Detection of interictal discharges with convolutional neural networks using discrete ordered multichannel intracranial EEG

Detection algorithms for electroencephalography (EEG) data, especially in the field of interictal epileptiform discharge (IED) detection, have traditionally employed handcrafted features which utilised specific characteristics of neural responses. Although these algorithms achieve high accuracy, mere detection of an IED holds little clinical significance. In this work, we consider deep learning for epileptic subjects to accommodate automatic feature generation from intracranial EEG data, while also providing clinical insight. Convolutional neural networks are trained in a subject independent fashion to demonstrate how meaningful features are automatically learned in a hierarchical process. We illustrate how the convolved filters in the deepest layers provide insight towards the different types of IEDs within the group, as confirmed by our expert clinicians. The morphology of the IEDs found in filters can help evaluate the treatment of a patient. To improve the learning of the deep model, moderately different score classes are utilised as opposed to binary IED and non-IED labels. The resulting model achieves state of the art classification performance and is also invariant to time differences between the IEDs. This study suggests that deep learning is suitable for automatic feature generation from intracranial EEG data, while also providing insight into the dat

Real-life management of patients with breakthrough cancer pain caused by bone metastases in Spain

Purpose: We aimed to explore the characteristics, and real-life therapeutic management of patients with breakthrough cancer pain (BTcP) caused by bone metastases in Spain, and to evaluate physicians' opinion of and satisfaction with prescribed BTcP therapy. Participants and methods: For the purposes of this study, an ad-hoc questionnaire was developed consisting of two domains: a) organizational aspects and care standards; b) clinical and treatment variables of bone metastatic BTcP patients. In addition, physicians' satisfaction with their prescribed BTcP therapy was assessed. Specialists collected data from up to five patients receiving treatment for BTcP caused by bone metastasis, all patients gave their consent to participate prior to inclusion. Results: A total of 103 cancer pain specialists (radiation oncologists [38.8%], pain specialists [33.0%], and palliative care (PC) specialists [21.4%]) were polled, and data on 386 BTcP patients with bone metastatic disease were collected. Only 33% of the specialists had implemented specific protocols for BTcP management, and 19.4% had established referral protocols for this group of patients. Half of all participants (50.5%) address quality of life and quality of care in their patients; however, only 27.0% did so from the patient's perspective, as they should do. Most patients had multiple metastases and were prescribed rapid-onset fentanyl preparations (71.2%), followed by immediate-release morphine (9.3%) for the treatment of BTcP. Rapid-onset fentanyl was prescribed more often in PC units (79.0%) than in pain units (75.9%) and radiation oncology units (61.1%) (p<0.01). Furthermore, most physicians (71.8%) were satisfied with the BTcP therapy prescribed. Conclusions: Our results demonstrate the need for routine assessment of quality of life in patients with bone BTcP. These findings also underscore the necessity for a multidisciplinary therapeutic strategy for breakthrough pain in clinical practice in Spain

Type 2 diabetes mellitus alters cardiac mitochondrial content and function in a non-obese mice model

Type 2 diabetes mellitus (T2DM) is associated with an increase of premature appearance of several disorders such as cardiac complications. Thus, we test the hypothesis that a combination of a high fat diet (HFD) and low doses of streptozotocin (STZ) recapitulate a suitable mice model of T2DM to study the cardiac mitochondrial disturbances induced by this disease. Animals were divided in 2 groups: the T2DM group was given a HFD and injected with 2 low doses of STZ, while the CNTRL group was given a standard chow and a buffer solution. The combination of HFD and STZ recapitulate the T2DM metabolic profile showing higher blood glucose levels in T2DM mice when compared to CNTRL, and also, insulin resistance. The kidney structure/function was preserved. Regarding cardiac mitochondrial function, in all phosphorylative states, the cardiac mitochondria from T2DM mice presented reduced oxygen fluxes when compared to CNTRL mice. Also, mitochondria from T2DM mice showed decreased citrate synthase activity and lower protein content of mitochondrial complexes. Our results show that in this non-obese T2DM model, which recapitulates the classical metabolic alterations, mitochondrial function is impaired and provides a useful model to deepen study the mechanisms underlying these alterations.This study was supported by Coordenacao de aperfeicoamento de pessoal de nivel superior (CAPES), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)

