Abstract Background Multiple genomic and transciptomic biomarkers have been associated with response to immune checkpoint inhibitor (CPI) therapy. Emerging evidence suggests that each solid tumour type has a unique mix of factors determining CPI response, reflecting the subtle differences in antigen repertoire and immune microenvironment across histologies. Compiling large-scale sequencing datasets of patients treated with CPI therapy, from a range of solid tumour types, allows detailed comparison of the contrasting immune drivers per histology. Understanding these differences enhances our understanding of the pathways influencing CPI response, which may be of utility for therapeutic and biomarker development. Methods We compiled data from 13 CPI treated cohorts, across 6 solid tumour types, encompassing 1,453 patients (n = 1,453 with exome data, n = 674 with RNAseq data). All raw data was accessed, and reprocessed through a standardised state of the art bioinformatics pipeline. A comphrehensive range of genomic & transcriptomic biomarker metrics were derived across the cohort. A combined predictive model was constructred encompassing all biomarkers, & the importance weighting was calculated for each biomarker, in each tumour type. Results TMB was found to be a universal predictor of response across all tumour types, except for renal cell carcinoma (RCC). Instead CPI response in RCC appears to be strongly driven by expression of human endogeneuos retroviruses (hERV). In malignant melanoma, while TMB (nsSNVs) was associated with CPI response, the number of expressed indel mutations was found to be a stronger predictor. Shared antigen expression also demonstrated tumour specific predictive patterns. A signature of high immune inflitatation was found to be another universal predictor of response across multiple tumour types, however differences in the varying importance of immune cell subsets across histologies was observed. The rate of HLA LOH, and other immune evasion mechanisms also varied dramatically by cancer type. Conclusions The determinants of immunotherapy response vary across solid tumour types, offering unique insight into both tumour intrinsic and extrinsic drivers of immunogenicity. Legal entity responsible for the study The Francis Crick Institute. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

This article presents a low-cost laboratory that has been designed and developed to enhance learning experience and help students gain skills and knowledge in the field of distributed systems. In order to build a comprehensive distributed file system, we used the laboratory consisting of 40 card-sized Raspberry Pi devices, with the accent on stability, scalability, and low cost. Aiming to assess the impact of this new learning environment on the learning process and its outcomes, we surveyed students following the completion of three project stages during the 17 laboratory exercises in one academic year, ensuring that we maintained the same subjects of study during the experiments. Supported by interesting answers on various sets of questions, we provide a valuable insight into students' experience, obstacles and observations during system's implementation. This particular insight paves the way toward further laboratory improvement, adopting this approach in other courses related to ours, and encouraging teachers to embrace similar practice regardless of the field of education.

A fully integrated single-photon avalanche diode (SPAD) using a controllable fast mixed quenching and active resetting circuit (QRC) fabricated in a $0.35-\mu\mathrm{m}$ high-voltage CMOS process is presented in this paper. The QRC features a fast active quenching time of 0.52 ns and a minimum dead-time of 4.57 ns, which corresponds to a maximum count rate of 218 Mcps. To validate the quenching performance, the circuit was integrated together with a large-area SPAD having an active diameter of $90\ \mu\mathrm{m}$ with a capacitance of 150 fF. A pad for a pico-probe was integrated on the chip, leading to a total capacitive load of 275 fF in SPAD cathode's node during transient measurements.

Abstract An extensive review of the literature on the diagnostic and clinical accuracy of Kurjak’s antenatal neurodevelopmental test (KANET) and the summarized results of the multi-center study involving 10 centers revealed that four-dimensional ultrasonography (4D US) has become a powerful tool and KANET a valuable test that empowers the clinicians worldwide to evaluate the fetal behavior in a systematic way and contribute to the detection of fetuses that might be at high risk for neurological impairments and in particular cerebral palsy (CP). After 10 years of clinical use, many published papers and multi-center studies, hundreds of trained physicians and numerous tests performed all over the world, KANET has proven its value and has been showing encouraging results so far. The aim of this paper is to show the results from the studies done so far and to reveal the clinical value of the KANET. We expect that data from the larger ongoing collaborative study, the short- and long-term postnatal follow-up will continue to improve our knowledge. Ultimately, we all strive to prevent the CP disorders, autism spectrum disorder (ASD) and other neurological impairments and we are convinced that KANET might be helpful in the realization of this important aim.

This study analyzes farm households’ adaptation in a broad livelihood context, showing how both household internal dynamics and broader external factors, such as agro-ecological, climatic, and institutional economic and political frame conditions, influence both the perception of and adaptation to climate variations and change. Nearly a third of the households in Bosnia and Herzegovina (BH) are engaged in agriculture as one livelihood strategy to cope with the multiple shocks experienced over the past three decades, resulting in economic decline and loss of income opportunities. Based on a household survey, we analyzed the livelihoods of households in three agricultural regions in BH: how they are affected by climate change, their perceptions of climatic change, as well as various household adaptation strategies. The results were discussed in the context of the sustainable livelihoods approach. Our results indicate that rural households are relatively asset poor and highly dependent on agriculture, irrespective of geographical location or wealth. Their access to assets is further constrained by the ongoing changes in economic and political structures and processes. Negative effects of climate change were reported in terms of yield decline and reduced quality of products. On a positive note, the level of adoption of different agricultural practices and technologies indicates signs of an overall intensification strategy of agricultural production in BH, as well as adaptation to the perceived changes in climate and climate variability using the available asset base.

E-learning represents novel learning way, which increase teaching flexibility and availability of learning resources. This paper explores the evaluation of student success at e-learning platform. Authors used multi-method approach for data analysis (i.e. Social Network Analysis, K-means Clustering and Linear Regression). This approach presents novelty in the field of e-learning, which provides more detailed analysis that enable more relevant results. The research was conducted with student group at the University of Novi Sad, Faculty of Technical Sciences, Serbia. Results indicate that digital resources at the e-learning platform make strong effects on student success. Moreover, results indicate that students with the similar grades belongs to the same clusters.

Com melhores condições de vida e os avanços na medicina, a expectativa de vida do brasileiro está cada vez maior. A fim de promover melhorias de vida para uma parcela da população que está aumentando, o presente projeto buscou desenvolver um produto de moda que atenda às necessidades do público idoso, particularmente dos que apresentam limitações nos membros superiores. Em visitas feitas à abrigos de idosos, foram realizadas entrevistas, obtendo informações mais precisas para nortear a pesquisa de maneira eficiente, e assim contribuir para o desenvolvimento de um produto que facilita o ato de vestir, ergonômico, e com maiores chances de sucesso no mercado. A pesquisa é de natureza aplicada, de caráter exploratório e utiliza uma abordagem qualitativa. Além disso, os procedimentos técnicos utilizados foram bibliográficos e de pesquisa-ação, o que possibilitou uma investigação mais profunda e subjetiva do público-alvo, permitindo a compreensão de seus comportamentos e experiências individuais, culminando em um maior conhecimento sobre o grupo analisado. Ao final do projeto, foi criada uma peça eficiente destinada aos idosos, proporcionando conforto e facilidade de uso, facilitando seu dia-a-dia.