Showing papers by "Tulane University published in 2012"
TL;DR: Burnout is more common among physicians than among other US workers, and Physicians in specialties at the front line of care access seem to be at greatest risk.
Abstract: Methods: We conducted a national study of burnout in a large sample of US physicians from all specialty disciplines using the American Medical Association Physician Masterfile and surveyed a probability-based sample of the general US population for comparison. Burnout was measured using validated instruments. Satisfaction with work-life balance was explored. Results: Of 27276 physicians who received an invitation to participate, 7288 (26.7%) completed surveys. When assessed using the Maslach Burnout Inventory, 45.8%ofphysiciansreportedatleast1symptomofburnout. Substantial differences in burnout were observed by specialty, with the highest rates among physicians at the front line of care access (family medicine, general internalmedicine,andemergencymedicine).Comparedwith a probability-based sample of 3442 working US adults, physicians were more likely to have symptoms of burnout (37.9% vs 27.8%) and to be dissatisfied with worklife balance (40.2% vs 23.2%) (P.001 for both). Highest level of education completed also related to burnout in a pooled multivariate analysis adjusted for age, sex, relationship status, and hours worked per week. Comparedwithhighschoolgraduates,individualswithanMD or DO degree were at increased risk for burnout (odds ratio [OR], 1.36; P.001), whereas individuals with a bachelor’sdegree(OR,0.80;P=.048),master’sdegree(OR, 0.71;P=.01),orprofessionalordoctoraldegreeotherthan an MD or DO degree (OR, 0.64; P=.04) were at lower risk for burnout. Conclusions: Burnout is more common among physicians than among other US workers. Physicians in specialties at the front line of care access seem to be at greatest risk.
2,546 citations
TL;DR: Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo, providing evidence against the use of this combination in such patients.
Abstract: Background A combination of prednisone, azathioprine, and N-acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety and efficacy of this three-drug regimen is unknown. Methods In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups — receiving a combination of prednisone, azathioprine, and NAC (combination therapy), NAC alone, or placebo — in a 1:1:1 ratio. The primary outcome was the change in longitudinal measurements of forced vital capacity during a 60-week treatment period. Results When approximately 50% of data had been collected (with 77 patients in the combination-therapy group and 78 in the placebo group), a planned interim analysis revealed that patients in the combination-therapy group, as compared with the placebo group, had an increased rate of death (8 vs. 1, P = 0.01) and hospitalization (23 vs. 7, P<0.001). These observations, coupled with no evidence of physiological or clinical benefit for combination therapy, prompted the independent data and safety monitoring board to recommend termination of the combination-therapy group at a mean follow-up of 32 weeks. Data from the ongoing comparison of the NAC-only group and the placebo group are not reported here. Conclusions Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo. These findings provide evidence against the use of this combination in such patients. (Funded by the National Heart, Lung, and Blood Institute and the Cowlin Family Fund; ClinicalTrials.gov number, NCT00650091.)
1,280 citations
TL;DR: The authors synthesize the expanding corporate social responsibility (CSR) literature from an economic perspective and develop a CSR taxonomy that connects disparate approaches to the subject and explore whether CSR should exist and investigate conditions when CSR may produce higher welfare than other public good provision channels.
Abstract: *This paper synthesizes the expanding corporate social responsibility (CSR) literature. We define CSR from an economic perspective and develop a CSR taxonomy that connects disparate approaches to the subject. We explore whether CSR should exist and investigate conditions when CSR may produce higher welfare than other public good provision channels. We also explore why CSR does exist. Here, we integrate theoretical predictions with empirical findings from economic and noneconomic sources. We find limited systematic empirical evidence in favor of CSR mechanisms related to induced innovation, moral hazard, shareholder preferences, or labor markets. In contrast, we uncover consistent empirical evidence in favor of CSR mechanisms related to consumer markets, private politics, and public politics. (JEL D21, L21, M14)
842 citations
TL;DR: This article investigated boundary conditions for the IKEA effect and found that labor leads to love only when labor results in successful completion of tasks; when participants built and then destroyed their creations, or failed to complete them, the effect dissipated.
555 citations
Goethe University Frankfurt1, Tufts University2, Erasmus University Rotterdam3, University of Tromsø4, University of Eastern Finland5, Ludwig Maximilian University of Munich6, French Institute of Health and Medical Research7, University of Milan8, University of Edinburgh9, University of Miami10, EHESP11, Columbia University12, Uppsala University13, University of Gothenburg14, Tulane University15, University of Cambridge16, Utrecht University17
TL;DR: The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven and no conclusion can be derived for the use of c IMT progression as a surrogate in clinical trials.
538 citations
TL;DR: In this article, the authors assess what we have learned about tax evasion since Michael Allingham and Agnar Sandmo launched the modern analysis of tax evasion in 1972 and conclude that we still have many gaps in our understanding of how to measure, explain, and control tax evasion.
Abstract: In this paper, I assess what we have learned about tax evasion since Michael Allingham and Agnar Sandmo launched the modern analysis of tax evasion in 1972. I focus on three specific questions and the answers to these questions that have emerged over the years. First, how do we measure the extent of evasion? Second, how can we explain these patterns of behavior? Third, how can we use these insights to control evasion? In the process, I illustrate my own answers to these questions by highlighting various specific examples of research. My main conclusion is that we have learned many things but that we also still have many gaps in our understanding of how to measure, explain, and control tax evasion. I also give some suggestions—and some predictions—about where promising avenues of future research may lie.
456 citations
TL;DR: This review serves as an excellent literature reference for those working on protein fusion tags and provides summaries of well‐characterized purification strategies that have been used to increase product yields and have widespread application in many areas of biotechnology including drug discovery, therapeutics, and pharmacology.
Abstract: Protein fusion tags are indispensible tools used to improve recombinant protein expression yields, enable protein purification, and accelerate the characterization of protein structure and function. Solubility-enhancing tags, genetically engineered epitopes, and recombinant endoproteases have resulted in a versatile array of combinatorial elements that facilitate protein detection and purification in microbial hosts. In this comprehensive review, we evaluate the most frequently used solubility-enhancing and affinity tags. Furthermore, we provide summaries of well-characterized purification strategies that have been used to increase product yields and have widespread application in many areas of biotechnology including drug discovery, therapeutics, and pharmacology. This review serves as an excellent literature reference for those working on protein fusion tags.
408 citations
TL;DR: A detailed review of selected observational studies and a meta-analysis documents substantial methodological concerns that limit the usefulness of these studies in setting, much less reversing, dietary recommendations.
Abstract: Recent reports of selected observational studies and a meta-analysis have stirred controversy and have become the impetus for calls to abandon recommendations for reduced sodium intake by the US general population. A detailed review of these studies documents substantial methodological concerns that limit the usefulness of these studies in setting, much less reversing, dietary recommendations. Indeed, the evidence base supporting recommendations for reduced sodium intake in the general population remains robust and persuasive. The American Heart Association is committed to improving the health of all Americans through implementation of national goals for health promotion and disease prevention, including its recommendation to reduce dietary sodium intake to <1500 mg/d.
406 citations
Mayo Clinic1, University of Cincinnati2, Cleveland Clinic3, American Academy of Dermatology4, University of California, San Francisco5, Harvard University6, Yale University7, Oregon Health & Science University8, University of Miami9, University of Connecticut10, Saint Vincent Hospital11, University of Pennsylvania12, University of South Florida13, Tulane University14, Georgetown University15
TL;DR: The appropriate use criteria process synthesizes evidence-based medicine, clinical practice experience, and expert judgment to optimize the use of MMS for scenarios in which the expected clinical benefit is anticipated to be the greatest.
