Ambulance Emergency Response Optimization in Developing Countries

The lack of emergency medical transportation is viewed as the main barrier to the access of emergency medical care in low and middle-income countries (LMICs). In this paper, we present a robust optimization approach to optimize both the location and routing of emergency response vehicles, accounting for uncertainty in travel times and spatial demand characteristic of LMICs. We traveled to Dhaka, Bangladesh, the sixth largest and third most densely populated city in the world, to conduct field research resulting in the collection of two unique datasets that inform our approach. This data is leveraged to develop machine learning methodologies to estimate demand for emergency medical services in a LMIC setting and to predict the travel time between any two locations in the road network for different times of day and days of the week. We combine our robust optimization and machine learning frameworks with real data to provide an in-depth investigation into three policy-related questions. First, we demonstrate that outpost locations optimized for weekday rush hour lead to good performance for all times of day and days of the week. Second, we find that significant improvements in emergency response times can be achieved by re-locating a small number of outposts and that the performance of the current system could be replicated using only 30% of the resources. Lastly, we show that a fleet of small motorcycle-based ambulances has the potential to significantly outperform traditional ambulance vans. In particular, they are able to capture three times more demand while reducing the median response time by 42% due to increased routing flexibility offered by nimble vehicles on a larger road network. Our results provide practical insights for emergency response optimization that can be leveraged by hospital-based and private ambulance providers in Dhaka and other urban centers in LMICs

Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries

Oesophageal cancers (adenocarcinomas [AC] and squamous cell carcinomas [SCC]) are characterized by high incidence/mortality in many countries. We aimed to delineate its global incidence and mortality, and studied whether socioeconomic development and its incidence rate were correlated. The age-standardized rates (ASRs) of incidence and mortality of this medical condition in 2012 for 184 nations from the GLOBOCAN database; national databases capturing incidence rates, and the WHO mortality database were examined. Their correlations with two indicators of socioeconomic development were evaluated. Joinpoint regression analysis was used to generate trends. The ratio between the ASR of AC and SCC was strongly correlated with HDI (r = 0.535 [men]; r = 0.661 [women]) and GDP (r = 0.594 [men]; r = 0.550 [women], both p < 0.001). Countries that reported the largest reduction in incidence in male included Poland (Average Annual Percent Change [AAPC] = −7.1, 95%C.I. = −12,−1.9) and Singapore (AAPC = −5.8, 95%C.I. = −9.5,−1.9), whereas for women the greatest decline was seen in Singapore (AAPC = −12.3, 95%C.I. = −17.3,−6.9) and China (AAPC = −5.6, 95%C.I. = −7.6,−3.4). The Philippines (AAPC = 4.3, 95%C.I. = 2,6.6) and Bulgaria (AAPC = 2.8, 95%C.I. = 0.5,5.1) had a significant mortality increase in men; whilst Columbia (AAPC = −6.1, 95%C.I. = −7.5,−4.6) and Slovenia (AAPC = −4.6, 95%C.I. = −7.9,−1.3) reported mortality decline in women. These findings inform individuals at increased risk for primary prevention

Advances in lung bioengineering: Where we are, where we need to go, and how to get there

Lung transplantation is the only potentially curative treatment for end-stage lung failure and successfully improves both long-term survival and quality of life. However, lung transplantation is limited by the shortage of suitable donor lungs. This discrepancy in organ supply and demand has prompted researchers to seek alternative therapies for end-stage lung failure. Tissue engineering (bioengineering) organs has become an attractive and promising avenue of research, allowing for the customized production of organs on demand, with potentially perfect biocompatibility. While breakthroughs in tissue engineering have shown feasibility in practice, they have also uncovered challenges in solid organ applications due to the need not only for structural support, but also vascular membrane integrity and gas exchange. This requires a complex engineered interaction of multiple cell types in precise anatomical locations. In this article, we discuss the process of creating bioengineered lungs and the challenges inherent therein. We summarize the relevant literature for selecting appropriate lung scaffolds, creating decellularization protocols, and using bioreactors. The development of completely artificial lung substitutes will also be reviewed. Lastly, we describe the state of current research, as well as future studies required for bioengineered lungs to become a realistic therapeutic modality for end-stage lung disease. Applications of bioengineering may allow for earlier intervention in end-stage lung disease and have the potential to not only halt organ failure, but also significantly reverse disease progression

Adopting a systems-thinking approach to optimise dietary and exercise referral practices for cancer survivors

