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1.
New Phytol ; 239(2): 562-575, 2023 07.
Article in English | MEDLINE | ID: mdl-36653954

ABSTRACT

Some rhizomatous grass and sedge species form tussocks that impact ecosystem structure and function. Despite their importance, tussock development and size controls are poorly understood due to the decadal to centennial timescales over which tussocks form. We explored mechanisms regulating tussock development and size in a ubiquitous arctic tussock sedge (Eriophorum vaginatum) using field observations and a mass balance model coupled with a tiller population model. Model-data fusion was used to quantify parameter and prediction uncertainty, determine model sensitivity, and test hypotheses on the factors regulating tussock size. The model accurately captured the dynamics of tussock development, characteristics, and size observed in the field. Tussock growth approached maximal size within several decades, which was determined by feedbacks between the mass balance of tussock root necromass and density-dependent tillering. The model also predicted that maximal tussock size was primarily regulated by tiller root productivity and necromass bulk density and less so by tiller demography. These predictions were corroborated by field observations of tussock biomass and root characteristics. The study highlights the importance of belowground processes in regulating tussock development and size and enhances our understanding of the influence of tussocks on arctic ecosystem structure and function.


Subject(s)
Cyperaceae , Ecosystem , Biomass , Arctic Regions , Poaceae
2.
World J Clin Pediatr ; 11(6): 455-462, 2022 Nov 09.
Article in English | MEDLINE | ID: mdl-36439903

ABSTRACT

Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver, type 2 diabetes, metabolic syndrome, and cardiovascular disease. From a pathogenic point of view, insulin resistance (IR) represents the key factor underlying the spectrum of these obesity consequences. As observed in adults, recent data supported the occurrence of microalbuminuria (MA) as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity. In fact, a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics. Based on the clinical and prognostic relevance of this relationship in daily practice (including an increased risk of chronic kidney disease development overtime), more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity. In this paper, we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity: (1) What is the prevalence of pediatric MA? (2) What is the state of art of MA in children with obesity? and (3) Is there a link between IR and MA in children with obesity?

3.
Children (Basel) ; 9(9)2022 Aug 27.
Article in English | MEDLINE | ID: mdl-36138612

ABSTRACT

Pediatric obesity is associated with an increased risk of morbidity during childhood. Alongside the well-known metabolic syndrome, during the last decades scientific research has deeply investigated the risk of sleep breathing disorders. Among them, obstructive sleep apnea (OSA) commonly affects children with obesity. The presence of OSA heightens the risk of metabolic impairment and weight gain. Therefore, it deserves specific treatment. However, polysomnography (PSG) is not always available in clinical settings, and alternative diagnostic tools are needed. This study aimed to investigate the predictivity of the pediatric sleep questionnaire (PSQ) for moderate-to-severe OSA diagnosis. Children and adolescents with obesity and suspected OSA with available full-night cardiorespiratory PSG were retrospectively enrolled. Receiver operating curve analysis was performed to test the ability of PSQ in predicting moderate-to-severe OSA (AHI > 5 episode/h). The final sample included 60 children and adolescents. The PSQ showed a good area under the curve (AUC) of 0.88 (95% CI 0.78−0.98, p < 0.0001). Moreover, a value above or equal to 0.65 showed an 80% sensitivity and 100% specificity for moderate and severe OSA. These findings suggest that PSQ might be used in clinical settings with limited access to PSG for stratifying disease severity and for selecting children with urgent need of sleep study.

4.
J Phys Chem Lett ; 13(29): 6831-6838, 2022 Jul 28.
Article in English | MEDLINE | ID: mdl-35857895

ABSTRACT

We study the influence of a linear energy bias on a nonequilibrium excitation on a chain of molecules coupled to local vibrations (a tilted Holstein model) using both a random-walk rate kernel theory and a nonperturbative, massively parallelized adaptive-basis algorithm. We uncover structured and discrete vibronic resonance behavior fundamentally different from both linear response theory and homogeneous polaron dynamics. Remarkably, resonance between the phonon energy ℏω and the bias δϵ occurs not only at integer but also fractional ratios δϵ/(ℏω) = m/n, which effect long-range n-bond m-phonon tunneling. These observations are reproduced in a model calculation of a recently demonstrated Cy3 system, and the effect of dipole-dipole-type non-nearest-neighbor coupling and vibrationally relaxed initial states is also considered. Potential applications range from molecular electronics to optical lattices and artificial light harvesting via vibronic engineering of coherent quantum transport.

