In-Hospital Formula Supplementation in Appalachian Women Intending to Exclusively Breastfeed.

OBJECTIVE: In-hospital formula supplementation places infants at risk for early breastfeeding cessation. The study's aim was to identify predictive and protective factors for in-hospital formula supplementation in individuals documented as wanting to exclusively breastfeed and residing in a geographic region with adverse social determinants of health and low breastfeeding rates. Additionally, we wished to determine if lactation consultation served as a protective factor against supplementation. METHODS: In this cross-sectional study, we retrospectively reviewed 500 randomly selected charts of newborns born in a 12 month period at a regional tertiary care hospital. We included healthy, full-term neonates having a recorded maternal decision to exclusively breastfeed. Maternal-newborn dyad characteristics were compared between those exclusively breastfeeding and those with in-hospital formula supplementation. RESULTS: Of the 500 charts, 70% of individuals desired to exclusively breastfeed. Overall, 41% of breastfed newborns were supplemented with formula before discharge, and 32% of women met with lactation consultants prior to supplementation. No statistically significant association was present between exclusive breastfeeding at discharge and meeting with a hospital lactation consultant (p = 0.55). When controlling for the confounders of maternal demographics and lactation consultation, significant associations with formula supplementation included Cesarean delivery (odd ratio: 2.08, 95% confidence interval: 1.04-4.16), primiparity (2.48, 1.27-4.87), and high school level of education (2.78, 1.33-5.78). CONCLUSIONS: Maternal characteristics of high school level educational, primiparity, and Caesarean delivery place individuals at risk for in-hospital formula supplementation in individuals wishing to exclusively breastfeed. Addressing barriers to exclusive breastfeeding is essential to enhance maternal and newborn health equity.

Should Nursing Schools Boycott Traditional College Ranking Systems?

New measures would focus on advancing health equity.

Inflammatory Bowel Disease Infusion Therapy Adherence in a Rural Pediatric Population.

INTRODUCTION: Biologic therapy is often used in patients with inflammatory bowel disease (IBD), which includes Crohn's Disease (CD) and ulcerative colitis (UC). While biologic therapy improves outcomes, it is dependent on strict compliance for optimal benefit. Limited information is available to describe IBD infusion therapy compliance and adherence barriers in a rural, geographically dispersed pediatric population. METHODS: Parents/guardians and patients (aged 0-21 years) with a diagnosis of IBD and scheduled biologic therapy infusions were offered a survey consisting of a mix of multiple-choice and open-ended questions. Surveys were offered via in-person paper format or telephone. RESULTS: Of the 27 pediatric patients completing the survey, the mean age was 14 years old (SD 3.7 years) with 19 patients having CD and eight patients with UC. The results showed that more than half of the patients (59%) had to reschedule, miss, or delayed their infusion therapy at least once. Therapy compliance was maintained as patients were able to reschedule a new appointment within two weeks. The most common reasons for missing appointments were forgetfulness and school conflicts. Patients wanting to maintain health and avoid flare-ups were reported as key drivers for therapy. CONCLUSION: Pediatric patients in rural and geographically disperse areas continue to have long commutes and other barriers to IBD specialty care. Forgetfulness and school activities were reported as barriers to biological therapy adherence. Protective factors including knowledge of therapy health benefits, parental involvement, and staff support can help maintain high adherence rates in this population.

Substrate reduction therapy for Krabbe disease and metachromatic leukodystrophy using a novel ceramide galactosyltransferase inhibitor.

Krabbe disease (KD) and metachromatic leukodystrophy (MLD) are caused by accumulation of the glycolipids galactosylceramide (GalCer) and sulfatide and their toxic metabolites psychosine and lysosulfatide, respectively. We discovered a potent and selective small molecule inhibitor (S202) of ceramide galactosyltransferase (CGT), the key enzyme for GalCer biosynthesis, and characterized its use as substrate reduction therapy (SRT). Treating a KD mouse model with S202 dose-dependently reduced GalCer and psychosine in the central (CNS) and peripheral (PNS) nervous systems and significantly increased lifespan. Similarly, treating an MLD mouse model decreased sulfatides and lysosulfatide levels. Interestingly, lower doses of S202 partially inhibited CGT and selectively reduced synthesis of non-hydroxylated forms of GalCer and sulfatide, which appear to be the primary source of psychosine and lysosulfatide. Higher doses of S202 more completely inhibited CGT and reduced the levels of both non-hydroxylated and hydroxylated forms of GalCer and sulfatide. Despite the significant benefits observed in murine models of KD and MLD, chronic CGT inhibition negatively impacted both the CNS and PNS of wild-type mice. Therefore, further studies are necessary to elucidate the full therapeutic potential of CGT inhibition.

Ecological prediction at macroscales using big data: Does sampling design matter?

Although ecosystems respond to global change at regional to continental scales (i.e., macroscales), model predictions of ecosystem responses often rely on data from targeted monitoring of a small proportion of sampled ecosystems within a particular geographic area. In this study, we examined how the sampling strategy used to collect data for such models influences predictive performance. We subsampled a large and spatially extensive data set to investigate how macroscale sampling strategy affects prediction of ecosystem characteristics in 6,784 lakes across a 1.8-million-km2 area. We estimated model predictive performance for different subsets of the data set to mimic three common sampling strategies for collecting observations of ecosystem characteristics: random sampling design, stratified random sampling design, and targeted sampling. We found that sampling strategy influenced model predictive performance such that (1) stratified random sampling designs did not improve predictive performance compared to simple random sampling designs and (2) although one of the scenarios that mimicked targeted (non-random) sampling had the poorest performing predictive models, the other targeted sampling scenarios resulted in models with similar predictive performance to that of the random sampling scenarios. Our results suggest that although potential biases in data sets from some forms of targeted sampling may limit predictive performance, compiling existing spatially extensive data sets can result in models with good predictive performance that may inform a wide range of science questions and policy goals related to global change.

Translational studies of intravenous and intracerebroventricular routes of administration for CNS cellular biodistribution for BMN 250, an enzyme replacement therapy for the treatment of Sanfilippo type B.

BMN 250 is being developed as enzyme replacement therapy for Sanfilippo type B, a primarily neurological rare disease, in which patients have deficient lysosomal alpha-N-acetylglucosaminidase (NAGLU) enzyme activity. BMN 250 is taken up in target cells by the cation-independent mannose 6-phosphate receptor (CI-MPR, insulin-like growth factor 2 receptor), which then facilitates transit to the lysosome. BMN 250 is dosed directly into the central nervous system via the intracerebroventricular (ICV) route, and the objective of this work was to compare systemic intravenous (IV) and ICV delivery of BMN 250 to confirm the value of ICV dosing. We first assess the ability of enzyme to cross a potentially compromised blood-brain barrier in the Naglu-/- mouse model and then assess the potential for CI-MPR to be employed for receptor-mediated transport across the blood-brain barrier. In wild-type and Naglu-/- mice, CI-MPR expression in brain vasculature is high during the neonatal period but virtually absent by adolescence. In contrast, CI-MPR remains expressed through adolescence in non-affected non-human primate and human brain vasculature. Combined results from IV administration of BMN 250 in Naglu-/- mice and IV and ICV administration in healthy juvenile non-human primates suggest a limitation to therapeutic benefit from IV administration because enzyme distribution is restricted to brain vascular endothelial cells: enzyme does not reach target neuronal cells following IV administration, and pharmacological response following IV administration is likely restricted to clearance of substrate in endothelial cells. In contrast, ICV administration enables central nervous system enzyme replacement with biodistribution to target cells.

Building therapeutic connections with the acutely ill through standardised patient simulation in nurse education an evaluation study.

BACKGROUND: Phenomenological empathy and sense of coherence are two researched communication approaches used to improve therapeutic connections with patients in a variety of nurse related settings. The aim of this study is to evaluate students' feedback concerning how this event has enabled that understanding, development and refinement of skill-sets in PE and SoC when managing the acutely ill during simulation. METHODS: 114 third year bachelor degree-nursing students were given the opportunity to complete an evaluation, developed for the specific purpose of this study. The evaluation contained six closed questions on a four point Likert-scale and three open questions, handed out upon completion of the standardised patient simulation of the acutely ill. Comments written in response to the open questions were analysed using manifest content analysis and closed questions using SPSS to produce descriptive frequencies. RESULTS: 100 students completed the evaluation. Student nurses', regardless of previous experience or age, indicated the need for more education and practice in phenomenological empathy and sense of coherence to enhance their ability to build therapeutic connections with the acutely ill. CONCLUSIONS: Teaching phenomenological empathy and sense of coherence, as an integral part of standardised patient simulation is necessary to motivate student nurses ability to build therapeutic relationships with the acutely ill to enhance person centred care.

