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07, 95% confidence interval [6.51; 18.82], p less then 0.0001). The need to continue with invasive ventilation was most strongly associated with the duration mechanical ventilation prior to transfer from the ICU (OR 4.73 [3.25; 6.89]), followed by a low body mass index (OR 0.38 [0.26; 0.58]), pre-existing neuromuscular disorders (OR 2.98 [1.88; 4.73]), and advanced age (OR 2.96 [1.87; 4.69]) (each p less then 0.0001). CONCLUSION Weaning duration has decreased over time, but prolonged weaning is still unsuccessful in one third of patients.Overall, the results warrant the establishment of specialized weaning centers. Variables associated with death and weaningfailure can be integrated into ICU decision-making processes.in English, Portuguese Introdução Desde março 2020, Portugal tem sofrido os efeitos da pandemia COVID-19. A mortalidade por todas as causas aumentou em março e abril de 2020 comparativamente a anos anteriores, mas este aumento não é explicado pelas mortes reportadas de COVID-19. O objetivo deste estudo foi analisar e considerar outros critérios para estimar o excesso de mortalidade durante a pandemia COVID-19. Material e Métodos Utilizaram-se bases de dados públicas para estimar o excesso de mortalidade por idade e região entre 1 de março e 22 de abril, propondo níveis basais ajustados ao período de estado de emergência em vigor. Resultados Apesar da incerteza inerente, é seguro assumir um excesso de mortalidade observada de 2400 a 4000 mortes. O excesso de mortalidade encontra-se associado aos grupos etários mais idosos (idade superior a 65 anos). Discussão Os dados sugerem uma explicação tripartida para o excesso de mortalidade COVID-19, COVID-19 não identificado e diminuição do acesso a cuidados de saúde. As estimativas efetuadas possuem implicações ao nível da comunicação de acções não farmacológicas, da investigação científica e dos profissionais de saúde. Conclusão Da análise dos resultados é possível concluir que o excesso de mortalidade ocorrido entre 1 de março e 22 de abril foi 3 a 5 vezes superior ao explicado pelas mortes por COVID-19 reportadas oficialmente.Background An essential component of palliative care (PC) is providing psychological and existential support to the family caregivers. However, there is scant research on the existential journeys of family caregivers throughout the disease trajectory and beyond. Objective This study aimed to obtain a deep understanding of the existential journeys of family caregivers from prognosis notification until after the death. Setting/Participants A purposive sample of 22 caregivers of terminally ill family members who had died was recruited at a PC bereavement program in Canada and participated to qualitative phenomenological interviews. Data Collection Interpretative phenomenological analysis was used to analyze the data derived from in-depth interviews. Results The participants' existential journeys can be described by three dynamic dimensions (1) from avoidance to integration of death, (2) from meaninglessness to meaningfulness, and (3) from transformation to transmission. The findings highlight the importance to family caregivers of having opportunities to share their experiences as a way to progress on the existential journey. Conclusions PC should extend beyond the death of the loved one and expand to include existential aspects of the caregiving experience.Sparse regularization such as ℓ1 regularization is a quite powerful and widely used strategy for high-dimensional learning problems. The effectiveness of sparse regularization has been supported practically and theoretically by several studies. However, one of the biggest issues in sparse regularization is that its performance is quite sensitive to correlations between features. Ordinary ℓ1 regularization selects variables correlated with each other under weak regularizations, which results in deterioration of not only its estimation error but also interpretability. In this letter, we propose a new regularization method, independently interpretable lasso (IILasso), for generalized linear models. Our proposed regularizer suppresses selecting correlated variables, so that each active variable affects the response independently in the model. Hence, we can interpret regression coefficients intuitively, and the performance is also improved by avoiding overfitting. We analyze the theoretical property of the IILasso and show that the proposed method is advantageous for its sign recovery and achieves almost minimax optimal convergence rate. Synthetic and real data analyses also indicate the effectiveness of the IILasso.Models of associative memory with discrete state synapses learn new memories by forgetting old ones. In contrast to non-integrative models of synaptic plasticity, models with integrative, filter-based synapses exhibit an initial rise in the fidelity of recall of stored memories. This rise to a peak is driven by a transient process and is then followed by a return to equilibrium. In a series of papers, we have employed a first passage time (FPT) approach to define and study memory lifetimes, incrementally developing our methods, from both simple and complex binary-strength synapses to simple multistate synapses. Here, we complete this work by analyzing FPT memory lifetimes in multistate, filter-based synapses. To achieve this, we integrate out the internal filter states so that we can work with transitions only in synaptic strength. We then generalize results on polysynaptic generating functions from binary strength to multistate synapses, allowing