Single-pixel image reconstruction from experimental data using neural networks.

Single-pixel cameras that measure image coefficients have various promising applications, in particular for hyper-spectral imaging. Here, we investigate deep neural networks that when fed with experimental data can output high-quality images in real time. Assuming that the measurements are corrupted by mixed Poisson-Gaussian noise, we propose to map the raw data from the measurement domain to the image domain based on a Tikhonov regularization. This step can be implemented as the first layer of a deep neural network, followed by any architecture of layers that acts in the image domain. We also describe a framework for training the network in the presence of noise. In particular, our approach includes an estimation of the image intensity and experimental parameters, together with a normalization scheme that allows varying noise levels to be handled during training and testing. Finally, we present results from simulations and experimental acquisitions with varying noise levels. Our approach yields images with improved peak signal-to-noise ratios, even for noise levels that were foreseen during the training of the networks, which makes the approach particularly suitable to deal with experimental data. Furthermore, while this approach focuses on single-pixel imaging, it can be adapted for other computational optics problems.

3D denoised completion network for deep single-pixel reconstruction of hyperspectral images.

Single-pixel imaging acquires an image by measuring its coefficients in a transform domain, thanks to a spatial light modulator. However, as measurements are sequential, only a few coefficients can be measured in the real-time applications. Therefore, single-pixel reconstruction is usually an underdetermined inverse problem that requires regularization to obtain an appropriate solution. Combined with a spectral detector, the concept of single-pixel imaging allows for hyperspectral imaging. While each channel can be reconstructed independently, we propose to exploit the spectral redundancy between channels to regularize the reconstruction problem. In particular, we introduce a denoised completion network that includes 3D convolution filters. Contrary to black-box approaches, our network combines the classical Tikhonov theory with the deep learning methodology, leading to an explainable network. Considering both simulated and experimental data, we demonstrate that the proposed approach yields hyperspectral images with higher quantitative metrics than the approaches developed for grayscale images.

Adaptive noise reduction for power Doppler imaging using SVD filtering in the channel domain and coherence weighting of pixels.

Objective. Ultrafast power Doppler (UPD) is an ultrasound method that can image blood flow at several thousands of frames per second. In particular, the high number of data provided by UPD enables the use of singular value decomposition (SVD) as a clutter filter for suppressing tissue signal. Notably, is has been demonstrated in various applications that SVD filtering increases significantly the sensitivity of UPD to microvascular flows. However, UPD is subjected to significant depth-dependent electronic noise and an optimal denoising approach is still being sought.Approach. In this study, we propose a new denoising method for UPD imaging: the Coherence Factor Mask (CFM). This filter is first based on filtering the ultrasound time-delayed data using SVD in the channel domain to remove clutter signal. Then, a spatiotemporal coherence mask that exploits coherence information between channels for identifying noisy pixels is computed. The mask is finally applied to beamformed images to decrease electronic noise before forming the power Doppler image. We describe theoretically how to filter channel data using a single SVD. Then, we evaluate the efficiency of the CFM filter for denoisingin vitroandin vivoimages and compare its performances with standard UPD and with three existing denoising approaches.Main results. The CFM filter gives gains in signal-to-noise ratio and contrast-to-noise ratio of up to 22 dB and 20 dB, respectively, compared to standard UPD and globally outperforms existing methods for reducing electronic noise. Furthermore, the CFM filter has the advantage over existing approaches of being adaptive and highly efficient while not requiring a cut-off for discriminating noise and blood signals nor for determining an optimal coherence lag.Significance. The CFM filter has the potential to help establish UPD as a powerful modality for imaging microvascular flows.

Xq26.2-q26.3 microduplication in two brothers with intellectual disabilities: clinical and molecular characterization.

Partial duplications involving the long arm of the X chromosome are associated with mental retardation, short stature, microcephaly, hypopituitarism and a wide range of physical findings. We identified an inherited Xq26.2-Xq26.3 duplication in two brothers with severe mental retardation, hypotonia, growth delay, craniofacial disproportion and dental malocclusion. Chromosome analysis was normal and multiplex ligation-dependent probe amplification analysis detected duplication on Xq26. Further characterization by array comparative genomic hybridization and quantitative PCR helped to determine proximal and distal duplication breakpoints giving a size of approximately 2.8 Mb. The duplication encompasses 24 known genes, including the X-linked mental retardation genes ARHGEF6, PHF6, HPRT1 and SLC9A6. Clinical and molecular characterization of Xq duplications will shed more light into the phenotypic implication of functional disomy of X-chromosome genes.

