ftp ejde.math.txstate.edu (login: ftp) SOLUTION DEPENDENCE ON PROBLEM PARAMETERS FOR INITIAL-VALUE PROBLEMS ASSOCIATED WITH THE STIELTJES STURM-LIOUVILLE EQUATIONS

Abstract. We examine properties of solutions to a 2n-dimensional Stieltjes Sturm-Liouville initial-value problem. Existence and uniqueness of a solution has been previously proven, but we present a proof in order to establish properties of boundedness, bounded variation, and continuity. These properties are then used to prove that the solutions depend continuously on the coefficients and on the initial conditions under certain hypotheses. In a future paper, these results will be extended to eigenvalue problems, and we will examine dependence on the endpoints and boundary data in addition to the coefficients. We will find conditions under which the eigenvalues depend continuously and differentiably on these parameters. 1

Effectiveness of Flow Management and Rainbow Trout Harvest on Long-Term Viability of Native Yellowstone Cutthroat Trout in the South Fork Snake River

The South Fork Snake River supports one of the last remaining large-river populations of Yellowstone cutthroat trout (YCT, Onchorynchus clarkia bouvierii). Rainbow (O. mykiss) and rainbow x cutthroat hybrid trout (collectively, RHT) established a self-sustaining population in the upper South Fork in the mid-1980s. In 2003, density of each species was 1400 fish per mile. In 2004, U.S. Bureau of Reclamation began delivering a spring “freshet” from Palisades Dam, and Idaho Department of Fish and Game removed harvest limits on RHT. We evaluated current and future effectiveness of these management actions with astochastic simulation model parameterized with observed data. Total RHT + YCT recruitment is positively correlated with winter flow, and RHT recruitment is negatively correlated with maximum freshet flow. There is little temporal overlap in spawning, and hybridization alone does not explain the observed RHT invasion rate. Nonetheless, continued removal of RHT from spawning tributaries is necessary to prevent long-term loss of YCT. A model of juvenile competition between the two species based on experimental results of Seiler and Keeley explains observed invasion rates. Current densities of 1700 YCT/mi and 925 RHT/mi indicate reversal in population trends since 2004, and our analysis suggests that this is due primarily to harvest of RHT, which increased from 7 percent in 2003 to 20 percent in 2005. About 15 percent exploitation on RHT is required to prevent YCT extinction. We considered a likely future scenario to include mean winter flow of 1600 cfs (72% of 1987-2007 mean but necessary to enable the freshet operation), maximum freshet flow averaging 20,000 cfs,and RHT harvest at 20. A percent assuming environmental variance as observed since 1987, the 25-yr population projection is about 1100 fish/mi of each species. Increased percentage of YCT requires higher RHT harvest and/or higher maximum flows, and increased abundance requires higher winter flows

The status of platinum anticancer drugs in the clinic and in clinical trials

Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, LipoplatinTM and ProLindacTM). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

Introduction: Toward an Engaged Feminist Heritage Praxis

We advocate a feminist approach to archaeological heritage work in order to transform heritage practice and the production of archaeological knowledge. We use an engaged feminist standpoint and situate intersubjectivity and intersectionality as critical components of this practice. An engaged feminist approach to heritage work allows the discipline to consider women’s, men’s, and gender non-conforming persons’ positions in the field, to reveal their contributions, to develop critical pedagogical approaches, and to rethink forms of representation. Throughout, we emphasize the intellectual labor of women of color, queer and gender non-conforming persons, and early white feminists in archaeology

Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma

Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63–0.75], p = 1.86×10−18), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21–1.43], p = 3.87×10−11). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50–0.67], p = 1.17×10−12) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53–0.72], p = 8.88×10−10). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41–0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54–1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING: Bill & Melinda Gates Foundation

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n = 109,122 individuals. We identified 59 sentinel variants (p < 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that the independent signals colocalized with cell-type-specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes

INCREASING HYDROGEN PRODUCTION IN ELECTROLYSIS WITH A MAGNETIC FIELD

Hydrogen is an important energy carrier that has no carbon emissions when energy is extracted and also can be used as energy storage to increase the practicality of many renewable energy sources. The prominent methods of hydrogen production make use of fossil fuels, resulting in carbon emissions. Electrolysis is a lesser used technology for hydrogen production in which electricity splits water molecules into oxygen and hydrogen gases. If the electricity is sourced from renewable energies, this process releases little to no carbon and the resulting hydrogen is termed “green hydrogen.” While electrolysis and fossil fuel methods have comparable efficiencies of hydrogen production, the use of electricity results in electrolysis having a significantly higher cost. To make electrolysis feasible for large-scale hydrogen production, energy losses must be decreased to improve its efficiency. This study investigates the combined impact of electrolyte concentration and the application of a magnetic field on hydrogen production rates in alkaline electrolysis. Previous studies have shown the existence of an optimal electrolyte concentration that results in the highest rate of hydrogen production, typically around 30 wt% at room temperature. Other studies have shown that applying a magnetic field increases the conductivity of the electrolyte solution, which should increase the rate of hydrogen production. If the magnetic field is oriented to result in an upward Lorentz force, the resulting convection along with the Lorentz force encourages gas bubbles to dislodge from the electrodes, which reduces resistance and increases the active area of the electrodes. In this project, alkaline electrolysis was performed at room temperature using 1.8 V with KOH as the electrolyte. The flow rate of the electrolyte solution was fixed at 50 cc/min, and the volume of hydrogen produced was measured with a water displacement system. The electrolyte concentration was varied between 5 wt% - 30 wt%. At each selected concentration level, electrolysis was performed once without a magnet and once with a 1T magnetic field, created by permanent magnets oriented to create an upward Lorentz force. The results showed that at each concentration level, the magnetic field increased the rate of hydrogen production, with the largest increase at 10 wt%. The optimal concentration was approximately 30 wt% with no magnetic field, but with a 1 T magnetic field the optimal concentration was reduced to 10 wt%. Thus, applying a magnetic field calls for a reduction in electrolyte concentration, which results in cost savings, in addition to the benefit of a higher hydrogen production rate