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1.
Phys Rev Lett ; 130(19): 192502, 2023 May 12.
Article in English | MEDLINE | ID: mdl-37243659

ABSTRACT

We present the first measurement of the α-ß-ν angular correlation in the Gamow-Teller ß^{+} decay of ^{8}B. This was accomplished using the Beta-decay Paul Trap, expanding on our previous work on the ß^{-} decay of ^{8}Li. The ^{8}B result is consistent with the V-A electroweak interaction of the standard model and, on its own, provides a limit on the exotic right-handed tensor current relative to the axial-vector current of |C_{T}/C_{A}|^{2}<0.013 at the 95.5% confidence level. This represents the first high-precision angular correlation measurements in mirror decays and was made possible through the use of an ion trap. By combining this ^{8}B result with our previous ^{8}Li results, we demonstrate a new pathway for increased precision in searches for exotic currents.

2.
Sci Total Environ ; 661: 364-374, 2019 Apr 15.
Article in English | MEDLINE | ID: mdl-30677682

ABSTRACT

Stream temperature is a measure of water quality that reflects the balance of atmospheric heat exchange at the air-water interface and gains or losses of water along a stream reach. In urban areas, stormwater sewers deliver water with varying magnitude and temperature to streams at variable timescales. Understanding the impacts of stormwater through space and time is therefore difficult to do with conventional approaches like in situ sensors. To study the impacts of stormwater on creek water temperatures, we combined in situ water temperature observations with thermal infrared (TIR) imagery collected via unoccupied aerial vehicle (UAV). Imagery was collected in May, June, and July of 2017. As ongoing work with UAV-based TIR suggests that this imagery is prone to poor accuracy, we focused on creating several data products beyond absolute water temperatures that can be used to assess temporal and spatial water temperature variations. In particular, TIR data products were used to extract the length of the observed stormwater plume as well as the width of the creek cross-section impacted by stormwater. From these values, we conclude that relatively narrow stormwater plumes affecting a small fraction of creek width can alter creek water temperatures for considerable distances downstream. We also applied TIR data to constrain results of a deterministic stream temperature model (HFLUX 3.0) that simulates the physical processes affecting stream heat exchanges. Stormwater plume lengths obtained from TIR imagery were used to refine spatially-distributed simulations, demonstrating that relative temperature information obtained from UAV imagery can provide useful calibration targets for stream temperature models. Overall, our work demonstrates the added value of UAV datasets for understanding urban stream temperatures, calibrating water quality models, and for modeling and monitoring of the impact of spatially explicit hydrologic processes on stream temperature.

4.
Aliment Pharmacol Ther ; 48(3): 290-299, 2018 08.
Article in English | MEDLINE | ID: mdl-29797529

ABSTRACT

BACKGROUND: Obesity and decreased physical activity mirror increasing prevalence of nonalcoholic fatty liver disease (NAFLD). AIM: We aimed to investigate associations between aerobic fitness, anthropometrics and disease parameters in patients with nonalcoholic steatohepatitis (NASH). We hypothesised that NASH subjects have lower aerobic power and capacity than untrained, sedentary, normal subjects. METHODS: Forty subjects (60% obese, 40% overweight) with biopsy-confirmed NASH and NAFLD activity score (NAS) ≥4 were enrolled in a clinical trial where anthropometrics, laboratories, liver fat content by MRI, activity, and aerobic fitness by cycle ergometry data were obtained. RESULTS: NASH subjects were significantly deconditioned compared to 148 untrained, sedentary, healthy subjects from our laboratory in aerobic power (VO2peak) (NASH 16.8 ± 6.6 vs control 28.4 ± 10.6 mL/kg/min, P < 0.0001) and capacity (VO2 at lactate threshold [LT]) (NASH 8.3 ± 2.5 vs control 14.1 ± 5.9 mL/kg/min, P < 0.0001). NASH subjects' fitness was comparable to the "least fit" tertile of controls: VO2peak [NASH 16.8 ± 6.6 vs "least fit" 17.3 ± 3.3, P = 0.64]) and VO2 at LT (NASH 8.3 ± 2.5 vs "least fit" 9.3 ± 2.1, P = 0.31). Fitness was similar in obese compared to overweight subjects (adjusted for gender) and was not correlated with visceral adiposity or NAS. Engaging in dedicated cardiovascular activity correlated with higher VO2peak and VO2peak at LT. CONCLUSIONS: Aerobic deconditioning was universally present in NASH subjects. NASH subjects' fitness was similar to our laboratory's "least fit" untrained, sedentary control subjects. Further research investigating NASH patients' ability to improve low baseline aerobic fitness is warranted.


Subject(s)
Non-alcoholic Fatty Liver Disease , Overweight , Physical Fitness , Adult , Biopsy , Exercise , Female , Humans , Liver/diagnostic imaging , Liver/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/pathology , Overweight/diagnosis , Overweight/pathology
5.
Diagn Interv Imaging ; 98(11): 801-808, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28416166

ABSTRACT

PURPOSE: To assess the 2-year effectiveness and safety of balloon-occluded retrograde transvenous obliteration (BRTO) for gastric varices (GVs) in liver transplant recipients. MATERIALS AND METHODS: Eleven liver transplant recipients underwent consecutive BRTO for GVs at four institutions. Patients included eight (73%) men and three (27%) women with mean age of 56 years±12 (SD) (range: 26-67 years). Underlying cause of liver transplantation was hepatitis C virus (HCV)-related cirrhosis in five (45%), alcohol- and HCV-related cirrhosis in three (27%), primary biliary cirrhosis in two (18%), and alcoholic cirrhosis in one (9%). Five (45%) patients underwent BRTO for actively bleeding GVs, three (17%) for high-risk GVs, and three (17%) for augmentation of portal venous flow through obliteration of gastrorenal shunts. Mean time between liver transplantation and BRTO was 78 months (range: 0.1-276 months). Technical success, GVs obliterative rates, and immediate complications were recorded. Post-BRTO hemorrhagic, transplant, and overall survival rates were evaluated at 6, 12, and 24 months. RESULTS: All (100%) procedures were technically successful. Complete GVs obliteration was achieved in ten patients (91%). Two major complications (18%) occurred in the immediate post-procedure period. One patient developed complete portal vein thrombosis, and another patient developed consumptive coagulopathy, ultimately leading to death. No post-BRTO hemorrhagic recurrences were seen at 6, 12, or 24 months. One patient (9%) had delayed upper gastrointestinal bleeding at 34 months after the procedure which was managed conservatively. Transplant and overall survival rates were 91% at 6, 12, and 24 months. CONCLUSION: BRTO has high technical success and complete GVs obliterative rates in liver transplant recipients with few complications and high graft survival rates.


Subject(s)
Balloon Occlusion , Esophageal and Gastric Varices/therapy , Gastrointestinal Hemorrhage/therapy , Liver Transplantation , Adult , Aged , Balloon Occlusion/adverse effects , Esophageal and Gastric Varices/complications , Female , Gastrointestinal Hemorrhage/etiology , Humans , Male , Middle Aged , Transplant Recipients
7.
Dig Dis Sci ; 61(6): 1721-7, 2016 06.
Article in English | MEDLINE | ID: mdl-26725062

ABSTRACT

BACKGROUND AND AIMS: Direct oral anticoagulants (DOAC) are important new anticoagulant therapies that are not well studied in patients with chronic liver disease. The aim of this study was to compare rates of bleeding in cirrhosis patients treated with DOAC (factor Xa inhibitors: rivaroxaban and apixaban) to those in cirrhosis patients treated with traditional anticoagulation (warfarin and low molecular weight heparin). METHODS: We identified a total of 39 patients with cirrhosis who received anticoagulation therapy over a 3-year period (20 DOAC and 19 traditional anticoagulation) from a research database. Medical records were reviewed to obtain clinical data to compare between the groups. RESULTS: Clinical characteristics between the two groups were similar. There were three documented bleeding events in the traditional anticoagulation group and four bleeding events in the DOAC group (p = 0.9). There were two major bleeding events in the traditional anticoagulation group and one major bleeding event in the DOAC group. There were no documented reports of drug-induced liver injury during this study period. Among all patients, no significant predictors of bleeding were identified using univariate regression and Cox proportional hazard modeling. CONCLUSIONS: This is the first clinical study evaluating the use of DOAC in patients with cirrhosis. DOAC display similar safety characteristics when compared to traditional anticoagulation in patients with cirrhosis and are potentially attractive agents for anticoagulation therapy. Larger studies are now needed to better understand the safety and efficacy of these agents in cirrhosis.


Subject(s)
Anticoagulants/adverse effects , Hemorrhage/chemically induced , Liver Cirrhosis/complications , Administration, Oral , Anticoagulants/administration & dosage , Humans , Risk Factors
8.
Reprod Biol Endocrinol ; 13: 124, 2015 Nov 14.
Article in English | MEDLINE | ID: mdl-26577904

ABSTRACT

BACKGROUND: We tested the hypothesis that organelles in bovine oocytes undergo changes in number and spatial distribution in a manner specific for phase of follicle development. METHODS: Cumulus-oocyte-complexes were collected from Hereford heifers by ultrasound-guided follicle aspiration from dominant follicles in the growing phase (n = 5; Day 0 = ovulation), static phase (n = 5), regressing phase (n = 7) of Wave 1 and from preovulatory follicles (n = 5). Oocytes were processed and transmission electron micrographs of ooplasm representing peripheral, perinuclear and central regions were evaluated using standard stereological methods. RESULTS: The number of mitochondria and volume occupied by lipid droplets was higher (P < 0.03) in oocytes from regressing follicles (193.0 ± 10.4/1000 µm(3) and 3.5 ± 0.7 %) than growing and preovulatory stages (118.7 ± 14.4/1000 µm(3) and 1.1 ± 0.3 %; 150.5 ± 28.7/1000 µm(3) and 1.6 ± 0.2 %, respectively). Oocytes from growing, static and preovulatory follicles had >70 % mitochondria in the peripheral regions whereas oocytes from regressing follicles had an even distribution. Oocytes from growing follicles had more lipid droplets in peripheral region than in central region (86.9 vs. 13.1 %). Percent surface area of mitochondria in contact with lipid droplets increased from growing (2.3 %) to static, regressing or preovulatory follicle stage (8.9, 6.1 and 6.2 %). The amount, size and distribution of other organelles did not differ among phases (P > 0.11). CONCLUSIONS: Our hypothesis was supported in that mitochondrial number increased and translocation occurred from a peripheral to an even distribution as follicles entered the regressing phase. In addition, lipid droplets underwent spatial reorganization from a peripheral to an even distribution during the growing phase and mitochondria-lipid contact area increased with follicle maturation.


Subject(s)
Cattle/growth & development , Oocytes/ultrastructure , Ovarian Follicle/growth & development , Animals , Cattle/metabolism , Female , Follicular Fluid/metabolism , Oocytes/growth & development , Oocytes/metabolism , Organelles/metabolism , Organelles/ultrastructure
9.
Phys Rev Lett ; 115(18): 182501, 2015 Oct 30.
Article in English | MEDLINE | ID: mdl-26565463

ABSTRACT

In the standard model, the weak interaction is formulated with a purely vector-axial-vector (V-A) structure. Without restriction on the chirality of the neutrino, the most general limits on tensor currents from nuclear ß decay are dominated by a single measurement of the ß-ν[over ¯] correlation in ^{6}He ß decay dating back over a half century. In the present work, the ß-ν[over ¯]-α correlation in the ß decay of ^{8}Li and subsequent α-particle breakup of the ^{8}Be^{*} daughter was measured. The results are consistent with a purely V-A interaction and in the case of couplings to right-handed neutrinos (C_{T}=-C_{T}^{'}) limits the tensor fraction to |C_{T}/C_{A}|^{2}<0.011 (95.5% C.L.). The measurement confirms the ^{6}He result using a different nuclear system and employing modern ion-trapping techniques subject to different systematic uncertainties.

10.
J Clin Imaging Sci ; 4: 24, 2014.
Article in English | MEDLINE | ID: mdl-24987571

ABSTRACT

OBJECTIVES: Gastric varices primarily occur in cirrhotic patients with portal hypertension and splenomegaly and thus are probably associated with thrombocytopenia. However, the prevalence and severity of thrombocytopenia are unknown in this clinical setting. Moreover, one-third of patients after balloon-occluded retrograde transvenous obliteration (BRTO) have aggravated splenomegaly, which potentially may cause worsening thrombocytopenia. The aim of the study is to determine the prevalence and degree of thrombocytopenia in patients with gastric varices associated with gastrorenal shunts undergoing BRTO, to determine the prognostic factors of survival after BRTO (platelet count included), and to assess the effect of BRTO on platelet count over a 1-year period. MATERIALS AND METHODS: This is a retrospective review of 35 patients who underwent BRTO (March 2008-August 2011). Pre- and post-BRTO platelet counts were noted. Potential predictors of bleeding and survival (age, gender, liver disease etiology, platelet count, model for end stage liver disease [MELD]-score, presence of ascites or hepatocellular carcinoma) were analyzed (multivariate analysis). A total of 91% (n = 32/35) of patients had thrombocytopenia (<150,000 platelet/cm(3)) pre-BRTO. Platelet counts at within 48-h, within 2 weeks and at 30-60 days intervals (up to 6 months) after BRTO were compared with the baseline pre-BRTO values. RESULTS: 35 Patients with adequate platelet follow-up were found. A total of 92% and 17% of patients had a platelet count of <150,000/cm(3) and <50,000/cm(3), respectively. There was a trend for transient worsening of thrombocytopenia immediately (<48 h) after BRTO, however, this was not statistically significant. Platelet count was not a predictor of post-BRTO rebleeding or patient survival. However, MELD-score, albumin, international normalized ratio (INR), and etiology were predictors of rebleeding. CONCLUSION: Thrombocytopenia is very common (>90% of patients) in patients undergoing BRTO. However, BRTO (with occlusion of the gastrorenal shunt) has little effect on the platelet count. Long-term outcomes of BRTO for bleeding gastric varices using sodium tetradecyl sulfate in the USA are impressive with a 4-year variceal rebleed rate and transplant-free survival rate of 9% and 76%, respectively. Platelet count is not a predictor of higher rebleeding or patient survival after BRTO.

11.
Phys Rev Lett ; 111(6): 061102, 2013 Aug 09.
Article in English | MEDLINE | ID: mdl-23971550

ABSTRACT

The Canadian Penning Trap mass spectrometer has made mass measurements of 33 neutron-rich nuclides provided by the new Californium Rare Isotope Breeder Upgrade facility at Argonne National Laboratory. The studied region includes the 132Sn double shell closure and ranges in Z from In to Cs, with Sn isotopes measured out to A=135, and the typical measurement precision is at the 100 ppb level or better. The region encompasses a possible major waiting point of the astrophysical r process, and the impact of the masses on the r process is shown through a series of simulations. These first-ever simulations with direct mass information on this waiting point show significant increases in waiting time at Sn and Sb in comparison with commonly used mass models, demonstrating the inadequacy of existing models for accurate r-process calculations.

12.
Rev Sci Instrum ; 84(7): 073504, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23902060

ABSTRACT

The gas Cherenkov detectors at NIF and Omega measure several ICF burn characteristics by detecting multi-MeV nuclear γ emissions from the implosion. Of primary interest are γ bang-time (GBT) and burn width defined as the time between initial laser-plasma interaction and peak in the fusion reaction history and the FWHM of the reaction history respectively. To accurately calculate such parameters the collaboration relies on Monte Carlo codes, such as GEANT4 and ACCEPT, for diagnostic properties that cannot be measured directly. This paper describes a series of experiments performed at the High Intensity γ Source (HIγS) facility at Duke University to validate the geometries and material data used in the Monte Carlo simulations. Results published here show that model-driven parameters such as intensity and temporal response can be used with less than 50% uncertainty for all diagnostics and facilities.

13.
Phys Rev Lett ; 110(9): 092501, 2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23496704

ABSTRACT

A novel technique for ß-delayed neutron spectroscopy has been demonstrated using trapped ions. The neutron-energy spectrum is reconstructed by measuring the time of flight of the nuclear recoil following neutron emission, thereby avoiding all the challenges associated with neutron detection, such as backgrounds from scattered neutrons and γ rays and complicated detector-response functions. (137)I(+) ions delivered from a (252)Cf source were confined in a linear Paul trap surrounded by radiation detectors, and the ß-delayed neutron-energy spectrum and branching ratio were determined by detecting the ß(-) and recoil ions in coincidence. Systematic effects were explored by determining the branching ratio three ways. Improvements to achieve higher detection efficiency, better energy resolution, and a lower neutron-energy threshold are proposed.

14.
Phys Rev Lett ; 110(9): 092502, 2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23496705

ABSTRACT

A measurement of the α-ß-ν[over ¯] angular correlation in the Gamow-Teller decay (8)Li→(8)Be(*)+ν[over ¯]+ß, (8)Be(*)→α+α has been performed using ions confined in a linear Paul trap surrounded by silicon detectors. The energy difference spectrum of the α particles emitted along and opposite the direction of the ß particle is consistent with the standard model prediction and places a limit of 3.1% (95.5% confidence level) on any tensor contribution to the decay. From this result, the amplitude of any tensor component C(T) relative to that of the dominant axial-vector component C(A) of the electroweak interaction is limited to |C(T)/C(A)|<0.18 (95.5% confidence level). This experimental approach is facilitated by several favorable features of the (8)Li ß decay and has different systematic effects than the previous ß-ν[over ¯] correlation results for a pure Gamow-Teller transition obtained from studying (6)He ß decay.

15.
Disabil Rehabil ; 35(12): 995-1005, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23035881

ABSTRACT

PURPOSE: This study explores the experiences and sense of burden of family carers of survivors of malignant middle cerebral artery infarctions who had undergone decompressive hemicraniectomy. To date, there have been no studies examining carer outcomes among this unique population. This study, taken alongside an already published study of survivor outcomes, provides a more holistic picture with regard to sequelae within the sample. METHOD: Six family carers completed the Sense of Competence Questionnaire and the Hospital Anxiety and Depression Scale. These results were compared with existing normative data. Carers also consented to a semi-structured interview. Interview data were examined using thematic content analysis. Consistent with the mixed methods design, quantitative and qualitative findings were integrated for further analysis. RESULTS: While carers experienced many losses, their overall sense of burden was not outside 'Average' limits, nor did they experience clinically significant symptoms of depression. All carers identified methods of coping with the demands of caregiving. These included intrapersonal, interpersonal and practical strategies. All carers apart from one were able to identify areas of post-traumatic growth. CONCLUSION: Carers will benefit from information, support and care. In addition, problem solving skills are essential in managing the myriad difficulties that arise in the aftermath of stroke.


Subject(s)
Adaptation, Psychological , Caregivers/psychology , Cost of Illness , Decompressive Craniectomy/methods , Infarction, Middle Cerebral Artery/surgery , Adult , Caregivers/statistics & numerical data , Decompressive Craniectomy/mortality , Family/psychology , Female , Humans , Infarction, Middle Cerebral Artery/mortality , Interviews as Topic , Male , Middle Aged , Qualitative Research , Quality of Life , Social Support , Socioeconomic Factors , Stress, Psychological , Surveys and Questionnaires , Survivors
16.
Rev Sci Instrum ; 83(10): 10D719, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23126893

ABSTRACT

Fiber-optic transmission and recording systems, based on Mach-Zehnder modulators, have been developed and installed at the National Ignition Facility (NIF), and are being developed for other pulsed-power facilities such as the Z accelerator at Sandia, with different requirements. We present the design and performance characteristics for the mature analog links, based on the system developed for the Gamma Reaction History diagnostic at the OMEGA laser and at NIF. For a single detector channel, two Mach-Zehnders are used to provide high dynamic range at the full recording bandwidth with no gaps in the coverage. We present laboratory and shot data to estimate upper limits on the radiation effects as they impact recorded data quality. Finally, we will assess the technology readiness level for mature and developing implementations of Mach-Zehnder links for these environments.

17.
Disabil Rehabil ; 34(17): 1444-55, 2012.
Article in English | MEDLINE | ID: mdl-22233165

ABSTRACT

PURPOSE: This study examines long-term neuropsychological and psychosocial outcomes of survivors of malignant middle cerebral artery infarction treated via decompressive hemicraniectomy. METHOD: A case series design facilitated a detailed analysis of the outcomes among five participants. Neuropsychological domains assessed included premorbid and current IQ, sustained, selective and divided attention, visual and auditory memory, executive functioning and visuo-spatial ability. Psychosocial domains assessed included self-rated depression, anxiety and quality of life. Participants and their main carer were asked about their retrospective view of surgery. RESULTS: All participants showed neuropsychological impairments in multiple cognitive domains, with preserved ability in others. Effects of laterality of brain function were evident in some domains. Clinically significant depression was evident in two participants. Overall quality of life was within average limits in three of four assessed participants. Four participants retrospectively considered surgery as having been a favourable course of action. CONCLUSION: While neuropsychological impairments are highly likely post-surgery, preserved abilities and social support may serve a protective function against depression and an unacceptably poor quality of life. Results do not support the suggestion that decompressive hemicraniectomy following malignant middle cerebral artery infarction necessarily leads to unacceptable neuropsychological or psychosocial outcomes. [ IMPLICATIONS FOR REHABILITATION: • Malignant middle cerebral artery infarction is a life threatening condition.• The neurosurgical procedure, "decompressive hemicraniectomy" has been shown to be life-saving among patients with this condition.• There is little known about the long-term neuropsychological and psychosocial outcomes following decompressive hemicraniectomy for malignant middle cerebral artery infarction.• This study concludes that neuropsychological impairments are highly probable post-surgery. However, preserved abilities and social support may serve a protective function against depression and an unacceptably poor quality of life.]


Subject(s)
Depression/etiology , Infarction, Middle Cerebral Artery/psychology , Infarction, Middle Cerebral Artery/surgery , Quality of Life/psychology , Survivors/psychology , Adolescent , Adult , Age Factors , Cognition Disorders/complications , Decompressive Craniectomy/methods , Depression/psychology , Executive Function , Female , Humans , Infarction, Middle Cerebral Artery/rehabilitation , Male , Middle Aged , Neuropsychological Tests/statistics & numerical data , Recovery of Function , Retrospective Studies , Social Support , Time Factors , Treatment Outcome , Young Adult
18.
Genes Brain Behav ; 10(7): 720-33, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21679297

ABSTRACT

The α7-nicotinic acetylcholine receptor (nAChR) has long been a procognitive therapeutic target to treat schizophrenia. Evidence on the role of this receptor in cognition has been lacking, however, in part due to the limited availability of suitable ligands. The behavior of α7-nAChR knockout (KO) mice has been examined previously, but cognitive assessments using tests with cross-species translatability have been limited to date. Here, we assessed the cognitive performance of α7-nAChR KO and wild-type (WT) littermate mice in the attentional set-shifting task of executive functioning, the radial arm maze test of spatial working memory span capacity and the novel object recognition test of short-term memory. The reward motivation of these mutants was assessed using the progressive ratio breakpoint test. In addition, we assessed the exploratory behavior and sensorimotor gating using the behavioral pattern monitor and prepulse inhibition, respectively. α7-nAChR KO mice exhibited normal set-shifting, but impaired procedural learning (rule acquisition) in multiple paradigms. Spatial span capacity, short-term memory, motivation for food, exploration and sensorimotor gating were all comparable to WT littermates. The data presented here support the notion that this receptor is important for such procedural learning, when patterns in the environment become clear and a rule is learned. In combination with the impaired attention observed previously in these mice, this finding suggests that agonist treatments should be examined in clinical studies of attention and procedural learning, perhaps in combination with cognitive behavioral therapy.


Subject(s)
Attention/physiology , Executive Function/physiology , Maze Learning/physiology , Motivation/physiology , Receptors, Nicotinic/physiology , Animals , Cognition/physiology , Exploratory Behavior/physiology , Memory, Short-Term/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Pattern Recognition, Physiological/physiology , Receptors, Nicotinic/genetics , Recognition, Psychology/physiology , Sensory Gating/physiology , alpha7 Nicotinic Acetylcholine Receptor
19.
Genet Med ; 13(3): 230-54, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21325949

ABSTRACT

PURPOSE: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. METHODS: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25­30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. RESULTS: As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). CONCLUSION: An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders.


Subject(s)
Metabolic Diseases/diagnosis , Neonatal Screening , Tandem Mass Spectrometry , Amino Acids/blood , Carnitine/analogs & derivatives , Carnitine/blood , Humans , Infant, Newborn , International Cooperation , Reference Values , Sensitivity and Specificity , Software
20.
Rev Sci Instrum ; 81(10): 10D318, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21033844

ABSTRACT

We describe the evaluation of a microchannel plate (MCP) photomultiplier tube (PMT), incorporating a 3 µm pore MCP and constant voltage anode and cathode gaps. The use of the small pore size results in PMTs with response functions of the order of 85 ps full-width-half-maximum, while the constant electric field across the anode and cathode gaps produces a uniform response function over the entire operating range of the device. The PMT was characterized on a number of facilities and employed on gas Cherenkov detectors fielded on various deuterium tritium fuel (DT) implosions on the Omega Laser Facility at the University of Rochester. The Cherenkov detectors are part of diagnostic development to measure Gamma ray reaction history for DT implosions on the National Ignition Facility.

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