Clinical profiles of placenta accreta spectrum: the PACCRETA population-based study.

OBJECTIVE: To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section. DESIGN: Prospective population-based study. SETTING: All 176 maternity hospitals of eight French regions. POPULATION: Two hundred and forty-nine women with PAS, from a source population of 520 114 deliveries. METHODS: Women with PAS were classified into two risk-profile groups, with or without the high-risk combination of placenta praevia (or an anterior low-lying placenta) and at least one prior caesarean. These two groups were described and compared. MAIN OUTCOME MEASURES: Population-based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes. RESULTS: The PAS population-based incidence was 4.8/10 000 (95% CI 4.2-5.4/10 000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group with both factors, PAS was more often suspected antenatally (77% versus 17%; P < 0.001) and more often percreta (38% versus 5%; P < 0.001). This group also had more hysterectomies (53% versus 21%, P < 0.001) and higher rates of blood product transfusions, maternal complications, preterm births and neonatal intensive care unit admissions. Sensitivity analysis showed similar results after exclusion of women who delivered vaginally. CONCLUSION: More than half the cases of PAS occurred in women without the combination of placenta praevia and a prior caesarean delivery, and these women had better maternal and neonatal outcomes. We cannot completely rule out that some of the women who delivered vaginally had placental retention rather than PAS; however, we found similar results among women who delivered by caesarean. TWEETABLE ABSTRACT: Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes.

Iron deficiency during first-line chemotherapy in metastatic cancers: a prospective epidemiological study.

PURPOSE: Anemia is common in oncology and negatively impacts quality of life. However, there is lack of knowledge about iron deficiency (ID) epidemiology. The aim of this study was to prospectively assess iron status in patients with locally advanced or metastatic cancer beginning chemotherapy. METHODS: In this prospective, multicenter cohort study, anemia and ID were evaluated in patients with locally advanced or metastatic solid tumors and lymphoma before starting chemotherapy. Blood samples were collected at inclusion (W0), 6 weeks (W6), and 12 weeks (W12). Prevalence was evaluated in the general population, according to tumor location and was correlated with tumor response. RESULTS: One hundred twenty-nine patients were enrolled between 2013 and 2015; 119 had solid tumors and 10 lymphomas. At W0, there were no significant difference between locations with a prevalence around 50-60% (range 47.2-70.4%) and only a trend for colorectal cancer (70.4%, P = 0.069) due to a higher prevalence of absolute ID (18.5%). Prevalence of ID+ decreased between W0 and W6 and remained stable until W12 due to the proportion of patients with ID and without anemia. However, anemia prevalence increased during W0 and W6 and remained stable to W6 from W12 due to patients with anemia but without ID. A significant correlation between tumor response and ID prevalence was found (P = 0.036). CONCLUSIONS: We confirm the high prevalence of ID and anemia in cancer patients. ID status is correlated to tumor response providing a strong rationale for iron monitoring during cancer management.

[Perinatal health and medical administrative data: What uses, which stakeholders, what the issues for birth data? - Special REDSIAM]. / Périnatalité et bases de données médico-administratives : quels usages, quels acteurs, quels enjeux pour les données sur les naissances ? ­ Spécial REDSIAM.

BACKGROUND: The uses of medical administrative data (MAD/BDMA) emerged in perinatal health following the work on regionalization of very pre-term birth. They have become more numerous since the late 2000s. The objective of this article is to take stock of the existing work carried out within the REDSIAM-perinatality group, on MAD/BDMA and their uses for the period of "birth". METHODS: The studied MADs are the Hospital Discharge Data (PMSI) and the French national health database (SNIIRAM). The material includes knowledge shared by the members of the REDSIAM-perinatality group, scientific references and gray literature. RESULTS: Our exploratory study shows that the uses of MAD in perinatal health are diversified at the local, regional and national levels. The works and publications, increasing, take the form of public access of processed data. Collective thinking makes it possible to move from a localized use to an institution, a network or several, to a national use and an inscription in public authorities' responses. In 2015/2016, two institutional sites provide access to data on maternal and child health: Data.Drees and ATIH ScanSanté. MAD/BDMA uses are multiple: epidemiological use (count of births by gestational age, weight in particular; perinatal indicators), quality of care, planning (maternity activities, regionalization of care). There is an increasing interest among stakeholders, producers and/or operators of MAD/BDMA (decision-makers, professionals or researchers). CONCLUSION: The BDMA, including the PMSI and the SNIIRAM, are used and relevant in Perinatal health with the rise of health networks, the territorialisation of health, in an increased demand for quality of care. Their use will increase the reliability of the data collected and an inscription in the validation studies, more and more numerous in the field of BDMA. The algorithms need to be more finely compiled, validated and enhanced.

Characteristics of Four Upward-Pointing Cosmic-Ray-like Events Observed with ANITA.

We report on four radio-detected cosmic-ray (CR) or CR-like events observed with the Antarctic Impulsive Transient Antenna (ANITA), a NASA-sponsored long-duration balloon payload. Two of the four were previously identified as stratospheric CR air showers during the ANITA-I flight. A third stratospheric CR was detected during the ANITA-II flight. Here, we report on characteristics of these three unusual CR events, which develop nearly horizontally, 20-30 km above the surface of Earth. In addition, we report on a fourth steeply upward-pointing ANITA-I CR-like radio event which has characteristics consistent with a primary that emerged from the surface of the ice. This suggests a possible τ-lepton decay as the origin of this event, but such an interpretation would require significant suppression of the standard model τ-neutrino cross section.

Amino Acid Specific Stable Nitrogen Isotope Values in Avian Tissues: Insights from Captive American Kestrels and Wild Herring Gulls.

Through laboratory and field studies, the utility of amino acid compound-specific nitrogen isotope analysis (AA-CSIA) in avian studies is investigated. Captive American kestrels (Falco sparverius) were fed an isotopically characterized diet and patterns in δ15N values of amino acids (AAs) were compared to those in their tissues (muscle and red blood cells) and food. Based upon nitrogen isotope discrimination between diet and kestrel tissues, AAs could mostly be categorized as source AAs (retaining baseline δ15N values) and trophic AAs (showing 15N enrichment). Trophic discrimination factors based upon the source (phenylalanine, Phe) and trophic (glutamic acid, Glu) AAs were 4.1 (muscle) and 5.4 (red blood cells), lower than those reported for metazoan invertebrates. In a field study involving omnivorous herring gulls (Larus argentatus smithsonianus), egg AA isotopic patterns largely retained those observed in the laying female's tissues (muscle, red blood cells, and liver). Realistic estimates of gull trophic position were obtained using bird Glu and Phe δ15N values combined with ß values (difference in Glu and Phe δ15N in primary producers) for aquatic and terrestrial food webs. Egg fatty acids were used to weight ß values for proportions of aquatic and terrestrial food in gull diets. This novel approach can be applied to generalist species that feed across ecosystem boundaries.

[Record linkage of hospital discharge data and first health certificates: a test in the Val d'Oise]. / Chaînage d'enregistrements de séjours PMSI aux premiers certificats de santé: un test dans le Val d'Oise.

BACKGROUND: Our objective was to test the feasibility of an indirect linkage of data on births from health certificates (HC) with hospital discharge (HD) data. METHODS: The linkage was carried out for live births between April 1st and June 30th, 2011 in six of the nine maternity units in the district of Val d'Oise. The HC and HD had 3284 and 3550 births registered during this period, respectively. Linkage was conducted using variables available in both sources: number of fetuses, baby's birth date, gender, maternity unit of birth, maternal age, municipality of residence, gestational age and birth-weight. Two linkage methods were tested: a deterministic and a semi-deterministic method and a probabilistic approach. The latter method calculates a probability estimate for the strength of the relationship between two linked observations related to the discriminatory power and the error rate of the matched variables. For cases that were linked despite discordance on some of the matching variables, random samples of observations were checked against both HC and HD records to compute rates of false matches. RESULTS: The deterministic and semi-deterministic method linked 92.5% and 85.6% of observations in the HC and HD, respectively. The probabilistic method achieved a linkage rate of 99.6% for HC and 92.7% for HD. Cases only linked by the probabilistic method were more often preterm and had low birth-weight. Cases matched using the probabilistic method only had an error rate of 0.4% with 95% CI [0.2-0.6%]. CONCLUSION: Common items in the HC and HD make it possible to achieve a high rate of linkage. The probabilistic method links more births and, in particular, those at higher risk, and error rates were low.

Etravirine concentrations in the cervicovaginal compartment in HIV-1-infected women receiving etravirine-containing antiretroviral therapy: DIVA 02 study.

We studied the penetration of etravirine and HIV shedding in the genital tract among 12 HIV-1-infected women receiving an etravirine-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median etravirine concentrations were 663 ng/ml in BP and 857 ng/ml in CVF, with a CVF/BP etravirine ratio of approximately 1.2. This good penetration of etravirine may contribute to the control of viral replication in the female genital tract.

Formation of oriented nanostructures in diamond using metallic nanoparticles.

A simple, fast and cost-effective etching technique to create oriented nanostructures such as pyramidal and cylindrical shaped nanopores in diamond membranes by self-assembled metallic nanoparticles is proposed. In this process, a diamond film is annealed with thin metallic layers in a hydrogen atmosphere. Carbon from the diamond surface is dissolved into nanoparticles generated from the metal film, then evacuated in the form of hydrocarbons and, consequently, the nanoparticles enter the crystal volume. In order to understand and optimize the etching process, the role of different parameters such as type of catalyst (Ni, Co, Pt, and Au), hydrogen gas, temperature and time of annealing, and microstructure of diamond (polycrystalline and nanocrystalline) were investigated. With this technique, nanopores with lateral sizes in the range of 10-100 nm, and as deep as about 600 nm, in diamond membranes were produced without any need for a lithography process, which opens the opportunities for fabricating porous diamond membranes for chemical sensing applications.

Detection of magnetic circular dichroism using a transmission electron microscope.

A material is said to exhibit dichroism if its photon absorption spectrum depends on the polarization of the incident radiation. In the case of X-ray magnetic circular dichroism (XMCD), the absorption cross-section of a ferromagnet or a paramagnet in a magnetic field changes when the helicity of a circularly polarized photon is reversed relative to the magnetization direction. Although similarities between X-ray absorption and electron energy-loss spectroscopy in a transmission electron microscope (TEM) have long been recognized, it has been assumed that extending such equivalence to circular dichroism would require the electron beam in the TEM to be spin-polarized. Recently, it was argued on theoretical grounds that this assumption is probably wrong. Here we report the direct experimental detection of magnetic circular dichroism in a TEM. We compare our measurements of electron energy-loss magnetic chiral dichroism (EMCD) with XMCD spectra obtained from the same specimen that, together with theoretical calculations, show that chiral atomic transitions in a specimen are accessible with inelastic electron scattering under particular scattering conditions. This finding could have important consequences for the study of magnetism on the nanometre and subnanometre scales, as EMCD offers the potential for such spatial resolution down to the nanometre scale while providing depth information--in contrast to X-ray methods, which are mainly surface-sensitive.

Do perinatal guidelines have an impact on obstetric practices?

BACKGROUND: The publication of several sets of French guidelines was unfortunately not accompanied by planned assessment of their impact on practices. The goal of this study was to assess the impact of eight French perinatal guidelines on actual obstetric practices. METHODS: Historical cohort setting in France: the Audipog database of 299,412 pregnancies from 1994 to 2006, from which we extracted a sub-sample by randomLy selecting from each participating maternity ward all births occurring during a single month of each year (n=107,450 pregnancies). The main outcome measure was the incidence of pertinent perinatal indicators related to these guidelines. These included site of delivery for low-birth-weight infants (1998), caesarean delivery (2000), preterm delivery (2002), breastfeeding (2002), smoking and pregnancy (2004), immediate postpartum hemorrhages (2004), early discharge after delivery (2004) and episiotomies (2005). Standardised rates, before and after the year of each guideline, were compared using a Chi(2) test. RESULTS: The percentage of children weighing less than 1500 g at birth born in Level III hospitals increased through 1999 but dropped subsequently, without ever returning to the 1994 level (P<0.0001). The overall caesarean rate climbed slowly but regularly from 1994 through 2006 (P<0.0001). Use of antenatal corticosteroids for women hospitalised for threatened preterm labour and in children born before 33 weeks has fluctuated since the release of the guideline (P>0.05). Exclusive breastfeeding at discharge from the maternity ward has increased slowly (P<0.0001). The percentage of deliveries with active management of the third stage of labour rose notably from 1999 to 2006 (P<0.0001), and smoking cessation during pregnancy rose slightly in 2006 (P<0.0001). Since 1994, early discharges have become slowly, slightly, but regularly more frequent for all women (P<0.0001). The guideline on episiotomies has had a slight positive effect in the short term (P<0.0001). CONCLUSIONS: Globally, the impact on actual practices of clinical practice guidelines, except the guideline concerning the active management of the third stage of labour, was low. Most of the changes observed in practices began before the pertinent guideline was published.

[Screening and healthcare for pregnant women with psycho-social vulnerability : A French national study]. / Dépistage et parcours de soins en cas de vulnérabilités psycho-sociales maternelles : une enquête nationale française.

INTRODUCTION: Psycho-social vulnerabilities are a medical risk factor for both fetus and mother. Association between socioeconomic status and prenatal follow-up has been well established and inadequate follow-up is associated with higher morbidity and mortality in women in unfavorable situations. OBJECTIVE: The objective is to identify screening strategies and to describe existing systems for pregnant women in psycho-social vulnerability in French maternity hospitals. MATERIAL AND METHODES: This is a national survey conducted by questionnaire in all French maternities. RESULTS: Screening by means of targeted questions is carried out by 96.7% of maternity units. Early prenatal interviews are offered systematically by 64% of maternity units and access to them is still difficult for women in vulnerable situations. In order to organize care pathways, 28.7% of maternities have a structured unit within their establishment and 81% state that they have mobilizable caregivers. Multidisciplinary meetings for the coordination of the various stakeholders are held by 85.8% of maternity units. Collaboration with networks and associations is emphasized. CONCLUSION: A large proportion of maternities seek to identify women in situation of psycho-social vulnerabilities and to organize care paths. However, the resources implemented still appear insufficient for many maternity units. Each maternity hospital has resources and is developing initiatives to deal with the difficulties of care.

A phase I study of UFT-oral vinorelbine in metastatic breast cancer.

BACKGROUND: Despite current treatment options, metastatic breast cancer (MBC) remains essentially incurable, requiring research on new drugs or combinations to improve survival and quality of life. PATIENTS AND METHODS: This phase I study was designed to define the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose of all-oral tegafur-uracil (UFT)/folinic acid combined with vinorelbine as chemotherapy for MBC. Starting doses were 40 mg/m(2)/week of oral vinorelbine administered continuously and 250 mg/m(2)/day of UFT plus 90 mg/day of folinic acid from day 1 to day 28, followed by a 1-week rest period. RESULTS: Ten patients were included. Eight were evaluable for toxicity and antitumor response. The second dose level was shown to be the MTD. At this dose, 2 out of 5 patients receiving oral vinorelbine at 40 mg/m(2)/week and UFT at 300 mg/m(2)/day developed DLT consisting of grade 3 asthenia and grade 3 nausea despite standard prophylaxis. Other toxicities were grade 1 diarrhea and anemia. There were no treatment-related deaths. CONCLUSIONS: The recommended dose for this combination seems to be the first dose level. A stable response was observed for 6 patients (average 33 weeks). This combination appears to be well-tolerated and offers an alternative to intravenous chemotherapy.

[Total pharyngolaryngectomy in the 21st century: indications, oncologic and functional outcomes]. / Les pharyngo-laryngectomies totales au 21ème siècle : indications, résultats carcinologiques et fonctionnels.