5.
AIDS Behav ; 26(12): 3981-3990, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35829971

ABSTRACT

Young men who have sex with men (YMSM) remain at disproportionate risk for HIV acquisition in the United States (US), yet use of evidence-based prevention strategies, including routine HIV testing and pre-exposure prophylaxis (PrEP), remain low. Smartphones and mobile app usage are nearly ubiquitous in this population. Given the potential for scalability, a mobile app to increase HIV testing and PrEP use among YMSM has the potential to make an extraordinary public health impact if efficacious. Based on extensive formative, community-engaged research, we developed a theory-driven mobile app-MyChoices-to increase HIV testing and PrEP uptake among YMSM. In a pilot randomized controlled trial (RCT), participants (n = 60) were randomized 2:1 to receive MyChoices or standard of care (SOC). Data from 3 to 6-month post-baseline assessments demonstrate that the app was highly acceptable (System Usability Score; mean = 75.8, SD = 10.7) and feasible (94% used the MyChoices app at least once; mean = 15.3 sessions, SD = 9.8). While not powered to assess efficacy, those in the MyChoices arm had 22% higher prevalence of HIV testing over follow-up compared to those in the SOC arm (NS). There was no difference in PrEP uptake. A fully-powered efficacy trial is warranted; if efficacy is demonstrated, the MyChoices app could be easily scaled to reach YMSM across the US.


Subject(s)
HIV Infections , Mobile Applications , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Male , Humans , United States/epidemiology , Homosexuality, Male , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/prevention & control , Pre-Exposure Prophylaxis/methods , HIV Testing
6.
Acta Crystallogr F Struct Biol Commun ; 78(Pt 5): 185-192, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35506763

ABSTRACT

Receptor tyrosine kinase-like orphan receptors (RORs) are monotopic membrane proteins belonging to the receptor tyrosine kinase (RTK) family. RTKs play a role in the control of most basic cellular processes, including cell proliferation, differentiation, migration and metabolism. New emerging roles for RORs in cancer progression have recently been proposed: RORs have been shown to be overexpressed in various malignancies but not in normal tissues, and moreover an abnormal expression level of RORs on the cellular surface is correlated with high levels of cytotoxicity in primary cancer cells. Monoclonal antibodies against the extracellular part of RTKs might be of importance to prevent tumor cell growth: targeting extracellular kringle domain molecules induces the internalization of RORs and decreases cell toxicity. Here, the recombinant production and crystallization of the isolated KRD of ROR1 and its high-resolution X-ray crystal structure in a P3121 crystal form at 1.4 Šresolution are reported. The crystal structure is compared with previously solved three-dimensional structures of kringle domains of human ROR1 and ROR2, their complexes with antibody fragments and structures of other kringle domains from homologous proteins.


Subject(s)
Kringles , Receptor Tyrosine Kinase-like Orphan Receptors , Antibodies, Monoclonal , Cell Proliferation , Crystallography, X-Ray , Humans , Receptor Tyrosine Kinase-like Orphan Receptors/chemistry , Receptor Tyrosine Kinase-like Orphan Receptors/genetics
7.
J Am Heart Assoc ; 10(23): e023956, 2021 12 07.
Article in English | MEDLINE | ID: mdl-34743550

ABSTRACT

Background We previously reported that resuscitation delivering electrical shocks guided by real-time ventricular fibrillation amplitude spectral area (AMSA) enabled return of spontaneous circulation (ROSC) with fewer shocks, resulting in less myocardial dysfunction. We now hypothesized that AMSA could also guide delivery of epinephrine, expecting further outcome improvement consequent to less electrical and adrenergic burdens. Methods and Results A swine model of ventricular fibrillation was used to compare after 10 minutes of untreated ventricular fibrillation a guidelines-driven (n=8) resuscitation protocol, delivering shocks every 2 minutes and epinephrine every 4 minutes, with an AMSA-driven shocks (n=8) protocol, delivering epinephrine every 4 minutes, and with an AMSA-driven shocks and epinephrine (ADSE; n=8) protocol. For guidelines-driven, AMSA-driven shocks, and ADSE protocols, the time to ROSC (mean±SD) was 569±164, 410±111, and 400±80 seconds (P=0.045); the number of shocks (mean±SD) was 5±2, 3±1, and 3±2 (P=0.024) with ADSE fewer than guidelines-driven (P=0.03); and the doses of epinephrine (median [interquartile range]) were 2.0 (1.3-3.0), 1.0 (1.0-2.8), and 1.0 (0.3-3.0) (P=0.419). The ROSC rate was similar, yet survival after ROSC favored AMSA-driven protocols (guidelines-driven, 3/6; AMSA-driven shocks, 6/6; and ADSE, 7/7; P=0.019 by log-rank test). Left ventricular function and survival after ROSC correlated inversely with electrical burden (ie, cumulative unsuccessful shocks, J/kg; P=0.020 and P=0.046) and adrenergic burden (ie, total epinephrine doses, mg/kg; P=0.042 and P=0.002). Conclusions Despite similar ROSC rates achieved with all 3 protocols, AMSA-driven shocks and ADSE resulted in less postresuscitation myocardial dysfunction and better survival, attributed to attaining ROSC with less electrical and adrenergic myocardial burdens.


Subject(s)
Electroconvulsive Therapy , Epinephrine , Ventricular Fibrillation , Adrenergic Agents/metabolism , Animals , Disease Models, Animal , Electroconvulsive Therapy/methods , Epinephrine/therapeutic use , Myocardium/metabolism , Survival Analysis , Swine , Ventricular Fibrillation/therapy
8.
Environ Sci Technol ; 55(19): 12791-12800, 2021 10 05.
Article in English | MEDLINE | ID: mdl-34520184

ABSTRACT

This work evaluates efficacies of plausible ballast water management strategies and standards by integrating a global species spread risk assessment with a policy cost-effectiveness analysis. Specifically, we consider species spread risks and costs of port- and vessel-based strategies under both current organism concentration standards and stricter standards proposed by California. For each scenario, we estimate species spread risks and patterns using a higher-order analysis of a global ship-borne species spread model and estimate fleet costs for vessel- and barge-based ballast water treatment systems for each standard. We find that stricter standards may reduce species spread risk by a factor of 17 globally and would greatly simplify the complex network of ship-borne species spread. The current policy of IMO standards is most cost-effectively achieved through ship-based treatment, and that any additional risk reduction will be most cost-effectively achieved by port-based (or barge-based) technologies, particularly if these are strategically implemented at the top ports within the largest clusters. Barge-based ballast water management would require a shift in governance, and we suggest that this next level of policymaking could be feasible for special areas designated by the IMO, by State or multistate authorities, or by voluntary port applications.


Subject(s)
Introduced Species , Water Purification , Ships , Water , Water Supply
9.
J Struct Biol ; 213(1): 107696, 2021 03.
Article in English | MEDLINE | ID: mdl-33493635

ABSTRACT

The use of immunomodulatory agents for the treatment of cancer is gaining a growing biopharmaceutical interest. Antibody-cytokine fusion proteins, namely immunocytokines, represent a promising solution for the regulation of the immune system at the site of disease. The three-dimensional arrangement of these molecules can profoundly influence their biological activity and pharmacokinetic properties. Structural techniques might provide important insight in the 3D arrangement of immunocytokines. Here, we performed structure investigations on clinical grade fusion proteins L19-IL2, IL12-L19L19 and L19L19-IL2 to elucidate their quaternary organization. Crystallographic characterization of the common L19 antibody fragment at a resolution of 2.0-Å was combined with low-resolution studies of the full-length chimeric molecules using small-angle synchrotron X-ray scattering (SAXS) and negative stain electron microscopy. Characterization of the full-length quaternary structures of the immunocytokines in solution by SAXS consistently supported the diabody structure in the L19-IL2 immunocytokine and allowed generation of low-resolution models of the chimeric proteins L19L19-IL2 and IL12-L19L19. Comparison with 3D reconstructions obtained from negative-stain electron microscopy revealed marked flexibility associated to the linker regions connecting the cytokine and the antibody components of the chimeric proteins. Collectively, our results indicate that low-resolution molecular structure characterizations provide useful complementary insights for the quality control of immunocytokines, constituting a powerful tool to guide the design and the subsequent optimization steps towards clinical enhancement of these chimeric protein reagents.


Subject(s)
Cytokines/chemistry , Animals , Cell Line, Tumor , Humans , Mice , Molecular Structure , Recombinant Fusion Proteins/chemistry , Scattering, Small Angle , X-Ray Diffraction/methods
10.
Sensors (Basel) ; 22(1)2021 Dec 27.
Article in English | MEDLINE | ID: mdl-35009691

ABSTRACT

Soil temperatures play an important role in determining the distribution and function of organisms. However, soil temperature is decoupled from air temperature and varies widely in space. Characterizing and predicting soil temperature requires large and expensive networks of data loggers. We developed an open-source soil temperature data logger and created online resources to ensure our design was accessible. We tested data loggers constructed by students, with little prior electronics experience, in the lab, and in the field in Alaska. The do-it-yourself (DIY) data logger was comparably accurate to a commercial system with a mean absolute error of 2% from -20-0 °C and 1% from 0-20 °C. They captured accurate soil temperature data and performed reliably in the field with less than 10% failing in the first year of deployment. The DIY loggers were ~1.7-7 times less expensive than commercial systems. This work has the potential to increase the spatial resolution of soil temperature monitoring and serve as a powerful educational tool. The DIY soil temperature data logger will reduce data collection costs and improve our understanding of species distributions and ecological processes. It also provides an educational resource to enhance STEM, accessibility, inclusivity, and engagement.


Subject(s)
Cold Temperature , Soil , Humans , Temperature
11.
Perfusion ; 36(2): 138-145, 2021 03.
Article in English | MEDLINE | ID: mdl-32650697

ABSTRACT

INTRODUCTION: The frequency of extracorporeal membrane oxygenation in pediatric patients continues to increase, especially in patients with complex congenital heart disease. Providing adequate anticoagulation is necessary for patients on extracorporeal membrane oxygenation and is achieved with adequate heparin administration. Antithrombin is administered to potentiate heparin's effects. However, the efficacy of antithrombin supplementation is unclear and a clear clinical benefit has not been established. We present a large retrospective study examining the effects of antithrombin on pediatric patients receiving extracorporeal membrane oxygenation. METHODS: Data for this study were obtained from the Pediatric Health Information System and Pediatric Health Information System+ databases from 2004 to 2015. Pediatric patients receiving extracorporeal membrane oxygenation with a congenital heart disease diagnosis were included and divided into groups that did or did not utilize antithrombin. For all admissions, the following were captured: age of admission, gender, year of admission, length of stay, billed charges, inpatient mortality, the presence of specific congenital malformations of the heart, specific cardiac surgeries, and comorbidities. RESULTS: A total of 9,193 admissions were included and 865 (9.4%) utilized antithrombin. Between groups, there were significantly different frequencies of co-morbidities, cardiac lesion types and antithrombin usage over the study period. There were significantly lower odds in the antithrombin group of venous thrombosis. Antithrombin was not significantly associated with hemorrhage; however, antithrombin was associated with increased inpatient mortality and a decrease in length of stay and billed charges. CONCLUSION: Antithrombin administration is associated with increased mortality, a shorter length of stay, and decreased billing cost. Recently, antithrombin usage has been decreasing-potentially due to the reported lack of clinical benefit. Together, these results reinforce that antithrombin may not be indicated for all pediatric extracorporeal membrane oxygenation patients.


Subject(s)
Antithrombins , Extracorporeal Membrane Oxygenation , Anticoagulants , Child , Heparin , Humans , Infant , Retrospective Studies
12.
Sci Rep ; 10(1): 19558, 2020 11 11.
Article in English | MEDLINE | ID: mdl-33177658

ABSTRACT

Rapid climate change has wide-ranging implications for the Arctic region, including sea ice loss, increased geopolitical attention, and expanding economic activity resulting in a dramatic increase in shipping activity. As a result, the risk of harmful non-native marine species being introduced into this critical region will increase unless policy and management steps are implemented in response. Using data about shipping, ecoregions, and environmental conditions, we leverage network analysis and data mining techniques to assess, visualize, and project ballast water-mediated species introductions into the Arctic and dispersal of non-native species within the Arctic. We first identify high-risk connections between the Arctic and non-Arctic ports that could be sources of non-native species over 15 years (1997-2012) and observe the emergence of shipping hubs in the Arctic where the cumulative risk of non-native species introduction is increasing. We then consider how environmental conditions can constrain this Arctic introduction network for species with different physiological limits, thus providing a tool that will allow decision-makers to evaluate the relative risk of different shipping routes. Next, we focus on within-Arctic ballast-mediated species dispersal where we use higher-order network analysis to identify critical shipping routes that may facilitate species dispersal within the Arctic. The risk assessment and projection framework we propose could inform risk-based assessment and management of ship-borne invasive species in the Arctic.

13.
Glob Chang Biol ; 26(11): 6616-6629, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32311220

ABSTRACT

Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.


Subject(s)
Ecosystem , Microclimate , Climate Change , Snow , Temperature
14.
Neurourol Urodyn ; 39(3): 890-897, 2020 03.
Article in English | MEDLINE | ID: mdl-32022321

ABSTRACT

BACKGROUND: There is a gap between pudendal neuralgia (PN) due to pudendal entrapment syndrome and PN without pudendal entrapment syndrome. The latter could have atypical symptoms. AIM: Defining a rate of atypical PN from a clinical series of female patients with chronic pelvic-perineal pain. METHODS: The atypical PN was defined as a pain not meeting clinical criteria for pudendal entrapment syndrome. The effect size was the rate of atypical PN. Such a rate was expected to be found among patients screened for enrollment in clinical series on pudendal neuropathic pain. A systematic search was performed looking for clinical series on PN. Studies must report information on female patients, pelvic-perineal pain, at least a clinical criterion for diagnosing the pudendal neurogenic origin of pain, the proportion of patients with pain not meeting the clinical criterion/a for diagnosing the pudendal entrapment pain. RESULTS: From 2637 references, nine studies were included for qualitative analysis. Three of them were not suitable for data synthesis: one assessed the rate of PN after hip arthroscopy; second enrolled miscellaneous patients, a third investigated patients with gynecological diseases. Six studies involved patients with suspicion of pudendal entrapment symptoms (205 patients observed), allowing data synthesis. One of these series was judged as being of good quality. The overall rate of atypical PN is 0.013 (95% confidence interval, 0.008-0.021), I2 0%. Further analysis suggests the risk of bias for all studies. CONCLUSIONS: Atypical PN in females is low when clinical criteria for pudendal entrapment syndrome are applied.


Subject(s)
Chronic Pain/physiopathology , Nerve Compression Syndromes/physiopathology , Neuralgia/physiopathology , Pelvic Pain/physiopathology , Pudendal Neuralgia/diagnosis , Female , Humans , Pelvis , Perineum , Pudendal Nerve , Pudendal Neuralgia/physiopathology
15.
New Phytol ; 223(1): 180-192, 2019 07.
Article in English | MEDLINE | ID: mdl-30883787

ABSTRACT

The response of vegetation to climate change has implications for the carbon cycle and global climate. It is frequently assumed that a species responds uniformly across its range to climate change. However, ecotypes - locally adapted populations within a species - display differences in traits that may affect their gross primary productivity (GPP) and response to climate change. To determine if ecotypes are important for understanding the response of ecosystem productivity to climate we measured and modeled growing season GPP in reciprocally transplanted and experimentally warmed ecotypes of the abundant Arctic sedge Eriophorum vaginatum. Transplanted northern ecotypes displayed home-site advantage in GPP that was associated with differences in leaf area index. Southern ecotypes exhibited a greater response in GPP when transplanted. The results demonstrate that ecotypic differentiation can impact the morphology and function of vegetation with implications for carbon cycling. Moreover they suggest that ecotypic control of GPP may limit the response of ecosystem productivity to climate change. This investigation shows that ecotypes play a substantial role in determining GPP and its response to climate. These results have implications for understanding annual to decadal carbon cycling where ecotypes could influence ecosystem function and vegetation feedbacks to climate change.