us to examine the dynamics of synaptic strength changes in an ensemble of synapses rather than just a single synapse. To derive analytical results for FPT memory lifetimes, we partition the synaptic dynamics into two distinct phases the first, pre-peak phase studied with a drift-only approximation, and the second, post-peak phase studied with approximations to the full strength transition probabilities. These approximations capture the underlying dynamics very well, as demonstrated by the extremely good agreement between results obtained by simulating our model and results obtained from the Fokker-Planck or integral equation approaches to FPT processes.Large-scale fluorescence calcium imaging methods have become widely adopted for studies of long-term hippocampal and cortical neuronal dynamics. Pyramidal neurons of the rodent hippocampus show spatial tuning in freely foraging or head-fixed navigation tasks. Development of efficient neural decoding methods for reconstructing the animal's position in real or virtual environments can provide a fast readout of spatial representations in closed-loop neuroscience experiments. Here, we develop an efficient strategy to extract features from fluorescence calcium imaging traces and further decode the animal's position. We validate our spike inference-free decoding methods in multiple in vivo calcium imaging recordings of the mouse hippocampus based on both supervised and unsupervised decoding analyses. We systematically investigate the decoding performance of our proposed methods with respect to the number of neurons, imaging frame rate, and signal-to-noise ratio. Our proposed supervised decoding analysis is ultrafast and robust, and thereby appealing for real-time position decoding applications based on calcium imaging.Continuous attractors have been used to understand recent neuroscience experiments where persistent activity patterns encode internal representations of external attributes like head direction or spatial location. However, the conditions under which the emergent bump of neural activity in such networks can be manipulated by space and time-dependent external sensory or motor signals are not understood. Here, we find fundamental limits on how rapidly internal representations encoded along continuous attractors can be updated by an external signal. We apply these results to place cell networks to derive a velocity-dependent nonequilibrium memory capacity in neural networks.Objectives This paper aimed to present real-world data of treatment results of a single center in patients with systemic Juvenile Idiopathic arthritis (SJIA), in which methotrexate (MTX) along with glucocorticoids was preferred as the first-line treatment option.Methods The medical records of 50 patients (58 episodes) with SJIA were evaluated. All patients with SJIA were hospitalized and were given high dose glucocorticoid treatment along with subcutaneous MTX. A biological agent was added in which disease activity control was not available with MTX.Results Forty-one (70.6%) of 58 episodes were controlled by MTX, following discontinuation of steroids, while a biologic drug was needed in the remaining 17 (29.4%) episodes. The patients receiving MTX were divided into two groups Group I (n = 36) (41 episodes) consisted of patients receiving MTX alone, and Group II (n = 14) (17 episodes) consisted of patients receiving MTX plus a biologic agent. Group I was dominated by the monocyclic course (56.1%), whereas grouy biologics are not available.PURPOSE The combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neuroblastoma in the randomized Children's Oncology Group ANBL1221 trial. To more accurately assess response rate and toxicity, an expanded cohort was nonrandomly assigned to I/T/DIN/GM-CSF. PATIENTS AND METHODS Patients were eligible at first relapse or first designation of refractory disease. Oral T and intravenous (IV) irinotecan were administered on days 1 to 5 of 21-day cycles. DIN was administered IV (days 2-5), and GM-CSF was administered subcutaneously (days 6-12). find more The primary end point was objective response, analyzed on an intent-to-treat basis per the International Neuroblastoma Response Criteria. RESULTS Seventeen eligible patients were randomly assigned to I/T/DIN/GM-CSF (February 2013 to March 2015); 36 additional patients were nonrandomly assigned to I/T/DIN/GM-CSF (August 2016 to May 2017). Objective (ctudy of chemoimmunotherapy in the frontline setting is indicated, as is further evaluation of predictive biomarkers.PURPOSE To determine whether dexrazoxane provides effective cardioprotection during frontline treatment of pediatric acute myeloid leukemia (AML) without increasing relapse risk or noncardiac toxicities of the chemotherapy regimens. PATIENTS AND METHODS This was a multicenter study of all pediatric patients with AML without high allelic ratio FLT3/ITD treated in the Children's Oncology Group trial AAML1031 between 2011 and 2016. Median follow-up was 3.5 years. Dexrazoxane was administered at the discretion of treating physicians and documented at each course. Ejection fraction (EF) and shortening fraction (SF) were recorded after each course and at regular intervals in follow-up. Per protocol, anthracyclines were to be withheld if there was evidence of left ventricular systolic dysfunction (LVSD) defined as SF less then 28% or EF less then 55%. Occurrence of LVSD, trends in EF and SF, 5-year event-free survival (EFS) and overall survival (OS), and treatment-related mortality (TRM) were compared by dexrazoxane exposure.

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