INTRODUCTION: The development of laryngeal preservation protocols has considerably modified the indications for total (pharyngo-)laryngectomy (TPL). The objectives of our study are to analyze the current indications for TPL and to evaluate the oncologic and functional outcomes after TPL and their predictive factors. METHODS: All patients who underwent TPL for squamous cell carcinoma of the larynx or hypopharynx, at our institution, between 2000 and 2009, were included in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analyzes. RESULTS: A total of 130 patients were enrolled in our study including 119 men and 11 women, with a mean age of 65.9 years. TPL was realized for salvage in 65 patients. Extra-laryngeal tumor extension (n = 42) was the main indication for TPL in the 65 remaining patients. Overall survival was 49 and 41% at 3 and 5 years respectively. In multivariate analysis, primary tumor site (hypopharynx in comparison to larynx; p = 0.04) has a significant pejorative impact on overall survival. Oral alimentation (no enteral nutrition) was recovered successfully by 94% of the patients. In multivariate analysis, primary tumor site (hypopharynx) has a significant pejorative impact on functional results (deglutition: p < 0.0001; phonation: p = 0.03). CONCLUSION: Primary tumor site is one of the main predictive factor of oncologic and functional outcomes after TPL.

Linkage of extracellular plasminogen activator to the fibroblast cytoskeleton: colocalization of cell surface urokinase with vinculin.

Several cell types display binding sites for [125I]urokinase (Vassalli, J.-D., D. Baccino, D. Belin. 1985. J. Cell Biol. 100:86-92) which in certain cases are occupied with endogenous urokinase. These sites appear to focus urokinase at cell surfaces and hence may participate in tissue matrix destruction and cell invasion. Recently Pöllänen et al. (1987) demonstrated that the cell surface urokinase of human fibroblasts and fibrosarcoma cells is deposited underneath the cells in strands, apparently at sites of cell-to-substratum contact. Here, using immunofluorescence double labeling, we show that the urokinase strands present on human foreskin fibroblasts are colocalized with strands of vinculin, an intracellular actin-binding protein that is deposited at cell-to-substratum focal adhesion sites. Thus, this indicates linkage of the plasminogen/plasmin system both to sites of cell adhesion and to the cytoskeleton. The urokinase strands on HT 1080 fibrosarcoma cells are more numerous and have shapes that are more tortuous than those on normal fibroblasts. In intact HT 1080 cells, colocalized vinculin strands are obscured by an intense background of soluble vinculin but are apparent on isolated ventral plasma membranes. Certain properties of the urokinase strands suggest that they are related to the [125I]urokinase-binding sites that have been described by several groups: (a) incubating fibroblasts with dexamethasone for 48 h or at pH 3 at 5 degrees C for 10 min greatly decreases the number and intensity of the urokinase strands; (b) strands reappear when glucocorticoid-treated cells are incubated with exogenous 54-kD (but not 35-kD) urokinase, and this process is inhibited by a previously described 16-amino acid peptide that blocks [125I]urokinase binding to the cells.

Endothelial interleukin-8: a novel inhibitor of leukocyte-endothelial interactions.

Certain inflammatory stimuli render cultured human vascular endothelial cells hyperadhesive for neutrophils. This state is transient and reversible, in part because activated endothelial cells secrete a leukocyte adhesion inhibitor (LAI). LAI was identified as endothelial interleukin-8 (IL-8), the predominant species of which is an extended amino-terminal IL-8 variant. At nanomolar concentrations, purified endothelial IL-8 and recombinant human IL-8 inhibit neutrophil adhesion to cytokine-activated endothelial monolayers and protect these monolayers from neutrophil-mediated damage. These findings suggest that endothelial-derived IL-8 may function to attenuate inflammatory events at the interface between vessel wall and blood.

Host tree age as a selective pressure leading to local adaptation of a population of a polyphagous Lepidoptera in virgin boreal forest.

We tested the hypothesis that host tree age may act as a selective factor and lead to local adaptation of the hemlock looper (Lambdina fiscellaria), a geometrid Lepidoptera that has a wide geographical distribution and has evolved in different eco-zones characterized by different levels of floristic composition, age structure and fragmentation level. Considering that hemlock looper outbreaks mainly occurred in old forests, we compared the biological performances of two populations. The first population was collected in the northern virgin boreal forest, which is dominated by mature and overmature coniferous stands that have not suffered from human disturbance. The other population was collected in the southern mixed-wood forest, which is more diversified and has been modified by forest harvesting. Larvae were reared under controlled conditions on foliage from three age classes of balsam fir trees: juvenile, mature and overmature. Although we measured significant variations of biological performances between the two populations, no significant effect of the age of the balsam fir trees could be detected for males from both populations or for females from the southern population. However, northern females were strongly affected by the age of balsam fir trees on which they fed, as their pupal weight was 12% higher and their fecundity increased by 27% on overmature trees compared with juvenile ones. These results indicate that under the same selective pressure, females adapt their strategy to maximize their fitness, and thus they appear as the driving force of evolution through the local adaptation concept. Furthermore, the two populations evolved in distinct habitats and their adaptation reflects selective pressures occurring inside their original environment. This is the first report on local adaptation of an herbivore that is mediated by host tree age. Changes in forest age structure may have a considerable impact on insect local adaptation and presumably on their population dynamics.

