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Childhood cancer is the second cause of mortality of the population between 4 and 15 years. More than 20 million new cases of cancer in the world are expected by the year 2025, and 80% of the load will be on countries of low to middle income. In the past two decades, significant changes have been observed in patterns of incidence, prevalence, survival, and childhood cancer mortality in Mexico. An extensive review of all the published studies in Mexico by various health institutions revealed a steady 18-year trend of 150 new cases/million/year. The prevalence showed that acute leukemias constitute a 50% of all childhood cancer cases, followed by lymphoma (Hodkin and non-Hodgkin), and primary malignant brain tumors. A significant survival rate was observed in 8 thousand children with acute lymphoblastic leukemia with an overall 5-year survival rate of 62%, with a range of 45 to 73%. The national mortality rate for all types of cancer was 5.2/100,000/year, which is higher than what is reported in most middle-income countries. In the face of the current results, the need arises to modify how we approach this group of diseases by integrating a socio-educational healthcare of the Mexican children who are currently treated under unfavorable conditions. The current sanitary authorities must be aware of the importance of the transmission and adjustment of the care received by children with these diseases at a national level, to be in line with international standards. [ABSTRACT FROM AUTHOR]

Background: Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL. Methods: A total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation. Results: We identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed. Discussion: Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome. [ABSTRACT FROM AUTHOR]

To analyze the number of HSCTs performed in 2019 vs. 2020 and report the status of transplant centers (TCs) during and a year after the COVID-19 pandemic. We performed a comprehensive cross-sectional nationwide study including active TCs interrogating HSCT activity from 2019 through September 2021. An electronic survey was sent to TCs and consisted of items regarding the number and characteristics of procedures performed and were compared yearly. Changes to their institutions' transplant policies and practices during the COVID19 pandemic were also documented. Fifty centers were invited to participate, 33 responded. Most TCs were part of the public health system (63.7%). Almost half are in the country's capital, Mexico City (45.5%). Most centers performed <10 procedures per year. The number of HSCTs decreased from 835 in 2019–505 in 2020 (p <.001), representing a 40% reduction in transplant activity. The monthly transplant rate in 2021 increased to 58.3, compared to 42 in 2020 and close to 69.5 in 2019 (p <.001). All types of HSCTs decreased excluding haploidentical transplants. All institutions treated patients with COVID19, and over two-thirds experienced some form of hospital reconversion. Transplant activity stopped completely in 23 TCs (70%) during the pandemic with a median closure duration of 9.9 months (range, 1-21). In 2021, 9.1% of TCs remained closed, all of them in the public setting. The limited transplant activity in Mexico decreased significantly during the pandemic but is recovering and nearly in pre-pandemic levels. [ABSTRACT FROM AUTHOR]

This is the second part of a two-paper set that presents a methodology to determine an optimal radial reconfiguration plan for a medium voltage (MV) distribution network. It is applicable to primary distribution systems with multicost and multipoint alternative supply for short and medium terms. The optimization criterion is based on minimizing the operation costs, including the purchased energy cost and switching cost. In addition to the proposed methodology, a main contribution of the work is to evaluate the impact of the energy price on the operative topology working within a competitive market structure, where the demand is supplied from several purchase nodes featuring significantly different energy prices. The methodology is based on dynamic programming, heuristics, and a method to calculate the economic dispatch (ED) through radialization specifically designed for multicost and multipoint alternative supply, as is the case of distribution networks. The capacity of the network components, the service quality, and the dynamics of the demand are considered. Finally, the advantages of applying the methodology to a realistic distribution network are discussed. Index Terms--Ac power flow, economic dispatch, energy price, loss, minimization costs, network reconfiguration, radialization.

A new approach to improve the reconfiguration operations of distribution systems is presented in two papers. In this first part n economic dispatch (ED) through radialization method for medium voltage (MV) distribution networks with several alternative supply points and several energy prices is presented. The optimization criterion is based on energy purchase cost minimization to supply both the load and the loss. The ED through radialization (EDR) method assesses the economic impact of different energy prices for alternative supply points on the operative radial topology for a specific load level. Capacity limits of supply points and MV lines are considered, as well as the quality technical product using ac power flow calculations. The results obtained for a distribution network widely used in the literature show the effectiveness of the proposed methodology. The second part presents a methodology to determine the optimal reconfiguration plan for short and medium terms. This approach integrates purchase and switching costs associated to the reconfiguration plan. Index Terms--Ac power flow, economic dispatch, energy price, loss, minimization costs, network reconfiguration, radialization.

Paroxysmal dyskinesias are episodic movement disorders that can be inherited or are sporadic in nature. The pathophysiology underlying these disorders remains largely unknown but may involve disrupted ion homeostasis due to defects in cell-surface channels or nutrient transporters. In this study, we describe a family with paroxysmal exertion-induced dyskinesia (PED) over 3 generations. Their PED was accompanied by epilepsy, mild developmental delay, reduced CSF glucose levels, hemolytic anemia with echinocytosis, and altered erythrocyte ion concentrations. Using a candidate gene approach, we identified a causative deletion of 4 highly conserved amino acids (Q282_S285del) in the pore region of the glucose transporter 1 (GLUT1). Functional studies in Xenopus oocytes and human erythrocytes revealed that this mutation decreased glucose transport and caused a cation leak that alters intracellular concentrations of sodium, potassium, and calcium. We screened 4 additional families, in which PED is combined with epilepsy, developmental delay, or migraine, but not with hemolysis or echinocytosis, and identified 2 additional GLUT1 mutations (A275T, G314S) that decreased glucose transport but did not affect cation permeability. Combining these data with brain imaging studies, we propose that the dyskinesias result from an exertion-induced energy deficit that may cause episodic dysfunction of the basal ganglia, and that the hemolysis with echinocytosis may result from alterations in intracellular electrolytes caused by a cation leak through mutant GLUT1., Introduction Paroxysmal dyskinesias (PDs) are characterized by involuntary movements triggered by certain stimuli such as sudden movement or prolonged exercise. They are classified into paroxysmal kinesigenic dyskinesia (PKD or PKC [...]

A new decomposition method is presented that includes the network through ac modeling within the hydrothermal scheduling optimization process including the losses. In short-term hydrothermal scheduling, the transmission network is typically modeled with dc power flow techniques. Such modeling, however, can lead to impractical solutions when it is verified with ac power flow. Another proposal considers in thermal systems the ac network modeling but not the optimization of losses. The approach presented here addresses issues such as congestion management and control of service quality that often arise in large and weakly meshed networks--the typical pattern of power systems in Latin America. Generalized Benders decomposition and traditional, well-known optimization techniques are used to solve this problem. The master problem stage defines the generation levels by regarding the inter-temporal constraints, whereas the subproblem stage determines both the active and the reactive economical dispatches for each time interval of the load curve. It meets the electrical constraints through a modified ac optimal power flow (OPF). Another important contribution is the inclusion of accelerating techniques aimed at reducing the number of iterations and CPU time. The methodology was proven in a real system and test systems. Results are discussed in this paper. Index Terms--Benders decomposition, hydrothermal scheduling, optimal power flow, unit commitment.

The open access to the transmission network and the methods to allocate its costs are the key point that allows free competition in deregulated electric markets. All existing allocation methodologies have advantages and disadvantages that depend on their own features, the power system characteristics, and the price structure of the market. The comparison of network cost allocation methods has been the aim of many studies in order to improve them. In this paper, the analytical relation between areas of influence method and a method based on the economical benefit for allocation of transmission costs is presented. Common points of both methodologies are discussed as well as their advantages to be applied to pay transmission network expansions. It is concluded that both methodologies are equivalent only under certain conditions. Index Terms--Competitive markets, network pricing, spot pricing, transmission costs allocation.

In this first part of a two-paper set, the operative configuration (OC) is defined as the state (closed/open) of the protective and switching devices installed on the medium voltage distribution network. OC identification is fundamental for the outage management and state estimation of these networks, particularly for those with a low level of real-time supervision and control. In these networks, however, it is difficult to obtain the OC with conventional analytical techniques because of the scarcity or unavailability of monitored devices and measuring points. To overcome this, a novel methodology of inference is presented here. Part I develops a real-time approach based on power flow analysis, fuzzy fault currents calculation and rule-based Type-2 Fuzzy Logic Systems. Part II proposes an extended real-time approach based on fuzzy relation equations and fuzzy abductive inference. The performance of the methodology is evaluated on a real distribution feeder, and results are shown and discussed. Index Terms--Fuzzy sets, fuzzy logic, fuzzy systems, distribution networks, power flow analysis, state estimation.