Revisiting Scalar and Pseudoscalar Couplings with Nucleons

Certain dark matter interactions with nuclei are mediated possibly by a scalar or pseudoscalar Higgs boson. The estimation of the corresponding cross sections requires a correct evaluation of the couplings between the scalar or pseudoscalar Higgs boson and the nucleons. Progress has been made in two aspects relevant to this study in the past few years. First, recent lattice calculations show that the strange-quark sigma term $\sigma_s$ and the strange-quark content in the nucleon are much smaller than what are expected previously. Second, lattice and model analyses imply sizable SU(3) breaking effects in the determination on the axial-vector coupling constant $g_A^8$ that in turn affect the extraction of the isosinglet coupling $g_A^0$ and the strange quark spin component $\Delta s$ from polarized deep inelastic scattering experiments. Based on these new developments, we re-evaluate the relevant nucleon matrix elements and compute the scalar and pseudoscalar couplings of the proton and neutron. We also find that the strange quark contribution in both types of couplings is smaller than previously thought.Comment: 17 pages, Sec. II is revised and the pion-nucleon sigma term extracted from the scattering data is discussed. Version to appear in JHE

Systematics of the Oswaldoi Complex (Anopheles, Nyssorhynchus) in South America

Abstract Background Effective malaria control relies on accurate identification of those Anopheles mosquitoes responsible for the transmission of Plasmodium parasites. Anopheles oswaldoi s.l. has been incriminated as a malaria vector in Colombia and some localities in Brazil, but not ubiquitously throughout its Neotropical range. This evidence together with variable morphological characters and genetic differences supports that An. oswaldoi s.l. compromises a species complex. The recent fully integrated redescription of An. oswaldoi s.s. provides a solid taxonomic foundation from which to molecularly determine other members of the complex.\ud \ud \ud \ud Methods\ud DNA sequences of the Second Internal Transcribed Spacer (ITS2 - rDNA) (n = 192) and the barcoding region of the Cytochrome Oxidase I gene (COI - mtDNA) (n = 110) were generated from 255 specimens of An. oswaldoi s.l. from 33 localities: Brazil (8 localities, including the lectotype series of An. oswaldoi), Ecuador (4), Colombia (17), Trinidad and Tobago (1), and Peru (3). COI sequences were analyzed employing the Kimura-two-parameter model (K2P), Bayesian analysis (MrBayes), Mixed Yule-Coalescent model (MYC, for delimitation of clusters) and TCS genealogies. Results\ud Separate and combined analysis of the COI and ITS2 data sets unequivocally supported four separate species: two previously determined (An. oswaldoi s.s. and An. oswaldoi B) and two newly designated species in the Oswaldoi Complex (An. oswaldoi A and An. sp. nr. konderi). The COI intra- and inter-specific genetic distances for the four taxa were non-overlapping, averaging 0.012 (0.007 to 0.020) and 0.052 (0.038 to 0.064), respectively. The concurring four clusters delineated by MrBayes and MYC, and four independent TCS networks, strongly confirmed their separate species status. In addition, An. konderi of Sallum should be regarded as unique with respect to the above. Despite initially being included as an outgroup taxon, this species falls well within the examined taxa, suggesting a combined analysis of these taxa would be most appropriate. Conclusions: Through novel data and retrospective comparison of available COI and ITS2 DNA sequences, evidence is shown to support the separate species status of An. oswaldoi s.s., An. oswaldoi A and An. oswaldoi B, and at least two species in the closely related An. konderi complex (An. sp. nr. konderi, An. konderi of Sallum). Although An. oswaldoi s.s. has never been implicated in malaria transmission, An. oswaldoi B is a confirmed vector and the new species An. oswaldoi A and An. sp. nr. konderi are circumstantially implicated, most likely acting as secondary vectors.This study formed part of the PhD study of FRL conducted at the Natural History Museum, London, and awarded from Canterbury Christ Church University, Canterbury, Kent, U.K. This investigation received financial support from the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) (grant A50252 to YML), Canterbury Christ Church University (studentship to FRL). Additional funding was obtained through the Friends of the Natural History Museum, London to further the activities of the Mosquito Barcoding Initiative (to YML); the Consortium for the Barcode of Life (CBOL) (to YML and RCW) and the Sloane Foundation (to YML and RCW); the National Institute of Health (NIH), USA (grant 2R01AI054139 to Jan E. Conn) and COLCIENCIAS (grant 110134319196 to MLQ). We thank Dr. A. Papadopoulou for help with the MYC analysis and Dr. S. Mahamdallie for helpful suggestions and discussions during preparation of the manuscript.This manuscript was prepared in part whilst YML held a National Research Council Senior Research Associateship Award at the Walter Reed Army Institute of Research. This research was performed in part under a Memorandum of Understanding between the Walter Reed Army Institute of Research and the Smithsonian Institution, with institutional support provided by both organizations. The material to be published reflects the views of the authors and should not be construed to represent those of the Department of the Army or the Department of Defense

Sarcoma histiocítico: presentación de un caso probable

El sarcoma histiocítico es un desorden de células no Langerhans extremadamente raro con un curso clínico agresivo y limitadas opciones de tratamiento. Se presenta el caso de un paciente adulto joven de género masculino, con cuadro febril prolongado, compromiso hematológico persistente, hepatoesplenomegalia y linfadenopatias generalizadas con curso clínico fatal, en quien por las características clínicas, paraclínicas y de estudios histopatológicos como de inmunohistoquímica se llegó a dicha presunción diagnostica

Impact of Lack of Breast Feeding during Neonatal Age on the Development of Clinical Signs of Pneumonia and Hypoxemia in Young Infants with Diarrhea

Hypoxemia is a grave sequel of pneumonia, and an important predictor of a fatal outcome. Pneumonia in the neonatal period is often associated with lack of breast feeding. However, there is no published report on the impact of the cessation of breast feeding in the neonatal period on the development of pneumonia and hypoxemia. The purpose of our study was to assess the impact of non-breast feeding or stopping breast feeding during the neonatal period (henceforth to be referred to as non-breast fed) on clinical features of pneumonia and hypoxemia in 0-6-month-old infants with diarrhea admitted to an urban hospital in Bangladesh.We prospectively enrolled all infants (n = 107) aged 0 to 6 months who were admitted to the Special Care Ward (SCW) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (ICDDR,B) with diarrhea and pneumonia from September 2007 through December 2007.We compared the clinical features of pneumonia and hypoxemia of breast fed infants (n = 34) with those who were non-breast fed (n = 73).The median (inter-quartile range) duration of hypoxemia (hours) in non-breast-feds was longer than breast-fed infants [0.0 (0.0, 12.0) vs. 12.0 (0.0, 21.75); p = 0.021]. After adjusting for potential confounders such as inability to drink, fever, head nodding, cyanosis, grunting respiration, and lower chest wall in drawing, the non-breast-fed infants with pneumonia along with diarrhea had a higher probability of cough (OR 9.09; CI 1.34-61.71; p = 0.024), hypoxemia (OR 3.32; CI 1.23-8.93; p = 0.017), and severe undernutrition (OR 3.42; CI 1.29-9.12; p = 0.014).Non-breast feeding or cessation of breast feeding during the neonatal period may substantially increase the incidence of severe malnutrition, incidence of cough, and both the incidence and duration of hypoxemia in young infants presenting with pneumonia and diarrhea. The findings emphasize the paramount importance of the continuation of breast feeding in the neonatal period and early infancy

Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere’s Disease

Meniere’s disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case–control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661–2.627); p = 1.39 × 10−09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10−11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD

IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases

IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular and rheumatic diseases. We here compare these antibodies in systemic rheumatic conditions and study their properties. Anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective tissue disease (MCTD, 77), Systemic sclerosis (SSc, 331), Sj\uf6gren\u2019s syndrome (SjS, 324), primary antiphospholipid syndrome (PAPs, 65), undifferentiated connective tissue disease (UCTD, 118) and 515 matched healthy controls (HC). Cardiovascular score (CV) was broadly defined based on clinical disease symptoms. Anti-PC and anti-MDA peptide/protein characterization were compared using a proteomics de novo sequencing approach. anti-MDA and anti-PC were extracted from total IgM. The proportion of Treg cells was determined by flow cytometry. The maximal difference between cases and controls was shown for MCTD: significantly lower IgM Anti-PC but not anti-MDA among patients (median 49.3RU/ml vs 70.4 in healthy controls, p(t-test) = 0.0037). IgM low levels were more prevalent in MCTD, SLE, SjS, SSc and UCTD. IgM anti-PC variable region profiles were different from and more homologous than anti-MDA. Anti-PC but not anti-MDA were significantly negatively correlated with CV in the whole patient group. In contrast to IgM anti-PC, anti-MDA did not promote polarization of Tregs. Taken together, Anti-PC is decreased in MCTD and also in SLE, SjS and SSc but not in other studied diseases. Anti-PC may thus differentiate between these. In contrast, anti-MDA did not show these differences between diseases studied. Anti-PC level is negatively correlated with CV in the patient group cohort. In contrast to anti-PC, anti-MDA did not promote Treg polarization. These findings could have both diagnostic and therapeutic implications, one possibility being active or passive immunization with PC in some rheumatic conditions