Insights into image contrast from dislocations in ADF-STEM.

Competitive mechanisms contribute to image contrast from dislocations in annular dark-field scanning transmission electron microscopy (ADF-STEM). A clear theoretical understanding of the mechanisms underlying the ADF-STEM contrast is therefore essential for correct interpretation of dislocation images. This paper reports on a systematic study of the ADF-STEM contrast from dislocations in a GaN specimen, both experimentally and computationally. Systematic experimental ADF-STEM images of the edge-character dislocations reveal a number of characteristic contrast features that are shown to depend on both the angular detection range and specific position of the dislocation in the sample. A theoretical model based on electron channelling and Bloch-wave scattering theories, supported by numerical simulations based on Grillo's strain-channelling equation, is proposed to elucidate the physical origin of such complex contrast phenomena.

[Overview of induction of labor practices in France]. / État des lieux des pratiques de déclenchement en France.

OBJECTIVE: To describe induction of labor practices in France and to identify factors associated with the use of different methods. METHODS: The data came from the French prospective population-based cohort MEDIP (MEthodes de Déclenchement et Issues Périnatales), including consecutively during one month in 2015 all women with induction of labor and a live fetus in 7 perinatal networks. The characteristics of women, maternity units, gestational age, Bishop's score, decision mode, indication and methods of labor induction were described. Factors associated with the use of different methods were sought in univariate analyzes. RESULTS: The rate of induction of labor during the study was 21% and 3042 women were included (95.9% participation rate). The two main indications were prolonged pregnancy (28.7%) and premature rupture of the membranes (25.4%). More than one-third of women received intravenous oxytocin in first method, 57.3% prostaglandins, 4.5% balloon catheter and 1.4% another method. Among the prostaglandins, the vaginal device of dinoprostone was the most used (71.6%) then the gel (20.7%) and the vaginal misoprostol (6.7%). Women with a balloon were more often of higher body mass index and multiparous with scarred uterus. The balloon and misoprostol were mainly used in university public hospitals. CONCLUSIONS: The evolution of induction of labor methods, due to new data from the literature and the development of new drugs or devices, invites to regularly repeat population-based studies on induction of labor.

Magnetic circular dichroism in electron energy loss spectrometry.

The measurement of circular dichroism in the electron microscope is a new, emerging method and, as such, it is subject to constant refinement and improvement. Different ways can be envisaged to record the signal. We present an overview of the key steps in the energy-loss magnetic chiral dichroism (EMCD) experiment as well as a detailed review of the methods used in the intrinsic way where the specimen is used as a beam splitter. Lateral resolution up to 20-30 nm can be achieved, and the use of convergent beam techniques leads to an improved S/N ratio. Dichroic effects are shown for Ni and Co single crystal; as a counterexample, measurements were carried also for a non-magnetic (Ti) sample, where no dichroic effect was found.

Optimal aperture sizes and positions for EMCD experiments.

The signal-to-noise ratio (SNR) in energy-loss magnetic chiral dichroism (EMCD)--the equivalent of X-ray magnetic circular dichroism (XMCD) in the electron microscope--is optimized with respect to the detector shape, size and position. We show that an important increase in SNR over previous experiments can be obtained when taking much larger detector sizes. We determine the ideal shape of the detector but also show that round apertures are a good compromise if placed in their optimal position. We develop the theory for a simple analytical description of the EMCD experiment and then apply it to dynamical multibeam Bloch wave calculations and to an experimental data set. In all cases it is shown that a significant and welcome improvement of the SNR is possible.