Distributed Space Traffic Management Solutions with Emerging New Space Industry

Day-to-day services, from weather forecast to logistics, rely on space-based infrastructures whose integrity is crucial to stakeholders and end-users worldwide. Current trends point towards congestion of the near-Earth space environment increasing at a rate greater than existing systems support, and thus demand novel cost-efficient approaches to traffic detection, characterization, tracking, and management to ensure space remains a safe, integral part of societies and economies worldwide. Whereas machine-learning (ML) and artificial intelligence (AI) have been extensively proposed to address congestion and alleviate big-data problems of the future, little has been done so far to tackle the need for transnational coordination and conflict-resolution in the context of space traffic management (STM). In STM, there is an ever-growing need for distributing information and coordinating actions (e.g., avoidance manoeuvres) to reduce the operational costs borne by individual entities and to decrease the latencies of actionable responses taken upon the detection of hazardous conditions by one-to-two orders of magnitude. However, these needs are not exclusive to STM, as evidenced by the widespread adoption of solutions to distributing, coordinating, and automating actions in other industries such as air traffic management (ATM), where a short-range airborne collision avoidance system (ACAS) automatically coordinates evasive manoeuvres whenever a conjunction is detected. Within this context, this paper aims at establishing a roadmap of promising technologies (e.g., blockchain), protocols and processes that could be adapted from different domains (railway, automotive, aerial, and maritime) to build an integrated traffic coordination and communication architecture to simplify and harmonise stakeholders’ satellite operations. This paper is organised into seven sections. First, Section 1 introduces the problem of STM, highlighting its complexity. Following this introduction, Section 2 discusses needs and requirements of various stakeholders such as commercial operators, space situational awareness (SSA) service providers, launch-service providers, satellite and constellation owners, governmental agencies, regulators, and insurance companies. Then, Section 3 addresses existing gaps and challenges in STM, focusing on globally coordinated approaches. Next, Section 4 reviews technologies for distributed, secure, and persistent communications, and proposed solutions to address some of these challenges from non-space sectors. Thereafter, Section 5 briefly covers the history of STM proposals and presents the state-of-the-art solution being proposed for modern STM. Following this review, Section 6 devises a step-by-step plan for exploiting and deploying some of the identified technologies within a five-to-ten-year timeline to close several existing gaps. Finally, Section 7 concludes the paper

Neoadjuvant Treatment for Nonmetastatic Pancreatic Cancer

Pancreatic adenocarcinoma is one of the most lethal malignancies among solid tumors. Unfortunately, several patients are diagnosed at metastatic stage or with unresectable disease due to vascular compromise involving the pancreas without any chance of curative treatment. There are also two other groups of patients: resectable patients at upfront diagnosis and “borderline resectable” pancreatic cancer patients. This last group represents those patients where surgery is not always possible without a preoperative treatment allowing surgeons to perform an R0 resection. Achieving an R0 resection is the only curative option for pancreatic cancer patients; nevertheless, many R0-resected patients will relapse within 2 years from surgery. Despite adjuvant treatment, reported median overall survival is only 28 months for patients with resectable pancreatic adenocarcinoma; thus, neoadjuvant treatment has been explored in order to improve survival. We aim to describe the controversial reported data and to show the recommendations that are suggested for these patients; however, we need to remark that there is no strong data that support neoadjuvant treatment. Currently, clinical trials are ongoing, and probably soon this approach will become a standard of care among borderline resectable patients and probably in selected resectable patients too

Gauge invariant perturbation theory and non-critical string models of Yang-Mills theories

We carry out a gauge invariant analysis of certain perturbations of $D-2$-branes solutions of low energy string theories. We get generically a system of second order coupled differential equations, and show that only in very particular cases it is possible to reduce it to just one differential equation. Later, we apply it to a multi-parameter, generically singular family of constant dilaton solutions of non-critical string theories in $D$ dimensions, a generalization of that recently found in arXiv:0709.0471[hep-th]. According to arguments coming from the holographic gauge theory-gravity correspondence, and at least in some region of the parameters space, we obtain glue-ball spectra of Yang-Mills theories in diverse dimensions, putting special emphasis in the scalar metric perturbations not considered previously in the literature in the non critical setup. We compare our numerical results to those studied previously and to lattice results, finding qualitative and in some cases, tuning properly the parameters, quantitative agreement. These results seem to show some kind of universality of the models, as well as an irrelevance of the singular character of the solutions. We also develop the analysis for the T-dual, non trivial dilaton family of solutions, showing perfect agreement between them.Comment: A new reference added