Georgeite: A Rare Copper Mineral with Important Drinking Water Implications.

Significant research has been conducted on copper corrosion and solubility in drinking water, including the establishment of the "cupric hydroxide model". The model describes the temporal aging and associated solubility changes of copper minerals beginning with the most soluble solid, cupric hydroxide. Although the model explains copper levels in field observations well, there are aspects of the model that are not well understood, including a lack of evidence of the presence of cupric hydroxide in drinking water distribution systems. This study aimed to understand the effect of water chemistry on the solubility and properties of newly precipitated cupric solids, including mineral identification. Bench-scale copper precipitation tests were performed in water under a matrix of pH and dissolved inorganic carbon conditions. Copper solids were analyzed using a combination of materials analysis tools including XRD, FT-IR, TGA, and inorganic carbon analyses. Copper solids were X-ray amorphous, isotropic, and were light blue to blue. Based on repeated analysis, georgeite (Cu2(CO3)(OH)2·6H2O) was conclusively identified as the solid at all test conditions. Georgeite is an extremely rare, amorphous malachite analog, and because of its rarity, very little has been reported on its presence in any environment.

Creating multithemed ecological regions for macroscale ecology: Testing a flexible, repeatable, and accessible clustering method.

Understanding broad-scale ecological patterns and processes often involves accounting for regional-scale heterogeneity. A common way to do so is to include ecological regions in sampling schemes and empirical models. However, most existing ecological regions were developed for specific purposes, using a limited set of geospatial features and irreproducible methods. Our study purpose was to: (1) describe a method that takes advantage of recent computational advances and increased availability of regional and global data sets to create customizable and reproducible ecological regions, (2) make this algorithm available for use and modification by others studying different ecosystems, variables of interest, study extents, and macroscale ecology research questions, and (3) demonstrate the power of this approach for the research question-How well do these regions capture regional-scale variation in lake water quality? To achieve our purpose we: (1) used a spatially constrained spectral clustering algorithm that balances geospatial homogeneity and region contiguity to create ecological regions using multiple terrestrial, climatic, and freshwater geospatial data for 17 northeastern U.S. states (~1,800,000 km2); (2) identified which of the 52 geospatial features were most influential in creating the resulting 100 regions; and (3) tested the ability of these ecological regions to capture regional variation in water nutrients and clarity for ~6,000 lakes. We found that: (1) a combination of terrestrial, climatic, and freshwater geospatial features influenced region creation, suggesting that the oft-ignored freshwater landscape provides novel information on landscape variability not captured by traditionally used climate and terrestrial metrics; and (2) the delineated regions captured macroscale heterogeneity in ecosystem properties not included in region delineation-approximately 40% of the variation in total phosphorus and water clarity among lakes was at the regional scale. Our results demonstrate the usefulness of this method for creating customizable and reproducible regions for research and management applications.

Effects of Land Use on Lake Nutrients: The Importance of Scale, Hydrologic Connectivity, and Region.

Catchment land uses, particularly agriculture and urban uses, have long been recognized as major drivers of nutrient concentrations in surface waters. However, few simple models have been developed that relate the amount of catchment land use to downstream freshwater nutrients. Nor are existing models applicable to large numbers of freshwaters across broad spatial extents such as regions or continents. This research aims to increase model performance by exploring three factors that affect the relationship between land use and downstream nutrients in freshwater: the spatial extent for measuring land use, hydrologic connectivity, and the regional differences in both the amount of nutrients and effects of land use on them. We quantified the effects of these three factors that relate land use to lake total phosphorus (TP) and total nitrogen (TN) in 346 north temperate lakes in 7 regions in Michigan, USA. We used a linear mixed modeling framework to examine the importance of spatial extent, lake hydrologic class, and region on models with individual lake nutrients as the response variable, and individual land use types as the predictor variables. Our modeling approach was chosen to avoid problems of multi-collinearity among predictor variables and a lack of independence of lakes within regions, both of which are common problems in broad-scale analyses of freshwaters. We found that all three factors influence land use-lake nutrient relationships. The strongest evidence was for the effect of lake hydrologic connectivity, followed by region, and finally, the spatial extent of land use measurements. Incorporating these three factors into relatively simple models of land use effects on lake nutrients should help to improve predictions and understanding of land use-lake nutrient interactions at broad scales.

