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From its commissioning in 2006 to the present, the Spanish Control Centre for Renewable Energies (CECRE) has been a worldwide pioneer and reference centre in the integration of renewable energies in the electrical system. In the last 15 years, CECRE has allowed a high penetration of renewable energies in Spanish electrical system by means of the supervision and control of renewable facilities, while ensuring the power supply security. This paper defines the bases of renewable energy operation in CECRE and introduces forecasting systems for renewable energies. Furthermore, this paper describes the participation of renewable energies in balancing services and congestion management. Finally, new challenges for Spanish transmission system operator (TSO) are presented for the integration of renewable energies along with the energy transition and decarbonization.

The studies carried out to date on vulvodynia treatment with botulinum neurotoxin type A (BoNT/A) have followed generic injection protocols and reported contradictory outcomes on its effects. The aim of the present study was thus to propose a protocol for injecting BoNT/A into targeted painful points, to comprehensively assess the clinical effect of BoNT/A treatment and identify the risk/protective factors for successful treatment. Thirty-five vestibulodynia patients were treated with submucosal injections of incobotulinumtoxinA and assessed 8, 12 and 24 weeks after their treatment. Their clinical and pelvic statuses were assessed from self-reported questionnaires (Visual Analogue Scale (VAS), Female Sexual Function Index (FSFI), Marinoff’s Dyspareunia Scale (MDS), Hospital Anxiety and Depression Scale (HADS), Catastrophizing Scale (CS)), physical examinations and surface electromyography (sEMG). The patients reported a reduction in provoked vestibulodynia (p < 0.01), improved sexual function (>FSFI, p < 0.01; p = 0.01) and psychological status (p < 0.01), and lower pelvic floor hyperactivity at rest (p = 0.01). Factors such as smoking, painful comorbidities, vulvar pain sensitivity and sexual function were significantly associated with successful treatment. The results indicate the beneficial effects of BoNT/A in treating vestibulodynia and reinforce the importance of adapting the treatment according to its clinical presentation and the patient’s medical background.

Summary: We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.

Due to its high sensitivity, electrohysterography (EHG) has emerged as an alternative technique for predicting preterm labor. The main obstacle in designing preterm labor prediction models is the inherent preterm/term imbalance ratio, which can give rise to relatively low performance. Numerous studies obtained promising preterm labor prediction results using the synthetic minority oversampling technique. However, these studies generally overestimate mathematical models’ real generalization capacity by generating synthetic data before splitting the dataset, leaking information between the training and testing partitions and thus reducing the complexity of the classification task. In this work, we analyzed the effect of combining feature selection and resampling methods to overcome the class imbalance problem for predicting preterm labor by EHG. We assessed undersampling, oversampling, and hybrid methods applied to the training and validation dataset during feature selection by genetic algorithm, and analyzed the resampling effect on training data after obtaining the optimized feature subset. The best strategy consisted of undersampling the majority class of the validation dataset to 1:1 during feature selection, without subsequent resampling of the training data, achieving an AUC of 94.5 ± 4.6%, average precision of 84.5 ± 11.7%, maximum F1-score of 79.6 ± 13.8%, and recall of 89.8 ± 12.1%. Our results outperformed the techniques currently used in clinical practice, suggesting the EHG could be used to predict preterm labor in clinics.

Swallowing is a complex sequence of highly regulated and coordinated skeletal and smooth muscle activity. Previous studies have attempted to determine the temporal relationship between the muscles to establish the activation sequence pattern, assessing functional muscle coordination with cross-correlation or coherence, which is seriously impaired by volume conduction. In the present work, we used conditional Granger causality from surface electromyography signals to analyse the directed functional coordination between different swallowing muscles in both healthy and dysphagic subjects ingesting saliva, water, and yoghurt boluses. In healthy individuals, both bilateral and ipsilateral muscles showed higher coupling strength than contralateral muscles. We also found a dominant downward direction in ipsilateral supra and infrahyoid muscles. In dysphagic subjects, we found a significantly higher right-to-left infrahyoid, right ipsilateral infra-to-suprahyoid, and left ipsilateral supra-to-infrahyoid interactions, in addition to significant differences in the left ipsilateral muscles between bolus types. Our results suggest that the functional coordination analysis of swallowing muscles contains relevant information on the swallowing process and possible dysfunctions associated with dysphagia, indicating that it could potentially be used to assess the progress of the disease or the effectiveness of rehabilitation therapies.

The aim of this case-case study was to determine the differences between dysplastic and common naevus-associated melanomas (NAM) and de novo melanomas. A total of 1,021 prospectively collected patients with invasive cutaneous melanoma from an oncology referral centre were included in the study. Of these, 75.51% had de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM, compared with de novo melanomas, were associated with intermittently photo-exposed sites, atypical melanocytic naevi, decreased tumour thickness, and presence of MC1R non-synonymous variants. Common NAM were more frequent on the trunk and of superficial spreading type. Comparison of dysplastic with common NAM showed significant difference only with regard to mitoses. Both subtypes of NAM shared less aggressive traits than de novo melanomas, albeit with no significant differences in survival after multivariate adjustment. In conclusion, NAM present with less aggressive traits, mostly due to a greater awareness among patients of changing moles than due to their intrinsic biological characteristics.

Melanoma results from a complex interplay between environmental factors and individual genetic susceptibility. Familial melanoma is attributable to predisposition genes with variable penetrance. The aim of this study was to identify differences between familial melanoma and sporadic cases in our population, based on the presence of CDKN2A mutations and MC1R variants. Comparing 107 patients with familial melanoma from 87 families (17% CDKN2A mutated) with 1,390 cases of sporadic melanomas, the former were younger and exhibited an increased prevalence of atypical naevi and squamous cell carcinoma (SCC). CDKN2A mutation carriers presented more atypical naevi, multiple melanomas, and basal cell carcinoma, while non-carriers were more likely to have light-coloured hair, atypical naevi, and SCC. MC1R variants decreased the age at diagnosis in all groups and were associated with an increased prevalence of SCC, especially in patients with familial melanoma without CDKN2A mutations. These characteristics may help to establish prevention measures targeting patients with familial melanoma in the Mediterranean area.

One of the remaining challenges for the scientific-technical community is predicting preterm births, for which electrohysterography (EHG) has emerged as a highly sensitive prediction technique. Sample and fuzzy entropy have been used to characterize EHG signals, although they require optimizing many internal parameters. Both bubble entropy, which only requires one internal parameter, and dispersion entropy, which can detect any changes in frequency and amplitude, have been proposed to characterize biomedical signals. In this work, we attempted to determine the clinical value of these entropy measures for predicting preterm birth by analyzing their discriminatory capacity as an individual feature and their complementarity to other EHG characteristics by developing six prediction models using obstetrical data, linear and non-linear EHG features, and linear discriminant analysis using a genetic algorithm to select the features. Both dispersion and bubble entropy better discriminated between the preterm and term groups than sample, spectral, and fuzzy entropy. Entropy metrics provided complementary information to linear features, and indeed, the improvement in model performance by including other non-linear features was negligible. The best model performance obtained an F1-score of 90.1 ± 2% for testing the dataset. This model can easily be adapted to real-time applications, thereby contributing to the transferability of the EHG technique to clinical practice.

The optimization performed in this study is based on the finite dimensions model of the concentric ring electrode as opposed to the negligible dimensions model used in the past. This makes the optimization problem comprehensive, as all of the electrode parameters including, for the first time, the radius of the central disc and individual widths of concentric rings, are optimized simultaneously. The optimization criterion used is maximizing the accuracy of the surface Laplacian estimation, as the ability to estimate the Laplacian at each electrode constitutes primary biomedical significance of concentric ring electrodes. For tripolar concentric ring electrodes, the optimal configuration was compared to previously proposed linearly increasing inter-ring distances and constant inter-ring distances configurations of the same size and based on the same finite dimensions model. The obtained analytic results suggest that previously proposed configurations correspond to almost two-fold and more than three-fold increases in the Laplacian estimation error compared with the optimal configuration proposed in this study, respectively. These analytic results are confirmed using finite element method modeling, which was adapted to the finite dimensions model of the concentric ring electrode for the first time. Moreover, the finite element method modeling results suggest that optimal electrode configuration may also offer improved sensitivity and spatial resolution.

Chronic pelvic pain (CPP) is a complex condition with a high economic and social burden. Although it is usually treated with botulinum neurotoxin type A (BoNT/A) injected into the pelvic floor muscles (PFM), its effect on their electrophysiological condition is unknown. In this study, 24 CPP patients were treated with BoNT/A. Surface electromyographic signals (sEMG) were recorded at Weeks 0 (infiltration), 8, 12 and 24 from the infiltrated, non-infiltrated, upper and lower PFM. The sEMG of 24 healthy women was also recorded for comparison. Four parameters were computed: root mean square (RMS), median frequency (MDF), Dimitrov’s index (DI) and sample entropy (SampEn). An index of pelvic electrophysiological impairment (IPEI) was also defined with respect to the healthy condition. Before treatment, the CPP and healthy parameters of almost all PFM sides were significantly different. Post-treatment, there was a significant reduction in power (MDF), lower fatigue index (SampEn) in all sites in patients, mainly during PFM contractions, which brought their electrophysiological condition closer to that of healthy women (

Preterm birth is the leading cause of death in newborns and the survivors are prone to health complications. Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy. The current methods used in clinical practice to diagnose preterm labor, the Bishop score or cervical length, have high negative predictive values but not positive ones. In this work we analyzed the performance of computationally efficient classification algorithms, based on electrohysterographic recordings (EHG), such as random forest (RF), extreme learning machine (ELM) and K-nearest neighbors (KNN) for imminent labor (F1_2 and ELMF1_2 provided the highest F1-score values in the validation dataset, (88.17 ± 8.34% and 90.2 ± 4.43%) with the 50th percentile of EHG and obstetric inputs. ELMF1_2 outperformed RFF1_2 in sensitivity, being similar to those of ELMSens (sensitivity optimization). The 10th–90th percentiles did not provide a significant improvement over the 50th percentile. KNN performance was highly sensitive to the input dataset, with a high generalization capability.

Chronic pelvic pain (CPP) is a highly disabling disorder in women usually associated with hypertonic dysfunction of the pelvic floor musculature (PFM). The literature on the subject is not conclusive about the diagnostic potential of surface electromyography (sEMG), which could be due to poor signal characterization. In this study, we characterized the PFM activity of three groups of 24 subjects each: CPP patients with deep dyspareunia associated with a myofascial syndrome (CPP group), healthy women over 35 and/or parous (>35/P group, i.e., CPP counterparts) and under 35 and nulliparous (RMS), a predominance of low-frequency components (DI), greater complexity (>SampEn) and lower synchronization on the same side (35/P group. The same trend in differences was found between healthy women (35/P) associated with aging and parity. These results show that sEMG can reveal alterations in PFM electrophysiology and provide clinicians with objective information for CPP diagnosis.

Surface electromyography (sEMG) can be helpful for evaluating swallowing related muscle activity. Conventional recordings with disc electrodes suffer from significant crosstalk from adjacent muscles and electrode-to-muscle fiber orientation problems, while concentric ring electrodes (CREs) offer enhanced spatial selectivity and axial isotropy. The aim of this work was to evaluate CRE performance in sEMG recordings of the swallowing muscles. Bipolar recordings were taken from 21 healthy young volunteers when swallowing saliva, water and yogurt, first with a conventional disc and then with a CRE. The signals were characterized by the root-mean-square amplitude, signal-to-noise ratio, myopulse, zero-crossings, median frequency, bandwidth and bilateral muscle cross-correlations. The results showed that CREs have advantages in the sEMG analysis of swallowing muscles, including enhanced spatial selectivity and the associated reduction in crosstalk, the ability to pick up a wider range of EMG frequency components and easier electrode placement thanks to its radial symmetry. However, technical changes are recommended in the future to ensure that the lower CRE signal amplitude does not significantly affect its quality. CREs show great potential for improving the clinical monitoring and evaluation of swallowing muscle activity. Future work on pathological subjects will assess the possible advantages of CREs in dysphagia monitoring and diagnosis.

Electrohysterography (EHG) has been shown to provide relevant information on uterine activity and could be used for predicting preterm labor and identifying other maternal fetal risks. The extraction of high-quality robust features is a key factor in achieving satisfactory prediction systems from EHG. Temporal, spectral, and non-linear EHG parameters have been computed to characterize EHG signals, sometimes obtaining controversial results, especially for non-linear parameters. The goal of this work was to assess the performance of EHG parameters in identifying those robust enough for uterine electrophysiological characterization. EHG signals were picked up in different obstetric scenarios: antepartum, including women who delivered on term, labor, and post-partum. The results revealed that the 10th and 90th percentiles, for parameters with falling and rising trends as labor approaches, respectively, differentiate between these obstetric scenarios better than median analysis window values. Root-mean-square amplitude, spectral decile 3, and spectral moment ratio showed consistent tendencies for the different obstetric scenarios as well as non-linear parameters: Lempel–Ziv, sample entropy, spectral entropy, and SD1/SD2 when computed in the fast wave high bandwidth. These findings would make it possible to extract high quality and robust EHG features to improve computer-aided assessment tools for pregnancy, labor, and postpartum progress and identify maternal fetal risks.

Postpartum hemorrhage (PPH) is one of the major causes of maternal mortality and morbidity worldwide, with uterine atony being the most common origin. Currently there are no obstetrical techniques available for monitoring postpartum uterine dynamics, as tocodynamometry is not able to detect weak uterine contractions. In this study, we explored the feasibility of monitoring postpartum uterine activity by non-invasive electrohysterography (EHG), which has been proven to outperform tocodynamometry in detecting uterine contractions during pregnancy. A comparison was made of the temporal, spectral, and non-linear parameters of postpartum EHG characteristics of vaginal deliveries and elective cesareans. In the vaginal delivery group, EHG obtained a significantly higher amplitude and lower kurtosis of the Hilbert envelope, and spectral content was shifted toward higher frequencies than in the cesarean group. In the non-linear parameters, higher values were found for the fractal dimension and lower values for Lempel-Ziv, sample entropy and spectral entropy in vaginal deliveries suggesting that the postpartum EHG signal is extremely non-linear but more regular and predictable than in a cesarean. The results obtained indicate that postpartum EHG recording could be a helpful tool for earlier detection of uterine atony and contribute to better management of prophylactic uterotonic treatment for PPH prevention.

Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy and entails high costs for health systems. Currently, no reliable labor proximity prediction techniques are available for clinical use. Regular checks by uterine electrohysterogram (EHG) for predicting preterm labor have been widely studied. The aim of the present study was to assess the feasibility of predicting labor with a 7- and 14-day time horizon in TPL women, who may be under tocolytic treatment, using EHG and/or obstetric data. Based on 140 EHG recordings, artificial neural networks were used to develop prediction models. Non-linear EHG parameters were found to be more reliable than linear for differentiating labor in under and over 7/14 days. Using EHG and obstetric data, the

While progress has been made in design optimization of concentric ring electrodes maximizing the accuracy of the surface Laplacian estimation, it was based exclusively on the negligible dimensions model of the electrode. Recent proof of concept of the new finite dimensions model that adds the radius of the central disc and the widths of concentric rings to the previously included number of rings and inter-ring distances provides an opportunity for more comprehensive design optimization. In this study, the aforementioned proof of concept was developed into a framework allowing direct comparison of any two concentric ring electrodes of the same size and with the same number of rings. The proposed framework is illustrated on constant and linearly increasing inter-ring distances tripolar concentric ring electrode configurations and validated on electrocardiograms from 20 human volunteers. In particular, ratios of truncation term coefficients between the two electrode configurations were used to demonstrate the similarity between the negligible and the finite dimension models analytically (p = 0.077). Laplacian estimates based on the two models were calculated on electrocardiogram data for emulation of linearly increasing inter-ring distances tripolar concentric ring electrode. The difference between the estimates was not statistically significant (p >> 0.05) which is consistent with the analytic result.