Subject(s)
Carbon Cycle , Climate Change , Ecotype , Arctic Regions , Cyperaceae , Gases/metabolism , Geography , Photosynthesis , Plant Leaves/anatomy & histology , Seasons , Temperature
16.
Front Mol Biosci ; 6: 156, 2019.
Article in English | MEDLINE | ID: mdl-31998752

ABSTRACT

Synapse formation is a very elaborate process dependent upon accurate coordination of pre and post-synaptic specialization, requiring multiple steps and a variety of receptors and signaling molecules. Due to its relative structural simplicity and the ease in manipulation and observation, the neuromuscular synapse or neuromuscular junction (NMJ)-the connection between motor neurons and skeletal muscle-represents the archetype junction system for studying synapse formation and conservation. This junction is essential for survival, as it controls our ability to move and breath. NMJ formation requires coordinated interactions between motor neurons and muscle fibers, which ultimately result in the formation of a highly specialized post-synaptic architecture and a highly differentiated nerve terminal. Furthermore, to ensure a fast and reliable synaptic transmission following neurotransmitter release, ligand-gated channels (acetylcholine receptors, AChRs) are clustered on the post-synaptic muscle cell at high concentrations in sites opposite the presynaptic active zone, supporting a direct role for nerves in the organization of the post-synaptic membrane architecture. This organized clustering process, essential for NMJ formation and for life, relies on key signaling molecules and receptors and is regulated by soluble extracellular molecules localized within the synaptic cleft. Notably, several mutations as well as auto-antibodies against components of these signaling complexes have been related to neuromuscular disorders. The recent years have witnessed strong progress in the understanding of molecular identities, architectures, and functions of NMJ macromolecules. Among these, prominent roles have been proposed for neural variants of the proteoglycan agrin, its receptor at NMJs composed of the lipoprotein receptor-related protein 4 (LRP4) and the muscle-specific kinase (MuSK), as well as the regulatory soluble synapse-specific protease Neurotrypsin. In this review we summarize the current state of the art regarding molecular structures and (agrin-dependent) canonical, as well as (agrin-independent) non-canonical, MuSK signaling mechanisms that underscore the formation of neuromuscular junctions, with the aim of providing a broad perspective to further stimulate molecular, cellular and tissue biology investigations on this fundamental intercellular contact.

17.
J Virol Methods ; 261: 91-97, 2018 11.
Article in English | MEDLINE | ID: mdl-30125614

ABSTRACT

BACKGROUND: Commercially-available kits for HIV-1 detection include instructions for detecting HIV-1 in plasma and DBS, but don't support other specimen types. OBJECTIVES: Show quantitative stability of HIV-1 total nucleic acid (TNA) in blood and improved HIV-1 detection in alternative specimen types. STUDY DESIGN: Whole blood and DBS specimens, tested as part of an external quality assurance program for qualitative HIV-1 detection, were used to evaluated error rates (false negative [FN], false positive [FP] and indeterminant [IND] results) across assays (internally developed [IH], Roche Amplicor [RA], and Roche TaqMan Qual [TQ]) and specimen types (frozen whole blood [BLD], DBS and cell pellets [PEL]). A modified Roche TaqMan HIV-1 assay was used to quantify HIV-1 TNA. RESULTS: Significantly higher error rates were noted in DBS across all of the assays (4% vs. 0% for DBS and PEL, IH, p = 0.005; 4% vs. 0.1% for DBS and PEL, RA, p < 0.001; 10% vs. 1% for DBS and PEL or BLD, TQ, p < 0.001). HIV TNA concentration is stable in BLD (day 1 vs. day 10, p = 0.39) and higher than DBS (p < 0.001). CONCLUSIONS: Transporting refrigerated whole blood for centralized processing into alternative specimen types will improve the sensitivitiy of HIV-1 detection in samples with low virus loads.