Building a multi-scaled geospatial temporal ecology database from disparate data sources: fostering open science and data reuse.

Although there are considerable site-based data for individual or groups of ecosystems, these datasets are widely scattered, have different data formats and conventions, and often have limited accessibility. At the broader scale, national datasets exist for a large number of geospatial features of land, water, and air that are needed to fully understand variation among these ecosystems. However, such datasets originate from different sources and have different spatial and temporal resolutions. By taking an open-science perspective and by combining site-based ecosystem datasets and national geospatial datasets, science gains the ability to ask important research questions related to grand environmental challenges that operate at broad scales. Documentation of such complicated database integration efforts, through peer-reviewed papers, is recommended to foster reproducibility and future use of the integrated database. Here, we describe the major steps, challenges, and considerations in building an integrated database of lake ecosystems, called LAGOS (LAke multi-scaled GeOSpatial and temporal database), that was developed at the sub-continental study extent of 17 US states (1,800,000 km(2)). LAGOS includes two modules: LAGOSGEO, with geospatial data on every lake with surface area larger than 4 ha in the study extent (~50,000 lakes), including climate, atmospheric deposition, land use/cover, hydrology, geology, and topography measured across a range of spatial and temporal extents; and LAGOSLIMNO, with lake water quality data compiled from ~100 individual datasets for a subset of lakes in the study extent (~10,000 lakes). Procedures for the integration of datasets included: creating a flexible database design; authoring and integrating metadata; documenting data provenance; quantifying spatial measures of geographic data; quality-controlling integrated and derived data; and extensively documenting the database. Our procedures make a large, complex, and integrated database reproducible and extensible, allowing users to ask new research questions with the existing database or through the addition of new data. The largest challenge of this task was the heterogeneity of the data, formats, and metadata. Many steps of data integration need manual input from experts in diverse fields, requiring close collaboration.

Delivery of an enzyme-IGFII fusion protein to the mouse brain is therapeutic for mucopolysaccharidosis type IIIB.

Mucopolysaccharidosis type IIIB (MPS IIIB, Sanfilippo syndrome type B) is a lysosomal storage disease characterized by profound intellectual disability, dementia, and a lifespan of about two decades. The cause is mutation in the gene encoding α-N-acetylglucosaminidase (NAGLU), deficiency of NAGLU, and accumulation of heparan sulfate. Impediments to enzyme replacement therapy are the absence of mannose 6-phosphate on recombinant human NAGLU and the blood-brain barrier. To overcome the first impediment, a fusion protein of recombinant NAGLU and a fragment of insulin-like growth factor II (IGFII) was prepared for endocytosis by the mannose 6-phosphate/IGFII receptor. To bypass the blood-brain barrier, the fusion protein ("enzyme") in artificial cerebrospinal fluid ("vehicle") was administered intracerebroventricularly to the brain of adult MPS IIIB mice, four times over 2 wk. The brains were analyzed 1-28 d later and compared with brains of MPS IIIB mice that received vehicle alone or control (heterozygous) mice that received vehicle. There was marked uptake of the administered enzyme in many parts of the brain, where it persisted with a half-life of approximately 10 d. Heparan sulfate, and especially disease-specific heparan sulfate, was reduced to control level. A number of secondary accumulations in neurons [ß-hexosaminidase, LAMP1(lysosome-associated membrane protein 1), SCMAS (subunit c of mitochondrial ATP synthase), glypican 5, ß-amyloid, P-tau] were reduced almost to control level. CD68, a microglial protein, was reduced halfway. A large amount of enzyme also appeared in liver cells, where it reduced heparan sulfate and ß-hexosaminidase accumulation to control levels. These results suggest the feasibility of enzyme replacement therapy for MPS IIIB.

