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Find video protocols related to scientific articles indexed in Pubmed.
Does Favorable Selection Among Medicare Advantage Enrollees Affect Measurement of Hospital Readmission Rates?
Med Care Res Rev
PUBLISHED: 05-07-2014
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Literature indicates favorable selection among Medicare Advantage (MA) enrollees compared with fee-for-service (FFS) enrollees. This study examined whether favorable selection into MA affected readmission rates among Medicare-eligible veterans following hospitalization for congestive heart failure in the Veterans Affairs Health System (VA). We measured total (VA + Medicare FFS) 30-day all-cause readmission rates across hospitals and all of VA. We used Heckman's correction to adjust readmission rates to be representative of all Medicare-eligible veterans, not just FFS-enrolled veterans. The adjusted all-cause readmission rate among FFS veterans was 27.1% (95% confidence interval [CI] = 26.5% to 27.7%), while the adjusted readmission rate among Medicare-eligible veterans was 25.3% (95% CI = 23.6% to 27.1%) after correcting for favorable selection. Readmission rate estimates among FFS veterans generalize to all Medicare-eligible veterans only after accounting for favorable selection into MA. Estimation of quality metrics should carefully consider sample selection to produce valid policy inferences.
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Factors affecting medication adherence: patient perspectives from five veterans affairs facilities.
BMC Health Serv Res
PUBLISHED: 01-16-2014
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BackgroundIn the United States, more than 25 million people have diabetes. Medication adherence is known to be important for disease control. However, factors that consistently predict medication adherence are unclear and the literature lacks patient perspectives on how health care systems affect adherence to oral hypoglycemic agents (OHAs). This study explored facilitators and barriers to OHA adherence by obtaining the perspectives of Veterans Affairs (VA) patients with OHA prescriptions.MethodsA total of 45 patients participated in 12 focus groups that explored a wide range of issues that might affect medication adherence. Participants were patients at clinics in Seattle, Washington; San Antonio, Texas; Portland, Oregon; Salem, Oregon, and Warrenton, Oregon.ResultsKey system-level facilitators of OHA adherence included good overall pharmacy service and several specific mechanisms for ordering and delivering medications (automated phone refill service, Web-based prescription ordering), as well as providing pillboxes and printed lists of current medications to patients. Barriers mirrored many of the facilitators. Poor pharmacy service quality and difficulty coordinating multiple prescriptions emerged as key barriers.ConclusionsVA patient focus groups provided insights on how care delivery systems can encourage diabetes medication adherence by minimizing the barriers and enhancing the facilitators at both the patient and system levels. Major system-level factors that facilitated adherence were overall pharmacy service quality, availability of multiple systems for reordering medications, having a person to call when questions arose, counseling about the importance of adherence and providing tools such as pillboxes and updated medication lists.
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Thiazolidinediones and the risk of asthma exacerbation among patients with diabetes: a cohort study.
Allergy Asthma Clin Immunol
PUBLISHED: 01-01-2014
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Thiazolidinediones are oral diabetes medications that selectively activate peroxisome proliferator-activated receptor gamma and have potent anti-inflammatory properties. While a few studies have found improvements in pulmonary function with exposure to thiazolidinediones, there are no studies of their impact on asthma exacerbations. Our objective was to assess whether exposure to thiazolidinediones was associated with a decreased risk of asthma exacerbation.
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Opposite feedbacks in the Hippo pathway for growth control and neural fate.
Science
PUBLISHED: 08-29-2013
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Signaling pathways are reused for multiple purposes in plant and animal development. The Hippo pathway in mammals and Drosophila coordinates proliferation and apoptosis via the coactivator and oncoprotein YAP/Yorkie (Yki), which is homeostatically regulated through negative feedback. In the Drosophila eye, cross-repression between the Hippo pathway kinase LATS/Warts (Wts) and growth regulator Melted generates mutually exclusive photoreceptor subtypes. Here, we show that this all-or-nothing neuronal differentiation results from Hippo pathway positive feedback: Yki both represses its negative regulator, warts, and promotes its positive regulator, melted. This postmitotic Hippo network behavior relies on a tissue-restricted transcription factor network-including a conserved Otx/Orthodenticle-Nrl/Traffic Jam feedforward module-that allows Warts-Yki-Melted to operate as a bistable switch. Altering feedback architecture provides an efficient mechanism to co-opt conserved signaling networks for diverse purposes in development and evolution.
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The continuity and quality of primary care.
Med Care Res Rev
PUBLISHED: 07-17-2013
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Patients who have access to different health care systems, such as Medicare-eligible veterans, may obtain services in either or both health systems. We examined whether quality of diabetes care was associated with care continuity or veterans usual source of primary care in a retrospective cohort study of 1,867 Medicare-eligible veterans with diabetes in 2001 to 2004. Underprovision of quality of diabetes care was more common than overprovision. In adjusted analyses, veterans who relied only on Medicare fee-for-service (FFS) for primary care were more likely to be underprovided HbA1c testing than veterans who relied only on Veteran Affairs (VA) for primary care. Dual users of VA and Medicare FFS primary care were significantly more likely to be overprovided HbA1c and microalbumin testing than VA-only users. VA and Medicare providers may need to coordinate more effectively to ensure appropriate diabetes care to Medicare-eligible veterans, because VA reliance was a stronger predictor than care continuity.
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Highly sensitive detection of malaria parasitemia in a malaria-endemic setting: performance of a new loop-mediated isothermal amplification kit in a remote clinic in Uganda.
J. Infect. Dis.
PUBLISHED: 04-30-2013
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Current malaria diagnostic tests, including microscopy and antigen-detecting rapid tests, cannot reliably detect low-density infections. Molecular methods such as polymerase chain reaction (PCR) are highly sensitive but remain too complex for field deployment. A new commercial molecular assay based on loop-mediated isothermal amplification (LAMP) was assessed for field use.
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Clinical evaluation of a loop-mediated amplification kit for diagnosis of imported malaria.
J. Infect. Dis.
PUBLISHED: 04-30-2013
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Diagnosis of malaria relies on parasite detection by microscopy or antigen detection; both fail to detect low-density infections. New tests providing rapid, sensitive diagnosis with minimal need for training would enhance both malaria diagnosis and malaria control activities. We determined the diagnostic accuracy of a new loop-mediated amplification (LAMP) kit in febrile returned travelers.
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Alignment of new tuberculosis drug regimens and drug susceptibility testing: a framework for action.
Lancet Infect Dis
PUBLISHED: 03-24-2013
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New tuberculosis drug regimens are creating new priorities for drug susceptibility testing (DST) and surveillance. To minimise turnaround time, rapid DST will need to be prioritised, but developers of these assays will need better data about the molecular mechanisms of resistance. Efforts are underway to link mutations with drug resistance and to develop strain collections to enable assessment of new diagnostic assays. In resource-limited settings, DST might not be appropriate for all patients with tuberculosis. Surveillance data and modelling will help country stakeholders to design appropriate DST algorithms and to decide whether to change drug regimens. Finally, development of practical DST assays is needed so that, in countries where surveillance and modelling show that DST is advisable, these assays can be used to guide clinical decisions for individual patients. If combined judiciously during both development and implementation, new tuberculosis regimens and new DST assays have enormous potential to improve patient outcomes and reduce the burden of disease.
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Potential bias in medication adherence studies of prevalent users.
Health Serv Res
PUBLISHED: 02-13-2013
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We examined how the choice of historic medication use criteria for identifying prevalent users may bias estimated adherence changes associated with a medication copayment increase.
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Wide clinic-level variation in adherence to oral diabetes medications in the VA.
J Gen Intern Med
PUBLISHED: 01-31-2013
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While there has been extensive research into patient-specific predictors of medication adherence and patient-specific interventions to improve adherence, there has been little examination of variation in clinic-level medication adherence.
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Drosophila dyrk2 plays a role in the development of the visual system.
PLoS ONE
PUBLISHED: 01-01-2013
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The DYRKs (dual-specificity tyrosine phosphorylation-regulated kinases) are a conserved family of protein kinases that are associated with a number of neurological disorders, but whose biological targets are poorly understood. Drosophila encodes three Dyrks: minibrain/Dyrk1A, DmDyrk2, and DmDyrk3. Here we describe the creation and characterization of a DmDyrk2 null allele, DmDyrk2(1w17) . We provide evidence that the smell impaired allele smi35A(1) , is likely to encode DmDyrk2. We also demonstrate that DmDyrk2 is expressed late in the developing third antennal segment, an anatomical structure associated with smell. In addition, we find that DmDyrk2 is expressed in the morphogenetic furrow of the developing eye, that loss of DmDyrk2 in the eye produced a subtle but measurable defect, and that ectopic DmDyrk2 expression in the eye produced a strong rough eye phenotype characterized by increased secondary, tertiary and bristle interommatidial cells. This phenotype was dependent on DmDyrk2 kinase activity and was only manifest when expressed in post-mitotic non-neuronal progenitors. Together, these data indicate that DmDyrk2 is expressed in developing sensory systems, that it is required for the development of the visual system, and that the eye is a good model to identify DmDyrk2 targets.
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Operational implementation of LED fluorescence microscopy in screening tuberculosis suspects in an urban HIV clinic in Uganda.
PLoS ONE
PUBLISHED: 01-01-2013
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Light emitting diode (LED) fluorescence microscopy (FM) is an affordable, technology targeted for use in resource-limited settings and recommended for widespread roll-out by the World Health Organization (WHO). We sought to compare the operational performance of three LED FM methods compared to light microscopy in a cohort of HIV-positive tuberculosis (TB) suspects at an urban clinic in a high TB burden country.
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A multisite assessment of the quantitative capabilities of the Xpert MTB/RIF assay.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 08-13-2011
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The Xpert MTB/RIF is an automated molecular test for Mycobacterium tuberculosis that estimates bacterial burden by measuring the threshold-cycle (Ct) of its M. tuberculosis-specific real-time polymerase chain reaction. Bacterial burden is an important biomarker for disease severity, infection control risk, and response to therapy.