Abstract: The appropriate use criteria process synthesizes evidence-based medicine, clinical practice experience, and expert judgment. The American Academy of Dermatology in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery has developed appropriate use criteria for 270 scenarios for which Mohs micrographic surgery (MMS) is frequently considered based on tumor and patient characteristics. This document reflects the rating of appropriateness of MMS for each of these clinical scenarios by a ratings panel in a process based on the appropriateness method developed by the RAND Corp (Santa Monica, CA)/University of California–Los Angeles (RAND/UCLA). At the conclusion of the rating process, consensus was reached for all 270 (100%) scenarios by the Ratings Panel, with 200 (74.07%) deemed as appropriate, 24 (8.89%) as uncertain, and 46 (17.04%) as inappropriate. For the 69 basal cell carcinoma scenarios, 53 were deemed appropriate, 6 uncertain, and 10 inappropriate. For the 143 squamous cell carcinoma scenarios, 102 were deemed appropriate, 7 uncertain, and 34 inappropriate. For the 12 lentigo maligna and melanoma in situ scenarios, 10 were deemed appropriate, 2 uncertain, and 0 inappropriate. For the 46 rare cutaneous malignancies scenarios, 35 were deemed appropriate, 9 uncertain, and 2 inappropriate. These appropriate use criteria have the potential to impact health care delivery, reimbursement policy, and physician decision making on patient selection for MMS, and aim to optimize the use of MMS for scenarios in which the expected clinical benefit is anticipated to be the greatest. In addition, recognition of those scenarios rated as uncertain facilitates an understanding of areas that would benefit from further research. Each clinical scenario identified in this document is crafted for the average patient and not the exception. Thus, the ultimate decision regarding the appropriateness of MMS should be determined by the expertise and clinical experience of the physician.
398 citations
Vanderbilt University1, Hallym University2, Agency for Science, Technology and Research3, Imperial College London4, Harvard University5, China Medical University (Taiwan)6, Academia Sinica7, University of Tokyo8, Ehime University9, Peking Union Medical College10, Shanghai Jiao Tong University11, University of Southern California12, Guangxi Medical University13, National University of Singapore14, Southeast University15, Tulane University16, University of Hawaii17, University of Melbourne18, Singapore National Eye Center19, Kyushu University20, Wake Forest University21, Centers for Disease Control and Prevention22, Aichi Gakuin University23, University of California, San Francisco24
TL;DR: A meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians and three additional loci nearly reached the genome-wide significance threshold may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.
Abstract: Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry We performed a meta-analysis of associations between BMI and approximately 24 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively We identified ten BMI-associated loci at genome-wide significance (P < 50 × 10(-8)), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 50 × 10(-7) Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations
374 citations
TL;DR: The increase inwhite matter among children randomized to an improved rearing environment relative to children who remained in institutional care suggests the potential for developmental “catch up” in white matter growth, even following extreme environmental deprivation.
Abstract: We used structural MRI and EEG to examine brain structure and function in typically developing children in Romania (n = 20), children exposed to institutional rearing (n = 29), and children previously exposed to institutional rearing but then randomized to a high-quality foster care intervention (n = 25). In so doing, we provide a unique evaluation of whether placement in an improved environment mitigates the effects of institutional rearing on neural structure, using data from the only existing randomized controlled trial of foster care for institutionalized children. Children enrolled in the Bucharest Early Intervention Project underwent a T1-weighted MRI protocol. Children with histories of institutional rearing had significantly smaller cortical gray matter volume than never-institutionalized children. Cortical white matter was no different for children placed in foster care than never-institutionalized children but was significantly smaller for children not randomized to foster care. We were also able to explain previously reported reductions in EEG α-power among institutionally reared children compared with children raised in families using these MRI data. As hypothesized, the association between institutionalization and EEG α-power was partially mediated by cortical white matter volume for children not randomized to foster care. The increase in white matter among children randomized to an improved rearing environment relative to children who remained in institutional care suggests the potential for developmental “catch up” in white matter growth, even following extreme environmental deprivation.
TL;DR: Evidence-based psychosocial support interventions for AYAs with cancer and other life-threatening or chronic diseases are reviewed, particularly the positive effects of peer support, technology-based interventions, and skill- based interventions.
