Bio-Inspired Multi-Layer Spiking Neural Network Extracts Discriminative Features from Speech Signals

Spiking neural networks (SNNs) enable power-efficient implementations due to their sparse, spike-based coding scheme. This paper develops a bio-inspired SNN that uses unsupervised learning to extract discriminative features from speech signals, which can subsequently be used in a classifier. The architecture consists of a spiking convolutional/pooling layer followed by a fully connected spiking layer for feature discovery. The convolutional layer of leaky, integrate-and-fire (LIF) neurons represents primary acoustic features. The fully connected layer is equipped with a probabilistic spike-timing-dependent plasticity learning rule. This layer represents the discriminative features through probabilistic, LIF neurons. To assess the discriminative power of the learned features, they are used in a hidden Markov model (HMM) for spoken digit recognition. The experimental results show performance above 96% that compares favorably with popular statistical feature extraction methods. Our results provide a novel demonstration of unsupervised feature acquisition in an SNN

Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd) CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan

Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymopathy globally, and deficient individuals may experience severe hemolysis following treatment with 8-aminoquinolines. With increasing evidence of Plasmodium vivax infections throughout sub-Saharan Africa, there is a pressing need for population-level data at on the prevalence of G6PDd. Such evidence-based data will guide the expansion of primaquine and potentially tafenoquine for radical cure of P. vivax infections. This study aimed to quantify G6PDd prevalence in two geographically distinct areas in Sudan, and evaluating the performance of a qualitative CareStart rapid diagnostic test as a point-of-care test. Blood samples were analyzed from 491 unrelated healthy persons in two malaria-endemic sites in eastern and central Sudan. A pre-structured questionnaire was used which included demographic data, risk factors and treatment history. G6PD levels were measured using spectrophotometry (SPINREACT) and first-generation qualitative CareStart rapid tests. G6PD variants (202 G\u3eA; 376 A\u3eG) were determined by PCR/RFLP, with a subset confirmed by Sanger sequencing. The prevalence of G6PDd by spectrophotometry was 5.5% (27/491; at 30% of adjusted male median, AMM); 27.3% (134/491; at 70% of AMM); and 13.1% (64/490) by qualitative CareStart rapid diagnostic test. The first-generation CareStart rapid diagnostic test had an overall sensitivity of 81.5% (95%CI: 61.9 to 93.7) and negative predictive value of 98.8% (97.3 to 99.6). All persons genotyped across both study sites were wild type for the G6PD G202 variant. For G6PD A376G all participants in New Halfa had wild type AA (100%), while in Khartoum the AA polymorphism was found in 90.7%; AG in 2.5%; and GG in 6.8%. Phenotypic G6PD B was detected in 100% of tested participants in New Halfa while in Khartoum, the phenotypes observed were B (96.2%), A (2.8%), and AB (1%). The African A- phenotype was not detected in this study population. Overall, G6PDd prevalence in Sudan is low-to-moderate but highly heterogeneous. Point-of-care testing with the qualitative CareStart rapid diagnostic test demonstrated moderate performance with moderate sensitivity and specificity but high negative predicative value. The two sites harbored primarily the African B phenotype. A country-wide survey is recommended to understand GP6PD deficiencies more comprehensively in Sudan

Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome

BackgroundWe describe a severe form of congenital myasthenic syndrome (CMS) associated with congenital nephrosis and ocular malformations caused by two truncating mutations in the gene encoding the laminin beta2 subunit (LAMB2).Methods and resultsMutational analysis in the affected patient, who has a history of a serious untoward reaction to treatment with acetylcholinesterase inhibition, revealed two frame-shifting heteroallelic mutations, a maternally inherited 1478delG and a paternally inherited 4804delC. An anconeus muscle biopsy demonstrated a profound distortion of the architecture and function of the neuromuscular junction, which was strikingly similar to that seen in mice lacking laminin beta2 subunit. The findings included: pronounced reduction of the axon terminal size with encasement of the nerve endings by Schwann cells, severe widening of the primary synaptic cleft and invasion of the synaptic space by the processes of Schwann cells, and moderate simplification of postsynaptic folds and intact expression of the endplate acetylcholinesterase. The endplate potential quantal content was notably reduced, while the frequencies and amplitudes of miniature endplate potentials were only moderately diminished and the decay phases of miniature endplate potentials were normal. Western blot analysis of muscle and kidney tissue and immunohistochemistry of kidney tissue showed no laminin beta2 expression.ConclusionThis case, which represents a new type of synaptic CMS, exemplifies the wide variability of phenotypes associated with LAMB2 mutations and underscores the fundamental role that laminin beta2 plays in the development of the human neuromuscular junction

Patient-level performance evaluation of a smartphone-based malaria diagnostic application

Background Microscopic examination is commonly used for malaria diagnosis in the field. However, the lack of well-trained microscopists in malaria-endemic areas impacted the most by the disease is a severe problem. Besides, the examination process is time-consuming and prone to human error. Automated diagnostic systems based on machine learning offer great potential to overcome these problems. This study aims to evaluate Malaria Screener, a smartphone-based application for malaria diagnosis. Methods A total of 190 patients were recruited at two sites in rural areas near Khartoum, Sudan. The Malaria Screener mobile application was deployed to screen Giemsa-stained blood smears. Both expert microscopy and nested PCR were performed to use as reference standards. First, Malaria Screener was evaluated using the two reference standards. Then, during post-study experiments, the evaluation was repeated for a newly developed algorithm, PlasmodiumVF-Net. Results Malaria Screener reached 74.1% (95% CI 63.5–83.0) accuracy in detecting Plasmodium falciparum malaria using expert microscopy as the reference after a threshold calibration. It reached 71.8% (95% CI 61.0–81.0) accuracy when compared with PCR. The achieved accuracies meet the WHO Level 3 requirement for parasite detection. The processing time for each smear varies from 5 to 15 min, depending on the concentration of white blood cells (WBCs). In the post-study experiment, Malaria Screener reached 91.8% (95% CI 83.8–96.6) accuracy when patient-level results were calculated with a different method. This accuracy meets the WHO Level 1 requirement for parasite detection. In addition, PlasmodiumVF-Net, a newly developed algorithm, reached 83.1% (95% CI 77.0–88.1) accuracy when compared with expert microscopy and 81.0% (95% CI 74.6–86.3) accuracy when compared with PCR, reaching the WHO Level 2 requirement for detecting both Plasmodium falciparum and Plasmodium vivax malaria, without using the testing sites data for training or calibration. Results reported for both Malaria Screener and PlasmodiumVF-Net used thick smears for diagnosis. In this paper, both systems were not assessed in species identification and parasite counting, which are still under development. Conclusion Malaria Screener showed the potential to be deployed in resource-limited areas to facilitate routine malaria screening. It is the first smartphone-based system for malaria diagnosis evaluated on the patient-level in a natural field environment. Thus, the results in the field reported here can serve as a reference for future studies

Seaweed Extracts Enhance Salam Turfgrass Performance during Prolonged Irrigation Intervals and Saline Shock

The negative effects of the ongoing climate change include unusual prolonged droughts and increased salinity pressures on the agricultural lands. Consequently, crops are facing unprecedented environmental pressure, and this calls for more research toward controlling such major stresses. The current study investigates the effects of seaweed extract sprays of Ascophyllum nodosum (5 and 7 mL·L−1; 6 day intervals) on Paspalum vaginatum Salam' during prolonged irrigation intervals (2 and 6 day) and saline growing conditions (1 and 49.7 dS·m−1) for 6 weeks in containers under greenhouse conditions. Control plants showed reduced turf quality, photochemical efficiency, root length and dry weight, total non-structural carbohydrates, and K and Ca compositions. Seaweed extracts increased turf quality, leaf photochemical efficiency, root length and dry weight, total non-structural carbohydrates, K, Ca, and proline in treated plants during prolonged irrigation intervals as well as saline shock conditions. There were also increases in the antioxidant defensive mechanisms such as catalase (CAT), superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities and non-enzymatic antioxidants as well as reduced lipid peroxidation. The application of SWE at 7 mL·L−1 showed higher performance in treated plants during prolonged irrigation intervals as well as saline conditions. Our findings imply that several mechanisms including drought tolerance, osmotic adjustment and antioxidant defense system may interact to enhance the performance of plants in the face of environmental stress following SWE treatments

Guidelines for developing optical clocks with 10−1810^{-18} fractional frequency uncertainty

There has been tremendous progress in the performance of optical frequency standards since the first proposals to carry out precision spectroscopy on trapped, single ions in the 1970s. The estimated fractional frequency uncertainty of today's leading optical standards is currently in the $10^{-18}$ range, approximately two orders of magnitude better than that of the best caesium primary frequency standards. This exceptional accuracy and stability is resulting in a growing number of research groups developing optical clocks. While good review papers covering the topic already exist, more practical guidelines are needed as a complement. The purpose of this document is therefore to provide technical guidance for researchers starting in the field of optical clocks. The target audience includes national metrology institutes (NMIs) wanting to set up optical clocks (or subsystems thereof) and PhD students and postdocs entering the field. Another potential audience is academic groups with experience in atomic physics and atom or ion trapping, but with less experience of time and frequency metrology and optical clock requirements. These guidelines have arisen from the scope of the EMPIR project "Optical clocks with $1 imes 10^{-18}$ uncertainty" (OC18). Therefore, the examples are from European laboratories even though similar work is carried out all over the world. The goal of OC18 was to push the development of optical clocks by improving each of the necessary subsystems: ultrastable lasers, neutral-atom and single-ion traps, and interrogation techniques. This document shares the knowledge acquired by the OC18 project consortium and gives practical guidance on each of these aspects

Novel Evolved Immunoglobulin (Ig)-Binding Molecules Enhance the Detection of IgM against Hepatitis C Virus

Detection of specific antibodies against hepatitis C virus (HCV) is the most widely available test for viral diagnosis and monitoring of HCV infections. However, narrowing the serologic window of anti-HCV detection by enhancing anti-HCV IgM detection has remained to be a problem. Herein, we used LD5, a novel evolved immunoglobulin-binding molecule (NEIBM) with a high affinity for IgM, to develop a new anti-HCV enzyme-linked immunosorbent assay (ELISA) using horseradish peroxidase-labeled LD5 (HRP-LD5) as the conjugated enzyme complex. The HRP-LD5 assay showed detection efficacy that is comparable with two kinds of domestic diagnostic kits and the Abbott 3.0 kit when tested against the national reference panel. Moreover, the HRP-LD5 assay showed a higher detection rate (55.9%, 95% confidence intervals (95% CI) 0.489, 0.629) than that of a domestic diagnostic ELISA kit (Chang Zheng) (53.3%, 95% CI 0.463, 0.603) in 195 hemodialysis patient serum samples. Five serum samples that were positive using the HRP-LD5 assay and negative with the conventional anti-HCV diagnostic ELISA kits were all positive for HCV RNA, and 4 of them had detectable antibodies when tested with the established anti-HCV IgM assay. An IgM confirmation study revealed the IgM reaction nature of these five serum samples. These results demonstrate that HRP-LD5 improved anti-HCV detection by enhancing the detection of anti-HCV IgM, which may have potential value for the early diagnosis and screening of hepatitis C and other infectious diseases

Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website