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The lens in focus: a comparison of lens development in Drosophila and vertebrates.
Mol. Genet. Genomics
PUBLISHED: 07-01-2011
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The evolution of the eye has been a major subject of study dating back centuries. The advent of molecular genetics offered the surprising finding that morphologically distinct eyes rely on conserved regulatory gene networks for their formation. While many of these advances often stemmed from studies of the compound eye of the fruit fly, Drosophila melanogaster, and later translated to discoveries in vertebrate systems, studies on vertebrate lens development far outnumber those in Drosophila. This may be largely historical, since Spemann and Mangolds paradigm of tissue induction was discovered in the amphibian lens. Recent studies on lens development in Drosophila have begun to define molecular commonalities with the vertebrate lens. Here, we provide an overview of Drosophila lens development, discussing intrinsic and extrinsic factors controlling lens cell specification and differentiation. We then summarize key morphological and molecular events in vertebrate lens development, emphasizing regulatory factors and networks strongly associated with both systems. Finally, we provide a comparative analysis that highlights areas of research that would help further clarify the degree of conservation between the formation of dioptric systems in invertebrates and vertebrates.
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Reliance on Veterans Affairs outpatient care by Medicare-eligible veterans.
Med Care
PUBLISHED: 06-21-2011
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To examine longitudinal changes in Medicare-eligible veterans reliance on the Department of Veterans Affairs (VA) healthcare system for primary and specialty care over 4 years.
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Feasibility of magnetic bead technology for concentration of mycobacteria in sputum prior to fluorescence microscopy.
BMC Infect. Dis.
PUBLISHED: 05-13-2011
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Direct sputum smear microscopy is the mainstay of TB diagnosis in most low and middle income countries, and is highly specific for Mycobacterium tuberculosis in such settings. However it is limited by low sensitivity, particularly in HIV co-infected patients. Concentration by centrifugation has been reported to be more sensitive than direct smear preparation, but is only suitable for referral laboratories. Simpler concentration methods that could be applied in peripheral laboratories are urgently needed.
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Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling.
Neural Dev
PUBLISHED: 05-03-2011
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The concept of an equivalence group, a cluster of cells with equal potential to adopt the same specific fate, has served as a useful paradigm to understand neural cell type specification. In the Drosophila eye, a set of five cells, called the R7 equivalence group, generates a single photoreceptor neuron and four lens-secreting epithelial cells. This choice between neuronal versus non-neuronal cell fates rests on differential requirements for, and cross-talk between, Notch/Delta- and Ras/mitogen-activated protein kinase (MAPK)-dependent signaling pathways. However, many questions remain unanswered related to how downstream events of these two signaling pathways mediate distinct cell fate decisions.
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Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study.
Lancet
PUBLISHED: 04-18-2011
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The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings.
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Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis.
PLoS Med.
PUBLISHED: 04-07-2011
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Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings.
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Robustness of a loop-mediated isothermal amplification reaction for diagnostic applications.
FEMS Immunol. Med. Microbiol.
PUBLISHED: 03-16-2011
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We evaluated the robustness of loop-mediated isothermal amplification (LAMP) of DNA for bacterial diagnostic applications. Salmonella enterica serovar Typhi was used as the target organism and compared with a real-time quantitative PCR (qPCR) for testing assay performance and reproducibly, as well as the impact of pH and temperature stability. This isothermal amplification method appeared to be particularly robust across 2 pH units (7.3-9.3) and temperature values (57-67 °C). The detection limit was comparable to that observed using optimized home-brew qPCR assays. The specificity of the amplification reaction remained high even at temperatures markedly different from the optimal one. Exposing reagents to the ambient temperature during the preparation of the reaction mixture as well as prolonging times for preparing the amplification reaction did not yield false-positive results. LAMP remained sensitive and specific despite the addition of untreated biological fluids such as stool or urine that commonly inhibit PCR amplification. Whereas the detection of microorganisms from whole blood or a blood-culture medium typically requires extensive sample purification and removal of inhibitors, LAMP amplification remained more sensitive than conventional qPCR when omitting such preparatory steps. Our results demonstrate that LAMP is not only easy to use, but is also a very robust, innovative and powerful molecular diagnostic method for both industrialized and developing countries.
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Rapid and accurate detection of Mycobacterium tuberculosis in sputum samples by Cepheid Xpert MTB/RIF assay--a clinical validation study.
PLoS ONE
PUBLISHED: 03-05-2011
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A crucial impediment to global tuberculosis control is the lack of an accurate, rapid diagnostic test for detection of patients with active TB. A new, rapid diagnostic method, (Cepheid) Xpert MTB/RIF Assay, is an automated sample preparation and real-time PCR instrument, which was shown to have good potential as an alternative to current reference standard sputum microscopy and culture.
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Diagnostics as essential tools for containing antibacterial resistance.
Drug Resist. Updat.