Surface Laplacian estimates via concentric ring electrodes (CREs) have proven to enhance spatial resolution compared to conventional disc electrodes, which is of great importance for P-wave analysis. In this study, Laplacian estimates for traditional bipolar configuration (BC), two tripolar configurations with linearly decreasing and increasing inter-ring distances (TCLDIRD and TCLIIRD, respectively), and quadripolar configuration (QC) were obtained from cardiac recordings with pentapolar CREs placed at CMV1 and CMV2 positions. Normalized P-wave amplitude (NAP) was computed to assess the contrast to study atrial activity. Signals were of good quality (20−30 dB). Atrial activity was more emphasized at CMV1 (NAP ≃ 0.19−0.24) compared to CMV2 (NAP ≃ 0.08−0.10). Enhanced spatial resolution of TCLIIRD and QC resulted in higher NAP values than BC and TCLDIRD. Comparison with simultaneous standard 12-lead ECG proved that Laplacian estimates at CMV1 outperformed all the limb and chest standard leads in the contrast to study P-waves. Clinical recordings with CRE at this position could allow more detailed observation of atrial activity and facilitate the diagnosis of associated pathologies. Furthermore, such recordings would not require additional electrodes on limbs and could be performed wirelessly, so it should also be suitable for ambulatory monitoring, for example, using cardiac Holter monitors.

Among many of the electrode designs used in electrocardiography (ECG), concentric ring electrodes (CREs) are one of the most promising due to their enhanced spatial resolution. Their development has undergone a great push due to their use in recent years; however, they are not yet widely used in clinical practice. CRE implementation in textiles will lead to a low cost, flexible, comfortable, and robust electrode capable of detecting high spatial resolution ECG signals. A textile CRE set has been designed and developed using screen-printing technology. This is a mature technology in the textile industry and, therefore, does not require heavy investments. Inks employed as conductive elements have been silver and a conducting polymer (poly (3,4-ethylenedioxythiophene) polystyrene sulfonate; PEDOT:PSS). Conducting polymers have biocompatibility advantages, they can be used with flexible substrates, and they are available for several printing technologies. CREs implemented with both inks have been compared by analyzing their electric features and their performance in detecting ECG signals. The results reveal that silver CREs present a higher average thickness and slightly lower skin-electrode impedance than PEDOT:PSS CREs. As for ECG recordings with subjects at rest, both CREs allowed the uptake of bipolar concentric ECG signals (BC-ECG) with signal-to-noise ratios similar to that of conventional ECG recordings. Regarding the saturation and alterations of ECGs captured with textile CREs caused by intentional subject movements, silver CREs presented a more stable response (fewer saturations and alterations) than those of PEDOT:PSS. Moreover, BC-ECG signals provided higher spatial resolution compared to conventional ECG. This improved spatial resolution was manifested in the identification of P1 and P2 waves of atrial activity in most of the BC-ECG signals. It can be concluded that textile silver CREs are more suitable than those of PEDOT:PSS for obtaining BC-ECG records. These developed textile electrodes bring the use of CREs closer to the clinical environment.

Developing new types of optimized electrodes for specific biomedical applications can substantially improve the quality of the sensed signals. Concentric ring electrodes have been shown to provide enhanced spatial resolution to that of conventional disc electrodes. A sensor with different electrode sizes and configurations (monopolar, bipolar, etc.) that provides simultaneous records would be very helpful for studying the best signal-sensing arrangement. A 5-pole electrode with an inner disc and four concentric rings of different sizes was developed and tested on surface intestinal myoelectrical recordings from healthy humans. For good adaptation to a curved body surface, the electrode was screen-printed onto a flexible polyester substrate. To facilitate clinical use, it is self-adhesive, incorporates a single connector and can perform dry or wet (with gel) recordings. The results show it to be a versatile electrode that can evaluate the optimal configuration for the identification of the intestinal slow wave and reject undesired interference. A bipolar concentric record with an outer ring diameter of 30 mm, a foam-free adhesive material, and electrolytic gel gave the best results.

