A self-powered single-chip wireless sensor platform

Internet of things” require a large array of low-cost sensor nodes, wireless connectivity, low power operation and system intelligence. On the other hand, wireless biomedical implants demand additional specifications including small form factor, a choice of wireless operating frequencies within the window for minimum tissue loss and bio-compatibility This thesis describes a low power and low-cost internet of things system suitable for implant applications that is implemented in its entirety on a single standard CMOS chip with an area smaller than 0.5 mm2. The chip includes integrated sensors, ultra-low-power transceivers, and additional interface and digital control electronics while it does not require a battery or complex packaging schemes. It is powered through electromagnetic (EM) radiation using its on-chip miniature antenna that also assists with transmit and receive functions. The chip can operate at a short distance (a few centimeters) from an EM source that also serves as its wireless link. Design methodology, system simulation and optimization and early measurement results are presented

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

A Self-powered Single Chip Wireless Platform

Internet of things” require a large array of low-cost sensor nodes, wireless connectivity, low power operation and system intelligence. On the other hand, wireless biomedical implants demand additional specifications including small form factor, a choice of wireless operating frequencies within the window for minimum tissue loss and bio-compatibility This thesis describes a low power and low-cost internet of things system suitable for implant applications that is implemented in its entirety on a single standard CMOS chip with an area smaller than 0.5 mm2. The chip includes integrated sensors, ultra-low-power transceivers, and additional interface and digital control electronics while it does not require a battery or complex packaging schemes. It is powered through electromagnetic (EM) radiation using its on-chip miniature antenna that also assists with transmit and receive functions. The chip can operate at a short distance (a few centimeters) from an EM source that also serves as its wireless link. Design methodology, system simulation and optimization and early measurement results are presented

Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan.

In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). In this study, we aimed to identify a molecular-clinical correlation and somatic mutation for exploring risk-adapted treatment, drug targets, and potential genetic predisposition. In total, 52 frozen tumor tissues of childhood MBs were collected. RNA sequencing (RNA-Seq) and DNA methylation array data were generated. Molecular subgrouping and clinical correlation analysis were performed. An adjusted Heidelberg risk stratification scheme was defined for updated clinical risk stratification. We selected 51 genes for somatic variant calling using RNA-Seq data. Relevant clinical findings were defined. Potential drug targets and genetic predispositions were explored. Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The adjusted Heidelberg scheme showed its applicability. Potential drug targets were detected in the pathways of DNA damage response. Among the 10 patients with SHH MBs analyzed using whole exome sequencing studies, five patients exhibited potential genetic predispositions and four patients had relevant germline mutations. The findings of this study provide valuable information for updated risk adapted treatment and personalized care of childhood MBs in our cohort series and in Taiwan

Compreensão textual em alunos de segunda e terceira séries: uma abordagem cognitiva Text comprehension in second and third graders: a cognitive approach

Este estudo teve como objetivo analisar a compreensão de leitura textual de alunos de 2ª e 3ª séries. Participaram 76 crianças, com média de idade de 8,1 anos. Cada criança lia a história, recontava-a e, posteriormente, respondia a questões. Os recontos foram analisados segundo o Modelo de Compreensão Textual de Kintsch & van Dijk (1978) e Kintsch (1988, 1998). A amostra relatou, em média, 21,07% da estrutura proposicional da história, sendo mais freqüente o relato de macroproposições. Alunos da terceira série foram superiores aos da segunda série no relato de microproposições menos relevantes do texto e em responder a questões pontuais sobre a história. Foi encontrada uma correlação significativa entre idade e o reconto da macroestrutura textual. Os resultados sugerem que durante os primeiros anos de escolarização ocorreu uma melhora da memorização de detalhes, enquanto que a retenção das idéias essenciais foi influenciada pelas variações de idade das crianças.<br>This study aimed to analyze text comprehension of students of the 2nd and 3rd grades. The sample was constituted by 76 children, at an average of 8.1 years old. Each child read the story, retold it and, afterwards, answered questions about it. The retellings were analyzed according to the model of Text Comprehension of Kintsch and van Dijk (1978) and Kintsch (1988, 1998). The sample recalled a mean of 21.07% of the proposition structure of the story, being the report of macropropositions more frequent. Students of the third grade told larger percentage of irrelevant micropropositions of the text and they were superior in answering to specific questions than students of the second grade. A significant correlation was found between age and macroproposition's retelling. The results suggest that during the first years of schooling there is an improvement of the detail-remembering, whereas the retention of the essential ideas is influenced by age differences

A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates

Tuberculosis is a respiratory disease that is treatable with antibiotics. An increasing prevalence of resistance means that to ensure a good treatment outcome it is desirable to test the susceptibility of each infection to different antibiotics. Conventionally, this is done by culturing a clinical sample and then exposing aliquots to a panel of antibiotics, each being present at a pre-determined concentration, thereby determining if the sample isresistant or susceptible to each sample. The minimum inhibitory concentration (MIC) of a drug is the lowestconcentration that inhibits growth and is a more useful quantity but requires each sample to be tested at a range ofconcentrations for each drug. Using 96-well broth micro dilution plates with each well containing a lyophilised pre-determined amount of an antibiotic is a convenient and cost-effective way to measure the MICs of several drugs at once for a clinical sample. Although accurate, this is still an expensive and slow process that requires highly-skilled and experienced laboratory scientists. Here we show that, through the BashTheBug project hosted on the Zooniverse citizen science platform, a crowd of volunteers can reproducibly and accurately determine the MICs for 13 drugs and that simply taking the median or mode of 11-17 independent classifications is sufficient. There is therefore a potential role for crowds to support (but not supplant) the role of experts in antibiotic susceptibility testing

Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach

Abstract: The World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis. However, molecular diagnostics to date have focused largely on first-line drugs and predicting susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, we used a multivariable linear mixed model alongside whole genome sequencing and a quantitative microtiter plate assay to relate genomic mutations to minimum inhibitory concentration (MIC) in 15,211 Mycobacterium tuberculosis clinical isolates from 23 countries across five continents. We identified 492 unique MIC-elevating variants across 13 drugs, as well as 91 mutations likely linked to hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms