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Objectives: This study aims to determine the current state of CDD diagnosis and epilepsy treatment in an upper‐middle‐income country. Methods: Forty‐seven families of the Brazilian CDD Association were invited to participate in an online survey to gather information about the diagnosis and treatment of epilepsy. Results: Forty‐three families (91.5%) of unrelated patients with confirmed genetic diagnosis of CDD participated. The median age was 7 years (ranging from 1.3–25 years) and the male: female ratio was 1:6. Early and severe epilepsy started during infancy in 74.4%. Seizures occurred daily in 61.9% and 83.7% had clusters of seizures. The mean age of diagnosis was 3.3 years (ranging from 37 days to 16 years), and younger patients had an earlier diagnosis (p < 0.001). Patients were seen by an average of 4.4 physicians (1–15) before the diagnosis. The most relevant obstacles to genetic testing were cost (55.8%) and late requests by physicians (27.9%). At the moment of the assessment, patients received a mean of 3.6 ASMs/day (ranging from 1 to 5). Thirty‐four (79.1%) caregivers reported side effects throughout life, including life‐threatening events in 16.3%. Significance: Based on our findings, a sense of urgency for genetic assessment implementation is evident since the delay in the diagnosis with unnecessary use of resources and excessive polytherapy with serious side effects cause a higher burden to the healthcare system, caregivers, and patients. Plain Language Summary: In this study, we assessed the diagnosis and treatment of patients with genetically confirmed DEE‐CDKL5 from the Brazilian Association of CDD with an online survey. Caregivers reported a long delay in the diagnosis associated with cost and late referral to genetic testing, considered the last resource for one‐third of the patients. Patients received a high number of ASM, mainly under polytherapy, with serious side effects. Although it is promising that younger patients received earlier diagnosis, public policies for genetic testing are needed to improve CDD patients' care. [ABSTRACT FROM AUTHOR]

Cyclin‐dependent kinase‐like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental disease caused by mutations in the X‐linked CDKL5 gene and characterized by early‐onset epilepsy, intellectual disability, and autistic features. To date, the etiological mechanisms underlying CDD are largely unknown and no effective therapies are available. The Cdkl5 knock‐out (KO) mouse has been broadly employed in preclinical studies on CDD; Cdkl5‐KO mice display neurobehavioral abnormalities recapitulating most CDD symptoms, including alterations in motor, sensory, cognitive, and social abilities. However, most available preclinical studies have been carried out on adult Cdkl5‐KO mice, so little is known about the phenotypic characteristics of this model earlier during development. Furthermore, major autistic‐relevant phenotypes, for example, social and communication deficits, have been poorly investigated and mostly in male mutants. Here, we assessed the autistic‐relevant behavioral phenotypes of Cdkl5‐KO mice during the first three post‐natal weeks and in adulthood. Males and females were tested, the latter including both heterozygous and homozygous mutants. Cdkl5 mutant pups showed qualitative and quantitative alterations in ultrasonic communication, detected first at 2 weeks of age and confirmed later in adulthood. Increased levels of anxiety‐like behaviors were observed in mutants at 3 weeks and in adulthood, when stereotypies, reduced social interaction and memory deficits were also observed. These behavioral effects of the mutation were evident in both sexes, being more marked and varied in homozygous than heterozygous females. These findings provide novel evidence for the autistic‐relevant behavioral profile of the Cdkl5 mouse model, thus supporting its use in future preclinical studies investigating CDD pathology and autism spectrum disorders. Lay Summary: Cyclin‐dependent kinase‐like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disease characterized by several symptoms, including autistic features. Here we demonstrate the presence of a variety of autistic‐relevant behavioral alterations in the preclinical model of CDD, i.e., the Cdkl5 knock‐out (Cdkl5‐KO) mouse, taking into account sex and age differences. Our results support the validity of this genetic mouse line for modeling CDD and its use for future preclinical pharmacological and molecular studies on this disorder. [ABSTRACT FROM AUTHOR]

