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1.
Nature ; 586(7830): 538-542, 2020 10.
Article in English | MEDLINE | ID: mdl-33087912

ABSTRACT

Monolithic integration of control technologies for atomic systems is a promising route to the development of quantum computers and portable quantum sensors1-4. Trapped atomic ions form the basis of high-fidelity quantum information processors5,6 and high-accuracy optical clocks7. However, current implementations rely on free-space optics for ion control, which limits their portability and scalability. Here we demonstrate a surface-electrode ion-trap chip8,9 using integrated waveguides and grating couplers, which delivers all the wavelengths of light required for ionization, cooling, coherent operations and quantum state preparation and detection of Sr+ qubits. Laser light from violet to infrared is coupled onto the chip via an optical-fibre array, creating an inherently stable optical path, which we use to demonstrate qubit coherence that is resilient to platform vibrations. This demonstration of CMOS-compatible integrated photonic surface-trap fabrication, robust packaging and enhanced qubit coherence is a key advance in the development of portable trapped-ion quantum sensors and clocks, providing a way towards the complete, individual control of larger numbers of ions in quantum information processing systems.

2.
Ann Oncol ; 33(12): 1250-1268, 2022 12.
Article in English | MEDLINE | ID: mdl-36228963

ABSTRACT

BACKGROUND: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. RESULTS: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Phthalazines/adverse effects , Germ Cells/pathology , BRCA1 Protein/genetics
4.
Res Rep Health Eff Inst ; (190): 1-75, 2017 Jan.
Article in English | MEDLINE | ID: mdl-31898879