Microarray comparative genomic hybridization detection of chromosomal imbalances in uterine cervix carcinoma

BACKGROUND: Chromosomal Comparative Genomic Hybridization (CGH) has been applied to all stages of cervical carcinoma progression, defining a specific pattern of chromosomal imbalances in this tumor. However, given its limited spatial resolution, chromosomal CGH has offered only general information regarding the possible genetic targets of DNA copy number changes. METHODS: In order to further define specific DNA copy number changes in cervical cancer, we analyzed 20 cervical samples (3 pre-malignant lesions, 10 invasive tumors, and 7 cell lines), using the GenoSensor microarray CGH system to define particular genetic targets that suffer copy number changes. RESULTS: The most common DNA gains detected by array CGH in the invasive samples were located at the RBP1-RBP2 (3q21-q22) genes, the sub-telomeric clone C84C11/T3 (5ptel), D5S23 (5p15.2) and the DAB2 gene (5p13) in 58.8% of the samples. The most common losses were found at the FHIT gene (3p14.2) in 47% of the samples, followed by deletions at D8S504 (8p23.3), CTDP1-SHGC- 145820 (18qtel), KIT (4q11-q12), D1S427-FAF1 (1p32.3), D9S325 (9qtel), EIF4E (eukaryotic translation initiation factor 4E, 4q24), RB1 (13q14), and DXS7132 (Xq12) present in 5/17 (29.4%) of the samples. CONCLUSION: Our results confirm the presence of a specific pattern of chromosomal imbalances in cervical carcinoma and define specific targets that are suffering DNA copy number changes in this neoplasm

Overexpression of cathepsin f, matrix metalloproteinases 11 and 12 in cervical cancer

BACKGROUND: Cervical carcinoma (CC) is one of the most common cancers among women worldwide and the first cause of death among the Mexican female population. CC progression shows a continuum of neoplastic transitions until invasion. Matrix metalloproteinases (MMPs) and cathepsins play a central role on the enhancement of tumor-induced angiogenesis, cell migration, proliferation, apoptosis and connective tissue degradation. MMPs -2 and -9 expression has been widely studied in cervical cancer. Nevertheless, no other metalloproteinases or cathepsins have been yet related with the progression and/or invasion of this type of cancer. METHODS: Three HPV18 CC cell lines, two HPV16 CC cell lines and three HPV16 tumor CC tissues were compared with three morphologically normal, HPV negative, cervical specimens by cDNA arrays. Overexpression of selected genes was confirmed by end point semiquantitative reverse transcription-PCR with densitometry. In situ hybridization and protein expression of selected genes was further studied by means of two tissue microarrays, one consisting of 10 HSIL and 15 CC and the other one of 15 normal cervical and 10 LSIL tissues. RESULTS: TIMP1, Integrins alpha 1 and 4, cadherin 2 and 11, Cathepsins F, B L2, MMP 9, 10 11 and 12 were upregulated and Cathepsin S, L, H and C, Cadherins 3 and 4, TIMP3, MMP 13, Elastase 2 and Integrin beta 8 were found to be downregulated by cDNA arrays. Endpoint RT-PCR with densitometry gave consistent results with the cDNA array findings for all three genes selected for study (CTSF, MMP11 and MMP12). In situ hybridization of all three genes confirmed overexpression in all the HSIL and CC. Two of the selected proteins were detected in LSIL, HSIL and CC by immunohistochemistry. CONCLUSION: Novel undetected CC promoting genes have been identified. Increased transcription of these genes may result in overexpression of proteins, such as CTSF, MMP11 and MMP12 which could contribute to the pathogenesis of CC

Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens