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.

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.

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.

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.

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.

A parallel study of different array-CGH platforms in a set of Spanish patients with developmental delay and intellectual disability.

Developmental delay and intellectual disability, which occur in 1-3% of the population, account for a large number of the cases regularly seen in genetic units. Chromosomal microarray analysis has been shown to be a valuable clinical diagnostic assay and it should be the first-tier clinical diagnostic test for individuals with these conditions. However and due to several difficulties such as the platform resolution, the cost, and the inexperience with genomic data bases, the implementation of this test in many cytogenetic laboratories has been delayed. In an attempt to provide more insights of the benefits derived by using the chromosomal microarray analysis, this study presents the experience of two clinical centers using three different microarray platforms. The results obtained using a custom microarray (KaryoArray®) and two different commercial medium- and high-resolution whole-genome oligonucleotide microarrays have been compared. An overall diagnostic yield of around 15% has been obtained. However, the custom microarray platform has been shown to be more convenient for a clinical setting, since it allows the detection of more pathogenic copy number variants and less common variants.

A prospective evaluation of neonatal hypoglycaemia in infants of women with gestational diabetes mellitus.

OBJECTIVE: To analyse first-day-of-life glucose levels in infants of women with gestational diabetes (GDM) and the influence of maternal, gestational and peripartum factors on the development of neonatal hypoglycaemia. STUDY DESIGN: Prospective cohort study including newborns of GDM mothers. Capillary blood glucose (CBG) was measured serially on the first day of life. CBG values were defined as normal (≥ 2.5 mmol/l), mild hypoglycaemia (2.2-2.4 mmol/l), moderate hypoglycaemia (1.6-2.1 mmol/l) and severe hypoglycaemia (<1.6 mmol/l). RESULTS: One hundred and ninety infants were included: 23 (12.1%) presented mild, 20 (10.5%) moderate and only 5 (2.6%) severe hypoglycaemia. Hypoglycaemic infants were more frequently large-for-gestational-age (29.3% vs 11.3%, p=0.003), had lower umbilical cord pH (7.28 vs 7.31, p=0.03) and their mothers had more frequently been hyperglycaemic during labour (18.8% vs 8.5%, p=0.04). In multivariate analysis Pakistani origin (OR: 2.94; 95% CI: 1.14-7.55) and umbilical cord venous pH (OR: 0.04, 95% CI: 0.261-0.99) were significantly and independently associated with hypoglycaemia. CONCLUSIONS: Mild and moderate neonatal hypoglycaemias were common although severe episodes were unusual in infants of women with GDM. Hypoglycaemia is mainly influenced by ethnicity and cord blood pH, although maternal peripartum glycaemic control and large-for-gestational-age condition may also play a role.

A170P mutation in SHOX gene in a patient not presenting with Madelung deformity.

Idiopathic short stature is a multifactorial disease caused by defects in several genes. Among them, short stature homeobox-containing gene (SHOX) mutations have an incidence of 2%-15% within the idiopathic short population. The authors report a patient with moderate intellectual disability, short stature and no other radiological traits referred for subtelomeric screening. MLPA and sequencing results showed a heterozygous mutation in SHOX gene (A170P). This mutation has been described to fully cosegregate with Madelung deformity in patients affected with Léri-Weill dyschondrosteosis and Langer mesomelic dysplasia. The authors report the first case of idiopathic short stature due to the A170P mutation in a patient without any radiological trait. The A170P mutation is the most prevalent mutation in the Spanish gypsy population affected with short stature disorders. The authors strongly recommend SHOX screening for deletions, duplications and point mutations in patients affected with short stature although they do not present any radiological traits.

Pandemic influenza a (2009 H1N1) in human immunodeficiency virus-infected catalan children.

No data are available on 2009 H1N1 influenza in human immunodeficiency virus (HIV)-infected children, a highly susceptible and vulnerable population. We report 13 cases of pandemic influenza among a cohort of HIV-infected pediatric patients. Clinical features of H1N1 influenza were similar to those described in the general population. Most patients received antivirals on an outpatient basis. An uneventful evolution was observed in all patients, only 2 of whom required hospitalization. Influenza had no effect on the evolution of HIV infection.

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.

QT interval in newborns of different ethnic origin: usefulness of neonatal ECG screening.

The cost-effectiveness of neonatal electrocardiographic (ECG) screening has been questioned. The objective of this study was to establish normal values for the QT interval in newborns of different ethnic origin. Between 2005 and 2006, ECGs were obtained during the first 48 h of life from 1305 at-term newborns at the Hospital del Mar in Barcelona, Spain. The mean corrected QT interval (QTc) was 417.79+/-28.47 ms. A QTc longer than 440 ms was observed in 240 newborns (18.33%). The frequency of a pathologic QTc in Spanish newborns was 17.9%, compared with 27.7% in those of Maghreb or Near Eastern origin (P=.016), and 28.2% in those of Indian or Pakistani origin (P=.033). The QTc may vary for genetic reasons. A routine neonatal ECG is advisable only in ethnic groups in which the QTc is lengthened, to help counter the greater risk of sudden death in these infants.

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.

Neonatal withdrawal syndrome after chronic maternal drinking of mate.

The premature newborn of a mother who reported drinking mate during pregnancy presented with increased jitteriness and irritability, high-pitched cry, hypertonia in the limbs, and brisk tendon reflexes consistent with neonatal withdrawal syndrome. High concentrations of caffeine and theobromine were detected in various maternal and neonatal biological matrices (placenta, cord serum, neonatal urine, maternal and neonatal hair, meconium, and breast milk), demonstrating both acute and chronic prenatal and postnatal exposure to these methylxanthines, contained in high amounts in homemade mate. Symptoms progressively disappeared at 84 hours of age, although intermittent irritability was still present when the infant was discharged at 24 days of age. Fluctuating caffeine (and theobromine) content in different breast milk feeds likely generated the baby's irritability, due to either the physiological stimulatory effects of the methylxanthines or postnatal withdrawal syndrome as the substances cleared from the body. The mother was strongly advised to initiate a considerable, progressive, constant reduction of mate consumption to a maximum of 2 cups a day for the duration of breastfeeding.

Areca-nut abuse and neonatal withdrawal syndrome.

Areca-nut chewing occurs widely in South Asia and the Indian subcontinent. Here we present a case of neonatal withdrawal syndrome in an infant born to a woman who was a chronic areca-nut user. Arecoline, the principal neuroactive alkaloid in areca nuts, was found in the mother's placenta.

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.

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.

[Recommendations of the CEVIHP/SEIP/AEP/PNS on antiretroviral treatment in HIV-infected children and teenagers]. / Recomendaciones CEVIHP/SEIP/AEP/PNS respecto al tratamiento antirretroviral en niños y adolescentes infectados por el VIH.