Subject(s)
HIV Infections/diagnosis , HIV-1/isolation & purification , RNA, Viral/analysis , Specimen Handling/methods , Diagnostic Errors , HIV-1/genetics , RNA, Viral/genetics , Sensitivity and Specificity
18.
J Clin Microbiol ; 56(6)2018 06.
Article in English | MEDLINE | ID: mdl-29618501

ABSTRACT

The National Institute of Allergy and Infectious Diseases (NIAID) AIDS Clinical Trials Group (ACTG) stores specimens from its clinical trials in a biorepository and permits the use of these specimens for nonprotocol exploratory studies, once the studies for the original protocol are concluded. We sought to assess the comparability of the data generated from real-time HIV-1 RNA testing during two clinical trials with the data generated from the retesting of different aliquots of the same samples after years of storage at -80°C. Overall, there was 92% agreement in the data generated for 1,570 paired samples (kappa statistic = 0.757; 95% confidence interval [CI], 0.716 to 0.797), where samples were tested in one laboratory using the microwell plate (MWP) version of the Roche HIV-1 Monitor test within 1 to 37 days of collection and retested in another laboratory using the Cobas version of the assay after a median of 6.7 years of storage (range, 5.7 to 8.6 years). Historical external quality control data submitted to the NIAID Virology Quality Assurance program (VQA) by client laboratories using the same two versions of the Monitor assay were used to differentiate between systematic differences in the assays to evaluate the stability of HIV-1 RNA in the stored samples. No significant loss of RNA was noted in samples containing either a low concentration (<50 copies/ml) or a high concentration (≥50 copies/ml) of HIV-1 RNA (P = 0.10 and P = 0.90, respectively) regardless of the time in storage. These data confirm the quality of the plasma samples in the ACTG biorepository following long-term storage.


Subject(s)
HIV-1/genetics , Laboratories , Quality Control , RNA Stability , RNA, Viral/genetics , Specimen Handling/standards , Biological Specimen Banks , Data Analysis , HIV Infections/blood , HIV Infections/virology , Humans , Reagent Kits, Diagnostic , Sensitivity and Specificity , Viral Load
19.
Perfusion ; 33(7): 538-545, 2018 10.
Article in English | MEDLINE | ID: mdl-29638199

ABSTRACT

INTRODUCTION: Cardiopulmonary bypass (CPB) is known to cause a systemic inflammatory and immune response. OBJECTIVE: An in-vitro model of cardiotomy suction was designed to quantify the effects of incrementally increased air-blood exposure on leucocyte marker CD11b and cytokine activation in two common anticoagulants, heparin and citrate. METHODS: Fresh human blood was exposed to increasing amounts of air flow for ten minutes. Leucocyte and cytokine levels were measured prior to and after ten minutes of air flow. Cytokine levels were also measured after air exposure when incubated for 24 hours at 37oC. RESULTS: Leucocyte activation, measured by CD11b, was elevated between baseline and air flow rates up to 50 mL/min. After 10 minutes of air exposure, no measured cytokine levels were elevated. After 24 hours of incubation, cytokine levels of TNFα, IL-10, IL-6, and IL-8 were elevated. However, only IL-8 was significantly elevated in citrated blood, but not in heparinized blood, when compared to baseline samples that were also incubated for 24 hours. CONCLUSION: This study investigates CD11b levels in response to an air stimulus in blood that was anticoagulated with citrate or heparin. Exposure to an air stimulus activates leucocytes. Activation of CD11b was less when using heparin as an anticoagulant compared to citrate. Cytokine activation occurs with air stimulation, but levels do not immediately rise, indicating that time is required to generate free cytokines.


Subject(s)
Cardiopulmonary Bypass/methods , Cytokines/metabolism , Leukocytes/metabolism , Suction/methods , Humans
20.
Phys Rev Lett ; 116(8): 086403, 2016 Feb 26.
Article in English | MEDLINE | ID: mdl-26967431

ABSTRACT

We present evidence for Mott quantum criticality in an anisotropic two-dimensional system of coupled Hubbard chains at half-filling. In this scenario emerging from variational cluster approximation and cluster dynamical mean-field theory, the interchain hopping t_{⊥} acts as a control parameter driving the second-order critical end point T_{c} of the metal-insulator transition down to zero at t_{⊥}^{c}/t≃0.2. Below t_{⊥}^{c}, the volume of the hole and electron Fermi pockets of a compensated metal vanishes continuously at the Mott transition. Above t_{⊥}^{c}, the volume reduction of the pockets is cut off by a first-order transition. We discuss the relevance of our findings to a putative quantum critical point in layered organic conductors, whose location remains elusive so far.

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