CDKL5 deficiency disorder (CDD) is a genetically caused developmental epileptic encephalopathy that causes severe communication impairments. Communication of individuals with CDD is not well understood in the literature and currently available measures are not well validated in this population. Accurate and sensitive measurement of the communication of individuals with CDD is important for understanding this condition, clinical practice, and upcoming interventional trials. The aim of this descriptive qualitative study was to understand how individuals with CDD communicate, as observed by caregivers. Participants were identified through the International CDKL5 Disorder Database and invited to take part if their child had a pathogenic variant of the CDKL5 gene and they had previously completed the Communication and Symbolic Behavior Checklist (CSBS‐DP ITC). The sample comprised caregivers of 23 individuals with CDD, whose ages ranged from 2 to 30 years (median 13 years), 15 were female, and most did not use words. Semistructured interviews were conducted via videoconference and analyzed using a conventional content analysis. Three overarching categories were identified: mode, purpose and meaning, and reciprocal exchanges. These categories described the purposes and mechanism of how some individuals with CDD communicate, including underpinning influential factors. Novel categories included expressing a range of emotions, and reciprocal exchanges (two‐way interactions that varied in complexity). Caregivers observed many communication modes for multiple purposes. Understanding how individuals with CDD communicate improves understanding of the condition and will guide research to develop accurate measurement for clinical practice and upcoming medication trials. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess the treatment response of infantile‐onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies. Methods: We evaluated patients with ES from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC), with onset from 2 months to 2 years, treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, vigabatrin, and/or the ketogenic diet. We excluded children with tuberous sclerosis complex, trisomy 21, or unknown etiology with normal development because of known differential treatment responses. We compared the two cohorts for time to treatment and ES remission at 14 days and 3 months. Results: We evaluated 59 individuals with CDD (79% female, median ES onset 6 months) and 232 individuals from the NISC database (46% female, median onset 7 months). In the CDD cohort, seizures prior to ES were common (88%), and hypsarrhythmia and its variants were present at ES onset in 34%. Initial treatment with ACTH, oral corticosteroids, or vigabatrin started within 1 month of ES onset in 27 of 59 (46%) of the CDD cohort and 182 of 232 (78%) of the NISC cohort (p <.0001). Fourteen‐day clinical remission of ES was lower for the CDD group (26%, 7/27) than for the NISC cohort (58%, 106/182, p =.0002). Sustained ES remission at 3 months occurred in 1 of 27 (4%) of CDD patients vs 96 of 182 (53%) of the NISC cohort (p <.0001). Comparable results were observed with longer lead time (≥1 month) or prior treatment. Ketogenic diet, used within 3 months of ES onset, resulted in ES remission at 1 month, sustained at 3 months, in at least 2 of 13 (15%) individuals with CDD. Significance: Compared to the broad group of infants with ES, children with ES in the setting of CDD often experience longer lead time to treatment and respond poorly to standard treatments. Development of alternative treatments for ES in CDD is needed. [ABSTRACT FROM AUTHOR]

Modelling rainfall extremes and dry periods over the Southeast Asia (SEA) region is challenging due to the characteristics of the region, which consists of the Maritime Continent and a mountainous region; it also experiences monsoonal conditions, as it is located between the Asian summer monsoon and the Australian summer monsoon. Representing rainfall extremes is important for flood and drought assessments in the region. This paper evaluates extreme rainfall climatic indices from regional climate models from CORDEX Southeast Asia and compares them with the results of high‐resolution global climate models with a comparable spatial resolution from the HighResMIP experiment. Observations indicate a high intensity of rainfall over areas affected by tropical cyclones and long consecutive dry day periods over some areas in Indochina and the southern end of Indonesia. In the model simulations, we find that both coupled and sea surface temperature‐forced HighResMIP model experiments are more similar to the observations than CORDEX model results. However, the models produce a poorer simulation of precipitation intensity‐related indices due to model biases in the rainfall intensity. This bias is higher in CORDEX than in HighResMIP and is evident in both the low‐ and high‐resolution HighResMIP model versions. The comparable performances of HighResSST (atmosphere‐only runs) and Hist‐1950 (coupled ocean–atmosphere runs) demonstrate the accuracy of the ocean model. Comparable performances were also found for the two different resolutions of HighResMIP, suggesting that there is no improvement in the performance of the high‐resolution HighResMIP model compared to the low‐resolution HighResMIP model. [ABSTRACT FROM AUTHOR]

CDKL5 deficiency disorder (CDD) is an epileptic encephalopathy associated with medically refractory epilepsy. We sought to determine whether prolonged corrected QT interval (QTc) or other cardiac conduction abnormalities were seen in CDD in a clinical cohort. A cohort of individuals with CDD was evaluated in the Children's Hospital Colorado's International Foundation for CDKL5 Research designated Center of Excellence clinic with routine electrocardiograms obtained as part of routine clinical care. Retrospective review of electrocardiograms was completed. ECGs from 44 individuals (7 male, 37 female, age range 0–34.5 years) with pathogenic mutations and findings consistent with CDD were evaluated. Multiple ECGs were available from the 44 individuals obtained from 1996 to 2020. Prolonged QTc was found in two individuals (4.5%) and either resolved or was not confirmed on Holter monitor; no additional interventions were performed. A total of 11 individuals had echocardiograms for a variety of indications including unexplained tachycardia and ECG abnormalities; all were normal. Two individuals in the cohort died during the study with no abnormal findings on ECG. The incidence of prolonged QTc or other significant actionable cardiac abnormalities was rare in a cohort of individuals with CDD though was higher than the prevalence seen within the general population. Further studies in a larger, confirmatory cohort over a longer period are needed. [ABSTRACT FROM AUTHOR]

