Cyclic Damage Accumulation in the Femoral Constructs Made With Cephalomedullary Nails

Background: The purpose of this study was to evaluate the risk of peri-prosthetic fracture of constructs made with cephalomedullary (CM) long and short nails. The nails were made with titanium alloy (Ti-6Al-4V) and stainless steel (SS 316L). Methods: Biomechanical evaluation of CM nail constructs was carried out with regard to post-primary healing to determine the risk of peri-implant/peri-prosthetic fractures. Therefore, this research comprised of, non-fractured, twenty-eight pairs of cadaveric femora that were randomized and implanted with four types of fixation CM nails resulting in four groups. These constructs were cyclically tested in bi-axial mode for up to 30,000 cycles. All the samples were then loaded to failure to measure failure loads. Three frameworks were carried out through this investigation, Michaelis–Menten, phenomenological, and probabilistic Monte Carlo simulation to model and predict damage accumulation. Findings: Damage accumulation resulting from bi-axial cyclic loading in terms of construct stiffness was represented by Michaelis–Menten equation, and the statistical analysis demonstrated that one model can explain the damage accumulation during cyclic load for all four groups of constructs (P \u3e 0.05). A two-stage stiffness drop was observed. The short stainless steel had a significantly higher average damage (0.94) than the short titanium nails (0.90, P \u3c 0.05). Long titanium nail group did not differ substantially from the short stainless steel nails (P \u3e 0.05). Results showed gender had a significant effect on load to failure in both torsional and bending tests (P \u3c 0.05 and P \u3c 0.001, respectively). Interpretation: Kaplan–Meier survival analysis supports the use of short titanium CM nail. We recommend that clinical decisions should take age and gender into consideration in the selection of implants

Biomechanical Evaluation of Recurrent Dissociation of Modular Humeral Prostheses

The purpose of the study was to evaluate the force and torque required to dissociate a humeral head from the unimplanted modular total shoulder replacement system from different manufacturers and to determine if load and torque to dissociation are reduced in the presence of bodily fluids. Impingement, taper contamination, lack of compressive forces, and interference of taper fixation by the proximal humerus have all been reported as possible causes for dissociation. Experimental values determined in this research were compared with literature estimates of dissociation force of the humeral head under various conditions to gain more understanding of the causes of recurrent dissociations of the humeral head. This study examined biomechanical properties under dry and wet conditions under clinically practiced methods. Mean load to dissociation (1513 N ± 508 N) was found to be greater than that exerted by the activities of daily living (578 N) for all implants studied. The mean torque to dissociation was (49.77 N·m ± 19.07 N·m). Analysis of R2 correlation coefficients and p-values (α = 0.05) did not show any significant correlation between dry/bovine, dry/wet, or wet/bovine for load, displacement, or torsional stiffness in the majority of tests performed. Wetting the taper with water or bovine serum did not reduce the dissociation force to a statistically significant degree. Torque and lack of compressive forces at the rotator cuff may be the cause of dissociation at values less than those of activities of daily living. Torque data are provided by this study, but further research is needed to fully appreciate the role of torque in recurrent dissociations

The enigmatic core L1451-mm: a first hydrostatic core? or a hidden VeLLO?

We present the detection of a dust continuum source at 3-mm (CARMA) and 1.3-mm (SMA), and 12CO(2-1) emission (SMA) towards the L1451-mm dense core. These detections suggest a compact object and an outflow where no point source at mid-infrared wavelengths is detected using Spitzer. An upper limit for the dense core bolometric luminosity of 0.05 Lsun is obtained. By modeling the broadband SED and the continuum interferometric visibilities simultaneously, we confirm that a central source of heating is needed to explain the observations. This modeling also shows that the data can be well fitted by a dense core with a YSO and disk, or by a dense core with a central First Hydrostatic Core (FHSC). Unfortunately, we are not able to decide between these two models, which produce similar fits. We also detect 12CO(2-1) emission with red- and blue-shifted emission suggesting the presence of a slow and poorly collimated outflow, in opposition to what is usually found towards young stellar objects but in agreement with prediction from simulations of a FHSC. This presents the best candidate, so far, for a FHSC, an object that has been identified in simulations of collapsing dense cores. Whatever the true nature of the central object in L1451-mm, this core presents an excellent laboratory to study the earliest phases of low-mass star formation.Comment: 15 pages, 9 figures, emulateapj. Accepted by Ap

Cyclic Damage Accumulation in the Femoral Constructs Made With Cephalomedullary Nails

Background: The purpose of this study was to evaluate the risk of peri-prosthetic fracture of constructs made with cephalomedullary (CM) long and short nails. The nails were made with titanium alloy (Ti-6Al-4V) and stainless steel (SS 316L). Methods: Biomechanical evaluation of CM nail constructs was carried out with regard to post-primary healing to determine the risk of peri-implant/peri-prosthetic fractures. Therefore, this research comprised of, non-fractured, twenty-eight pairs of cadaveric femora that were randomized and implanted with four types of fixation CM nails resulting in four groups. These constructs were cyclically tested in bi-axial mode for up to 30,000 cycles. All the samples were then loaded to failure to measure failure loads. Three frameworks were carried out through this investigation, Michaelis–Menten, phenomenological, and probabilistic Monte Carlo simulation to model and predict damage accumulation. Findings: Damage accumulation resulting from bi-axial cyclic loading in terms of construct stiffness was represented by Michaelis–Menten equation, and the statistical analysis demonstrated that one model can explain the damage accumulation during cyclic load for all four groups of constructs (P > 0.05). A two-stage stiffness drop was observed. The short stainless steel had a significantly higher average damage (0.94) than the short titanium nails (0.90, P < 0.05). Long titanium nail group did not differ substantially from the short stainless steel nails (P > 0.05). Results showed gender had a significant effect on load to failure in both torsional and bending tests (P < 0.05 and P < 0.001, respectively). Interpretation: Kaplan–Meier survival analysis supports the use of short titanium CM nail. We recommend that clinical decisions should take age and gender into consideration in the selection of implant

Thomas H. Moore House

Prepared by the Fall 2013 Conservation of Historic Building Materials class. This Historic Structure Report contains historical context, building chronology, physical descriptions, current conditions assessment, and recommended treatment and use for the historic property. The purpose of this report is to provide a current assessment of the condition of the property, recommendations for needed repairs and options for future consideration.https://scholarworks.gsu.edu/history_heritagepreservation/1030/thumbnail.jp

Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer

BACKGROUND: Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer. METHODS: We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models. RESULTS: Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model. CONCLUSIONS: In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies

2019 Scholars at Work Conference Program

Program for the 2019 Scholars at Work Conference at Minnesota State University, Mankato on March 29, 2019

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019 : A systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC

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

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC