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101.
Dione T. Kobayashi Jing Shi Laurie Stephen Karri L. Ballard Ruth Dewey James Mapes Brett Chung Kathleen McCarthy Kathryn J. Swoboda Thomas O. Crawford Rebecca Li Thomas Plasterer Cynthia Joyce the Biomarkers for Spinal Muscular Atrophy Study Group Wendy K. Chung Petra Kaufmann Basil T. Darras Richard S. Finkel Douglas M. Sproule William B. Martens Michael P. McDermott Darryl C. De Vivo the Pediatric Neuromuscular Clinical Research Network Michael G. Walker Karen S. Chen 《PloS one》2013,8(4)
Objectives
Spinal Muscular Atrophy (SMA) presents challenges in (i) monitoring disease activity and predicting progression, (ii) designing trials that allow rapid assessment of candidate therapies, and (iii) understanding molecular causes and consequences of the disease. Validated biomarkers of SMA motor and non-motor function would offer utility in addressing these challenges. Our objectives were (i) to discover additional markers from the Biomarkers for SMA (BforSMA) study using an immunoassay platform, and (ii) to validate the putative biomarkers in an independent cohort of SMA patients collected from a multi-site natural history study (NHS).Methods
BforSMA study plasma samples (N = 129) were analyzed by immunoassay to identify new analytes correlating to SMA motor function. These immunoassays included the strongest candidate biomarkers identified previously by chromatography. We selected 35 biomarkers to validate in an independent cohort SMA type 1, 2, and 3 samples (N = 158) from an SMA NHS. The putative biomarkers were tested for association to multiple motor scales and to pulmonary function, neurophysiology, strength, and quality of life measures. We implemented a Tobit model to predict SMA motor function scores.Results
12 of the 35 putative SMA biomarkers were significantly associated (p<0.05) with motor function, with a 13th analyte being nearly significant. Several other analytes associated with non-motor SMA outcome measures. From these 35 biomarkers, 27 analytes were selected for inclusion in a commercial panel (SMA-MAP) for association with motor and other functional measures.Conclusions
Discovery and validation using independent cohorts yielded a set of SMA biomarkers significantly associated with motor function and other measures of SMA disease activity. A commercial SMA-MAP biomarker panel was generated for further testing in other SMA collections and interventional trials. Future work includes evaluating the panel in other neuromuscular diseases, for pharmacodynamic responsiveness to experimental SMA therapies, and for predicting functional changes over time in SMA patients. 相似文献102.
Tang J Cormier E Gilmour J Price MA Prentice HA Song W Kamali A Karita E Lakhi S Sanders EJ Anzala O Amornkul PN Allen S Hunter E Kaslow RA;IAVI African HIV Research Network 《Journal of virology》2011,85(17):8894-8902
As part of an ongoing study of early human immunodeficiency virus type 1 (HIV-1) infection in sub-Saharan African countries, we have identified 134 seroconverters (SCs) with distinct acute-phase (peak) and early chronic-phase (set-point) viremias. SCs with class I human leukocyte antigen (HLA) variants B*44 and B*57 had much lower peak viral loads (VLs) than SCs without these variants (adjusted linear regression beta values of -1.08 ± 0.26 log(10) [mean ± standard error] and -0.83 ± 0.27 log(10), respectively; P < 0.005 for both), after accounting for several nongenetic factors, including gender, age at estimated date of infection, duration of infection, and country of origin. These findings were confirmed by alternative models in which major viral subtypes (A1, C, and others) in the same SCs replaced country of origin as a covariate (P ≤ 0.03). Both B*44 and B*57 were also highly favorable (P ≤ 0.03) in analyses of set-point VLs. Moreover, B*44 was associated with relatively high CD4(+) T-cell counts during early chronic infection (P = 0.02). Thus, at least two common HLA-B variants showed strong influences on acute-phase as well as early chronic-phase VL, regardless of the infecting viral subtype. If confirmed, the identification of B*44 as another favorable marker in primary HIV-1 infection should help dissect mechanisms of early immune protection against HIV-1 infection. 相似文献
103.
Joan Puig-Barberà Juan García-de-Lomas Javier Díez-Domingo Alberto Arnedo-Pena Montserrat Ruiz-García Ramón Limón-Ramírez Silvia Pérez-Vilar José Luis Micó-Esparza Miguel Tortajada-Girbés Concha Carratalá-Munuera Rosa Larrea-González Juan Manuel Beltrán-Garrido Maria del Carmen Otero-Reigada Joan Mollar-Maseres Patricia Correcher-Medina Germán Schwarz-Chavarri Vicente Gil-Guillén for the Valencia Hospital Network for the Study of Influenza Respiratory Virus Disease 《PloS one》2014,9(11)
Background
Most evidence of the effectiveness of influenza vaccines comes from studies conducted in primary care, but less is known about their effectiveness in preventing serious complications. Here, we examined the influenza vaccine effectiveness (IVE) against hospitalization with PCR-confirmed influenza in the predominant A(H3N2) 2011–2012 influenza season.Methods
A hospital-based, test-negative study was conducted in nine hospitals in Valencia, Spain. All emergency admissions with a predefined subset of symptoms were eligible. We enrolled consenting adults age 18 and over, targeted for influenza vaccination because of comorbidity, with symptoms of influenza-like-illness within seven days of admission. We estimated IVE as (1-adjusted vaccination odds ratio)*100 after accounting for major confounders, calendar time and recruitment hospital.Results
The subjects included 544 positive for influenza A(H3N2) and 1,370 negative for influenza admissions. Age was an IVE modifying factor. Regardless of vaccine administration, IVE was 72% (38 to 88%) in subjects aged under 65 and 21% (−5% to 40%) in subjects aged 65 and over. By type of vaccine, the IVE of classical intramuscular split-influenza vaccine, used in subjects 18 to 64, was 68% (12% to 88%). The IVE for intradermal and virosomal influenza vaccines, used in subjects aged 65 and over, was 39% (11% to 58%) and 16% (−39% to 49%), respectively.Conclusions
The split-influenza vaccine was effective in preventing influenza-associated hospitalizations in adults aged under 65. The intradermal vaccine was moderately effective in those aged 65 and over. 相似文献104.
105.
Italian Network for Quality Assurance of Tumor Biomarkers 《The International journal of biological markers》2005,20(3):189-194
The clinical interest in HER-2/neu is related to trastuzumab, a drug used to treat patients with invasive breast carcinoma overexpressing the HER-2/neu protein. It is very important to correctly identify those patients who may benefit from trastuzumab by accurate assessment of the HER-2/neu status. Of the various methods available, the Dako Herceptest for immunohistochemical assay is considered the most reliable to reach this goal. The aim of this study was to investigate within a group of Italian laboratories the reproducibility of the results of HER-2/neu assessment by means of the Dako scoring system on slides stained with the Herceptest kit. This study was also conceived as the continuation of one of our previous studies, which was similar in its aims but different in the classification criteria adopted. Our results show that, whereas the intra-observer reproducibility was generally satisfactory, the interobserver reproducibility was not. Moreover, our findings confirm that the two extreme classes (0 and 3+) are more easy to identify than the other two and that the Herceptest does not allow to discriminate optimally between scoring classes 2+ and 3+. These findings are relevant in clinical practice where the treatment choice is based on categories defined by this assay, suggesting the need of adopting educational programs and/or new reference materials to improve the assay performance. 相似文献
106.
Silke Metzger Carolin Walter Olaf Riess Raymund A. C. Roos J?rgen E. Nielsen David Craufurd REGISTRY Investigators of the European Huntington’s Disease Network Huu Phuc Nguyen 《PloS one》2013,8(7)
The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis. 相似文献
107.
Mai CT Law DJ Mason CA McDowell BD Meyer RE Musa D;National Birth Defects Prevention Network 《Birth defects research. Part A, Clinical and molecular teratology》2007,79(12):811-814
Birth defects surveillance systems collect population-based birth defects data from multiple sources to track trends in prevalence, identify risk factors, refer affected families to services, and evaluate prevention efforts. Strong state and federal public health and legal mandates are in place to govern the collection and use of these data. Despite the prima facie appeal of "opt-in" and similar strategies to those who view data collection as a threat to privacy, the use of these strategies in lieu of population-based surveillance can severely limit the ability of public health agencies to accurately access the health status of a group within a defined geographical area. With the need for population-based data central to their mission, birth defects programs around the country take their data stewardship role seriously, recognizing both moral and legal obligations to protect the data by employing numerous safeguards. Birth defects surveillance systems are shaped by the needs of the community they are designed to serve, with the goal of preventing birth defects or alleviating the burdens associated with them. 相似文献
108.
Zhang S Mada SR Mattison D Caritis S Venkataramanan R;OPRU Network 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,856(1-2):141-147
A sensitive and specific method for the determination of 17alpha-hydroxyprogesterone caproate (17-OHPC) in human plasma using high-performance liquid chromatography and mass spectrometry has been developed and validated. Plasma samples were processed by a solid phase extraction (SPE) procedure using Oasis HLB extraction cartridge prior to chromatography. Medroxyprogesterone acetate (MPA) was used as the internal standard. Chromatography was performed using Waters C18 Symmetry analytical column, 3.5 microm, 2.1 mm x 10 mm, using a gradient elusion with a mobile phase consisting of acetonitrile [A] and 5% acetonitrile in water [B], with 0.1% formic acid being added to both [A] and [B], at a flow rate 0.2 ml/min. The retention times of 17-OHPC and MPA were 8.1 and 5.0 min, respectively, with a total run time of 15 min. Analysis was performed on Thermo Electron Finnigan TSQ Quantum Ultra mass spectrometer in a selected reaction-monitoring (SRM), positive mode using electron spray ionization (ESI) as an interface. Positive ions were measured using extracted ion chromatogram mode. The extracted ions following SRM transitions monitored were m/z 429.2-->313.13 and 429.2-->271.1, for 17-OHPC and m/z 385.1-->276 for MPA. The extraction recoveries at concentrations of 5, 10 and 50 ng/ml were 97.1, 92.6 and 88.7%, respectively. The assay was linear over the range 0.5-50 ng/ml for 17-OHPC. The analysis of standard samples for 17-OHPC 0.5, 1, 2.5, 5, 10, 25 and 50 ng/ml demonstrated a relative standard deviation of 16.7, 12.4, 13.7, 1.4, 5.2, 3.7 and 5.3%, respectively (n=6). This method is simple, adaptable to routine application, and allows easy and accurate measurement of 17-OHPC in human plasma. 相似文献
109.
GP Dolan PR Myles SJ Brett JE Enstone RC Read PJ Openshaw MG Semple WS Lim BL Taylor J McMenamin KG Nicholson B Bannister JS Nguyen-Van-Tam;the Influenza Clinical Information Network 《PloS one》2012,7(8):e41638
Introduction
The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy.Methods
A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical ''hubs'' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15–44 years, using univariate and multivariable techniques.Results
Of the 395 women aged 15–44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR = 0.49 (95% CI: 0.30–0.82)), require supplemental oxygen on admission (OR = 0.40 (95% CI: 0.20–0.80)), or have underlying co-morbidities (p-trend <0.001). However, they were equally likely to be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to die, after adjustment for potential confounders (adj. OR = 0.93 (95% CI: 0.46–1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died.Conclusions
Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1)pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups. 相似文献110.
Lander Ega?a-Gorro?o Tuixent Escribà Nicolas Boulanger Alberto Crespo Guardo Agathe León Manel Enric Bargalló Felipe Garcia José María Gatell Montserrat Plana Mireia Arnedo HIV Controllers Consortium of the AIDS Spanish Network 《PloS one》2014,9(9)