ABSTRACT

INTRODUCTION: Ambient air pollution causes substantial morbidity and mortality in the United States and worldwide. To reduce this burden of adverse health effects, a broad array of strategies to reduce ambient air pollution has been developed and applied over past decades to achieve substantial reductions in ambient air pollution levels. This has been especially true in California, where the improvement of air quality has been a major focus for more than 50 years. Direct links between regulatory policies, changes in ambient pollutant concentrations, and improvements in public health have not been extensively documented. Data from the Children's Health Study (CHS), a multiyear study of children's respiratory health development, offered a unique opportunity to evaluate the effects of long-term reductions in air pollution on children's health. METHODS: We assessed whether changes in ambient air quality and emissions were reflected in three important indices of children's respiratory health: lung-function growth, lung-function level, and bronchitic symptoms. To make the best use of available data, these analyses were performed across the longest chronological period and largest CHS population available for the respective lung-function or bronchitic symptoms data sets. During field study operations over the course of the CHS, children's health status was documented annually by testing lung-function performance and the completion of standardized questionnaires covering a broad range of respiratory symptoms. Air quality data for the periods of interest were obtained from community monitoring stations, which operated in collaboration with regional air monitoring networks over the 20-year study time frame. Over the 20-year sampling period, common protocols were applied to collect data across the three cohorts of children. Each cohort's data set was assessed to investigate the relationship between temporal changes in lung-function development, prevalence of bronchitic symptoms, and ambient air pollution concentrations during a similar, vulnerable adolescent growth period (age 11 to 15 years). Analyses were performed separately for particulate matter ≤10 µm in aerodynamic diameter (PM10), particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5), ozone (O3), and nitrogen dioxide (NO2). Emissions data and regulatory policies were collected from the staff of state and regional regulatory agencies, modeling estimates, and archived reports. RESULTS: Emissions in the regions of California studied during the 20-year period decreased by 54% for oxides of nitrogen (NOₓ), 65% for reactive organic gases (ROG), 21% for PM2.5, and 15% for PM10. These reductions occurred despite a concurrent 22% increase in population and a 38% increase in motor vehicle miles driven during that time frame. Air quality improved over the same time frame, with reductions in NO2 and PM2.5 in virtually all of the CHS communities. Annual average NO2 decreased by about 53% (from ~41 to 19 ppb) in the highest NO2-reporting community (Upland) and by about 28% (from ~10 to 7 ppb) in one of the lowest NO2-reporting communities (Santa Maria). Reductions in annual average PM2.5 concentrations ranged from 54% (~33 to 15 µg/m³) in the community with the highest concentration (Mira Loma) to 13% (~9 to 8 µg/m³) in a community with one of the lowest concentrations (Santa Maria). Improvements in PM10 and O3 (measured during eight daytime hours, 10 AM to 6 PM) were most evident in the CHS communities that initially had the highest levels of PM and O3. Trends in annual average NO2, PM2.5, and PM10 ambient air concentrations in the communities with higher-pollution levels were generally consistent with observed trends in NOₓ, ROG, PM2.5, and PM10 emissions.Significant improvements in lung-function growth in progressive cohorts were observed as air quality improved over the study period. Improvements in four-year growth of both forced expiratory volume in the first second of exhalation (FEV1) and forced vital capacity (FVC) were associated with declining levels of NO2 (P < 0.0001), PM2.5 (P < 0.01), and PM10 (P < 0.001). These associations persisted after adjustment for important potential confounders. Further, significant improvements in lung-function growth were observed in both boys and girls and among asthmatic and non-asthmatic children. Within-community decreases in O3 exposure were not significantly associated with lung-function growth. The proportion of children with clinically low FEV1 (defined as <80% predicted) at age 15 declined significantly, from 7.9% to 3.6% across the study periods, respectively, as the air quality improved (P < 0.005). We found little evidence to suggest that improvements in lung-function development were attributable to temporal confounding.Reductions in outdoor levels of NO2, O3, PM10, and PM2.5 across the cohort years of participation were associated with significant reductions in the prevalence of bronchitic symptoms regardless of asthma status, but observed improvements were larger in children with asthma. Among asthmatic children, the reductions in prevalence of bronchitic symptoms at age 10 were 21% (P < 0.01) for NO2, 34% (P < 0.01) for O3, 39% (P < 0.01) for PM10, and 32% (P < 0.01) for PM2.5 for reductions of 4.9 ppb, 3.6 ppb, 5.8 µg/m³, and 6.8 µg/m³, respectively. Similar reductions in prevalence of bronchitic symptoms were observed at age 15 among these same asthmatic children. As in the lung-function analyses, we found little evidence that temporal confounding accounted for the observed associations of symptoms reduction with air quality improvement.The large number and breadth of regulatory activities, as well as the prolonged phase-in periods of several policy approaches to reduce emissions, precluded the close temporal linkage of specific policies with specific changes in health status. However, the combination of policies addressing motor vehicle emissions - from on-board diagnostics to emission controls, from low-sulfur fuels to vehicle smog-check recertification, and from re-formulated gasoline to the various strategies contained within the San Pedro Bay Ports Clean Air Plan (especially the Clean Truck Program) - all contributed to an impressive and substantial reduction in emissions. These reductions collectively improved local and regional air quality, and improvements in local and regional air quality were associated with improvements in respiratory health. CONCLUSIONS: This study provides evidence that multiyear improvements in air quality and emissions, primarily driven through a broad array of science-based regulatory policy initiatives, have resulted in improved public health outcomes. Our study demonstrates that improvements in air quality, brought about by science-based regulatory actions, are associated with improved respiratory health in children. These respiratory health metrics include reductions in respiratory symptoms and improvements in lung-function development in a population widely accepted to be at risk and highly vulnerable to the effects of air pollution. Our research findings underscore the importance of sustained air regulatory efforts as an effective means of achieving improved respiratory health in communities and regions affected by airborne pollution.

5.
Phys Rev Lett ; 108(11): 113002, 2012 Mar 16.
Article in English | MEDLINE | ID: mdl-22540471

ABSTRACT

Antihydrogen atoms (H¯) are confined in an Ioffe trap for 15-1000 s-long enough to ensure that they reach their ground state. Though reproducibility challenges remain in making large numbers of cold antiprotons (p¯) and positrons (e(+)) interact, 5±1 simultaneously confined ground-state atoms are produced and observed on average, substantially more than previously reported. Increases in the number of simultaneously trapped H¯ are critical if laser cooling of trapped H¯ is to be demonstrated and spectroscopic studies at interesting levels of precision are to be carried out.