PUBLISHED: 01-11-2011
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Antibacterial drugs are overused and often inappropriately selected. This exacerbates drug resistance and exacts a high burden from acute respiratory tract, bloodstream, sexually-transmitted, diarrheal and other infections. Appropriate use of existing diagnostic tests, and developing better ones, could avert these costs and would avoid selective pressure from unnecessary antibacterial use. Product profiles of resistance-averting tests would specify WHO ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free and Deliverable) criteria and request susceptibility as well as etiological information. Advances in genomics, nanoscience, microfluidics and bioengineering, as well as innovative funding paradigms can help to overcome research and development barriers for such diagnostics if they are deliberately and forcefully applied. Rapid uptake of new tests requires timely translation of research on cost-benefit analyses into policy, value-based subsidies and reimbursements, as well as behavioral change of health care providers and users.
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Slowing of the hippocampal ? rhythm correlates with anesthetic-induced amnesia.
Anesthesiology
PUBLISHED: 11-03-2010
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Temporary, antegrade amnesia is one of the core desirable endpoints of general anesthesia. Multiple lines of evidence support a role for the hippocampal ? rhythm, a synchronized rhythmic oscillation of field potentials at 4-12 Hz, in memory formation. Previous studies have revealed a disruption of the ? rhythm at surgical levels of anesthesia. We hypothesized that ?-rhythm modulation would also occur at subhypnotic but amnestic concentrations. Therefore, we examined the effect of three inhaled agents on properties of the ? rhythm considered critical for the formation of hippocampus-dependent memories.
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Building a fly eye: terminal differentiation events of the retina, corneal lens, and pigmented epithelia.
Curr. Top. Dev. Biol.
PUBLISHED: 10-21-2010
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In the past, vast differences in ocular structure, development, and physiology throughout the animal kingdom led to the widely accepted notion that eyes are polyphyletic, that is, they have independently arisen multiple times during evolution. Despite the dissimilarity between vertebrate and invertebrate eyes, it is becoming increasingly evident that the development of the eye in both groups shares more similarity at the genetic level than was previously assumed, forcing a reexamination of eye evolution. Understanding the molecular underpinnings of cell type specification during Drosophila eye development has been a focus of research for many labs over the past 25 years, and many of these findings are nicely reviewed in Chapters 1 and 4. A somewhat less explored area of research, however, considers how these cells, once specified, develop into functional ocular structures. This review aims to summarize the current knowledge related to the terminal differentiation events of the retina, corneal lens, and pigmented epithelia in the fly eye. In addition, we discuss emerging evidence that the different functional components of the fly eye share developmental pathways and functions with the vertebrate eye.
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Determination of the influence of primary drying rates on the microscale structural attributes and physicochemical properties of protein containing lyophilized products.
J Pharm Sci
PUBLISHED: 09-17-2010
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This work investigated the impact of primary drying conditions on the microstructure and protein stability of bovine serum albumin (BSA) containing lyophilized cakes. Two primary drying conditions were employed (termed conservative, slower drying rate and aggressive, higher drying rate) at two protein loadings (5 and 50 mg mL(-1)). The cake attributes were characterized using micro-X-ray computed tomography (micro-CT), scanning electron microscopy, manometric temperature measurements, Fourier transform infrared spectroscopy (FTIR) and size exclusion chromatography (SEC). The combination of analytical techniques revealed that although the aggressive drying conditions produced intact cakes which retained their macrostructure, they had undergone various degrees of microcollapse. The study demonstrates the applicability of micro-CT for resolving microstructural attributes of the freeze-dried cakes such as residual porosity, pore size distribution and connectivity. Micro-CT data showed significant differences in residual porosity and matrix connectivity between aggressively and conservatively dried cakes. The FTIR data show that at each protein loading, there is no observable difference in the secondary structure of the protein and the SEC data show comparable stability in the cakes produced under different primary drying conditions. Good content uniformity was observed with respect to BSA and sucrose distribution in the cakes.
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Use of outpatient care in Veterans Health Administration and Medicare among veterans receiving primary care in community-based and hospital outpatient clinics.
Health Serv Res
PUBLISHED: 09-14-2010
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To examine differences in use of Veterans Health Administration (VA) and Medicare outpatient services by VA primary care patients.
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Rapid molecular detection of tuberculosis and rifampin resistance.
N. Engl. J. Med.
PUBLISHED: 09-10-2010
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Global control of tuberculosis is hampered by slow, insensitive diagnostic methods, particularly for the detection of drug-resistant forms and in patients with human immunodeficiency virus infection. Early detection is essential to reduce the death rate and interrupt transmission, but the complexity and infrastructure needs of sensitive methods limit their accessibility and effect.
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Containment of bioaerosol infection risk by the Xpert MTB/RIF assay and its applicability to point-of-care settings.
J. Clin. Microbiol.
PUBLISHED: 08-18-2010
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The recently introduced Xpert MTB/RIF assay (Xpert) has point-of-care potential, but its capacity for biohazard containment remained to be studied. We compared the bioaerosols generated by the Xpert assay to acid-fast bacillus (AFB) microscope slide smear preparation. The Xpert assay sample treatment reagent (SR) was also studied for its sterilizing capacity, stability, and effect on assay sensitivity after prolonged treatment. During the preparation of AFB smears, sputum samples spiked with Mycobacterium bovis BCG at 5 × 10(8) CFU/ml produced 16 and 325 CFU/m(3) air measured with an Andersen impactor or BioSampler, respectively. In contrast, neither the sample preparation steps for the Xpert assay nor its automated processing produced any culturable bioaerosols. In testing of SR sterilizing capacity, clinical sputum samples from strongly smear-positive tuberculosis patients treated with SR at a 2:1 ratio eliminated Mycobacterium tuberculosis growth in all but 1/39 or 3/45 samples cultured on solid or liquid medium, respectively. These few unsterilized samples had a mean 13.1-day delay in the time to positive culture. SR treatment at a 3:1 ratio eliminated growth in all samples. SR retained a greater than 6-log-unit killing capacity despite storage at temperatures spanning 4 to 45°C for at least 3 months. The effect of prolonged SR sample treatment was also studied. Spiked sputum samples could be incubated in SR for up to 3 days without affecting Xpert sensitivity for M. tuberculosis detection and up to 8 h without affecting specificity for rifampin resistance detection. These results suggest that benchtop use of the Xpert MTB/RIF assay limits infection risk to the user.
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Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events.
Dev. Biol.
PUBLISHED: 08-13-2010
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Orthodenticle (Otd)-related transcription factors are essential for anterior patterning and brain morphogenesis from Cnidaria to Mammals, and genetically underlie several human retinal pathologies. Despite their key developmental functions, relatively little is known regarding the molecular basis of how these factors regulate downstream effectors in a cell- or tissue-specific manner. Many invertebrate and vertebrate species encode two to three Otd proteins, whereas Drosophila encodes a single Otd protein. In the fly retina, Otd controls rhabdomere morphogenesis of all photoreceptors and regulates distinct Rhodopsin-encoding genes in a photoreceptor subtype-specific manner. Here, we performed a structure-function analysis of Otd during Drosophila eye development using in vivo rescue experiments and in vitro transcriptional regulatory assays. Our findings indicate that Otd requires at least three distinct transcriptional regulatory domains to control photoreceptor-specific rhodopsin gene expression and photoreceptor morphogenesis. Our results also uncover a previously unknown role for Otd in preventing co-expression of sensory receptors in blue vs. green-sensitive R8 photoreceptors. Sequence analysis indicates that many of the transcriptional regulatory domains identified here are conserved in multiple Diptera Otd-related proteins. Thus, these studies provide a basis for identifying shared molecular pathways involved in a wide range of developmental processes.
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Dynamic antibody responses to the Mycobacterium tuberculosis proteome.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-28-2010
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Considerable effort has been directed toward controlling tuberculosis, which kills almost two million people yearly. High on the research agenda is the discovery of biomarkers of active tuberculosis (TB) for diagnosis and for monitoring treatment outcome. Rational biomarker discovery requires understanding host-pathogen interactions leading to biomarker expression. Here we report a systems immunology approach integrating clinical data and bacterial metabolic and regulatory information with high-throughput detection in human serum of antibodies to the entire Mycobacterium tuberculosis proteome. Sera from worldwide TB suspects recognized approximately 10% of the bacterial proteome. This result defines the M. tuberculosis immunoproteome, which is rich in membrane-associated and extracellular proteins. Additional analyses revealed that during active tuberculosis (i) antibody responses focused on an approximately 0.5% of the proteome enriched for extracellular proteins, (ii) relative target preference varied among patients, and (iii) responses correlated with bacillary burden. These results indicate that the B cell response tracks the evolution of infection and the pathogen burden and replicative state and suggest functions associated with B cell-rich foci seen in tuberculous lung granulomas. Our integrated proteome-scale approach is applicable to other chronic infections characterized by diverse antibody target recognition.
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Performance of three LED-based fluorescence microscopy systems for detection of tuberculosis in Uganda.
PLoS ONE
PUBLISHED: 07-27-2010
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Direct smear microscopy using Ziehl-Neelsen (ZN) staining is the mainstay of tuberculosis (TB) diagnosis in most high burden countries, but is limited by low sensitivity in routine practice, particularly in high human immunodeficiency virus (HIV) prevalence settings.
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Mitochondrial DNA targets increase sensitivity of malaria detection using loop-mediated isothermal amplification.
J. Clin. Microbiol.
PUBLISHED: 06-16-2010
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Loop-mediated isothermal amplification (LAMP) of DNA offers the ability to detect very small quantities of pathogen DNA following minimal tissue sample processing and is thus an attractive methodology for point-of-care diagnostics. Previous attempts to diagnose malaria by the use of blood samples and LAMP have targeted the parasite small-subunit rRNA gene, with a resultant sensitivity for Plasmodium falciparum of around 100 parasites per microl. Here we describe the use of mitochondrial targets for LAMP-based detection of any Plasmodium genus parasite and of P. falciparum specifically. These new targets allow routine amplification from samples containing as few as five parasites per microl of blood. Amplification is complete within 30 to 40 min and is assessed by real-time turbidimetry, thereby offering rapid diagnosis with greater sensitivity than is achieved by the most skilled microscopist or antigen detection using lateral flow immunoassays.
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Biomarkers and diagnostics for tuberculosis: progress, needs, and translation into practice.
Lancet
PUBLISHED: 05-18-2010
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Human infection with Mycobacterium tuberculosis can progress to active disease, be contained as latent infection, or be eradicated by the host response. Tuberculosis diagnostics classify a patient into one of these categories. These are not fixed distinct states, but rather are continua along which patients can move, and are affected by HIV infection, immunosuppressive therapies, antituberculosis treatments, and other poorly understood factors. Tuberculosis biomarkers-host or pathogen-specific-provide prognostic information, either for individual patients or study cohorts, about these outcomes. Tuberculosis case detection remains difficult, partly because of inaccurate diagnostic methods. Investments have yielded some progress in development of new diagnostics, although the existing pipeline is limited for tests for sputum-smear-negative cases, childhood tuberculosis, and accurate prediction of reactivation of latent tuberculosis. Despite new, sensitive, automated molecular platforms for detection of tuberculosis and drug resistance, a simple, inexpensive point-of-care test is still not available. The effect of any new tests will depend on the method and extent of their introduction, the strength of the laboratories, and the degree to which access to appropriate therapy follows access to diagnosis. Translation of scientific progress in biomarkers and diagnostics into clinical and public health programmes is possible-with political commitment, increased funding, and engagement of all stakeholders.
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Elucidation of the internal physical and chemical microstructure of pharmaceutical granules using X-ray micro-computed tomography, Raman microscopy and infrared spectroscopy.
Eur J Pharm Biopharm
PUBLISHED: 05-03-2010
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X-ray micro-computed tomography (XMCT) was used in conjunction with confocal Raman mapping to measure the intra-granular pore size, binder volumes and to provide spatial and chemical maps of internal granular components in ?-lactose monohydrate granules formulated with different molecular weights of polyvinyl pyrrolidone (PVP). Infrared spectroscopy was used to understand the molecular association of binder domains. Granules were prepared by high-shear aqueous granulation from ?-lactose monohydrate and PVP K29/32 or K90. XMCT was used to visualise the granule microstructure, intra-granular binder distribution and measure intra-granular porosity, which was subsequently related to intrusion porosimetry measurements. Confocal Raman microscopy and infrared microscopy were employed to investigate the distribution of components within the granule and explore the nature of binder substrate interactions. XMCT data sets of internal granule microstructure provided values of residual porosity in the lactose:PVP K29/32 and lactose:PVP K90 granules of 32.41 ± 4.60% and 22.40 ± 0.03%, respectively. The binder volumes of the lactose:PVP K29/32 and lactose:PVP K90 granules were 2.98 ± 0.10% and 3.38 ± 0.07%, respectively, and were attributed to PVP-rich binder domains within the granule. Confocal Raman microscopy revealed anisotropic domains of PVP between 2 ?m and 20 ?m in size surrounded by larger particles of lactose, in both granule types. Raman data showed that PVP domains contained various amounts of lactose, whilst IR microscopy determined that the PVP was molecularly associated with lactose, rather than residual water. The work shows that XMCT can be applied to investigate granular microstructure and resolve the porosity and the excipient and binder volumes. Combining this technique with vibrational techniques provides further structural information and aids the interpretations of the XMCT images. When used complementarily, these techniques highlighted that porosity and binder volume were the most significant microstructural differences between the ?-lactose monohydrate granules formulated with the different grades of PVP.
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A large proportion of P. falciparum isolates in the Amazon region of Peru lack pfhrp2 and pfhrp3: implications for malaria rapid diagnostic tests.
PLoS ONE
PUBLISHED: 01-25-2010
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Malaria rapid diagnostic tests (RDTs) offer significant potential to improve the diagnosis of malaria, and are playing an increasing role in malaria case management, control and elimination. Peru, along with other South American countries, is moving to introduce malaria RDTs as components of malaria control programmes supported by the Global Fund for AIDS, TB and malaria. The selection of the most suitable malaria RDTs is critical to the success of the programmes.
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Increasing copayments and adherence to diabetes, hypertension, and hyperlipidemic medications.
Am J Manag Care
PUBLISHED: 01-12-2010
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To examine the impact of a medication copayment increase on adherence to diabetes, hypertension, and hyperlipidemic medications.
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Equivalence of two healthcare costing methods: bottom-up and top-down.
Health Econ
PUBLISHED: 12-16-2009
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This paper compares two quite different approaches to estimating costs: a bottom-up approach, represented by the US Department of Veterans Affairs (VA) Decision Support System that uses local costs of specific inputs; and a top-down approach, represented by the costing system created by the VA Health Economics Resource Center, which assigns the VA national healthcare budget to specific products using various weighting systems. Total annual costs per patient plus the cost for specific services (e.g. clinic visit, radiograph, laboratory, inpatient admission) were compared using scatterplots, correlations, mean difference, and standard deviation of individual differences. Analysis are based upon 2001 costs for 14 915 patients at 72 facilities. Correlations ranged from 0.24 for the cost of outpatient encounters to 0.77 for the cost of inpatient admissions, and 0.85 for total annual cost. The mean difference between costing methods was $707 ($4168 versus $3461) for total annual cost. The standard deviation of the individual differences was $5934. Overall, the agreement between the two costing systems varied by the specific cost being measured and increased with aggregation. Administrators and researchers conducting cost analyses need to carefully consider the purpose, methods, characteristics, strengths, and weaknesses when selecting a method for assessing cost.
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Novel and improved technologies for tuberculosis diagnosis: progress and challenges.
Clin. Chest Med.
PUBLISHED: 11-21-2009
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Despite a decade of success in improving cure rates for tuberculosis (TB), diagnosis and case detection remain a major obstacle to TB control. This article reviews the existing evidence base on TB diagnostics, describes the progress of new technologies, and ends with a review of cost-effectiveness and modeling studies on the potential effect of new diagnostics in TB control.
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Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology.
J. Clin. Microbiol.
PUBLISHED: 10-28-2009
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Current nucleic acid amplification methods to detect Mycobacterium tuberculosis are complex, labor-intensive, and technically challenging. We developed and performed the first analysis of the Cepheid Gene Xpert Systems MTB/RIF assay, an integrated hands-free sputum-processing and real-time PCR system with rapid on-demand, near-patient technology, to simultaneously detect M. tuberculosis and rifampin resistance. Analytic tests of M. tuberculosis DNA demonstrated a limit of detection (LOD) of 4.5 genomes per reaction. Studies using sputum spiked with known numbers of M. tuberculosis CFU predicted a clinical LOD of 131 CFU/ml. Killing studies showed that the assays buffer decreased M. tuberculosis viability by at least 8 logs, substantially reducing biohazards. Tests of 23 different commonly occurring rifampin resistance mutations demonstrated that all 23 (100%) would be identified as rifampin resistant. An analysis of 20 nontuberculosis mycobacteria species confirmed high assay specificity. A small clinical validation study of 107 clinical sputum samples from suspected tuberculosis cases in Vietnam detected 29/29 (100%) smear-positive culture-positive cases and 33/39 (84.6%) or 38/53 (71.7%) smear-negative culture-positive cases, as determined by growth on solid medium or on both solid and liquid media, respectively. M. tuberculosis was not detected in 25/25 (100%) of the culture-negative samples. A study of 64 smear-positive culture-positive sputa from retreatment tuberculosis cases in Uganda detected 63/64 (98.4%) culture-positive cases and 9/9 (100%) cases of rifampin resistance. Rifampin resistance was excluded in 54/55 (98.2%) susceptible cases. Specificity rose to 100% after correcting for a conventional susceptibility test error. In conclusion, this highly sensitive and simple-to-use system can detect M. tuberculosis directly from sputum in less than 2 h.
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Altered GABAA,slow inhibition and network oscillations in mice lacking the GABAA receptor beta3 subunit.
J. Neurophysiol.
PUBLISHED: 10-21-2009
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Phasic GABAergic inhibition in hippocampus and neocortex falls into two kinetically distinct categories, GABA(A,fast) and GABA(A,slow). In hippocampal area CA1, GABA(A,fast) is generally believed to underlie gamma oscillations, whereas the contribution of GABA(A,slow) to hippocampal rhythms has been speculative. Hypothesizing that GABA(A) receptors containing the beta(3) subunit contribute to GABA(A,slow) inhibition and that slow inhibitory synapses control excitability as well as contribute to network rhythms, we investigated the consequences of this subunits absence on synaptic inhibition and network function. In pyramidal neurons of GABA(A) receptor beta(3) subunit-deficient (beta(3)(-/-)) mice, spontaneous GABA(A,slow) inhibitory postsynaptic currents (IPSCs) were much less frequent, and evoked GABA(A,slow) currents were much smaller than in wild-type mice. Fittingly, long-lasting recurrent inhibition of population spikes was less powerful in the mutant, indicating that receptors containing beta(3) subunits contribute substantially to GABA(A,slow) currents in pyramidal neurons. By contrast, slow inhibitory control of GABA(A,fast)-producing interneurons was unaffected in beta(3)(-/-) mice. In vivo hippocampal network activity was markedly different in the two genotypes. In beta(3)(-/-) mice, epileptiform activity was observed, and theta oscillations were weaker, slower, less regular and less well coordinated across laminae compared with wild-type mice, whereas gamma oscillations were weaker and faster. The amplitude modulation of gamma oscillations at theta frequency ("nesting") was preserved but was less well coordinated with theta oscillations. With the caveat that seizure-induced changes in inhibitory circuits might have contributed to the changes observed in the mutant animals, our results point to a strong contribution of beta(3) subunits to slow GABAergic inhibition onto pyramidal neurons but not onto GABA(A,fast) -producing interneurons and support different roles for these slow inhibitory synapses in the generation and coordination of hippocampal network rhythms.
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Medicare managed care enrollment by disability-eligible and age-eligible veterans.