Pregnancy as an opportunity to diagnose human-immunodeficiency virus immigrant women in Catalonia. / El embarazo como una oportunidad de diagnóstico del virus de la inmunodeficiencia humana en mujeres inmigrantes en Catalunya.

INTRODUCTION: Mother-to-child transmission (MTCT) is relevant in the global epidemiology of human-immunodeficiency virus (HIV), as it represents the main route of infection in children. The study objectives were to determine the rate of HIV-MTCT and its epidemiological trend between the Spanish-born and immigrant population in Catalonia in the period 2000-2014. METHODS: A prospective observational study of mother-child pairs exposed to HIV, treated in 12 hospitals in Catalonia in the period 2000-2014. HIV-MTCT rate was estimated using a Bayesian logistic regression model. R and WinBUGS statistical software were used. RESULTS: The analysis included 909 pregnant women, 1,009 pregnancies, and 1,032 children. Data on maternal origin was obtained in 79.4% of women, of whom 32.7% were immigrants, with 53.0% of these from sub-Saharan Africa. The overall HIV-MTCT rate was 1.4% (14/1,023; 95% CI; 0.8-2.3). The risk of MTCT-HIV was 10-fold lower in women with good virological control (P=.01), which was achieved by two-thirds of them. The proportion of immigrants was significantly higher in the period 2008-2014 (P<.0001), for the HIV-diagnosis (P<.0001), and antiretroviral administration (P=.02) during pregnancy, and for undetectable viral load next to delivery (P<.001). There were no differences in the rate of MTCT-HIV among Spanish-born and immigrant women (P=.6). CONCLUSIONS: There is a gradual increase in HIV pregnant immigrants in Catalonia. Although most immigrant women were diagnosed during pregnancy, the rate of MTCT-HIV was no different from the Spanish-born women.

Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis.

BACKGROUND: Different biological matrices are suitable for drug testing in newborns presenting with an acute withdrawal syndrome. CASE REPORT: The newborn of a mother reporting alprazolam use during pregnancy presented with respiratory distress and clinical features consistent with neonatal withdrawal syndrome or neonatal sepsis of vertical transmission. Alprazolam and its main metabolite (alpha-hydroxyalprazolam) were detected in cord serum, neonatal urine and also in neonatal hair, meconium and placenta, accounting for both acute and chronic exposure to this benzodiazepine during intrauterine life. At the same time, the clinical diagnosis of neonatal sepsis was confirmed by isolation of Streptococcus agalactiae from otic cultures. The infant received oxygen therapy and antibiotic treatment and recovered completely at the age of 11 days. Although no congenital anomalies or behavioral alterations were diagnosed during hospitalization, periodic follow-ups were requested to check for potential long-term effects of prenatal exposure to alprazolam.

Acanthosis nigricans as an adverse effect of highly active antiretroviral therapy in an adolescent girl with human immunodeficiency virus infection.

We report an 11-year-old girl with acanthosis nigricans that appeared after 4 years of treatment with didanosine, stavudine and amprenavir. Laboratory studies showed hyperglycemia, hyperinsulinemia and hypertriglyceridemia. Withdrawal of amprenavir resulted in disappearance of acanthosis nigricans and improvement of metabolic abnormalities.

Safety and antiviral response at 12 months of lopinavir/ritonavir therapy in human immunodeficiency virus-1-infected children experienced with three classes of antiretrovirals.