The prolonged latent phase of Induction of Labour (IOL) is associated with increased risks of maternal mortality and morbidity. Electrohysterography (EHG) has outperformed traditional clinical measures monitoring labour progress. Although parity is agreed to be of particular relevance to the success of IOL, no previous EHG‐related studies have been found in the literature. We thus aimed to identify EHG‐biomarkers to predict IOL success (active phase of labour in ≤ 24 h) and determine the influence of the myoelectrical response on the parity of this group. Statistically significant and sustained differences between the successful and failed groups were found from 150 min in amplitude and non‐linear parameters, especially in Spectral Entropy and in their progression rates. In the nulliparous‐parous comparison, parous women showed statistically significantly higher amplitude progression rate. These biomarkers would therefore be useful for early detection of the risk of induction failure and would help to develop more robust and generalizable IOL success‐prediction systems. [ABSTRACT FROM AUTHOR]

The Bayes factor (BF) procedure was applied to examine the additive genetic component of several physiological and vitality variables for newborn pigs. Nine variables were studied: heart rate, arterial oxygen saturation, rectal temperature (all at birth and 60 min later), birth weight, interval between birth and first teats contact, and interval between birth and first colostrum intake. The available numbers of data ranged from 288 (heart rate at 60 min) to 839 records (birth weight) from [F.sub.2] Iberian x Meishan newborn pigs. We compared a model with zero heritability (nonheritable) with the one where the additive genetic background was included. The BF was used to discriminate between both candidate models. Very strong evidence of genetic background was detected for heart rate 60 min after birth (BF = 48.90), and strong evidence was detected for rectal temperature at birth (BF = 13.82). Posterior modes (means) of heritabilities were 0.29 (0.32) and 0.40 (0.39), respectively. In addition, substantial evidence of absence of genetic background was detected for arterial oxygen saturation at birth. Key Words: Bayes Factor, Neonate Metabolism, Survival, Vitality

Premature birth and its associated complications are one of the biggest global health problems, since there is currently no effective screening method in clinical practice to accurately identify the true Preterm Birth (PTB) from the false threatened ones. Despite the high prevalence of PTB in multiple gestation (MG) women which amounted up to 60%, in the literature there is any work about their uterine myoelectric activities in vivo system. Electrohysterography (EHG) has been emerged as an alternative technique for predicting PTB in single gestation (SG) women. The aim of this study was to characterize and compare the uterine myoelectrical activity in vivo system of SG and MG women in regular check-ups, to provide the basis for early detection and prevention of preterm labour in MG. A prospective observational cohort study was conducted on 31 SG and 18 MG women between the 28th and 32th WoG who underwent regular check-ups in the Polytechnic and University Hospital La Fe (Valencia, Spain). The 30-minute bipolar recording was filtered in the 0.1-4 Hz bandwidth and downsampled to 20 Hz. Signal analysis was performed in 120-second moving windows with 50% overlap, after removing artefacts by a double- blind expert process. A set of 8 temporal, spectral and non-linear parameters were calculated: root mean square (RMS), kurtosis of the Hilbert envelope (KHE), median frequency (MDF), H/L ratio, and sample entropy (SampEn) and bubble entropy (BubbEn) calculated in the whole bandwidth (WBW) and the fast wave high (FWH). The 10th, 50th and 90th percentiles of all windows analysed were calculated to obtain representative values of the recordings. For each parameter and percentile, statistically significant differences between the SG and MG groups and their statistical power (SP) were analysed to determine both the existence of an effect and substantive significance, respectively. In comparison to SG, MG EHG exhibited significant higher impulsiveness and higher predictability than SG which was reflected in the KHE (SP 10 = 85.2, p 10 < 0.001) and entropy measures (SampEn FWH: SP 50 = 62.0, p 50 = 0.0.016; SP 90 = 52.5, p 90 = 0.059. BubbEn FWH: SP 50 = 75.2, p 50 < 0.001; SP 90 = 60.3, p 90 = 0.002), suggesting an accelerated evolution of uterine electrophysiological condition. In addition, several EHG parameters were found to significantly correlate with foetal weight such as amplitude (RMS: r 90 = 0.311, p 90 = 0.006), signal impulsiveness (KHE: r 10 = 0.311, p 10 = 0.006) and entropy measures (SampEn FWH: r 50 = −0.317, p 50 = 0.005*; r 90 = −0.279, p 90 = 0.013*. BubbEn FWH: r 50 = −0.370, p 50 = 0.001*; r 90 = −0.313, p 90 = 0.005*), suggesting an electromechanical coupling between uterine overdistension and contractile activity in vivo system. In comparison to SG women, MG showed higher impulsiveness and predictability in early third gestational trimester, as reflected in KHE, SampEn and BubbEn, respectively. We found similar cell excitability between SG and MG women far from delivery. In addition, we confirmed the relationship between uterine overdistension and surface myoelectric activity, revealing the electromechanical coupling pathway in uterine smooth muscle. Therefore, contextualized EHG-biomarkers would provide valuable information for early detection of PTB risk, which would allow clinicians better PTB management through personalised therapeutic interventions. • EHG features in multiple pregnancy differ from singleton ones in third trimester. • Multiple pregnancies show greater impulsivity and predictability than singletons. • Uterine overdistension may cause accelerated biophysical process toward labour. • Overdistension should be considered as a risk factor for preterm birth prediction. [ABSTRACT FROM AUTHOR]