Med Care
PUBLISHED: 09-30-2009
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To assess factors associated with enrollment in a Medicare advantage (MA) plan versus Medicare fee-for-service plan in 2000-2004 by Medicare-eligible veterans. We also assessed whether these factors differed between disability-eligible veterans and age-eligible veterans.
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Implications of storing urinary DNA from different populations for molecular analyses.
PLoS ONE
PUBLISHED: 04-17-2009
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Molecular diagnosis using urine is established for many sexually transmitted diseases and is increasingly used to diagnose tumours and other infectious diseases. Storage of urine prior to analysis, whether due to home collection or bio-banking, is increasingly advocated yet no best practice has emerged. Here, we examined the stability of DNA in stored urine in two populations over 28 days.
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Organizational cost of quality improvement for depression care.
Health Serv Res
PUBLISHED: 01-17-2009
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We documented organizational costs for depression care quality improvement (QI) to develop an evidence-based, Veterans Health Administration (VA) adapted depression care model for primary care practices that performed well for patients, was sustained over time, and could be spread nationally in VA.
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Does the presence of a pharmacist in primary care clinics improve diabetes medication adherence?
BMC Health Serv Res
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Although oral hypoglycemic agents (OHAs) are an essential element of therapy for the management of type 2 diabetes, OHA adherence is often suboptimal. Pharmacists are increasingly being integrated into primary care as part of the move towards a patient-centered medical home and may have a positive influence on medication use. We examined whether the presence of pharmacists in primary care clinics was associated with higher OHA adherence.
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Proteome-scale antibody responses and outcome of Mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients.
J. Infect. Dis.
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Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies.
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Clinical research and development of tuberculosis diagnostics: moving from silos to synergy.
J. Infect. Dis.
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The development, evaluation, and implementation of new and improved diagnostics have been identified as critical needs by human immunodeficiency virus (HIV) and tuberculosis researchers and clinicians alike. These needs exist in international and domestic settings and in adult and pediatric populations. Experts in tuberculosis and HIV care, researchers, healthcare providers, public health experts, and industry representatives, as well as representatives of pertinent US federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health, United States Agency for International Development) assembled at a workshop proposed by the Diagnostics Working Group of the Federal Tuberculosis Taskforce to review the state of tuberculosis diagnostics development in adult and pediatric populations.
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Use of outpatient care in VA and Medicare among disability-eligible and age-eligible veteran patients.
BMC Health Serv Res
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More than half of veterans who use Veterans Health Administration (VA) care are also eligible for Medicare via disability or age, but no prior studies have examined variation in use of outpatient services by Medicare-eligible veterans across health system, type of care or time.
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Exceptionally stable fluorous emulsions for the intravenous delivery of volatile general anesthetics.
Anesthesiology
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IV delivery of volatile fluorinated anesthetics has a number of potential advantages when compared with the current inhalation method of administration. We reported previously that the IV delivery of sevoflurane can be achieved through an emulsion composed of a linear fluorinated diblock copolymer, a stabilizer, and the anesthetic. However, this original emulsion was subject to particle size growth that would limit its potential clinical utility. We hypothesized that the use of bulkier fluorous groups and smaller polyethylene glycol moieties in the polymer design would result in improved emulsion stability while maintaining anesthetic functionality.
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Measures of adherence to oral hypoglycemic agents at the primary care clinic level: the role of risk adjustment.
Med Care
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Prior research found that in the Veterans Affairs health care system (VA), the proportion of patients adherent to oral hypoglycemic agents varies from 50% to 80% across primary care clinics. This study examined whether variation in patient and facility characteristics determined those differences.
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New developments in malaria diagnostics: monoclonal antibodies against Plasmodium dihydrofolate reductase-thymidylate synthase, heme detoxification protein and glutamate rich protein.
MAbs
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Currently available rapid diagnostic tests (RDTs) for malaria show large variation in sensitivity and specificity, and there are concerns about their stability under field conditions. To improve current RDTs, monoclonal antibodies (mAbs) for novel malaria antigens have been developed and screened for their possible use in new diagnostic tests. Three antigens, glutamate rich protein (GLURP), dihydrofolate reductase-thymidylate synthase (DHFR-TS) and heme detoxification protein (HDP), were selected based on literature searches. Recombinant antigens were produced and used to immunize mice. Antibody-producing cell lines were subsequently selected and the resulting antibodies were screened for specificity against Plasmodium falciparum and Plasmodium vivax. The most optimal antibody couples were selected based on antibody affinity (expressed as dissociation constants, KD) and detection limit of crude antigen extract from P. falciparum 3D7 culture. The highest affinity antibodies have KD values of 0.10 nM ± 0.014 (D5) and 0.068 ± 0.015 nM (D6) for DHFR-TS mAbs, 0.10 ± 0.022 nM (H16) and 0.21 ± 0.022 nM (H18) for HDP mAbs and 0.11 ± 0.028 nM (G23) and 0.33 ± 0.093 nM (G22) for GLURP mAbs. The newly developed antibodies performed at least as well as commercially available histidine rich protein antibodies (KD of 0.16 ± 0.13 nM for PTL3 and 1.0 ± 0.049 nM for C1-13), making them promising reagents for further test development.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.