Mixed-reality for unmanned aerial vehicle operations in near earth environments

Future applications will bring unmanned aerial vehicles (UAVs) to near Earth environments such as urban areas, causing a change in the way UAVs are currently operated. Of concern is that UAV accidents still occur at a much higher rate than the accident rate for commercial airliners. A number of these accidents can be attributed to a UAV pilot's low situation awareness (SA) due to the limitations of UAV operating interfaces. The main limitation is the physical separation between the vehicle and the pilot. This eliminates any motion and exteroceptive sensory feedback to the pilot. These limitation on top of a small eld of view from the onboard camera results in low SA, making near Earth operations di cult and dangerous. Autonomy has been proposed as a solution for near Earth tasks but state of the art arti cial intelligence still requires very structured and well de ned goals to allow safe autonomous operations. Therefore, there is a need to better train pilots to operate UAVs in near Earth environments and to augment their performance for increased safety and minimization of accidents.In this work, simulation software, motion platform technology, and UAV sensor suites were integrated to produce mixed-reality systems that address current limitations of UAV piloting interfaces. The mixed reality de nition is extended in this work to encompass not only the visual aspects but to also include a motion aspect. A training and evaluation system for UAV operations in near Earth environments was developed. Modi cations were made to ight simulator software to recreate current UAV operating modalities (internal and external). The training and evaluation system has been combined with Drexel's Sensor Integrated Systems Test Rig (SISTR) to allow simulated missions while incorporating real world environmental e ects andUAV sensor hardware.To address the lack of motion feedback to a UAV pilot, a system was developed that integrates a motion simulator into UAV operations. The system is designed such that during ight, the angular rate of a UAV is captured by an onboard inertial measurement unit (IMU) and is relayed to a pilot controlling the vehicle from inside the motion simulator.Efforts to further increase pilot SA led to the development of a mixed reality chase view piloting interface. Chase view is similar to a view of being towed behind the aircraft. It combines real world onboard camera images with a virtual representation of the vehicle and the surrounding operating environment. A series of UAV piloting experiments were performed using the training and evaluation systems described earlier. Subjects' behavioral performance while using the onboard camera view and the mixed reality chase view interface during missions was analyzed. Subjects' cognitive workload during missions was also assessed using subjective measures such as NASA task load index and non-subjective brain activity measurements using a functional Infrared Spectroscopy (fNIR) system. Behavioral analysis showed that the chase view interface improved pilot performance in near Earth ights and increased their situational awareness. fNIR analysis showed that a subjects cognitive workload was signi cantly less while using the chase view interface. Real world ight tests were conducted in a near Earth environment with buildings and obstacles to evaluate the chase view interface with real world data. The interface performed very well with real world, real time data in close range scenarios.The mixed reality approaches presented follow studies on human factors performance and cognitive loading. The resulting designs serve as test beds for studying UAV pilot performance, creating training programs, and developing tools to augment UAV operations and minimize UAV accidents during operations in near Earth environments.Ph.D., Mechanical Engineering -- Drexel University, 201

In-play sports betting: a scoping study

Technology has changed the nature of gambling practices over the last decade and is continuing to do so. The online sports betting industry has become a rapidly growing sector of the global economy, with online sports betting contributing 37% of the annual online gambling market in Europe. There has been an integration of social and technological processes that has enabled the cultural saliency of contemporary online betting. One of the more newly introduced forms of online sports betting is in-play sports betting behaviour (the betting on events within a sporting event such as football and cricket). In-play sports betting features (such as 'cash out') are increasing in popularity amongst online gambling operators. A scoping study was carried out examining the evolution of this new form of gambling practice which included both a systematic literature review and the examination of 338 online gambling websites that offered sports betting. The present study identified a comprehensive list of what in-play betting features are currently being offered on online gambling websites as well as other information concerning in-play sports betting. A total of 16 academic papers and two 'grey literature' reports and were identified in the systematic review. Out of 338 online gambling websites that were visited, 26% of these offered at least on in-play betting feature. Results from the systematic review suggest that in-play sports betting has the potential to be more harmful than other ways of gambling because of the inherent structural characteristics

In-play sports betting: a scoping study

Technology has changed the nature of gambling practices over the last decade and is continuing to do so. The online sports betting industry has become a rapidly growing sector of the global economy, with online sports betting contributing 37% of the annual online gambling market in Europe. There has been an integration of social and technological processes that has enabled the cultural saliency of contemporary online betting. One of the more newly introduced forms of online sports betting is in-play sports betting behaviour (the betting on events within a sporting event such as football and cricket). In-play sports betting features (such as 'cash out') are increasing in popularity amongst online gambling operators. A scoping study was carried out examining the evolution of this new form of gambling practice which included both a systematic literature review and the examination of 338 online gambling websites that offered sports betting. The present study identified a comprehensive list of what in-play betting features are currently being offered on online gambling websites as well as other information concerning in-play sports betting. A total of 16 academic papers and two 'grey literature' reports and were identified in the systematic review. Out of 338 online gambling websites that were visited, 26% of these offered at least on in-play betting feature. Results from the systematic review suggest that in-play sports betting has the potential to be more harmful than other ways of gambling because of the inherent structural characteristics

Why do individuals engage in in-play sports betting? A qualitative interview study

Increasing technological advancements and changing consumer behavior has resulted in individuals having access to a wider range of online gambling markets and sporting events than ever before. Sports betting in real time has been aided by the accessibility of smartphone devices. Consequently, the popularity of live sports betting (i.e., 'in-play' betting) has spread across Europe and around the rest of world. The aim of the present exploratory study was to examine attitudes and opinions towards online sports betting. Qualitative interviews were conducted with 17 males and 2 females aged between 21 and 32 years. Participants were asked a range of semi-structured interview questions based on pre-determined topic areas. Socio-demographic data were collected and the Problem Gambling Severity Index (PGSI) was used to assess problem gambling. The data were analyzed using thematic analysis in order to identify themes. Analysis of the transcripts identified several notable areas including the ease of engaging in in-play sports betting, motivations for engaging in in-play sports betting (including increased excitement, demonstrating knowledge/skill and response to live odds), and different reasons for using the ‘cash-out’ feature. The findings will contribute to the design of future research investigating in-play sports betting behaviours

Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants

Background Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. Methods For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. Findings We pooled 1479 studies that had measured the blood pressures of 19·1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127·0 mm Hg (95% credible interval 125·7–128·3) in men and 122·3 mm Hg (121·0–123·6) in women; age-standardised mean diastolic blood pressure was 78·7 mm Hg (77·9–79·5) for men and 76·7 mm Hg (75·9–77·6) for women. Global age-standardised prevalence of raised blood pressure was 24·1% (21·4–27·1) in men and 20·1% (17·8–22·5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. Interpretation During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe. Funding Wellcome Trust

Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.

SLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L-serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8-year-old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant-negative N-glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L-serine

Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter's transformation

: Richter's Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio