Collaborative billiARds: Towards the ultimate gaming experience

Abstract. In this paper, we identify the features that enhance gaming experience in Augmented Reality (AR) environments. These include Tangible User Interface, force-feedback, audio-visual cues, collaboration and mobility. We base our findings on lessons learnt from existing AR games. We apply these results to billiARds which is an AR system that, in addition to visual and aural cues, provides force-feedback. billiARds supports interaction through a visionbased tangible AR interface. Two users can easily operate the proposed system while playing Collaborative billiARds game around a table. The users can collaborate through both virtual and real objects. User study confirmed that the resulting system delivers enhanced gaming experience by supporting the five features highlighted in this paper

Collaborative billiARds: Towards the Ultimate Gaming Experience

Abstract. In this paper, we identify the features that enhance gaming experience in Augmented Reality (AR) environments. These include Tangibl

Inequitable Gains and Losses from Conservation in a Global Biodiversity Hotspot

A billion rural people live near tropical forests. Urban populations need them for water, energy and timber. Global society benefits from climate regulation and knowledge embodied in tropical biodiversity. Ecosystem service valuations can incentivise conservation, but determining costs and benefits across multiple stakeholders and interacting services is complex and rarely attempted. We report on a 10-year study, unprecedented in detail and scope, to determine the monetary value implications of conserving forests and woodlands in Tanzania’s Eastern Arc Mountains. Across plausible ranges of carbon price, agricultural yield and discount rate, conservation delivers net global benefits (+US$8.2B present value, 20-year central estimate). Crucially, however, net outcomes diverge widely across stakeholder groups. International stakeholders gain most from conservation (+US$10.1B), while local-rural communities bear substantial net costs (-US$1.9B), with greater inequities for more biologically important forests. Other Tanzanian stakeholders experience conflicting incentives: tourism, drinking water and climate regulation encourage conservation (+US$72M); logging, fuelwood and management costs encourage depletion (-US$148M). Substantial global investment in disaggregating and mitigating local costs (e.g., through boosting smallholder yields) is essential to equitably balance conservation and development objectives

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

BACKGROUND: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. METHODS: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. FINDINGS: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8-8·8]; p<0·0001) and upper-middle-income (1·6 [1·2-2·2]; p=0·0024) country status; age 15-18 years (1·6 [1·1-2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8-3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3-2·4]; p=0·0001), and intensive treatment (1·8 [1·3-2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3-0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3-0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3-2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1-2·3]; p=0·020). INTERPRETATION: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. FUNDING: American Lebanese Syrian Associated Charities and the National Cancer Institute

Inequitable gains and losses from conservation in a global biodiversity hotspot

A billion rural people live near tropical forests. Urban populations need them for water, energy and timber. Global society benefits from climate regulation and knowledge embodied in tropical biodiversity. Ecosystem service valuations can incentivise conservation, but determining costs and benefits across multiple stakeholders and interacting services is complex and rarely attempted. We report on a 10-year study, unprecedented in detail and scope, to determine the monetary value implications of conserving forests and woodlands in Tanzania’s Eastern Arc Mountains. Across plausible ranges of carbon price, agricultural yield and discount rate, conservation delivers net global benefits (+US$8.2B present value, 20-year central estimate). Crucially, however, net outcomes diverge widely across stakeholder groups. International stakeholders gain most from conservation (+US$10.1B), while local-rural communities bear substantial net costs (-US$1.9B), with greater inequities for more biologically important forests. Other Tanzanian stakeholders experience conflicting incentives: tourism, drinking water and climate regulation encourage conservation (+US$72M); logging, fuelwood and management costs encourage depletion (-US$148M). Substantial global investment in disaggregating and mitigating local costs (e.g., through boosting smallholder yields) is essential to equitably balance conservation and development objectives

Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery

Achondroplasia causes narrowing of the foramen magnum and the spinal canal leading to increased mortality due to cervicomedullary compression in infants and significant morbidity due to spinal stenosis later in adulthood. Vosoritide is a C-natriuretic peptide analogue that has been shown to improve endochondral ossification in children with achondroplasia. The objective of this trial is to evaluate the safety of vosoritide and whether vosoritide can improve the growth of the foramen magnum and spinal canal in children that may require decompression surgery. An Achondroplasia Foramen Magnum Score will be used to identify infants at risk of requiring decompression surgery. This is a 2-year open label randomized controlled trial of vosoritide in infants with achondroplasia ages 0 to ≤12 months. Approximately 20 infants will be randomized 1:1 to either open label once daily subcutaneous vosoritide combined with standard of care or standard of care alone. The primary and secondary aims of the study are to evaluate the safety and efficacy of vosoritide in children with cervicomedullary compression at risk of requiring decompression surgery. The trial will be carried out in specialized skeletal dysplasia treatment centers with well established multidisciplinary care pathways and standardized approaches to the neurosurgical management of cervicomedually compression. After 2 years, infants randomized to standard of care alone will be eligible to switch to vosoritide plus standard of care for an additional 3 years. This pioneering trial hopes to address the important question as to whether treatment with vosoritide at an early age in infants at risk of requiring cervicomedullary decompression surgery is safe, and can improve growth at the foramen magnum and spinal canal alleviating stenosis. This in turn may reduce compression of surrounding structures including the neuraxis and spinal cord, which could alleviate future morbidity and mortality

Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway

PurposeDeoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway involved in the production and maintenance of a balanced pool of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis. dCK phosphorylates and therefore activates nucleoside analogs such as cytarabine, gemcitabine, decitabine, cladribine, and clofarabine that are used routinely in cancer therapy. Imaging probes that target dCK might allow stratifying patients into likely responders and nonresponders with dCK-dependent prodrugs. Here we present the biodistribution and radiation dosimetry of three fluorinated dCK substrates, (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC, developed for positron emission tomography (PET) imaging of dCK activity in vivo.MethodsPET studies were performed in nine healthy human volunteers, three for each probe. After a transmission scan, the radiopharmaceutical was injected intravenously and three sequential emission scans acquired from the base of the skull to mid-thigh. Regions of interest encompassing visible organs were drawn on the first PET scan and copied to the subsequent scans. Activity in target organs was determined and absorbed dose estimated with OLINDA/EXM. The standardized uptake value was calculated for various organs at different times.ResultsRenal excretion was common to all three probes. Bone marrow had higher uptake for L: -(18)F-FAC and L: -(18)F-FMAC than (18)F-FAC. Prominent liver uptake was seen in L: -(18)F-FMAC and L: -(18)F-FAC, whereas splenic activity was highest for (18)F-FAC. Muscle uptake was also highest for (18)F-FAC. The critical organ was the bladder wall for all three probes. The effective dose was 0.00524, 0.00755, and 0.00910 mSv/MBq for (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC, respectively.ConclusionThe biodistribution of (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC in humans reveals similarities and differences. Differences may be explained by different probe affinities for nucleoside transporters, dCK, and catabolic enzymes such as cytidine deaminase (CDA). Dosimetry demonstrates that all three probes can be used safely to image the deoxyribonucleoside salvage pathway in humans

Suppression of proline-directed protein kinase FAexpression inhibits the growth of human chronic myeloid leukaemia cells

Initial studies revealed that proline-directed protein kinase FA(PDPK FA) was overexpressed in various cancerous tissues relative to normal controls. However, the functional role of overexpressed PDPK FAin cancer remains to be established. In this report, we explore the potential role of PDPK FAin leukaemia cell growth by investigating the effects of partial inhibition of this kinase on the malignant phenotype of human chronic myeloid leukaemia cells (K562). Cloning of PDPK FAcDNA and its recombinant antisense expression vector and PDPK FA-specific antibody were successfully developed. Two stable antisense clones of K562 cells were subcloned which expressed 70% and 45% of PDPK FArespectively, compared with control-transfected clone in both immunoprecipitate activity assay and immunoblot analysis. In sharp contrast, these two antisense clones expressed no significant suppression of any other related PDPK family members, indicating the specificity of these two antisense clones. Moreover, these antisense clones proportionally and potentially exhibited cell growth retardation, poor clonogenic growth in soft agar and loss of serum independence. The results demonstrate that specific antisense suppression of PDPK FAis sufficient to interfere with the growth of K562 cells, indicating that PDPK FAis essential for human chronic myeloid leukaemia cell growth. © 2000 Cancer Research Campaig

Effect of prior treatments on selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma

Therapeutic regimens for previously treated multiple myeloma (MM) may not provide prolonged disease control and are often complicated by significant adverse events, including peripheral neuropathy. In patients with previously treated MM in the Phase 3 BOSTON study, once weekly selinexor, once weekly bortezomib, and 40&nbsp;mg dexamethasone (XVd) demonstrated a significantly longer median progression-free survival (PFS), higher response rates, deeper responses, a trend to improved survival, and reduced incidence and severity of bortezomib-induced peripheral neuropathy when compared with standard twice weekly bortezomib and 80&nbsp;mg dexamethasone (Vd). The pre-specified analyses described here evaluated the influence of the number of prior lines of therapy, prior treatment with lenalidomide, prior proteasome inhibitor (PI) therapy, prior immunomodulatory drug therapy, and prior autologous stem cell transplant (ASCT) on the efficacy and safety of XVd compared with Vd. In this 1:1 randomized study, enrolled patients were assigned to receive once weekly oral selinexor (100&nbsp;mg) with once weekly subcutaneous bortezomib (1.3&nbsp;mg/m2) and 40&nbsp;mg per week dexamethasone (XVd) versus standard twice weekly bortezomib and 80&nbsp;mg per week dexamethasone (Vd). XVd significantly improved PFS, overall response rate, time-to-next-treatment, and showed reduced all grade and grade ≥ 2 peripheral neuropathy compared with Vd regardless of prior treatments, but the benefits of XVd over Vd were more pronounced in patients treated earlier in their disease course who had either received only one prior therapy, had never been treated with a PI, or had prior ASCT. Treatment with XVd improved outcomes as compared to Vd regardless of prior therapies as well as manageable and generally reversible adverse events. XVd was associated with clinical benefit and reduced peripheral neuropathy compared to standard Vd in previously treated MM. These results suggest that the once weekly XVd regimen may be optimally administered to patients earlier in their course of disease, as their first bortezomib-containing regimen, and in those relapsing after ASCT. Trial registration: ClinicalTrials.gov (NCT03110562). Registered 12 April 2017. https://clinicaltrials.gov/ct2/show/NCT03110562

Virology, Pathology, and Clinical Manifestations of West Nile Virus Disease

Virologic characteristics of WNV likely interact with host factors in the pathogenesis of fever, meningitis, encephalitis, and flaccid paralysis