OBJECTIVE: To update antiretroviral recommendations in antiretroviral therapy (ART) in HIV-infected children and adolescents. METHODS: Theses guidelines have been formulated by a panel of members of the Plan Nacional sobre el SIDA (PNS) and the Asociacion Espanola de Pediatria (AEP) by reviewing the current available evidence of efficacy, safety, and pharmacokinetics in pediatric studies. Three levels of evidence have been defined according to the source of data: Level A: randomized and controlled studies; Level B: Cohort and case-control studies; Level C: Descriptive studies and experts' opinion. RESULTS: When to start ART should be made on an individual basis, discussed with the family, considering the risk of progression according to age, CD4 and viral load, the ART-related complications and adherence. The ART goal is to reach a maximum and durable viral suppression. This is not always possible, even with clinical and immunologic improvement. The difficulties of permanent adherence and side-effects are resulting in a more conservative trend to initiate ART, and to less toxic and simpler strategies. Currently, combinations of at least three drugs are of first choice both in acute and chronic infection. They must include 2 NA 1 1 NN or 2 NA 1 1 PI. ART is recommended in all symptomatic patients and, with few exceptions, in all infants in the first year of life. Older asymptomatic children should start ART according to CD4 count, especially CD4 percentage, that vary with age. Despite potent salvage therapies, it is common not to reach viral undetectability. Therapeutical options when ART fails are scarce due to cross-resistance. The cause of failure must be identified. Occasionally, there exists clinical and/or immunological progression, and a change of therapy with at least two new drugs still active for the patient, is warranted with the aim of increasing the CD4 count to a lower level of risk. Toxicity and adherence must be regularly monitored. Some aspects about post exposure prophylaxis and coinfection with HCV or HBV are discussed. CONCLUSIONS: A higher level of evidence with regard to ART effectiveness and toxicity in pediatrics is currently available, leading to a more conservative and individualized approach. Clinical symptoms and CD4 count are the main determinants to start and change ART.

The effects on infants of potent antiretroviral therapy during pregnancy: a report from Spain.

BACKGROUND: The purpose of our study was to assess the effects on infants of protease inhibitor (PI)-based antiretroviral therapy (ART) given to their HIV-positive mothers during pregnancy. MATERIAL/METHODS: A multicenter observational study was carried out at 11 centers in Spain, involving 124 HIV-1-infected pregnant women under ART and their infants. The mothers were classified according to the ART protocols used during pregnancy into two groups: group A, 52 women with > or =2 nucleoside reverse transcriptase inhibitors (NRTI) with or without NNRTI, for a mean time of 4.7+/-2.2 months; and group B, 72 women on protease inhibitor (PI)-based regimens for 5.4+/-2.6 months. RESULTS: Maternal therapy was well tolerated, with no serious adverse effects on pregnancy course. No newborn was infected with HIV-1. There were two deaths at birth (group B), both with extreme prematurity. Among the 126 ART-exposed infants (4 siblings), the most common toxicity was anemia (29%), without significant differences between the two groups. Low birthweight and prematurity were also common (21% and 14%, respectively). CONCLUSIONS: Optimal management of HIV-1 infection in women, regardless of their pregnancy status, can be recommended in more developed countries, without adverse effects on pregnancy outcome, and dramatically decreasing vertical transmission. HAART with PI versus potent ART during pregnancy was effective and safe for infants throughout the 12-month follow-up. In the light of recent advances in anti-HIV-1 pregnancy therapy, the long-term safety of these prophylactic and therapeutical strategies should be studied.

Older children and adolescents surviving with vertically acquired HIV infection.

This article describes the characteristics of children infected vertically with HIV surviving 10 years or more who were enrolled in the prospective European Collaborative Study. Thirty-four of 187 infected children were identified with a median age of 11.4 years (range, 10.1-15.9 years). Factors examined included clinical status, immunologic and virologic characteristics, type of antiretroviral therapy, and psychosocial characteristics. By 10 years of age, 6 (18%) children had progressed to Class A as determined by the system of the U.S. Centers for Disease Control and Prevention (CDC), 17 (52%) to class B, 7 (21%) to class C, and 3 (9%) had remained asymptomatic. At 73% (904 of 1234) of scheduled clinic visits, these children had no symptoms of HIV disease. Most children were in CDC immune categories 1 (18, 56%) or 2 (11, 34%) at their last visit. Three quarters (24 patients) were on combination therapy with three or more drugs, although 3 children had never received any antiretroviral therapy. Nineteen (56%) children were living with at least 1 parent and the mothers of 13 (38%) children had died. Most (77%) children had been told about their HIV infection. Children infected vertically with HIV who have survived their first 10 years are mainly free of serious symptoms. As they enter adolescence, additional services are needed including support with disclosure to others, therapy, and sexual health.