6.
Anal Bioanal Chem ; 403(10): 3051-6, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22566198

ABSTRACT

Anthelmintic drugs are used in clinical and veterinary practice for the treatment of infections caused by parasitic worms. Their extensive use in food-producing animals can cause the presence of residues in food. For consumer protection it is necessary to monitor the levels of anthelmintic residues to ensure that they remain within the legally permitted maximum acceptable concentrations. For this purpose, the use of multiplex screening methods is advantageous. Biochip array technology allows the simultaneous determination of multiple analytes from a single sample at a single point in time. This study reports the development of an Evidence biochip array for the multiplex screening of anthelmintic drugs. Simultaneous competitive chemiluminescent immunoassays are employed. The solid support and vessel is the biochip, which contains an array of discrete test sites. The assays were applied to the semiautomated bench-top analyser Evidence Investigator. The aminobenzimidazoles assay detected aminomebendazole, albendazole 2-aminosulphone and aminoflubendazole, the avermectins assay detected emamectin benzoate, eprinomectin, abamectin, ivermectin and doramectin, the benzimidazoles assay detected albendazole sulphone, albendazole, albendazole sulphoxide, oxibendazole, oxfendazole and flubendazole, the thiabendazole assay detected cambendazole, thiabendazole and 5-hydroxythiabendazole and the triclabendazole assay detected ketotriclabendazole, triclabendazole and triclabendazole sulphoxide. The limits of detection ranged from 0.3 ppb (aminobenzimidazoles) to 2.0 ppb (levamisole) in milk and from 0.15 ppb (aminobenzimidazoles) to 6.5 ppb (levamisole) in tissue. The average recovery range was 71-135 %. This multianalytical approach on a biochip platform is applicable to the screening of more than 20 anthelmintic drugs in different food matrices, leading to consolidation of tests and enhancement of the test result output.


Subject(s)
Anthelmintics/analysis , Drug Evaluation, Preclinical/methods , Microarray Analysis/methods , Animals , Cattle , Immunoassay/methods , Indicators and Reagents , Luminescent Measurements/methods , Milk/chemistry
7.
Am J Emerg Med ; 30(2): 267-74, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21208763

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the diagnostic efficacy of multiple tests-heart-type fatty acid-binding protein (H-FABP), cardiac troponin I (cTnI), creatine kinase-MB, and myoglobin-for the early detection of acute myocardial infarction among patients who present to the emergency department with chest pain. METHODS: A total of 1128 patients provided a total of 2924 venous blood samples. Patients with chest pain were nonselected and treated according to hospital guidelines. Additional cardiac biomarkers were assayed simultaneously at serial time points using the Cardiac Array (Randox Laboratories Ltd, Crumlin, United Kingdom). RESULTS: Heart-type fatty acid-binding protein had the greatest sensitivity at 0 to 3 hours (64.3%) and 3 to 6 hours (85.3%) after chest pain onset. The combination of cTnI measurement with H-FABP increased sensitivity to 71.4% at 3 to 6 hours and 88.2% at 3 to 6 hours. Receiver operating characteristic curves demonstrated that H-FABP had the greatest diagnostic ability with area under the curve at 0 to 3 hours of 0.841 and 3 to 6 hours of 0.894. The specificity was also high for the combination of H-FABP with cTnI at these time points. Heart-type fatty acid-binding protein had the highest negative predictive values of all the individual markers: 0 to 3 hours (93%) and 3 to 6 hours (97%). Again, the combined measurement of cTnI with H-FABP increased the negative predictive values to 94% at 0 to 3 hours, 98% at 3 to 6 hours, and 99% at 6 to 12 hours. CONCLUSION: Testing both H-FABP and cTnI using the Cardiac Array proved to be both a reliable diagnostic tool for the early diagnosis of myocardial infarction/acute coronary syndrome and also a valuable rule-out test for patients presenting at 3 to 6 hours after chest pain onset.


Subject(s)
Fatty Acid-Binding Proteins/blood , Myocardial Infarction/diagnosis , Aged , Chest Pain/diagnosis , Chest Pain/etiology , Creatine Kinase, MB Form/blood , Emergency Service, Hospital , Fatty Acid Binding Protein 3 , Female , Humans , Male , Middle Aged , Myocardial Infarction/blood , Myoglobin/blood , Protein Array Analysis , ROC Curve , Sensitivity and Specificity , Time Factors , Troponin I/blood
8.
Br J Cancer ; 104(1): 181-7, 2011 Jan 04.
Article in English | MEDLINE | ID: mdl-21102590

ABSTRACT

BACKGROUND: Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose-response are poorly understood. METHODS: We screened 11 970 individuals in Belarus aged 18 years or younger at the time of the accident who had estimated (131)I thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear-exponential functions. RESULTS: For thyroid doses <5 Gy, the dose-response was linear (n=85; EOR/Gy=2.15, 95% confidence interval: 0.81-5.47), but at higher doses the excess risk fell. The EOR/Gy was significantly increased among those with prior or screening-detected diffuse goiter, and larger for men than women, and for persons exposed before age 5 than those exposed between 5 and 18 years, although not statistically significant. A somewhat higher EOR/Gy was estimated for validated pre-screening cases. CONCLUSION: 10-15 years after the Chornobyl accident, thyroid cancer risk was significantly increased among individuals exposed to fallout as children or adolescents, but the risk appeared to be lower than in other Chornobyl studies and studies of childhood external irradiation.


Subject(s)
Chernobyl Nuclear Accident , Iodine Radioisotopes/adverse effects , Neoplasms, Radiation-Induced/diagnosis , Thyroid Neoplasms/etiology , Adolescent , Adult , Child , Cohort Studies , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Incidence , Male , Risk Factors , Thyroid Neoplasms/pathology , Young Adult
9.
Eur Respir J ; 37(3): 523-31, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20634264

ABSTRACT

A substantial body of evidence suggests an aetiological role of inflammation, and oxidative and nitrosative stress in asthma pathogenesis. Exhaled nitric oxide fraction (F(eNO)) may provide a noninvasive marker of oxidative and nitrosative stress, and aspects of airway inflammation. We examined whether children with elevated F(eNO) are at increased risk for new-onset asthma. We prospectively followed 2,206 asthma-free children (age 7-10 yrs) who participated in the Children's Health Study. We measured F(eNO) and followed these children for 3 yrs to ascertain incident asthma cases. Cox proportional hazard models were fitted to examine the association between F(eNO) and new-onset asthma. We found that F(eNO) was associated with increased risk of new-onset asthma. Children in the highest F(eNO) quartile had more than a two-fold increased risk of new-onset asthma compared to those with the lowest quartile (hazard ratio 2.1, 95% CI 1.3-3.5). This effect did not vary with the child's history of respiratory allergic symptoms. However, the effect of elevated F(eNO) on new-onset asthma was most apparent among those without a parental history of asthma. Our results indicate that children with elevated F(eNO) are at increased risk for new-onset asthma, especially if they have no parental history of asthma.


Subject(s)
Asthma/etiology , Asthma/metabolism , Hypersensitivity, Immediate , Nitric Oxide/metabolism , Respiratory Sounds/diagnosis , Child , Cohort Studies , Exhalation , Female , Humans , Inflammation , Male , Nitric Oxide/chemistry , Oxidative Stress , Proportional Hazards Models , Social Class , Surveys and Questionnaires
10.
Phys Rev Lett ; 106(7): 073002, 2011 Feb 18.
Article in English | MEDLINE | ID: mdl-21405511

ABSTRACT

Adiabatic cooling is shown to be a simple and effective method to cool many charged particles in a trap to very low temperatures. Up to 3×10(6) p are cooled to 3.5 K-10(3) times more cold p and a 3 times lower p temperature than previously reported. A second cooling method cools p plasmas via the synchrotron radiation of embedded e(-) (with many fewer e(-) than p in preparation for adiabatic cooling. No p are lost during either process-a significant advantage for rare particles.

11.
Phys Rev Lett ; 105(21): 213002, 2010 Nov 19.
Article in English | MEDLINE | ID: mdl-21231298

ABSTRACT

Centrifugal separation of antiprotons and electrons is observed, the first such demonstration with particles that cannot be laser cooled or optically imaged. The spatial separation takes place during the electron cooling of trapped antiprotons, the only method available to produce cryogenic antiprotons for precision tests of fundamental symmetries and for cold antihydrogen studies. The centrifugal separation suggests a new approach for isolating low energy antiprotons and for producing a controlled mixture of antiprotons and electrons.

12.
Thorax ; 64(3): 197-202, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18988661

ABSTRACT

BACKGROUND: Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesised that glutathione-S-transferase (GST)P1, GSTM1, exercise and ozone exposure have interrelated effects on the pathogenesis of asthma. METHODS: Associations of the well characterised null variant of GSTM1 and four single nucleotide polymorphisms (SNPs) that characterised common variation in the GSTP1 locus with new onset asthma in a cohort of 1610 school children were examined. Children's exercise and ozone exposure were classified using participation in team sports and community annual average ozone levels, respectively. RESULTS: A two SNP model involving putatively functional variants (rs6591255, rs1695 (Ile105Va)) best captured the association between GSTP1 and asthma. The risk of asthma was lower for those with the Val allele of Ile105Val (hazard ratio (HR) 0.60, 95% CI 0.4 to 0.8) and higher for the variant allele of rs6591255 (HR 1.40, 95% CI 1.1 to 1.9). The risk of asthma increased with level of exercise among ile(105) homozygotes but not among those with at least one val(105) allele (interaction p value = 0.02). The risk was highest among ile(105) homozygotes who participated in >or=3 sports in the high ozone communities (HR 6.15, 95% CI 2.2 to 7.4). GSTM1 null was independently associated with an increased risk of asthma and showed little variation with air pollution or GSTP1 genotype. These results were consistent in two independent fourth grade cohorts recruited in 1993 and 1996. CONCLUSION: Children who inherit a val(105) variant allele may be protected from the increased risk of asthma associated with exercise, especially in high ozone communities. GSTM1 null genotype was associated with an increased risk of asthma.


Subject(s)
Asthma/genetics , Environmental Exposure/adverse effects , Exercise/physiology , Glutathione S-Transferase pi/genetics , Glutathione Transferase/genetics , Ozone/toxicity , Polymorphism, Single Nucleotide/genetics , Air Pollutants/toxicity , Asthma/enzymology , Child , Cohort Studies , Female , Gene Frequency , Haplotypes , Humans , Male , Oxidative Stress/genetics
13.
Thorax ; 64(10): 889-93, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19706838

ABSTRACT

BACKGROUND: Obesity is a risk factor for asthma, particularly in women, but few cohort studies have evaluated abdominal obesity which reflects metabolic differences in visceral fat known to influence systemic inflammation. A study was undertaken to examine the relationship between the prevalence of asthma and measures of abdominal obesity and adult weight gain in addition to body mass index (BMI) in a large cohort of female teachers. METHODS: Prevalence odds ratios (ORs) for current asthma were calculated using multivariable linear modelling, adjusting for age, smoking and race/ethnicity. RESULTS: Of the 88 304 women in the analyses, 13% (n = 11,500) were obese (BMI > or = 30 kg/m(2)) at baseline; 1334 were extremely obese (BMI > or = 40 kg/m(2)). Compared with those of normal weight, the adjusted OR for adult-onset asthma increased from 1.40 (95% confidence interval (CI) 1.31 to 1.49) for overweight women to 3.30 (95% CI 2.85 to 3.82) for extremely obese women. Large waist circumference (>88 cm) was associated with increased asthma prevalence, even among women with a normal BMI (OR 1.37, 95% CI 1.18 to 1.59). Among obese women the OR for asthma was greater in those who were also abdominally obese than in women whose waist was < or = 88 cm (2.36 vs 1.57). Obese and overweight women were at greater risk of severe asthma episodes, measured by urgent medical visits and hospital admissions. CONCLUSIONS: This study confirms the association between excess weight and asthma severity and prevalence, and showed that a large waist was associated with increased asthma prevalence even among women considered to have normal body weight.


Subject(s)
Asthma/epidemiology , Obesity/epidemiology , Waist Circumference/physiology , Adult , Age of Onset , Aged , Asthma/complications , Asthma/pathology , Body Mass Index , California/epidemiology , Cohort Studies , Female , Humans , Middle Aged , Obesity/complications , Obesity/pathology , Prevalence , Risk Factors , Weight Gain , Young Adult
14.
Osteoarthritis Cartilage ; 17(6): 782-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19036616

ABSTRACT

OBJECTIVE: Published studies have tested over 90 genes for association with osteoarthritis (OA), but few positives reported have been independently replicated. Using a new case-control study, our aim was to attempt the replication of findings from 12 genes reported to have significant genetic association with OA and to further examine the role of genetic variation in six of these genes. METHODS: A case-control study was undertaken in Nottingham, UK. Hospital-referred index cases with symptomatic, radiographic OA (ROA) of the knee (n=1040) or hip (n=1004) were recruited. Asymptomatic controls (n=1123) were recruited from intravenous urography waiting lists and screened for radiographic hip and knee OA. Sixty-eight polymorphisms were genotyped in IL1A, IL1B, IL1RN, IL4R, IL6, COL2A1, ADAM12, ASPN, IGF1, TGFB1, ESR1 and VDR. Statistical analysis compared allele or genotype frequencies of these polymorphisms in all asymptomatic controls and the subset of controls without ROA vs all OA, knee OA and hip OA. The analyses were adjusted for age, gender and body mass index. RESULTS: We were unable to replicate any of the published genetic associations investigated. Our extended exploratory analyses identified some associations between polymorphisms in TGFB1, IGF1 and IL1RN and OA; but the strength of evidence varied with the control group used. CONCLUSION: Lack of replication is common and could be due to differences in study design, phenotype, populations examined or the occurrence of false positives in the initial study. Variants within TGFB1, IGF1 and IL1RN could have a role in OA susceptibility; however, replication of these findings is required in an independent study.


Subject(s)
Genetic Variation/genetics , Osteoarthritis/genetics , Epidemiologic Methods , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Osteoarthritis/diagnostic imaging , Radiography
15.
Allergy ; 64(9): 1342-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19236316

ABSTRACT

BACKGROUND: Tumor necrosis factor (TNF)-alpha has a recognized role in respiratory pathophysiology. One genetic variant (G-308A) in the promoter region affecting the expression of this cytokine may contribute to airway inflammatory diseases, but the studies on bronchitic symptoms were still inconclusive. Because ozone produces oxidative stress, increased airway TNF, and inflammation, the associations of the TNF-308 polymorphism with bronchitic symptoms may vary by ambient ozone exposure. METHODS: We studied associations of TNF-308 genotype with bronchitic symptoms among asthmatic children in Children's Health Study. The association of TNF G-308A polymorphism with bronchitic symptoms was investigated and we also determined whether the associations vary with ambient ozone exposure. RESULTS: Asthmatic children with TNF-308 GG genotype had a significantly reduced risk of bronchitic symptoms with low-ozone exposure (adjusted OR: 0.53; 95% CI: 0.31-0.91). The risk was not reduced in children living in high-ozone communities (adjusted OR: 1.42; 95% CI: 0.75-2.70). This difference in genotypic effects between low- and high-ozone environments was statistically significant among asthmatics (P for interaction = 0.01), but insignificant among nonasthmatic children. CONCLUSION: Our findings suggest a role of gene-environmental interactions on the occurrence of bronchitic symptoms among children with asthma.


Subject(s)
Asthma/physiopathology , Bronchial Hyperreactivity/chemically induced , Bronchial Hyperreactivity/genetics , Ozone/toxicity , Tumor Necrosis Factor-alpha/genetics , Adolescent , Child , Environmental Exposure , Female , Genotype , Humans , Male , Polymorphism, Genetic , Promoter Regions, Genetic , Surveys and Questionnaires , Tumor Necrosis Factor-alpha/immunology
16.
Community Dent Health ; 25(2): 98-102, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18637321