Purpose: Service referrals are required for cancer survivors to access specialist dietary and exercise support. Many system-level factors influence referral practices within the healthcare system. Hence, the aim of this study was to identify system-level factors and their interconnectedness, as well as strategies for optimising dietary and exercise referral practices in Australia. Methods: A full-day workshop involving national multidisciplinary key stakeholders explored system-level factors impacting dietary and exercise referral practices. Facilitated group discussions using the nominal group technique identified barriers and facilitators to referral practices based on the six World Health Organisation (WHO) building blocks. The systems-thinking approach generated six cognitive maps, each representing a building block. A causal loop diagram was developed to visualise factors that influence referral practices. Additionally, each group identified their top five strategies by leveraging facilitators and addressing barriers relevant to their WHO building block. Results: Twenty-seven stakeholders participated in the workshop, including consumers (n = 2), cancer specialists (n = 4), nursing (n = 6) and allied health professionals (n = 10), and researchers, representatives of peak bodies, not-for-profit organisations, and government agencies (n = 5). Common system-level factors impacting on referral practices included funding, accessibility, knowledge and education, workforce capacity, and infrastructure. Fifteen system-level strategies were identified to improve referral practices. Conclusion: This study identified system-level factors and strategies that can be applied to policy planning and practice in Australia

Genome maps across 26 human populations reveal population-specific patterns of structural variation.

Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome

Disease Burden of Clostridium difficile Infections in Adults, Hong Kong, China, 2006-2014

Cross-sectional studies suggest an increasing trend in incidence and relatively low recurrence rates of Clostridium difficile infections in Asia than in Europe and North America. The temporal trend of C. difficile infection in Asia is not completely understood. We conducted a territory-wide population-based observational study to investigate the burden and clinical outcomes in Hong Kong, China, over a 9-year period. A total of 15,753 cases were identified, including 14,402 (91.4%) healthcare-associated cases and 817 (5.1%) community-associated cases. After adjustment for diagnostic test, we found that incidence increased from 15.41 cases/100,000 persons in 2006 to 36.31 cases/100,000 persons in 2014, an annual increase of 26%. This increase was associated with elderly patients, for whom incidence increased 3-fold over the period. Recurrence at 60 days increased from 5.7% in 2006 to 9.1% in 2014 (p<0.001). Our data suggest the need for further surveillance, especially in Asia, which contains ≈60% of the world’s population

Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV

Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells

Identification and Specification of the Mouse Skeletal Stem Cell

SummaryHow are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs in situ, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues

Pandemic Influenza (H1N1) 2009 Is Associated with Severe Disease in India

Background: Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. In absence of reliable information on severity of the disease, the nations are unable to decide on the appropriate response against this disease. Methods: Based on the results of laboratory investigations, attendance in outpatient department, hospital admissions and mortality from the cases of influenza like illness from 1 August to 31 October 2009 in Pune urban agglomeration, risk of hospitalization and case fatality ratio were assessed to determine the severity of pandemic H1N1 and seasonal influenza-A infections. Results: Prevalence of pandemic H1N1 as well as seasonal-A cases were high in Pune urban agglomeration during the study period. The cases positive for pandemic H1N1 virus had significantly higher risk of hospitalization than those positive for seasonal influenza-A viruses (OR: 1.7). Of 93 influenza related deaths, 57 and 8 deaths from Pune (urban) and 27 and 1 death from Pune (rural) were from pandemic H1N1 positive and seasonal-A positive cases respectively. The case fatality ratio 0.86 % for pandemic H1N1 was significantly higher than that of seasonal-A (0.13%) and it was in category 3 of the pandemic severity index of CDC, USA. The data on the cumulative fatality of rural and urban Pune revealed that with time the epidemic is spreading to rural areas

Follow-up analyses to the O3 LIGO-Virgo-KAGRA lensing searches

Along their path from source to observer, gravitational waves may be gravitationally lensed by massive objects. This results in distortions of the observed signal which can be used to extract new information about fundamental physics, astrophysics, and cosmology. Searches for these distortions amongst the observed signals from the current detector network have already been carried out, though there have as yet been no confident detections. However, predictions of the observation rate of lensing suggest detection in the future is a realistic possibility. Therefore, preparations need to be made to thoroughly investigate the candidate lensed signals. In this work, we present some of the follow-up analyses and strategies that could be applied to assess the significance of such events and ascertain what information may be extracted about the lens-source system from such candidate signals by applying them to a number of O3 candidate events, even if these signals did not yield a high significance for any of the lensing hypotheses. For strongly-lensed candidates, we verify their significance using a background of simulated unlensed events and statistics computed from lensing catalogs. We also look for potential electromagnetic counterparts. In addition, we analyse in detail a candidate for a strongly-lensed sub-threshold counterpart that is identified by a new method. For microlensing candidates, we perform model selection using a number of lens models to investigate our ability to determine the mass density profile of the lens and constrain the lens parameters. We also look for millilensing signatures in one of the lensed candidates. Applying these additional analyses does not lead to any additional evidence for lensing in the candidates that have been examined. However, it does provide important insight into potential avenues to deal with high-significance candidates in future observations.Comment: 34 pages, 27 figure