State of the Art in AAC: A Systematic Review and Taxonomy

People with complex communication needs (CCNs) can use high-tech augmentative and alternative communication (AAC) devices and systems to compensate for communication difficulties. While many use AAC effectively, much research has highlighted challenges -- for instance, high rates of abandonment and solutions which are not appropriate for their end-users. Presently, we lack a detailed survey of this field to comprehend these shortcomings and understand how the accessibility community might direct its efforts to design more effective AAC. In response to this, we conduct a systematic review and taxonomy of high-tech AAC devices and interventions, reporting results from 562 articles identified in the ACM DL and SCOPUS databases. We provide a taxonomical overview of the current state of AAC devices -- e.g. their interaction modalities and characteristics. We describe the communities of focus explored, and the methodological approaches used. We contrast findings in the broader accessibility and HCI literature to delineate future avenues for exploration in light of the current taxonomy, offer a reassessment of the norms and incumbent research methodologies and present a discourse on the communities of focus for AAC and interventions.<br/

Trusting Tracking:Perceptions of Non-Verbal Communication Tracking in Videoconferencing

Videoconferencing is integral to modern work and living. Recently, technologists have sought to leverage data captured -- e.g. from cameras and microphones -- to augment communication. This might mean capturing communication information about verbal (e.g. speech, chat messages), or non-verbal exchanges (e.g. body language, gestures, tone of voice) and using this to mediate -- and potentially improve -- communication. However, such tracking has implications for user experience and raises wider concerns (e.g. privacy). To design tools which account for user needs and preferences, this study investigates perspectives on communication tracking through a global survey and interviews, exploring how daily behaviours and the impact of specific features influence user perspectives. We examine user preferences on non-verbal communication tracking, preferred methods of how this information is conveyed and to whom this should be communicated. Our findings aim to guide the development of non-verbal communication tools which augment videoconferencing that prioritise user needs

Pathway and network analysis of more than 2500 whole cancer genomes

The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments

Sex differences in oncogenic mutational processes.

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis.

Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis

Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Resistance to empirical β-lactams recommended in febrile neutropenia guidelines in Gram-negative bacilli bloodstream infections in Spain: a multicentre study

20.500.12530/87912Objectives To describe current resistance to the beta-lactams empirically recommended in the guidelines in bloodstream infection (BSI) episodes caused by Gram-negative bacilli (GNB). Methods Retrospective, multicentre cohort study of the last 50 BSI episodes in haematological patients across 14 university hospitals in Spain. Rates of inappropriate empirical antibiotic therapy (IEAT) and impact on mortality were evaluated. Results Of the 700 BSI episodes, 308 (44%) were caused by GNB, mainly Escherichia coli (141; 20.1%), Klebsiella spp. (56; 8%) and Pseudomonas aeruginosa (48; 6.9%). Among GNB BSI episodes, 80 (26%) were caused by MDR isolates. In those caused by Enterobacterales, 25.8% were ESBL producers and 3.5% were carbapenemase producers. Among P. aeruginosa BSI episodes, 18.8% were caused by MDR isolates. Overall, 34.7% of the isolated GNB were resistant to at least one of the three beta-lactams recommended in febrile neutropenia guidelines (cefepime, piperacillin/tazobactam and meropenem). Despite extensive compliance with guideline recommendations (91.6%), 16.6% of BSI episodes caused by GNB received IEAT, which was more frequent among MDR GNB isolates (46.3% versus 6.1%;

Supplementary Data from NK Cell Infiltrates and HLA Class I Expression in Primary HER2⁺ Breast Cancer Predict and Uncouple Pathological Response and Disease-free Survival

Supplementary Figure 1: HER2-positive Breast Cancer Study cohorts Supplementary Figure 2: TI-NK cells as categorical variable predicted pCR to anti-HER2 mAb-based neoadjuvant treatment with high sensitivity and specificity Supplementary Table I: TIL and TI-NK cell distribution according to tumor characteristics Supplementary Figure 3: Baseline TI-NK cell numbers association with DMFS in HER2-positive breast cancer patients receiving anti-HER2 mAb-based neoadjuvant therapy Supplementary Table II: Tumor HLA-I levels in relation to clinicopathological factors. Supplementary Figure 4: TI-NK cells associate with pCR regardless of tumor HLA-I expression levels. Supplementary Figure 5: Comparable clinical behavior of HLA low and HLA normal expressing tumors upon stratification by TI-NK cells.</p