Showing papers by "Tulane University published in 2015"
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
12,661 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.
5,792 citations
Case Western Reserve University1, Wake Forest University2, Tulane University3, National Institutes of Health4, United States Department of Veterans Affairs5, University of Alabama at Birmingham6, University of Tennessee Health Science Center7, University of Colorado Boulder8, Veterans Health Administration9, University of Utah10
TL;DR: In this article, the most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain, and the authors propose a target of less than 120 mm Hg.
Abstract: BACKGROUND The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. METHODS We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group. CONCLUSIONS Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).
4,125 citations
University of Oxford1, University of Basel2, Swiss Tropical and Public Health Institute3, University of California, San Francisco4, Tulane University5, Imperial College London6, World Health Organization7, University of Bath8, Institute for Health Metrics and Evaluation9, Wellcome Trust Centre for Human Genetics10, National Institutes of Health11
TL;DR: It is found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015, and interventions have averted 663 (542–753 credible interval) million clinical cases since 2000.
Abstract: Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.
2,135 citations
Tulane University1, Colorado State University2, University of Tübingen3, Applied Science Private University4, Université de Montréal5, United Arab Emirates University6, Rush University Medical Center7, Baylor College of Medicine8, Mount Sinai St. Luke's and Mount Sinai Roosevelt9, Nara Medical University10, National Technical University of Athens11, University of Illinois at Urbana–Champaign12, Creighton University13, Shanmugha Arts, Science, Technology & Research Academy14, University of Rome Tor Vergata15, Purdue University16, Wayne State University17, University of Glasgow18, New York Medical College19, Mayo Clinic20
TL;DR: The advances made toward understanding the basis of cancer immune evasion are discussed, the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection are summarized and some natural agents and phytochemicals merit further study.
1,064 citations
Emory University1, DePaul University2, University of Miami3, Baylor College of Medicine4, Pennsylvania State University5, University of California, Irvine6, Duke University7, University of Colorado Denver8, Medical University of South Carolina9, University of Oklahoma10, University of Texas Southwestern Medical Center11, University of Illinois at Chicago12, Tulane University13, University of California, San Francisco14, Icahn School of Medicine at Mount Sinai15, Harvard University16, Virginia Commonwealth University17, University of Pennsylvania18, Rush University Medical Center19, Oregon Health & Science University20
TL;DR: This document represents a continuation of the National Lipid Association recommendations developed by a diverse panel of experts who examined the evidence base and provided recommendations regarding the following topics: lifestyle therapies and strategies to improve patient outcomes by increasing adherence and using team-based collaborative care.
690 citations
TL;DR: The global prevalence and absolute burden of CKD in 2010 was estimated by pooling data from population-based studies by searching MEDLINE (January 1990 to December 2014), International Society of Nephrology Global Outreach Program funded projects, and bibliographies of retrieved articles and selected 33 studies reporting gender- and age-specific prevalence in representative population samples.
582 citations
TL;DR: The current understanding of how ribosomal stress provokes the accumulation of ribosome-free Ribosomal proteins, as well as the ribosomesome-independent functions of ribOSomal proteins in tumorigenesis, immune signaling, and development are overviewed.
Abstract: Although ribosomal proteins are known for playing an essential role in ribosome assembly and protein translation, their ribosome-independent functions have also been greatly appreciated. Over the past decade, more than a dozen of ribosomal proteins have been found to activate the tumor suppressor p53 pathway in response to ribosomal stress. In addition, these ribosomal proteins are involved in various physiological and pathological processes. This review is composed to overview the current understanding of how ribosomal stress provokes the accumulation of ribosome-free ribosomal proteins, as well as the ribosome-independent functions of ribosomal proteins in tumorigenesis, immune signaling, and development. We also propose the potential of applying these pieces of knowledge to the development of ribosomal stress-based cancer therapeutics.
484 citations
Sewanee: The University of the South1, Academy of Sciences of the Czech Republic2, University of Nevada, Reno3, University of Papua New Guinea4, Smithsonian Tropical Research Institute5, University of Utah6, Griffith University7, University of Brasília8, University of Ostrava9, Tulane University10, University of Oxford11, George Washington University12, University of Missouri–St. Louis13, American Museum of Natural History14, Chiba University15, University of Göttingen16, Wesleyan University17, Wright State University18, University of Connecticut19, Colorado Mesa University20, University of Minnesota21
TL;DR: A global dataset is used to investigate host range for over 7,500 insect herbivore species covering a wide taxonomic breadth and interacting with more than 2,000 species of plants in 165 families to ask whether relatively specialized and generalized herbivores represent a dichotomy rather than a continuum from few to many host families and species attacked and whether diet breadth changes with increasing plant species richness toward the tropics.
Abstract: Understanding variation in resource specialization is important for progress on issues that include coevolution, community assembly, ecosystem processes, and the latitudinal gradient of species richness. Herbivorous insects are useful models for studying resource specialization, and the interaction between plants and herbivorous insects is one of the most common and consequential ecological associations on the planet. However, uncertainty persists regarding fundamental features of herbivore diet breadth, including its relationship to latitude and plant species richness. Here, we use a global dataset to investigate host range for over 7,500 insect herbivore species covering a wide taxonomic breadth and interacting with more than 2,000 species of plants in 165 families. We ask whether relatively specialized and generalized herbivores represent a dichotomy rather than a continuum from few to many host families and species attacked and whether diet breadth changes with increasing plant species richness toward the tropics. Across geographic regions and taxonomic subsets of the data, we find that the distribution of diet breadth is fit well by a discrete, truncated Pareto power law characterized by the predominance of specialized herbivores and a long, thin tail of more generalized species. Both the taxonomic and phylogenetic distributions of diet breadth shift globally with latitude, consistent with a higher frequency of specialized insects in tropical regions. We also find that more diverse lineages of plants support assemblages of relatively more specialized herbivores and that the global distribution of plant diversity contributes to but does not fully explain the latitudinal gradient in insect herbivore specialization.
457 citations
TL;DR: This trial failed to identify a large advantage for robot-assisted techniques over standard open surgery for patients undergoing radical cystectomy, pelvic lymph node dissection, and urinary diversion and found no significant difference between the two groups.
444 citations
TL;DR: Together, the role of genetic sex, the programming effect of testosterone in the prenatal period in males, and the activational role of sex hormones at puberty produce two different biological systems in males and females that need to be studied separately.
Abstract: There are fundamental aspects of the control of metabolic homeostasis that are regulated differently in males and females. This sex asymmetry represents an evolutionary paradigm for females to resist the loss of energy stores. This perspective discusses the most fundamental sex differences in metabolic homeostasis, diabetes, and obesity. Together, the role of genetic sex, the programming effect of testosterone in the prenatal period in males, and the activational role of sex hormones at puberty produce two different biological systems in males and females that need to be studied separately. These sex-specific differences in energy homeostasis and metabolic dysfunction represent an untested source of factors that can be harnessed to develop relevant sex-based therapeutic avenues for diabetes, metabolic syndrome, and obesity.
Donka Hospital1, University of Liverpool2, University of Washington3, Pasteur Institute4, University of North Carolina at Chapel Hill5, Université de Sherbrooke6, Naval Medical Research Unit Six7, Tulane University8, Médecins Sans Frontières9, University of Nebraska Medical Center10, World Health Organization11, Central Manchester University Hospitals NHS Foundation Trust12, University of Toronto13
TL;DR: Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea, and despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.
Abstract: BackgroundIn March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. MethodsFrom March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. ResultsOf 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after t...
TL;DR: Intervention effects were evident for cortisol and parasympathetic nervous system reactivity only among children placed in foster care before age 24 and 18 months, respectively, providing experimental evidence of a sensitive period in humans during which the environment is particularly likely to alter stress response system development.
Abstract: Disruptions in stress response system functioning are thought to be a central mechanism by which exposure to adverse early-life environments influences human development. Although early-life adversity results in hyperreactivity of the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis in rodents, evidence from human studies is inconsistent. We present results from the Bucharest Early Intervention Project examining whether randomized placement into a family caregiving environment alters development of the autonomic nervous system and HPA axis in children exposed to early-life deprivation associated with institutional rearing. Electrocardiogram, impedance cardiograph, and neuroendocrine data were collected during laboratory-based challenge tasks from children (mean age = 12.9 y) raised in deprived institutional settings in Romania randomized to a high-quality foster care intervention (n = 48) or to remain in care as usual (n = 43) and a sample of typically developing Romanian children (n = 47). Children who remained in institutional care exhibited significantly blunted SNS and HPA axis responses to psychosocial stress compared with children randomized to foster care, whose stress responses approximated those of typically developing children. Intervention effects were evident for cortisol and parasympathetic nervous system reactivity only among children placed in foster care before age 24 and 18 months, respectively, providing experimental evidence of a sensitive period in humans during which the environment is particularly likely to alter stress response system development. We provide evidence for a causal link between the early caregiving environment and stress response system reactivity in humans with effects that differ markedly from those observed in rodent models.
TL;DR: Several obstacles blocking the mainstream use of stromal cells to enhance skeletal repair are identified and technological innovations or areas in which novel techniques might be particularly fruitful in continuing to advance the field of skeletal regenerative medicine are highlighted.
Abstract: Stem-cell-mediated bone repair has been used in clinical trials for the regeneration of large craniomaxillofacial defects, to slow the process of bone degeneration in patients with osteonecrosis of the femoral head and for prophylactic treatment of distal tibial fractures. Successful regenerative outcomes in these investigations have provided a solid foundation for wider use of stromal cells in skeletal repair therapy. However, employing stromal cells to facilitate or enhance bone repair is far from being adopted into clinical practice. Scientific, technical, practical and regulatory obstacles prevent the widespread therapeutic use of stromal cells. Ironically, one of the major challenges lies in the limited understanding of the mechanisms via which transplanted cells mediate regeneration. Animal models have been used to provide insight, but these models largely fail to reproduce the nuances of human diseases and bone defects. Consequently, the development of targeted approaches to optimize cell-mediated outcomes is difficult. In this Review, we highlight the successes and challenges reported in several clinical trials that involved the use of bone-marrow-derived mesenchymal or adipose-tissue-derived stromal cells. We identify several obstacles blocking the mainstream use of stromal cells to enhance skeletal repair and highlight technological innovations or areas in which novel techniques might be particularly fruitful in continuing to advance the field of skeletal regenerative medicine.
TL;DR: A new mechanism of cancer progression is suggested in which mutations develop in a rapid burst after ablation of replication repair, which implies a threshold compatible with cancer-cell survival.
Abstract: DNA replication-associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutation consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from children with inherited biallelic mismatch repair deficiency (bMMRD). High-grade bMMRD brain tumors exhibited massive numbers of substitution mutations (>250/Mb), which was greater than all childhood and most cancers (>7,000 analyzed). All ultra-hypermutated bMMRD cancers acquired early somatic driver mutations in DNA polymerase ɛ or δ. The ensuing mutation signatures and numbers are unique and diagnostic of childhood germ-line bMMRD (P < 10(-13)). Sequential tumor biopsy analysis revealed that bMMRD/polymerase-mutant cancers rapidly amass an excess of simultaneous mutations (∼600 mutations/cell division), reaching but not exceeding ∼20,000 exonic mutations in <6 months. This implies a threshold compatible with cancer-cell survival. We suggest a new mechanism of cancer progression in which mutations develop in a rapid burst after ablation of replication repair.
TL;DR: There has been a substantial increase in research interest to identify methodologies for optimizing fat graft survival, but despite some differences in harvest and implantation technique in the laboratory, these findings have not translated into a universal protocol for fat grafting.
Abstract: Background
Interest in and acceptance of autologous fat grafting for use in contour abnormalities, breast reconstruction, and cosmetic procedures have increased. However, there are many procedural variations that alter the effectiveness of the procedure and may account for the unpredictable resorption rates observed.
TL;DR: The trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry finds genetic variants at 12 new loci to be associated with blood pressure, providing new evidence for the role of DNA methylation in blood pressure regulation.
Abstract: We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
Case Western Reserve University1, Heilongjiang University2, Loyola University Chicago3, Johns Hopkins University4, University of North Carolina at Chapel Hill5, University of Michigan6, Emory University7, Vanderbilt University8, Tulane University9, National Institutes of Health10, University of Mississippi11, University of Virginia12, Icahn School of Medicine at Mount Sinai13, Wake Forest University14, University of Washington15, Northwestern University16, University of Alabama at Birmingham17, Harvard University18
TL;DR: This study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs, and provides a way to study a cross phenotype (CP) association by using summary Statistics fromGWASs of multiple phenotype.
Abstract: Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple—even distinct—traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci ( CHIC2 , HOXA-EVX1 , IGFBP1/IGFBP3 , and CDH17 ; p −8 ) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p −7 ) were also observed, including CACNA1D and WNT3 . Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes.
TL;DR: In this paper, a global compilation of organic carbon data and sedimentation rates shows that fjords sequester twice as much carbon as other ocean regions, and that they are hotspots for organic carbon burial.
Abstract: Fjords have been hypothesized to be hotspots of organic carbon burial. A global compilation of organic carbon data and sedimentation rates shows that fjords sequester twice as much carbon as other ocean regions.
Broad Institute1, University of Edinburgh2, Harvard University3, National Center for Immunization and Respiratory Diseases4, Scripps Research Institute5, Massachusetts Institute of Technology6, United States Department of the Army7, Tulane University8, National Institutes of Health9, Médecins Sans Frontières10, Cheikh Anta Diop University11, University of Sierra Leone12, University of Sydney13, Fred Hutchinson Cancer Research Center14
TL;DR: Analysis of sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic, confirms sustained human-to-human transmission within Sierra Leone and finds no evidence for import or export of EBOV across national borders after its initial introduction.
Kantonsspital St. Gallen1, The Royal Marsden NHS Foundation Trust2, University of Texas at Austin3, University of Texas MD Anderson Cancer Center4, National and Kapodistrian University of Athens5, University of Paris-Sud6, Duke University7, Fred Hutchinson Cancer Research Center8, Tulane University9, Harvard University10, Prostate Cancer Foundation11, University of Tokyo12, Oregon Health & Science University13, Cornell University14, University of Michigan15, University of Copenhagen16, Monash University17, University of Warwick18, Johns Hopkins University19, University of Bologna20, University of British Columbia21, RWTH Aachen University22, Queen Elizabeth Hospital Birmingham23, Université catholique de Louvain24, Karolinska Institutet25, Icahn School of Medicine at Mount Sinai26, Carlos III Health Institute27, Northwood University28, Radboud University Nijmegen29, Memorial Sloan Kettering Cancer Center30, Tel Aviv University31, University of California, San Francisco32, Toho University33, Princess Margaret Cancer Centre34
TL;DR: The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed available evidence for the ten most important areas of controversy in advanced prostate cancer management.
TL;DR: The first technological demonstration of a phosphorus-based active active terahertz device is described, exploiting a 10 nm thick flake of exfoliated crystalline black phosphorus as an active channel of a field-effect transistor.
Abstract: The first room-temperature terahertz (THz)-frequency nanodetector exploiting a 10 nm thick flake of exfoliated crystalline black phosphorus as an active channel of a field-effect transistor, is devised. By engineering and embedding planar THz antennas for efficient light harvesting, the first technological demonstration of a phosphorus-based active THz device is described.
TL;DR: The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance, and this function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3(-) and production of new bICarbonate to replace that consumed by normal or pathologic acids.
Abstract: Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3(-) and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3(-) is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.
University of Texas Health Science Center at San Antonio1, Georgia Regents University2, Vancouver Island Health Authority3, University of Rennes4, University of Lorraine5, University of California, Davis6, Monash University7, Tulane University8, Uppsala University9, University of Gothenburg10, Merck & Co.11
TL;DR: The C-WORTHY trial as mentioned in this paper was a randomized, open-label phase 2 trial of grazoprevir plus elbasvir with or without ribavirin in patients with hepatitis C virus (HCV) genotype 1 infection with baseline characteristics of poor response.
TL;DR: The origins of repeat positives need further explanation and better treatment options are needed, as high rates of retest positive are found among TV infected persons after single dose MTZ treatment.
Abstract: Trichomonas vaginalis (TV) is likely the most common non-viral sexually transmitted infection (STI) in the world. It is as an important source of reproductive morbidity, a facilitator of HIV transmission and acquisition, and thus it is an important public health problem. Despite its importance in human reproductive health and HIV transmission, it is not a reportable disease and surveillance is not generally done. This is problematic since most persons infected with TV are asymptomatic. Metronidazole (MTZ) has been the treatment of choice for women for decades, and single dose has been considered the first line of therapy. However, high rates of retest positive are found among TV infected persons after single dose MTZ treatment. This has not been explained by drug resistance since in vitro resistance is only 2–5 %. Treatment failure can range from 7–10 % and even higher among HIV+ women. Treatment efficacy may be influenced by vaginal ecology. The origins of repeat positives need further explanation and better treatment options are needed.
RTI International1, Jawaharlal Nehru Medical College, Aligarh2, Christiana Care Health System3, Aga Khan University4, Columbia University5, Moi University6, Indiana University – Purdue University Indianapolis7, Universidad Francisco Marroquín8, University of Colorado Denver9, Government Medical College, Nagpur10, Harvard University11, University of Zambia12, University of Alabama at Birmingham13, National Institutes of Health14, Cincinnati Children's Hospital Medical Center15, Tulane University16
TL;DR: Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall, and the risk of maternal infection seems to have been increased.
TL;DR: The many mechanisms by which CPPs can function are discussed, and a taxonomy of mechanisms that could be help organize future efforts in the field are described.
TL;DR: This position paper summarizes currently available knowledge and gaps in that knowledge, and recommends management options that could be useful until additional evidence emerges, including nonobstructive CAD as a cause of IHD and related adverse outcomes among women.
TL;DR: Adherence was independently associated with older age, male sex, higher education, higher income, use of mail order versus retail pharmacies, primary care versus nonendocrinology specialist prescribers, higher daily total pill burden, and lower out-of-pocket costs.
Abstract: OBJECTIVE Adults with diabetes typically take multiple medications for hyperglycemia, diabetes-associated conditions, and other comorbidities. Medication adherence is associated with improved outcomes, including reduced health care costs, hospitalization, and mortality. We conducted a retrospective analysis of a large pharmacy claims database to examine patient, medication, and prescriber factors associated with adherence to antidiabetic medications. RESEARCH DESIGN AND METHODS We extracted data on a cohort of >200,000 patients who were treated for diabetes with noninsulin medications in the second half of 2010 and had continuous prescription benefits eligibility through 2011. Adherence was defined as a medication possession ratio ≥0.8. We used a modified adherence measure that accounted for switching therapies. Logistic regression analysis was performed to determine factors independently associated with adherence. RESULTS Sixty-nine percent of patients were adherent. Adherence was independently associated with older age, male sex, higher education, higher income, use of mail order versus retail pharmacies, primary care versus nonendocrinology specialist prescribers, higher daily total pill burden, and lower out-of-pocket costs. Patients who were new to diabetes therapy were significantly less likely to be adherent. CONCLUSIONS Several demographic, clinical, and potentially modifiable system-level factors were associated with adherence to antidiabetic medications. Patients typically perceived to be healthy (those who are younger, new to diabetes, and on few other medications) may be at risk for nonadherence. For all patients, efforts to reduce out-of-pocket costs and encourage use of mail order pharmacies may result in higher adherence.
TL;DR: This review focuses on molecular containers formed by assembly processes driven by the hydrophobic effect, and summarizes the progress made in the field over the last ten years.
Abstract: This review focuses on molecular containers formed by assembly processes driven by the hydrophobic effect, and summarizes the progress made in the field over the last ten years. This small but growing facet of supramolecular chemistry discusses three classes of molecules used by researchers to investigate how self-assembly can be applied to form discrete, mono-dispersed, and structurally well-defined supramolecular entities. The approaches demonstrate the importance of preorganization of arrays of rigid moieties to define a specific form predisposed to bind, fold, or assemble. As the examples demonstrate, studying these systems and their properties is teaching us how to control supramolecular chemistry in water, shedding light on aspects of aqueous solutions chemistry, and illustrating novel applications that harness the unique properties of the hydrophobic effect.