Abstract: The delivery of quality care for adolescent and young adult (AYA) patients with cancer and survivors requires an understanding of the unique qualities of this group—the shared norms, attitudes, and beliefs that determine their behavior as well as the unique stresses they face on a day-to-day basis. All AYAs have typical concerns about being comfortable with who they are and who they want to become (identity development, including sexual identity), their bodies (body image), initiating intimate and emotional relationships, separating from parents, and making independent decisions about future goals such as career, higher education, and/or family (autonomy). Yet efforts of AYA patients with cancer and survivors to mature are often confounded by restrictions and limitations placed on them by their disease and treatment. This article promotes understanding of psychosocial challenges faced by AYAs when diagnosed with and treated for cancer. It reviews evidence-based psychosocial support interventions for AYAs with cancer and other life-threatening or chronic diseases, particularly the positive effects of peer support, technology-based interventions, and skill-based interventions. The article concludes with recommendations for clinical care that are intended to promote the ability of AYAs to cope with cancer. J Clin Oncol 30:1221-1226. © 2012 by American Society of Clinical Oncology
TL;DR: Adult (age 30) educational, economic, and social-emotional adjustment outcomes were investigated for participants in the Abecedarian Project, a randomized controlled trial of early childhood education for children from low-income families, providing strong evidence for educational benefits, mixed evidence for economic benefits, and little evidence for treatment-related social adjustment outcomes.
Abstract: Adult (age 30) educational, economic, and social–emotional adjustment outcomes were investigated for participants in the Abecedarian Project, a randomized controlled trial of early childhood education for children from low-income families. Of the original 111 infants enrolled (98% African American), 101 took part in the age 30 follow-up. Primary indicators of educational level, economic status, and social adjustment were examined as a function of early childhood treatment. Treated individuals attained significantly more years of education, but income-to-needs ratios and criminal involvement did not vary significantly as a function of early treatment. A number of other indicators were described for each domain. Overall, the findings provide strong evidence for educational benefits, mixed evidence for economic benefits, and little evidence for treatment-related social adjustment outcomes. Implications for public policy are discussed.
TL;DR: Banerjee and Dufloated as mentioned in this paper, "Poor Economics: A Radical Rethinking of the Way to Fight Global Poverty", by Abhijit Banerjee, and Esther Duflo.
Abstract: Poor Economics: A Radical Rethinking of the Way to Fight Global Poverty, by Abhijit Banerjee and Esther Duflo. Jackson, TN: PublicAffairs, 2011. 320 pp. ISBN: 978-1-58648-798-0 (hbk.). US$26.99. Po...
TL;DR: Clinicians can influence a large number of patients through brief interventions that promote physical activity, and encouragement toward participation in sport for some physically inactive patients qualifies as evidence-based therapy.
TL;DR: It is suggested that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors and could be recommended to obese persons with abnormal metabolicrisk factors for the purpose of weight loss.
Abstract: The effects of low-carbohydrate diets (≤45% of energy from carbohydrates) versus low-fat diets (≤30% of energy from fat) on metabolic risk factors were compared in a meta-analysis of randomized controlled trials Twenty-three trials from multiple countries with a total of 2,788 participants met the predetermined eligibility criteria (from January 1, 1966 to June 20, 2011) and were included in the analyses Data abstraction was conducted in duplicate by independent investigators Both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (27 mg/dL; 95% confidence interval: 08, 46), and low density lipoprotein cholesterol (37 mg/dL; 95% confidence interval: 10, 64), but a greater increase in high density lipoprotein cholesterol (33 mg/dL; 95% confidence interval: 19, 47) and a greater decrease in triglycerides (−140 mg/dL; 95% confidence interval: −194, −87) Reductions in body weight, waist circumference and other metabolic risk factors were not significantly different between the 2 diets These findings suggest that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors Low-carbohydrate diets could be recommended to obese persons with abnormal metabolic risk factors for the purpose of weight loss Studies demonstrating long-term effects of low-carbohydrate diets on cardiovascular events were warranted
TL;DR: Wang et al. as mentioned in this paper examined the trends in body mass index (BMI), waist circumference (WC) and prevalence of overweight, general obesity and abdominal obesity among Chinese adults from 1993 to 2009.
Abstract: The objective of this study is to examine the trends in body mass index (BMI), waist circumference (WC) and prevalence of overweight (BMI 25-27.49 kg m(-2) ), general obesity (BMI ≥ 27.5 kg m(-2) ) and abdominal obesity (WC ≥ 90 cm for men and ≥80 cm for women) among Chinese adults from 1993 to 2009. Data were obtained from the China Health and Nutrition Survey, which was conducted from 1993 to 2009 and included a total of 52,621 Chinese adults. During the period of 1993-2009, mean BMI values increased by 1.6 kg m(-2) among men and 0.8 kg m(-2) among women; mean WC values increased by 7.0 cm among men and 4.7 cm among women. The prevalence of overweight increased from 8.0 to 17.1% among men (P < 0.001) and from 10.7 to 14.4% among women (P < 0.001); the prevalence of general obesity increased from 2.9 to 11.4% among men (P < 0.001) and from 5.0 to 10.1% among women (P < 0.001); the prevalence of abdominal obesity increased from 8.5 to 27.8% among men (P < 0.001) and from 27.8 to 45.9% among women (P < 0.001). Similar significant trends were observed in nearly all age groups and regions for both men and women. The prevalence of overweight, general obesity and abdominal obesity among Chinese adults has increased greatly during the past 17 years.
TL;DR: This work evaluates established and novel approaches to uncover the molecular substrates, genetic pathways and neural circuits of anxiety using adult zebrafish, and provides a conceptual framework for the wider application of zebra fish and other aquatic models in anxiety research.
TL;DR: The Gini coefficient in 13 of 17 Latin American countries between 2000 and 2010, the decline was statistically significant and robust to changes in the time interval, inequality measures, and data sources as mentioned in this paper.
Abstract: Between 2000 and 2010, the Gini coefficient declined in 13 of 17 Latin American countries. The decline was statistically significant and robust to changes in the time interval, inequality measures, and data sources. In-depth country studies for Argentina, Brazil, and Mexico suggest two main phenomena underlie this trend: a fall in the premium to skilled labor and more progressive government transfers. The fall in the premium to skills resulted from a combination of supply, demand, and institutional factors. Their relative importance depends on the country.
TL;DR: This is the first study to demonstrate an association between telomere length and institutionalization, the first association between adversity and telomerre length in children, and contributes to the growing literature linking telomeres length and early adversity.
Abstract: Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity.
TL;DR: Overall, the current level of information indicates that endocannabinoid signaling acts to suppress HPA axis activity through concerted actions within the prefrontal cortex, amygdala, and hypothalamus.
TL;DR: It is found that humidity, like temperature, is an important determinant of mortality, and distributional impacts matter: mortality rates are likely to decline in cold and dry areas, but increase in hot and humid areas.
TL;DR: A meta-analysis of genome-wide association studies for kidney function–related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN), identified 17 loci newly associated with kidney function-related traits.
Abstract: Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.
TL;DR: Curcumin-loaded γ-cyclodextrin liposomes were demonstrated in vitro to have significant potential as delivery vehicles for the treatment of cancers of mesenchymal and epithelial origin and differences between mechanisms of cell death were evaluated.
TL;DR: The findings provide a better understanding of the mechanism(s) involved in stem cell aging and regenerative potential, and this in turn may affect tissue repair that declines with aging.
TL;DR: Respondent-driven sampling should be regarded as a (potentially superior) form of convenience sampling method, and caution is required when interpreting findings based on the sampling method.
Abstract: BACKGROUND: Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total population data. METHODS: Total population data on age, tribe, religion, socioeconomic status, sexual activity, and HIV status were available on a population of 2402 male household heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, using current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample). RESULTS: We recruited 927 household heads. Full and small RDS samples were largely representative of the total population, but both samples underrepresented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven sampling statistical inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven sampling bootstrap 95% confidence intervals included the population proportion. CONCLUSIONS: Respondent-driven sampling produced a generally representative sample of this well-connected nonhidden population. However, current respondent-driven sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience sampling method, and caution is required when interpreting findings based on the sampling method.
TL;DR: The Gini coefficient in 13 of 17 Latin American countries between 2000 and 2010, the decline was statistically significant and robust to changes in the time interval, inequality measures, and data sources as discussed by the authors.
TL;DR: Findings underline the importance of metagenomic analysis of the virome for understanding AIDS pathogenesis and identify at least 32 previously undescribed enteric viruses during pathogenic SIV infection.
TL;DR: The use of red blood cell (RBC) agglutination for separating plasma from finger-prick volumes of whole blood directly in paper is described and the utility of this approach by integrating plasma separation and a colorimetric assay in a single μPAD is demonstrated.
Abstract: Many diagnostic tests in a conventional clinical laboratory are performed on blood plasma because changes in its composition often reflect the current status of pathological processes throughout the body. Recently, a significant research effort has been invested into the development of microfluidic paper-based analytical devices (μPADs) implementing these conventional laboratory tests for point-of-care diagnostics in resource-limited settings. This paper describes the use of red blood cell (RBC) agglutination for separating plasma from finger-prick volumes of whole blood directly in paper, and demonstrates the utility of this approach by integrating plasma separation and a colorimetric assay in a single μPAD. The μPAD was fabricated by printing its pattern onto chromatography paper with a solid ink (wax) printer and melting the ink to create hydrophobic barriers spanning through the entire thickness of the paper substrate. The μPAD was functionalized by spotting agglutinating antibodies onto the plasma separation zone in the center and the reagents of the colorimetric assay onto the test readout zones on the periphery of the device. To operate the μPAD, a drop of whole blood was placed directly onto the plasma separation zone of the device. RBCs in the whole blood sample agglutinated and remained in the central zone, while separated plasma wicked through the paper substrate into the test readout zones where analyte in plasma reacted with the reagents of the colorimetric assay to produce a visible color change. The color change was digitized with a portable scanner and converted to concentration values using a calibration curve. The purity and yield of separated plasma was sufficient for successful operation of the μPAD. This approach to plasma separation based on RBC agglutination will be particularly useful for designing fully integrated μPADs operating directly on small samples of whole blood.
TL;DR: It is found that all microsporidia lost the tumor-suppressor gene retinoblastoma and transporters that could import nucleosides to fuel rapid growth, and analysis of genome polymorphisms revealed evidence for a sexual cycle that may provide genetic diversity to alleviate problems caused by clonal growth.
Abstract: Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungal-related parasites responsible for widespread disease, and here we address questions about microsporidia biology and evolution. We sequenced three microsporidian genomes from two species, Nematocida parisii and Nematocida sp1, which are natural pathogens of Caenorhabditis nematodes and provide model systems for studying microsporidian pathogenesis. We performed deep sequencing of transcripts from a time course of N. parisii infection. Examination of pathogen gene expression revealed compact transcripts and a dramatic takeover of host cells by Nematocida. We also performed phylogenomic analyses of Nematocida and other microsporidian genomes to refine microsporidian phylogeny and identify evolutionary events of gene loss, acquisition, and modification. In particular, we found that all microsporidia lost the tumor-suppressor gene retinoblastoma, which we speculate could accelerate the parasite cell cycle and increase the mutation rate. We also found that microsporidia acquired transporters that could import nucleosides to fuel rapid growth. In addition, microsporidian hexokinases gained secretion signal sequences, and in a functional assay these were sufficient to export proteins out of the cell; thus hexokinase may be targeted into the host cell to reprogram it toward biosynthesis. Similar molecular changes appear during formation of cancer cells and may be evolutionary strategies adopted independently by microsporidia to proliferate rapidly within host cells. Finally, analysis of genome polymorphisms revealed evidence for a sexual cycle that may provide genetic diversity to alleviate problems caused by clonal growth. Together these events may explain the emergence and success of these diverse intracellular parasites.