Patient Preferences for Diagnostic Testing in the Emergency Department: A Crossâ sectional Study

BackgroundDiagnostic testing is common during emergency department (ED) visits. Little is understood about patient preferences for such testing. We hypothesized that a patient’s willingness to undergo diagnostic testing is influenced by the potential benefit, risk, and personal cost.MethodsWe conducted a cross sectional survey among ED patients for diagnostic testing in two hypothetical scenarios: chest pain (CP) and mild traumatic brain injury (mTBI). Each scenario defined specific risks, benefits, and costs of testing. The odds of a participant desiring diagnostic testing were calculated using a series of nested multivariable logistic regression models.ResultsParticipants opted for diagnostic testing 68.2% of the time, including 69.7% of CP and 66.7% of all mTBI scenarios. In the CP scenario, 81% of participants desired free testing versus 59% when it was associated with a $100 copay (difference = 22$100 copayment (difference = 17%, 95% CI = 11% to 24%). Benefit and risk had mixed effects across the scenarios. In fully adjusted models, the association between cost and desire for testing persisted in the CP (odds ratio [OR] = 0.33, 95% CI = 0.23 to 0.47) and adult mTBI (OR = 0.47, 95% CI = 0.33 to 0.67) scenarios.ConclusionsIn this EDâ based study, patient preferences for diagnostic testing differed significantly across levels of risk, benefit, and cost of diagnostic testing. Cost was the strongest and most consistent factor associated with decreased desire for testing.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144652/1/acem13404.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144652/2/acem13404_am.pd

Herbivory and nutrients shape grassland soil seed banks

Anthropogenic nutrient enrichment and shifts in herbivory can lead to dramatic changes in the composition and diversity of aboveground plant communities. In turn, this can alter seed banks in the soil, which are cryptic reservoirs of plant diversity. Here, we use data from seven Nutrient Network grassland sites on four continents, encompassing a range of climatic and environmental conditions, to test the joint effects of fertilization and aboveground mammalian herbivory on seed banks and on the similarity between aboveground plant communities and seed banks. We find that fertilization decreases plant species richness and diversity in seed banks, and homogenizes composition between aboveground and seed bank communities. Fertilization increases seed bank abundance especially in the presence of herbivores, while this effect is smaller in the absence of herbivores. Our findings highlight that nutrient enrichment can weaken a diversity maintaining mechanism in grasslands, and that herbivory needs to be considered when assessing nutrient enrichment effects on seed bank abundance.EEA Santa CruzFil: Eskelinen, Anu. German Centre for Integrative Biodiversity Research; AlemaniaFil: Eskelinen, Anu. Helmholtz Centre for Environmental Research. Department of Physiological Diversity; AlemaniaFil: Eskelinen, Anu. University of Oulu. Ecology & Genetics; FinlandiaFil: Jessen, Maria Theresa. Helmholtz Centre for Environmental Research. Department of Physiological Diversity; AlemaniaFil: Jessen, Maria Theresa. German Centre for Integrative Biodiversity Research; AlemaniaFil: Jessen, Maria Theresa. Helmholtz Centre for Environmental Research – UFZ. Department of Community Ecology; AlemaniaFil: Bahamonde, Hector Alejandro. Universidad Nacional de La Plata. Ciencias Agrarias y Forestales; Argentina.Fil: Bakker, Jonathan D. University of Washington. School of Environmental and Forest Sciences; Estados UnidosFil: Borer, Elizabeth T. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Caldeira, Maria C. University of Lisbon. Forest Research Centre. Associate Laboratory TERRA. School of Agriculture; Portugal.Fil: Harpole, William Stanley. German Centre for Integrative Biodiversity Research (iDiv); AlemaniaFil: Harpole, William Stanley. Helmholtz Centre for Environmental Research – UFZ. Department of Community Ecology; AlemaniaFil: Harpole, William Stanley. Martin Luther University. Institute of Biology; AlemaniaFil: Jia, Meiyu. University of Washington. School of Environmental and Forest Sciences; Estados UnidosFil: Jia, Meiyu. East China University of Technology. School of Water Resources & Environmental Engineering; China.Fil: Jia, Meiyu. Beijing Normal University. College of Life Sciences; China.Fil: Lannes, Luciola S. São Paulo State University-UNESP. Department of Biology and Animal Sciences; Brasil.Fil: Nogueira, Carla. University of Lisbon. Forest Research Centre. Associate Laboratory TERRA. School of Agriculture; Portugal.Fil: Venterink, Harry Olde. Vrije Universiteit Brussel (VUB). Department of Biology; BélgicaFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Porath-Krause, Anita J. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Seabloom, Eric William. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Schroeder, Katie. University of Minnesota. Department of Ecology, Evolution & Behavior; Estados UnidosFil: Schroeder, Katie. University of Georgia. Odum School of Ecology; Estados UnidosFil: Tognetti, Pedro M. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Tognetti, Pedro M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA); Argentina.Fil: Tognetti, Pedro M. Swiss Federal Institute for Forest, Snow and Landscape Research WSL; SuizaFil: Yasui, Simone-Louise E. Queensland University of Technology. School of Biological and Environmental Sciences; Australia.Fil: Virtanen, Risto. University of Oulu. Ecology & Genetics; FinlandiaFil: Sullivan, Lauren L. University of Missouri. Division of Biological Sciences; Estados UnidosFil: Sullivan, Lauren L. Michigan State University. Department of Plant Biology; Estados UnidosFil: Sullivan, Lauren L. Michigan State University. W. K. Kellogg Biological Station; Estados UnidosFil: Sullivan, Lauren L. Michigan State University. Ecology, Evolution and Behavior Program; Estados Unido

Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is caused when defects of motile cilia lead to chronic airway infections, male infertility, and situs abnormalities. Multiple causative PCD mutations account for only 65% of cases, suggesting that many genes essential for cilia function remain to be discovered. By using zebrafish morpholino knockdown of PCD candidate genes as an in vivo screening platform, we identified c21orf59, ccdc65, and c15orf26 as critical for cilia motility. c21orf59 and c15orf26 knockdown in zebrafish and planaria blocked outer dynein arm assembly, and ccdc65 knockdown altered cilia beat pattern. Biochemical analysis in Chlamydomonas revealed that the C21orf59 ortholog FBB18 is a flagellar matrix protein that accumulates specifically when cilia motility is impaired. The Chlamydomonas ida6 mutant identifies CCDC65/FAP250 as an essential component of the nexin-dynein regulatory complex. Analysis of 295 individuals with PCD identified recessive truncating mutations of C21orf59 in four families and CCDC65 in two families. Similar to findings in zebrafish and planaria, mutations in C21orf59 caused loss of both outer and inner dynein arm components. Our results characterize two genes associated with PCD-causing mutations and elucidate two distinct mechanisms critical for motile cilia function: dynein arm assembly for C21orf59 and assembly of the nexin-dynein regulatory complex for CCDC65

Assessing socioeconomic health care utilization inequity in Israel: impact of alternative approaches to morbidity adjustment

<p/> <p>Background</p> <p>The ability to accurately detect differential resource use between persons of different socioeconomic status relies on the accuracy of health-needs adjustment measures. This study tests different approaches to morbidity adjustment in explanation of health care utilization inequity.</p> <p>Methods</p> <p>A representative sample was selected of 10 percent (~270,000) adult enrolees of Clalit Health Services, Israel's largest health care organization. The Johns-Hopkins University Adjusted Clinical Groups^®were used to assess each person's overall morbidity burden based on one year's (2009) diagnostic information. The odds of above average health care resource use (primary care visits, specialty visits, diagnostic tests, or hospitalizations) were tested using multivariate logistic regression models, separately adjusting for levels of health-need using data on age and gender, comorbidity (using the Charlson Comorbidity Index), or morbidity burden (using the Adjusted Clinical Groups). Model fit was assessed using tests of the Area Under the Receiver Operating Characteristics Curve and the Akaike Information Criteria.</p> <p>Results</p> <p>Low socioeconomic status was associated with higher morbidity burden (1.5-fold difference). Adjusting for health needs using age and gender or the Charlson index, persons of low socioeconomic status had greater odds of above average resource use for all types of services examined (primary care and specialist visits, diagnostic tests, or hospitalizations). In contrast, after adjustment for overall morbidity burden (using Adjusted Clinical Groups), low socioeconomic status was no longer associated with greater odds of specialty care or diagnostic tests (OR: 0.95, CI: 0.94-0.99; and OR: 0.91, CI: 0.86-0.96, for specialty visits and diagnostic respectively). Tests of model fit showed that adjustment using the comprehensive morbidity burden measure provided a better fit than age and gender or the Charlson Index.</p> <p>Conclusions</p> <p>Identification of socioeconomic differences in health care utilization is an important step in disparity reduction efforts. Adjustment for health-needs using a comprehensive morbidity burden diagnoses-based measure, this study showed relative underutilization in use of specialist and diagnostic services, and thus allowed for identification of inequity in health resources use, which could not be detected with less comprehensive forms of health-needs adjustments.</p

ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function

IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy phenotype

Background: Bidirectional intraflagellar transport (IFT) consists of two major protein complexes, IFT-A and IFT-B. In contrast to the IFT-B complex, all components of IFT-A have recently been linked to human ciliopathies when defective. We therefore hypothesised that mutations in additional IFT-B encoding genes can be found in patients with multisystemic ciliopathies. Methods: We screened 1628 individuals with reno-ocular ciliopathies by targeted next-generation sequencing of ciliary candidate genes, including all IFT-B encoding genes. Results: Consequently, we identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. Further, we detected a loss-of-stop mutation with extension of the deduced protein by 10 amino acids in an individual with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy and brain lesions including cerebellar atrophy, a phenotype to which the IFT81 variant might contribute. Cultured fibroblasts of this latter affected individual showed a significant decrease in ciliated cell abundance compared with controls and increased expression of the transcription factor GLI2 suggesting deranged sonic hedgehog signalling. Conclusions: This work describes identification of mutations of IFT81 in individuals with symptoms consistent with the clinical spectrum of ciliopathies. It might represent the rare case of a core IFT-B complex protein found associated with human disease. Our data further suggest that defects in the IFT-B core are an exceedingly rare finding, probably due to its indispensable role for ciliary assembly in development

Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease

Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or ‘primary’ cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in mice demonstrated that this allele is likely pathogenic

Mutations in SPAG1 Cause Primary Ciliary Dyskinesia Associated with Defective Outer and Inner Dynein Arms

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 20 genes, but collectively they account for only ∼65% of all PCDs. To identify mutations in additional genes that cause PCD, we performed exome sequencing on three unrelated probands with ciliary outer and inner dynein arm (ODA+IDA) defects. Mutations in SPAG1 were identified in one family with three affected siblings. Further screening of SPAG1 in 98 unrelated affected individuals (62 with ODA+IDA defects, 35 with ODA defects, 1 without available ciliary ultrastructure) revealed biallelic loss-of-function mutations in 11 additional individuals (including one sib-pair). All 14 affected individuals with SPAG1 mutations had a characteristic PCD phenotype, including 8 with situs abnormalities. Additionally, all individuals with mutations who had defined ciliary ultrastructure had ODA+IDA defects. SPAG1 was present in human airway epithelial cell lysates but was not present in isolated axonemes, and immunofluorescence staining showed an absence of ODA and IDA proteins in cilia from an affected individual, thus indicating that SPAG1 probably plays a role in the cytoplasmic assembly and/or trafficking of the axonemal dynein arms. Zebrafish morpholino studies of spag1 produced cilia-related phenotypes previously reported for PCD-causing mutations in genes encoding cytoplasmic proteins. Together, these results demonstrate that mutations in SPAG1 cause PCD with ciliary ODA+IDA defects and that exome sequencing is useful to identify genetic causes of heterogeneous recessive disorders

Genes, Education, and Labor Market Outcomes: Evidence from the Health and Retirement Study

Recent advances have led to the discovery of specific genetic variants that predict educational attainment. We study how these variants, summarized as a genetic score variable, are associated with human capital accumulation and labor market outcomes in the Health and Retirement Study (HRS). We demonstrate that the same genetic score that predicts education is also associated with higher wages, but only among individuals with a college education. Moreover, the genetic gradient in wages has grown in more recent birth cohorts, consistent with interactions between technological change and labor market ability. We also show that individuals who grew up in economically disadvantaged households are less likely to go to college when compared to individuals with the same genetic score, but from higher socioeconomic status households. Our findings provide support for the idea that childhood socioeconomic status is an important moderator of the economic returns to genetic endowments. Moreover, the finding that childhood poverty limits the educational attainment of high-ability individuals suggests the existence of unrealized human potential

ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function