ABSTRACT

AIM: The dental nurse is a key member of the dental team, having an important role in the delivery of oral healthcare. Despite this, there is considerable variation throughout Europe in relation to the level of training, permitted duties, and statutory registration of dental nurses. The purpose of this paper is to describe the opinions and attitudes of dental nurses to their roles and suitability of training in one European member state, Ireland, where statutory registration has recently been introduced. METHOD: A postal questionnaire was sent to 150 dental practitioners selected from the Irish Register of Dentists. The dentists were asked to distribute questionnaire to dental nurse(s) working in their practice. Information sought from the dental nurses included their employment setting, the nature of their employment, their level of training, additional qualifications held, their views on the key duties and responsibilities of a dental nurse, and the appropriate duration and content of a dental nurse training programme. RESULTS: Replies were received from 96 dental nurses (response rate = 64%). Fifty-five percent of respondents (n = 53) were employed in private practice, 39% (n = 37) were employed in the Health Board Dental Service, and 6% (n = 6) were employed in a dental hospital. Two thirds of respondents (n = 62) had been employed as dental nurses for more than five years. Eighty-six percent of respondents (n = 83) were in full-time employment. Seventy-three percent of respondents (n = 70) held a recognised dental nurse qualification. Sixty-five percent of respondents (n = 70) who held a dental nurse qualification felt that the appropriate duration of a dental nurse training programme was one year or less. Thirty-two percent of respondents (n = 30) had completed additional training in practice management, administration or computer skills. Ninety-five percent of respondents (n = 91) were interested in attending continuing education courses. Eighty-five percent of respondents (n = 82) felt that assistance at the administration of local anaesthetics was a key duty/responsibility for dental nurses, while only 20% of respondents (n = 19) felt that infection control procedures was a key duty. CONCLUSIONS: Within the group of dental nurses surveyed, there was a lack of clarity surrounding their perception of their key duties. This could present challenges to the effective delivery of oral healthcare regimens within Ireland. Further investigation of this situation in other European countries is indicated.


Subject(s)
Attitude of Health Personnel , Dental Auxiliaries/education , Dental Auxiliaries/statistics & numerical data , Dental Auxiliaries/psychology , Europe , Humans , Ireland , Professional Practice , Professional Role , Registries , Surveys and Questionnaires
17.
Rev Sci Instrum ; 89(10): 10I104, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30399732

ABSTRACT

Neutral beam injected fast ions play a dominant role in both the field reversed configuration (FRC) at TAE Technologies and the Madison Symmetric Torus (MST) reversed field pinch (RFP), making fast ion diagnosis a major pillar of both research programs. And as strongly self-organized plasmas, the FRC and RFP similarly exhibit dynamic relaxation events which can redistribute fast ions. Recently, a collaboration between TAE Technologies and the University of Wisconsin was conducted to develop a method for measuring a fast changing fast ion spatial profile with a fusion proton detector and to investigate commonalities between the two plasmas. The steerable detector was designed and built at TAE and installed on MST. The fusion proton emission profile resulting from injection of a 25 kV deuterium neutral beam is measured with better than 5 cm spatial resolution and 100 µs temporal resolution over the course of several 10s of shots. The fast ion density profile, forward modeled by tracing the orbits of the 3 MeV protons through a reconstructed magnetic equilibrium, is observed to flatten during global magnetic tearing mode activity, dropping by 30% in the core and increasing by a similar amount at the edge. The equilibrium profile is observed to be consistent with measurements made with a collimated neutron detector.

18.
Pediatr Obes ; 13(6): 342-347, 2018 06.
Article in English | MEDLINE | ID: mdl-28730729

ABSTRACT

INTRODUCTION: Traffic-related air pollution causes fatty liver, inflammation and fibrosis in animal models, but there have been few studies in humans. OBJECTIVES: To test the hypothesis that traffic-related air pollution causes non-alcoholic fatty liver disease (NAFLD) and increased markers for non-alcoholic steatohepatitis (NASH); and that NAFLD increases liver susceptibility to increased NASH risk. METHODS: Data collected prospectively from 74 overweight or obese children were obtained from the Yale Pediatric Obesity Clinic. Traffic-related air pollution was characterized as vehicle traffic volume on major roads within a 1 km residential buffer, and as residential nitrogen dioxide (NO2 ) exposure. Outcomes were hepatic fat fraction (HFF) measured by magnetic resonance imaging, liver enzymes using standard assays and plasma cytokeratin-18 (CK-18) by immunosorbent assays. RESULTS: Significant non-linear relationships with air pollution and CK-18 were found. Plasma CK-18 at follow-up increased from approximately 150 U/L to almost 200 U/L as residential traffic volume increased from 220 000 vehicle-km to 330 000 vehicle-km, after adjustment for baseline CK-18, age and gender. Among patients with NAFLD at baseline, CK-18 increased from 140 U/L to 200 U/L (a 1.5 standard deviation increase in CK-18) as NO2 increased from 8 to 10 ppb. CONCLUSIONS: Traffic-related air pollution was associated with CK-18. Effects were larger in children with pre-existing NAFLD at study entry.


