Big Data, Digitization, and Social Change (Ubiquity Symposium)

The term “big data” is something of a misnomer. Every generation of computers since the 1950s has been confronted with problems where data was way too large for the memory and processing power available. This seemed like an inconvenience of the technology that would someday be resolved when the next generation of computers came along. So what is different about big data today? The revolution is happening at the convergence of two trends: the expansion of the internet into billions of computing devices, and the digitization of almost everything. The internet gives us access to vast amounts of data. Digitization creates digital representations for many things once thought to be beyond the reach of computing technology. The result is an explosion of innovation of network-based big data applications and the automation of cognitive tasks. This revolution is introducing what Brynjolfsson and McAfee call the “Second Machine Age.” This symposium will examine this revolution from a number of angles

Event-Based Processing of Single Photon Avalanche Diode Sensors

© 2001-2012 IEEE. Single Photon Avalanche Diode sensor arrays operating in direct time of flight mode can perform 3D imaging using pulsed lasers. Operating at high frame rates, SPAD imagers typically generate large volumes of noisy and largely redundant spatio-temporal data. This results in communication bottlenecks and unnecessary data processing. In this work, we propose a neuromorphic processing solution to this problem. By processing the spatio-temporal patterns generated by the SPADs in a local, event-based manner, the proposed 128\times 128 pixel sensor-processor system reduces the size of output data from the sensor by orders of magnitude while increasing the utility of the output data in the context of challenging recognition tasks. To test the proposed system, the first large scale complex SPAD imaging dataset is captured using an existing 32\times 32 pixel sensor. The generated dataset consists of 24000 recordings and involves high-speed view-invariant recognition of airplanes with background clutter. The frame-based SPAD imaging dataset is converted via several alternative methods into event-based data streams and processed using the proposed 125\times 125 receptive field neuromorphic processor as well as a range of feature extractor networks and pooling methods. The output of the proposed event generation methods are then processed by an event-based feature extraction and classification system implemented in FPGA hardware. The event-based processing methods are compared to processing the original frame-based dataset via frame-based but otherwise identical architectures. The results show the event-based methods are superior to the frame-based approach both in terms of classification accuracy and output data-rate

Empagliflozin reduces kidney fibrosis and improves kidney function by alternative macrophage activation in rats with 5/6-nephrectomy

Background Sodium glucose cotransporter 2 (SGLT2) inhibitors originally developed for the treatment of type 2 diabetes are clinically very effective drugs halting chronic kidney disease progression. The underlying mechanisms are, however, not fully understood. Methods We generated single-cell transcriptomes of kidneys from rats with 5/6 nephrectomy before and after SGLT2 inhibitors treatment by single-cell RNA sequencing. Findings Empagliflozin treatment decreased BUN, creatinine and urinary albumin excretion compared to placebo by 39.8%, 34.1%, and 55%, respectively (p < 0.01 in all cases). Renal interstitial fibrosis and glomerulosclerosis was likewise decreased by 51% and 66.8%; respectively (p < 0.05 in all cases). 14 distinct kidney cell clusters could be identified by scRNA-seq. The polarization of M2 macrophages from state 1 (CD206-CD68- M2 macrophages) to state 5 (CD206+CD68+ M2 macrophages) was the main pro-fibrotic process, as CD206+CD68+ M2 macrophages highly expressed fibrosis-promoting genes and can convert into fibrocytes. Empagliflozin remarkably inhibited the expression of fibrosis-promoting (IFG1 and TREM2) and polarization-associated genes (GPNMB, LGALS3, PRDX5, and CTSB) in CD206+CD68+ M2 macrophages and attenuated inflammatory signals from CD8+ effector T cells. The inhibitory effect of empagliflozin on CD206+CD68+ M2 macrophages polarization was mainly achieved by affecting mitophagy and mTOR pathways. Interpretation We propose that the beneficial effects of empagliflozin on kidney function and morphology in 5/6 nephrectomyiced rats with established CKD are at least partially due to an inhibition of CD206+CD68+ M2 macrophage polarization by targeting mTOR and mitophagy pathways and attenuating inflammatory signals from CD8+ effector T cells. Fundings A full list of funding bodies that contributed to this study can be found in the Acknowledgements section

The head and neck cancer cell oncogenome: a platform for the development of precision molecular therapies

The recent elucidation of the genomic landscape of head and neck squamous cell carcinoma (HNSCC) has provided a unique opportunity to develop selective cancer treatment options. These efforts will require the establishment of relevant HNSCC models for preclinical testing. Here, we performed full exome and transcriptome sequencing of a large panel of HNSCC-derived cells from different anatomical locations and human papillomavirus (HPV) infection status. These cells exhibit typical mutations in TP53, FAT1, CDK2NA, CASP8, and NOTCH1, and copy number variations (CNVs) and mutations in PIK3CA, HRAS, and PTEN that reflect the widespread activation of the PI3K-mTOR pathway. SMAD4 alterations were observed that may explain the decreased tumor suppressive effect of TGF-β in HNSCC. Surprisingly, we identified HPV+ HNSCC cells harboring TP53 mutations, and documented aberrant TP53 expression in a subset of HPV+ HNSCC cases. This analysis also revealed that most HNSCC cells harbor multiple mutations and CNVs in epigenetic modifiers (e.g., EP300, CREBP, MLL1, MLL2, MLL3, KDM6A, and KDM6B) that may contribute to HNSCC initiation and progression. These genetically-defined experimental HNSCC cellular systems, together with the identification of novel actionable molecular targets, may now facilitate the pre-clinical evaluation of emerging therapeutic agents in tumors exhibiting each precise genomic alteration.Centro de Investigaciones Inmunológicas Básicas y Aplicada

Site-specific phosphorylation and caspase cleavage of GFAP are new markers of Alexander Disease severity

Alexander Disease (AxD) is a fatal neurodegenerative disorder caused by mutations in glial fibrillary acidic protein (GFAP), which supports the structural integrity of astrocytes. Over 70 GFAP missense mutations cause AxD, but the mechanism linking different mutations to disease-relevant phenotypes remains unknown. We used AxD patient brain tissue and induced pluripotent stem cell (iPSC)-derived astrocytes to investigate the hypothesis that AxD-causing mutations perturb key post-translational modifications (PTMs) on GFAP. Our findings reveal selective phosphorylation of GFAP-Ser13 in patients who died young, independently of the mutation they carried. AxD iPSC-astrocytes accumulated pSer13-GFAP in cytoplasmic aggregates within deep nuclear invaginations, resembling the hallmark Rosenthal fibers observed in vivo. Ser13 phosphorylation facilitated GFAP aggregation and was associated with increased GFAP proteolysis by caspase-6. Furthermore, caspase-6 was selectively expressed in young AxD patients, and correlated with the presence of cleaved GFAP. We reveal a novel PTM signature linking different GFAP mutations in infantile AxD

Burnout syndrome among psychiatric trainees in 22 countries: Risk increased by long working hours, lack of supervision, and psychiatry not being first career choice

Background: Postgraduate medical trainees experience high rates of burnout, but evidence regarding psychiatric trainees is missing. We aim to determine burnout rates among psychiatric trainees, and identify individual, educational and work-related factors associated with severe burnout.  Methods: In an online survey psychiatric trainees from 22 countries were asked to complete the Maslach Burnout Inventory (MBI-GS) and provide information on individual, educational and work-related parameters. Linear mixed models were used to predict the MBI-GS scores, and a generalized linear mixed model to predict severe burnout.  Results: This is the largest study on burnout and training conditions among psychiatric trainees to date. Complete data were obtained from 1980 out of 7625 approached trainees (26%; range 17.8-65.6%). Participants were 31.9 (SD 5.3) years old with 2.8 (SD 1.9) years of training. Severe burnout was found in 726 (36.7%) trainees. The risk was higher for trainees who were younger (P < 0.001), without children (P = 0.010), and had not opted for psychiatry as a first career choice (P = 0.043). After adjustment for socio-demographic characteristics, years in training and country differences in burnout, severe burnout remained associated with long working hours (P < 0.001), lack of supervision (P < 0.001), and not having regular time to rest (P = 0.001). Main findings were replicated in a sensitivity analysis with countries with response rate above 50%.  Conclusions: Besides previously described risk factors such as working hours and younger age, this is the first evidence of negative influence of lack of supervision and not opting for psychiatry as a first career choice on trainees' burnout

Prevention and control of meningococcal disease: Updates from the Global Meningococcal Initiative in Eastern Europe

Authors would like to thank Dr Olivier Ronveaux (Infectious Hazard Management, World Health Organization, Geneva, Switzerland) for his contributions during this GMI Roundtable Meeting and for providing permission to use his presentation content in this manuscript. The authors were assisted in the preparation of the manuscript by Hannah Birchby, a professional medical writer at CircleScience, an Ashfield Company, part of UDG Healthcare plc. Medical writing support was funded by Sanofi Pasteur.The Global Meningococcal Initiative (GMI) aims to prevent invasive meningococcal disease (IMD) worldwide through education, research and cooperation. In March 2019, a GMI meeting was held with a multidisciplinary group of experts and representatives from countries within Eastern Europe. Across the countries represented, IMD surveillance is largely in place, with incidence declining in recent decades and now generally at <1 case per 100,000 persons per year. Predominating serogroups are B and C, followed by A, and cases attributable to serogroups W, X and Y are emerging. Available vaccines differ between countries, are generally not included in immunization programs and provided to high-risk groups only. Available vaccines include both conjugate and polysaccharide vaccines; however, current data and GMI recommendations advocate the use of conjugate vaccines, where possible, due to the ability to interrupt the acquisition of carriage. Ongoing carriage studies are expected to inform vaccine effectiveness and immunization schedules. Additionally, IMD prevention and control should be guided by monitoring outbreak progression and the emergence and international spread of strains and antibiotic resistance through use of genomic analyses and implementation of World Health Organization initiatives. Protection of high-risk groups (such as those with complement deficiencies, laboratory workers, migrants and refugees) is recommended.S

Prevention and control of meningococcal disease: Updates from the Global Meningococcal Initiative in Eastern Europe

Authors would like to thank Dr Olivier Ronveaux (Infectious Hazard Management, World Health Organization, Geneva, Switzerland) for his contributions during this GMI Roundtable Meeting and for providing permission to use his presentation content in this manuscript. The authors were assisted in the preparation of the manuscript by Hannah Birchby, a professional medical writer at CircleScience, an Ashfield Company, part of UDG Healthcare plc. Medical writing support was funded by Sanofi Pasteur.The Global Meningococcal Initiative (GMI) aims to prevent invasive meningococcal disease (IMD) worldwide through education, research and cooperation. In March 2019, a GMI meeting was held with a multidisciplinary group of experts and representatives from countries within Eastern Europe. Across the countries represented, IMD surveillance is largely in place, with incidence declining in recent decades and now generally at <1 case per 100,000 persons per year. Predominating serogroups are B and C, followed by A, and cases attributable to serogroups W, X and Y are emerging. Available vaccines differ between countries, are generally not included in immunization programs and provided to high-risk groups only. Available vaccines include both conjugate and polysaccharide vaccines; however, current data and GMI recommendations advocate the use of conjugate vaccines, where possible, due to the ability to interrupt the acquisition of carriage. Ongoing carriage studies are expected to inform vaccine effectiveness and immunization schedules. Additionally, IMD prevention and control should be guided by monitoring outbreak progression and the emergence and international spread of strains and antibiotic resistance through use of genomic analyses and implementation of World Health Organization initiatives. Protection of high-risk groups (such as those with complement deficiencies, laboratory workers, migrants and refugees) is recommended.S

High throughput toxicity screening and intracellular detection of nanomaterials

EC FP7 NANoREG (Grant Agreement NMP4-LA-2013-310584)Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215403/With the growing numbers of nanomaterials (NMs), there is a great demand for rapid and reliable ways of testing NM safety—preferably using in vitro approaches, to avoid the ethical dilemmas associated with animal research. Data are needed for developing intelligent testing strategies for risk assessment of NMs, based on grouping and read-across approaches. The adoption of high throughput screening (HTS) and high content analysis (HCA) for NM toxicity testing allows the testing of numerous materials at different concentrations and on different types of cells, reduces the effect of inter-experimental variation, and makes substantial savings in time and cost.info:eu-repo/semantics/publishedVersio