INTRODUCTION: Many human immunodeficiency virus type 1 (HIV-1)-infected children have already failed treatment with 2 or even 3 classes of antiretrovirals. Coformulation of lopinavir with low dose ritonavir exhibits a potent antiretroviral effect. However, the data in heavily pretreated children are still scarce. This study evaluated the safety and effectiveness of combination therapy including lopinavir/ritonavir in children with prior exposure to all classes of oral antiretrovirals. METHODS: This was an open label multicenter observational study, in which data were reviewed according to a standardized protocol. The study population included all HIV-1-infected children with virologic failure (HIV-1 RNA >5000 copies/mL) followed in 12 Spanish hospitals for >12 months, experienced with the 3 classes of oral antiretrovirals, in whom a lopinavir/ritonavir-containing regimen was started. RESULTS: By March 2003, 45 patients had been treated with lopinavir/ritonavir for a median of 18 months (range, 3-28). The median age at baseline was 9.7 years (range, 4.3-17.1). The median times of prior treatment were 88 months (range, 31-145) with nucleoside reverse transcription inhibitors and 42 months (range, 19-63) with protease inhibitors. Twenty-five patients were classified as Centers for Disease Control and Prevention clinical category C. Median values for absolute and percentage CD4 at baseline were 501 (range, 6-1512) and 19% (range, 0.5-49), respectively, and plasma HIV-RNA was 5.0 log10 copies/mL (range, 4.1-6.1). During follow-up, 11 (24%) children switched from liquid to solid formulation. At 48 weeks, the median values for absolute and percentage CD4 increased by 199 cells/microL and 3%, respectively, and median plasma viral load declined 1.75 log10 copies/mL. Forty-two percent of children achieved a plasma RNA of <400 copies/mL (intent to treat analysis). Baseline genotypic resistance was available in 40 children. Nonresponders had 7.0 +/- 1.6 protease inhibitor-associated mutations at baseline compared with 4.8 +/- 1.7 in children achieving virologic suppression (P = 0.06). Adverse events were described in 18 children. Three children permanently discontinued and 4 transiently withdrew lopinavir/ritonavir. At 12 months, there were mild but not significant increases in plasma cholesterol and triglycerides. CONCLUSIONS: Lopinavir/ritonavir when given as part of salvage regimen is well-tolerated, although switching to pills is frequently required. The regimen has a potent and durable antiretroviral activity in most heavily pretreated children, despite the presence of multiple mutations to all classes of oral antiretrovirals.

Dynamics of the NK-cell subset redistribution induced by cytomegalovirus infection in preterm infants.

Human cytomegalovirus (HCMV) infection promotes an expansion of NK-cells expressing the CD94/NKG2C receptor. We prospectively monitored the effects of HCMV on the NK-cell receptor (NKG2C, NKG2A, KIR, LILRB1) distribution in preterm infants. As compared to non-infected moderately preterm newborns (n=19, gestational age: 32-37 weeks), very preterm infants (n=5, gestational age: <32 weeks) suffering symptomatic postnatal HCMV infection displayed increased numbers of NKG2C+, KIR+ NK-cells, encompassed by a reduction of NKG2A+ NK-cells. A similar profile was observed in HCMV-negative newborns (n=4) with asymptomatic infection, during follow-up at ~4 and 10 months of age. Of note, viremia remained detectable in three symptomatic cases at ~10 months despite the persistent expansion of NKG2C+ NK-cells. Our study provides original insights on the dynamics of the imprint exerted by primary HCMV infection on the NK-cell compartment, revealing that the expansion of NKG2C+ NK-cells may be insufficient to control viral replication in very preterm infants.

Efficient application of next-generation sequencing for the diagnosis of rare genetic syndromes.

AIMS: The causes of intellectual disability, which affects 1%-3% of the general population, are highly heterogeneous and the genetic defect remains unknown in around 40% of patients. The application of next-generation sequencing is changing the nature of biomedical diagnosis. This technology has quickly become the method of choice for searching for pathogenic mutations in rare uncharacterised genetic diseases. METHODS: Whole-exome sequencing was applied to a series of families affected with intellectual disability in order to identify variants underlying disease phenotypes. RESULTS: We present data of three families in which we identified the disease-causing mutations and which benefited from receiving a clinical diagnosis: Cornelia de Lange, Cohen syndrome and Dent-2 disease. The genetic heterogeneity and the variability in clinical presentation of these disorders could explain why these patients are difficult to diagnose. CONCLUSIONS: The accessibility to next-generation sequencing allows clinicians to save much time and cost in identifying the aetiology of rare diseases. The presented cases are excellent examples that demonstrate the efficacy of next-generation sequencing in rare disease diagnosis.