural characteristics of OP was quantified, and some suggestions were made for its application in food areas.
Helping smokers to quit is an important task of general practitioners (GPs). However, achieving tobacco abstinence is difficult, and smokers who fail may still want to improve their health in other ways. Therefore, Swiss GPs developed a multithematic coaching concept that encourages health behavior changes beyond smoking cessation alone.
To compare the effectiveness of such coaching with state-of-the-art smoking cessation counseling, we conducted a pragmatic cluster-randomized two-arm trial with 56 GPs in German-speaking Switzerland and 149 of their cigarette smoking patients. GPs were instructed in either multithematic health coaching or smoking cessation counseling. After 12 months, we compared their patients' improvements in cigarette consumption, body weight, physical inactivity, alcohol consumption, stress, unhealthy diet, and a health behavior of their own choice, using hierarchical logistic regression models and Fisher's exact and t tests.
Over 95% of all participants achieved clinically relevantty for GPs to support their smoking patients in improving their health behavior in additional and more flexible ways.
The findings of our study suggest that in general practice, multithematic health coaching is an effective smoking cessation intervention, and conversely, monothematic smoking cessation counseling also achieves the beneficial effects of a multithematic health behavior intervention. This opens up the possibility for GPs to support their smoking patients in improving their health behavior in additional and more flexible ways.The maintenance and proliferation of hematopoietic stem cells (HSCs) are tightly regulated by their niches in the bone marrow. The analysis of niche cells or stromal cell lines that can support HSCs has facilitated the finding of novel supporting factors for HSCs. Despite large efforts in the murine bone marrow; however, HSC expansion is still difficult ex vivo, highlighting the need for new approaches to elucidate the molecular elements that regulate HSCs. The zebrafish provides a unique model to study hematopoietic niches as HSCs are maintained in the kidney, allowing for a parallel view of hematopoietic niches over evolution. Here, using a stromal cell line from the zebrafish kidney, zebrafish kidney stromal (ZKS), we uncover that an inhibitor of canonical Wnt signaling, IWR-1-endo, is a potent regulator of HSCs. Coculture assays revealed that ZKS cells were in part supportive of maintenance, but not expansion, of gata2aGFP+runx1mCherry+ (gata2a+runx1+) HSCs. Transcriptome analysis revealed that, compared with candidate niche cells in the kidney, ZKS cells weakly expressed HSC maintenance factor genes, thpo and cxcl12, but highly expressed canonical Wnt ligand genes, wnt1, 7bb, and 9a. Thpo supplementation in ZKS culture slightly increased, but inhibition of canonical Wnt signaling by IWR-1-endo treatment largely increased the number of gata2a+runx1+ cells (>2-fold). Moreover, we found that gata2a+runx1+ cells can be maintained by supplementing both IWR-1-endo and Thpo without stromal cells. Collectively, our data provide evidence that IWR-1-endo can be used as a novel supporting factor for HSCs.
The neurofibromatoses comprise three different genetic conditions causing considerable morbidity and mortality neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). This review summarizes recent and ongoing clinical trials involving patients with neurofibromatoses to better understand the current state of clinical trial research centered around these conditions and inform areas of need.
A search was conducted using the Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases. Inclusion and exclusion criteria were designed to identify clinical trials focused on patients with NF1, NF2, or SWN completed in or after 2010 and in process as of December 31, 2021. Information was collected using standardized guidelines.
A total of 134 clinical trials were included, with 75 (56%) completed and 59 (44%) in process. For completed trials, 74% (n=56) involved patients with NF1, and of those based on specific tumors (n=26, 46%), the majority focused on plexing comorbid psychiatric conditions and quality of life among patients with any of the neurofibromatoses appear less common. These areas may warrant focus in future studies to improve clinical management.The photodynamic inactivation (PDI) of microorganisms has gained interest as an efficient option for conventional antibiotic treatments. Recently, Si(IV) phthalocyanines (SiPcs) have been highlighted as promising photosensitizers (PSs) to the PDI of microorganisms due to their remarkable absorption and emission features. To increase the potential of cationic SiPcs as PS drugs, one novel (1a) and two previously described (2a and 3a) axially substituted PSs with di-, tetra-, and hexa-ammonium units, respectively, were synthesized and characterized. Their PDI effect was evaluated for the first time against Escherichia coli and Staphylococcus aureus, a Gram-negative and a Gram-positive bacterium, respectively. The photodynamic treatments were conducted with PS concentrations of 3.0 and 6.0 μM under 60 min of white light irradiation (150 mW.cm-2). The biological results show high photodynamic efficiency for di- and tetra-cationic PSs 1a and 2a (6.0 μM), reducing the E. coli viability in 5.2 and 3.9 log, respectively (after 15 min of dark incubation before irradiation).
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