Cooling and heating degree‐days (CDD/HDD) are important metrics used in energy studies as a proxy for determining demand and consumption patterns of residential/commercial buildings and work spaces. Driven by the requirements of energy impact modellers, policymakers and building design experts; a new historical high‐spatial resolution, global gridded dataset of degree‐days constructed using various base (threshold) temperatures (Tb) is presented in this study. Derived using sub‐daily temperature from a quality‐controlled reanalysis data product (Global Land Data Assimilation System—GLDAS), the dataset called 'DegDays_0p25_1970_2018' includes monthly and annual (i) CDD; (ii) HDD; and (iii) CDD computed using wet‐bulb temperature (CDDwb) at 0.25° × 0.25° gridded resolution, covering 49 years over the period 1970–2018. The Tb used for assembling DegDays_0p25_1970_2018 include 18, 18.3, 22, 23, 24, 25°C for CDD and CDDwb; and 10, 15, 15.5, 16, 17 and 18°C for HDD, respectively. The data of individual indices are made publicly available in the commonly used scientific Network Common Data Form 4 (NetCDF4) and Georeferenced Tagged Image File (GeoTIFF) formats. DegDays_0p25_1970_2018 fills gaps in existing energy indicators' datasets by being the only high‐resolution historical global gridded time series based on multiple threshold temperatures, thus offering applications in wide‐ranging climate zones and thermal comfort environments. The richness of DegDays_0p25_1970_2018 lies in its flexibility by allowing users to aggregate the degree‐days not only at varying spatial scales (such as administrative levels, national boundaries, economic organizations e.g. OECD; with or without population weights), but also at varying temporal scales (such as seasons), thereby offering climatologists with a potential to examine global teleconnection patterns more discretely. [ABSTRACT FROM AUTHOR]

Communication data in the communication network of the islanded micro‐grid can be disturbed in many ways, such as data attack or packet loss. To improve the control effect on the voltages and frequencies obtained by droop control of distributed energy resources (DERs) facing communication data disturbance (CDD), a response hierarchical control strategy is proposed in this study. Based on the concept of the cyber physical system, the control structure is divided into two layers: the cyber layer and physical layer. In the cyber layer, firstly, the effect of the CDD on the micro‐grid system is analysed and then, an event‐triggered data compensation method combining the back‐propagation neural network and extreme learning machine is proposed in this layer to solve the problem of the CDD. In the physical layer, firstly, the droop control is used as the primary control to control the voltages and frequencies of DERs and then, a novel virtual leader‐following consensus control method considering time‐delay is proposed in this layer. Also, it is used to complete the secondary control of the voltage and frequency obtained by primary control. In the end, the simulation results confirm the effectiveness of the proposed hierarchical control strategy under CDD. [ABSTRACT FROM AUTHOR]

Multiple-input multiple-output orthogonal frequency division multiplexing has become an attractive air-interface solution for the next generation wireless networks because of its high spectrum efficiency. This paper addresses the security concern and proposes to achieve covert orthogonal frequency division multiplexing transmission using cyclic delay diversity featured multiple-input multiple-output technology. Particularly, our physical layer security scheme takes the advantage of cyclic delay diversity formed periodical frequency selective channel and utilizes uneven comb pilots to confuse unauthorized receivers and benefit authorized receivers. We conduct simulation study to evaluate the impact of different cyclic delay, antenna number, and interpolation algorithms on our scheme. Numerical results show that our scheme can provide authorized users with significant advantage over eavesdroppers without complicated upper-layer encryption and decryption. Moreover, the scheme has flexible choice of parameters and thus can be easily deployed in a variety of wireless networks with different requirements. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The toxicity in humans of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a man-made compound and environmental pollutant, is still debated. The industrial accident at Seveso, Italy, in 1976 exposed a large population of both sexes and of all ages to a massive concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Monitoring of soil and measurement of blood samples allowed classification of the exposed population into three categories: A, B and R (high, medium and low exposure, respectively). This article presents data from longitudinal health monitoring of the population, including liver function, immune function, neurological impairment, dermatological effects, reproductive pathology, and mortality. [ABSTRACT FROM AUTHOR]