Subject(s)
Air Pollution/adverse effects , Keratin-18/blood , Non-alcoholic Fatty Liver Disease/blood , Pediatric Obesity/complications , Traffic-Related Pollution/adverse effects , Air Pollutants/analysis , Apoptosis/physiology , Biomarkers/blood , Child , Female , Follow-Up Studies , Humans , Liver/pathology , Magnetic Resonance Imaging , Male , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/etiology , Prospective Studies , Risk Factors , Transaminases/blood , Vehicle Emissions/analysis
19.
Pediatr Obes ; 13(5): 312-320, 2018 05.
Article in English | MEDLINE | ID: mdl-28429404

ABSTRACT

BACKGROUND: Emerging experimental evidence suggests that air pollution may contribute to development of obesity and diabetes, but studies of children are limited. OBJECTIVES: We hypothesized that pollution effects would be magnified after bariatric surgery for treatment of obesity, reducing benefits of surgery. METHODS: In 75 obese adolescents, excess weight loss (EWL), high-density lipoprotein (HDL) cholesterol, triglycerides, alkaline phosphatase (ALP) and hemoglobin A1c (HbA1c ) were measured prospectively at baseline and following laparoscopic adjustable gastric banding (LAGB). Residential distances to major roads and the average two-year follow-up exposure to particulate matter <2.5 µm (PM2.5 ), nitrogen dioxide (NO2 ) and ozone were estimated. Associations of exposure with change in outcome and with attained outcome two years post-surgery were examined. RESULTS: Major-roadway proximity was associated with reduced EWL and less improvement in lipid profile and ALP after surgery. NO2 was associated with less improvement in HbA1c and lower attained HDL levels and change in triglycerides over two years post-surgery. PM2.5 was associated with reduced EWL and reduced beneficial change or attained levels for all outcomes except HbA1c . CONCLUSIONS: Near-roadway, PM2.5 and NO2 exposures at levels common in developed countries were associated with reduced EWL and metabolic benefits of LAGB. This novel approach provides a model for investigating metabolic effects of other exposures.


Subject(s)
Air Pollution/adverse effects , Bariatric Surgery/methods , Environmental Exposure/adverse effects , Pediatric Obesity/surgery , Adolescent , Alkaline Phosphatase/blood , Child , Female , Glycated Hemoglobin/analysis , Humans , Lipids/blood , Male , Nitrogen Dioxide/adverse effects , Nitrogen Dioxide/analysis , Ozone/adverse effects , Ozone/analysis , Pediatric Obesity/etiology , Prospective Studies , Treatment Outcome , Weight Loss/physiology
20.
J Dent ; 57: 86-90, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27889605

ABSTRACT

OBJECTIVES: The aim of this paper is to examine cavity design for posterior resin composite restorations and to discuss various resin composite filling techniques. DATA: Literature with regard to cavity preparation for amalgam and resin composite restorations has been reviewed. An overview of available bulkfill resin composite systems is provided and a categorization of these systems according to their clinical application and their intended use is outlined. SOURCES: A literature search was carried out by the authors in Medline. STUDY SELECTION: Pre-defined inclusion criteria based on keywords were included and reviewed. CONCLUSIONS: Minimum cavity preparations are advised for posterior resin composite restorations, preserving the greatest amount of healthy tooth structure. For resin composite restorations only the lesion of caries needs to be removed with all remaining tooth structure protected for the bonding process. The anticipated outcome of this philosophy will result in increased survival of teeth. Newer bulkfill restorative resins offer many advantages such as reduces time for placement.


Subject(s)
Composite Resins/therapeutic use , Dental Caries/therapy , Dental Cavity Preparation/classification , Dental Cavity Preparation/methods , Dental Restoration, Permanent/methods , Acrylic Resins , Composite Resins/chemistry , Dental Amalgam/chemistry , Dental Bonding , Dental Caries/pathology , Dental Materials/chemistry , Dental Restoration Failure , Dental Restoration, Permanent/classification , Humans , Molar/pathology , Polyurethanes , Time Factors , Viscosity
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