Laplace deconvolution on the basis of time domain data and its application to Dynamic Contrast Enhanced imaging

In the present paper we consider the problem of Laplace deconvolution with noisy discrete non-equally spaced observations on a finite time interval. We propose a new method for Laplace deconvolution which is based on expansions of the convolution kernel, the unknown function and the observed signal over Laguerre functions basis (which acts as a surrogate eigenfunction basis of the Laplace convolution operator) using regression setting. The expansion results in a small system of linear equations with the matrix of the system being triangular and Toeplitz. Due to this triangular structure, there is a common number $m$ of terms in the function expansions to control, which is realized via complexity penalty. The advantage of this methodology is that it leads to very fast computations, produces no boundary effects due to extension at zero and cut-off at $T$ and provides an estimator with the risk within a logarithmic factor of the oracle risk. We emphasize that, in the present paper, we consider the true observational model with possibly nonequispaced observations which are available on a finite interval of length $T$ which appears in many different contexts, and account for the bias associated with this model (which is not present when $T\rightarrow\infty$). The study is motivated by perfusion imaging using a short injection of contrast agent, a procedure which is applied for medical assessment of micro-circulation within tissues such as cancerous tumors. Presence of a tuning parameter $a$ allows to choose the most advantageous time units, so that both the kernel and the unknown right hand side of the equation are well represented for the deconvolution. The methodology is illustrated by an extensive simulation study and a real data example which confirms that the proposed technique is fast, efficient, accurate, usable from a practical point of view and very competitive.Comment: 36 pages, 9 figures. arXiv admin note: substantial text overlap with arXiv:1207.223

EXPRESSION OF DEFA1-3 AND RELATIONS WITH RISK FACTORSOF CARDIOVASCULAR DISEASES

The infiltration of immuno-inflammatory cells is one of the earliest and durable steps that lead to atherosclerosis. These cells produce many immune components that act as a double-edged sword in this inflammatory disease. Among these components, we note antimicrobial peptides, including defenses. Defenses are natural cationic peptides of the innate immune system. In Humans, these small peptides have a large antimicrobial spectrum. In addition, they play an important role in both infectious and inflammatory diseases. Our objective was to study the relation between alpha-defenses (DEFA) 1-3 genes expression and cardiovascular risk factors. This objective was built on the hypothesis that defenses may be involved in cardiovascular pathologies, and may serve as a new generation of biomarkers. To verify this hypothesis, we treated HL-60 differentiated cells with glucose decreased alphadefenses 1, 2 and 3 gene expression levels, while insulin treatment restored its expression. These findings suggest that DEFA1-3 are involved in the complex glucose-insulin metabolic pathway. In summary, DEFA1-3 genes expression is significantly correlated with glucose. These findings we suggest that DEFA1-3 could be involved in the evolution of cardiovascular complications

Cardiovascular effects of dietary salt intake in aged healthy cats: a 2-year prospective randomized, blinded, and controlled study

High salt dry expanded diets are commercially available for cats to increase water intake and urine volume, as part of the prevention or treatment of naturally occurring urinary stone formation (calcium oxalates and struvites). However, chronic high salt intake may have potential cardiovascular adverse effects in both humans, especially in aging individuals, and several animal models. The objective of this prospective, randomized, blinded, and controlled study was to assess the long-term cardiovascular effects of high salt intake in healthy aged cats. Twenty healthy neutered cats (10.1±2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other group a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, systolic and diastolic arterial blood pressure measurements, standard transthoracic echocardiography and conventional Doppler examinations were repeatedly performed on non-sedated cats by trained observers before and over 24 months after diet implementation. Radial and longitudinal velocities of the left ventricular free wall and the interventricular septum were also assessed in systole and diastole using 2-dimensional color tissue Doppler imaging. Statistics were performed using a general linear model. No significant effect of dietary salt intake was observed on systolic and diastolic arterial blood pressure values. Out of the 33 tested imaging variables, the only one affected by dietary salt intake was the radial early on late diastolic velocity ratio assessed in the endocardium of the left ventricular free wall, statistically lower in the high salt diet group at 12 months only (P = 0.044). In conclusion, in this study involving healthy aged cats, chronic high dietary salt intake was not associated with an increased risk of systemic arterial hypertension and myocardial dysfunction, as observed in some elderly people, salt-sensitive patients and animal models

Mutational analysis of the PLCE1 gene in steroid-resistant nephrotic syndrome

International audienceBackground: Mutations in the PLCE1 gene encoding phospholipase C epsilon 1 (PLCε1) have been recently described in patients with early-onset nephrotic syndrome (NS) and diffuse mesangial sclerosis (DMS). In addition, two cases of PLCE1 mutations associated with focal segmental glomerulosclerosis (FSGS) and later NS onset have been reported. Methods: In order to better assess the spectrum of phenotypes associated with PLCE1 mutations, we performed mutational analysis in a worldwide cohort of 139 patients (95 familial cases belonging to 68 families and 44 sporadic cases) with steroid-resistant NS presenting at a median age of 23.0 months (range 0-373). Results: We identified homozygous or compound heterozygous mutations in 33% (8/24) of DMS cases. PLCE1 mutations were found in 8% (6/78) of FSGS cases without NPHS2 mutations. Nine were novel mutations. No clear genotype-phenotype correlation was observed, with either truncating or missense mutations detected in both DMS and FSGS, and leading to a similar renal evolution. Surprisingly, 3 unaffected and unrelated individuals were also found to carry the homozygous mutations identified in their respective families. Conclusion: PLCE1 is a major gene of DMS and is mutated in a non-negligible proportion of FSGS cases without NPHS2 mutations. Although we did not identify additional variants in 19 candidate genes (16 other PLC genes, BRAF, IQGAP1 and NPHS1), we speculate that other modifier genes or environmental factors may play a role in the renal phenotype variability observed in individuals bearing PLCE1 mutations. This observation needs to be considered in the genetic counselling offered to patients

The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies

Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease

Roles and practices of general practitioners and psychiatrists in management of depression in the community

BACKGROUND: Little is known about depressed patients' profiles and how they are managed. The aim of the study is to compare GPs and psychiatrists for 1°) sociodemographic and clinical profile of their patients considered as depressed 2°) patterns of care provision. METHODS: The study design is an observational cross-sectional study on a random sample of GPs and psychiatrists working in France. Consecutive inclusion of patients seen in consultation considered as depressed by the physician. GPs enrolled 6,104 and psychiatrists 1,433 patients. Data collected: sociodemographics, psychiatric profile, environmental risk factors of depression and treatment. All clinical data were collected by participating physicians; there was no direct independent clinical assessment of patients to check the diagnosis of depressive disorder. RESULTS: Compared to patients identified as depressed by GPs, those identified by psychiatrists were younger, more often urban (10.5% v 5.4% – OR = 2.4), educated (42.4% v 25.4% – OR = 3.9), met DSM-IV criteria for depression (94.6% v 85.6% – OR = 2.9), had been hospitalized for depression (26.1% v 15.6% – OR = 2.0) and were younger at onset of depressive problems (all adjusted p < .001). No difference was found for psychiatric and somatic comorbidity, suicide attempt and severity of current depression. Compared to GPs, psychiatrists more often prescribed tricyclics and very novel antidepressants (7.8% v 2.3% OR = 5.0 and 6.8% v 3.0% OR = 3.8) with longer duration of antidepressant treatment. GPs' patients received more "non-conventional" treatment (8.8% v 2.4% OR = 0.3) and less psychotherapy (72.2% v 89.1% OR = 3.1) (all adjusted p < .001). CONCLUSION: Differences between patients mainly concerned educational level and area of residence with few differences regarding clinical profile. Differences between practices of GPs and psychiatrists appear to reflect more the organization of the French care system than the competence of providers

Assessment of factors associated with complete immunization coverage in children aged 12-23 months: a cross-sectional study in Nouna district, Burkina Faso

This study identifies specific factors associated with immunization status in Nouna health district (Burkina Faso) in order to advance improved intervention strategies in this district and in those with similar environmental and social contexts. While comprehensive communication may improve understanding about immunization, local interventions should also take into account religious specificities and critical economic periods. Communication problems need to be examined; for instance, many respondents did not understand what the health workers wanted; and or they assumed their child was already totally immunized. Particular approaches that take into consideration local distinctions need to be applied