Long-term citizen-collected data reveal geographical patterns and temporal trends in lake water clarity.

We compiled a lake-water clarity database using publically available, citizen volunteer observations made between 1938 and 2012 across eight states in the Upper Midwest, USA. Our objectives were to determine (1) whether temporal trends in lake-water clarity existed across this large geographic area and (2) whether trends were related to the lake-specific characteristics of latitude, lake size, or time period the lake was monitored. Our database consisted of >140,000 individual Secchi observations from 3,251 lakes that we summarized per lake-year, resulting in 21,020 summer averages. Using Bayesian hierarchical modeling, we found approximately a 1% per year increase in water clarity (quantified as Secchi depth) for the entire population of lakes. On an individual lake basis, 7% of lakes showed increased water clarity and 4% showed decreased clarity. Trend direction and strength were related to latitude and median sample date. Lakes in the southern part of our study-region had lower average annual summer water clarity, more negative long-term trends, and greater inter-annual variability in water clarity compared to northern lakes. Increasing trends were strongest for lakes with median sample dates earlier in the period of record (1938-2012). Our ability to identify specific mechanisms for these trends is currently hampered by the lack of a large, multi-thematic database of variables that drive water clarity (e.g., climate, land use/cover). Our results demonstrate, however, that citizen science can provide the critical monitoring data needed to address environmental questions at large spatial and long temporal scales. Collaborations among citizens, research scientists, and government agencies may be important for developing the data sources and analytical tools necessary to move toward an understanding of the factors influencing macro-scale patterns such as those shown here for lake water clarity.

Quantifying sample biases of inland lake sampling programs in relation to lake surface area and land use/cover.

We quantified potential biases associated with lakes monitored using non-probability based sampling by six state agencies in the USA (Michigan, Wisconsin, Iowa, Ohio, Maine, and New Hampshire). To identify biases, we compared state-monitored lakes to a census population of lakes derived from the National Hydrography Dataset. We then estimated the probability of lakes being sampled using generalized linear mixed models. Our two research questions were: (1) are there systematic differences in lake area and land use/land cover (LULC) surrounding lakes monitored by state agencies when compared to the entire population of lakes? and (2) after controlling for the effects of lake size, does the probability of sampling vary depending on the surrounding LULC features? We examined the biases associated with surrounding LULC because of the established links between LULC and lake water quality. For all states, we found that larger lakes had a higher probability of being sampled compared to smaller lakes. Significant interactions between lake size and LULC prohibit us from drawing conclusions about the main effects of LULC; however, in general lakes that are most likely to be sampled have either high urban use, high agricultural use, high forest cover, or low wetland cover. Our analyses support the assertion that data derived from non-probability-based surveys must be used with caution when attempting to make generalizations to the entire population of interest, and that probability-based surveys are needed to ensure unbiased, accurate estimates of lake status and trends at regional to national scales.

Anthropogenically driven changes in chloride complicate interpretation of base cation trends in lakes recovering from acidic deposition.

Declines in Ca and Mg in low ANC lakes recovering from acidic deposition are widespread across the northern hemisphere. We report overall increases between 1984 and 2004 in the concentrations of Ca + Mg and Cl in lakes representing the statistical population of nearly 4000 low ANC lakes in the northeast U.S. Increases in Cl occurred in nearly all lakes in urbanized southern New England, but only 18% of lakes in more remote Maine had Cl increases. This spatial pattern implicates road salt application as the major source of the increased Cl salts. Among the 48% of the lake population classified as salt-affected, the median changes in Cl (+133 microeq/L) and Ca + Mg (+47 microeq/ L) were large and positive in direction over the 20 years. However, in the unaffected lakes, Cl remained stable and Ca + Mg decreased (-3 microeq/L), consistent with reported long-term trends in base cations of acid-sensitive lakes. This discrepancy between the Cl groups suggests that changes in ion exchange processes in salt-affected watersheds have altered the geochemical cycling of Ca and Mg. One policy-relevant implication is that waters influenced by Cl salts complicate regional assessments of surface water recovery from "acid rain" related to the passage of the Clean Air Act.