184 research outputs found
Adaptive estimation in circular functional linear models
We consider the problem of estimating the slope parameter in circular
functional linear regression, where scalar responses Y1,...,Yn are modeled in
dependence of 1-periodic, second order stationary random functions X1,...,Xn.
We consider an orthogonal series estimator of the slope function, by replacing
the first m theoretical coefficients of its development in the trigonometric
basis by adequate estimators. Wepropose a model selection procedure for m in a
set of admissible values, by defining a contrast function minimized by our
estimator and a theoretical penalty function; this first step assumes the
degree of ill posedness to be known. Then we generalize the procedure to a
random set of admissible m's and a random penalty function. The resulting
estimator is completely data driven and reaches automatically what is known to
be the optimal minimax rate of convergence, in term of a general weighted
L2-risk. This means that we provide adaptive estimators of both the slope
function and its derivatives
Theoretical Properties of Projection Based Multilayer Perceptrons with Functional Inputs
Many real world data are sampled functions. As shown by Functional Data
Analysis (FDA) methods, spectra, time series, images, gesture recognition data,
etc. can be processed more efficiently if their functional nature is taken into
account during the data analysis process. This is done by extending standard
data analysis methods so that they can apply to functional inputs. A general
way to achieve this goal is to compute projections of the functional data onto
a finite dimensional sub-space of the functional space. The coordinates of the
data on a basis of this sub-space provide standard vector representations of
the functions. The obtained vectors can be processed by any standard method. In
our previous work, this general approach has been used to define projection
based Multilayer Perceptrons (MLPs) with functional inputs. We study in this
paper important theoretical properties of the proposed model. We show in
particular that MLPs with functional inputs are universal approximators: they
can approximate to arbitrary accuracy any continuous mapping from a compact
sub-space of a functional space to R. Moreover, we provide a consistency result
that shows that any mapping from a functional space to R can be learned thanks
to examples by a projection based MLP: the generalization mean square error of
the MLP decreases to the smallest possible mean square error on the data when
the number of examples goes to infinity
Clinical characteristics of 80 subjects with KCNQ2-related encephalopathy: Results from a family-driven survey
Variants of KCNQ2 are associated with a wide spectrum of disorders, ranging from Self-limiting Neonatal Epilepsy (SelNE) to Early Onset Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Comorbidities associated with this end of the spectrum have been seldomly described and their impact on the life of patients and their families is yet to be investigated. Collaborating with caregivers from different European family associations, we have developed a questionnaire aimed at investigating the onset and frequency of epileptic seizures, anti-seizure medications (ASM), hospitalizations, stages of development, and comorbidities. Responses from 80 patients, 40 males, from 14 countries have been collected. Median age 7.6 years (4 months - 43.6 years). Of 76 epileptic patients (93.6%), 55.3% were seizure-free with a mean age at last seizure of 26.7 months. Among patients with active epilepsy, those older have a lower frequency of seizures (p > 0.05). We were able to identify three different clusters of varying severity (Mild, Severe, Profound), based on neurodevelopmental features and symptoms, excluding epilepsy. Patients in a higher severity cluster had a higher mean number of comorbidities, which had a higher impact on families. Notably, patients in different clusters presented different epilepsy onset and courses. This study constitutes the most extensive data collection of patients with KCNQ2-DEE, with a focus on comorbidities in a wide age group. The participation of caregivers helps to define the impact of the disease on the lives of patients and families and can help identify new primary and secondary outcomes beyond seizures in future studies
Apnea of prematurity: from cause to treatment
Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment
Lessons from prospective longitudinal follow-up of a French APECED cohort
Background
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome is a rare disease caused by biallelic mutations of the AIRE gene, usually presenting with the triad hypoparathyroidism-adrenal failure-chronic mucocutaneous candidiasis (CMC) and nonendocrine manifestations. The aim of this study was to determine the molecular profile of the AIRE gene, the prevalence of rare manifestations, and to characterize immunological disturbances in a French cohort.
Patients and Methods
A national, multicenter prospective observational study to collect genetic, clinical, biological, and immunological data (NCT03751683).
Results
Twenty-five patients (23 families) were enrolled. Eleven distinct AIRE variants were identified, 2 of which were not previously reported: an intronic variant, c.653-70G > A, and a c.1066del (p.Arg356GlyfsX22) variant (exon 9). The most common was the Finnish variant c.769C > T (16 alleles), followed by the variant c.967_979del13 (15 alleles), which seemed associated with a less severe phenotype. Seventeen out of 25 patients were homozygote. The median number of clinical manifestations was 7; 19/25 patients presented with the hypoparathyroidism-adrenal failure-CMC triad, 8/13 showed pulmonary involvement, 20/25 had ectodermal dystrophy, 8/25 had malabsorption, and 6/23 had asplenia. Fifteen out of 19 patients had natural killer cell lymphopenia with an increase in CD4+ and CD8+ T lymphocytes and an age-dependent alteration of B lymphocyte homeostasis compared with matched controls (P < .001), related to the severity of the disease. All tested sera (n = 18) were positive for anti-interferon-α, 15/18 for anti-IL-22 antibodies, and 13/18 for anti-IL-17F antibodies, without clear phenotypic correlation other than with CMC.
Conclusion
This first prospective cohort showed a high AIRE genotype variability, with 2 new gene variants. The prevalence of potentially life-threatening nonendocrine manifestations was higher with systematic screening. These manifestations could, along with age-dependent B-cell lymphopenia, contribute to disease severity. Systematic screening for all the manifestations of the syndrome would allow earlier diagnosis, supporting vaccination and targeted therapeutic approaches
- …