Abstract Background Germline mutations in either of the two tumor-suppressor genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast and ovarian cancer cases. Most of these mutations consist of deletions, insertions, nonsense mutations, and splice variants, however an increasing number of large genomic rearrangements have been identified in these genes. Methods We analysed BRCA1 and BRCA2 genes by direct sequencing and MLPA. We confirmed the results by an alternative MLPA kit and characterized the BRCA1 deletion by Array CGH. Results We describe the first case of a patient with no strong family history of the disease who developed early-onset bilateral breast cancer with a de novo complete BRCA1 gene deletion in the germinal line. The detected deletion started from the region surrounding the VAT1 locus to the beginning of NBR1 gene, including the RND2, ΨBRCA1, BRCA1 and NBR2 complete genes. Conclusion This finding supports the large genomic rearrangement screening of BRCA genes in young breast cancer patients without family history, as well as in hereditary breast and ovarian cancer families previously tested negative for other variations.

Abstract Background Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. Methods We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. Results Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). Conclusions Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.

• EHG parameters reflect myometrial condition and changes provoked by tocolytic drugs. • Different response to drug was shown in women that will deliver at term vs preterm. • EHG high frequency content reduces faster in term women than preterm during therapy. • EHG complexity increased in preterms during therapy but barely changes for terms. • EHG parameters can separate term from preterm labor prior, during and after therapy. Although research studies using electrohysterography on women without tocolytic therapy have shown its potential for preterm birth diagnosis, tocolytics are usually administered in emergency rooms at the first sign of threatened preterm labor (TPL). Information on the uterine response during tocolytic treatment could prove useful for the development of tools able to predict true preterm deliveries under normal clinical conditions. The aim of this study was thus to analyze the effects of Atosiban on Electrohysterogram (EHG) parameters and to compare its effects on women who delivered preterm (WDP) and at term (WDT). Electrohysterograms recorded in different Atosiban therapy stages (before, during and after drug administration) on 40 WDT and 27 WDP were analyzed by computing linear, and non-linear EHG parameters. Results reveal that Atosiban does not greatly affect the EHG signal amplitude, but does modify its spectral content and reduces the energy associated with the fast wave high component in both WDP and WDT, with a faster response in the latter. EHG signal complexity remained constant in WDT, while it increased in WDP until it reached similar values to WDT during Atosiban treatment. The spectral and complexity parameters were able to separate (p < 0.05) WDT and WDP prior to and during tocolytic treatment and before and after treatment, respectively. The results pave the way for developing better and more reliable medical decision support systems based on EHG for preterm delivery prediction in TPL women in clinical scenarios. [ABSTRACT FROM AUTHOR]