Review of research in primary reading at Boston University: 1954-1959.

Thesis (Ed.M.)--Boston Universit

Risk of non-Hodgkin lymphoma associated with occupational exposure to solvents,metals, organic dusts and PCBs (Australia)

Objective: Several studies have suggested that there is an occupational component to the causation of non-Hodgkin lymphoma (NHL). We aimed to use accurate means to assess occupational exposures to solvents, metals, organic dusts and polychlorinated biphenyls (PCBs) in a case-control study. Methods: Cases were incident NHLs during 2000 and 2001 in two regions of Australia. Controls were randomly selected from the electoral roll and frequency matched to cases by age, sex and region. A detailed occupational history was taken from each subject. For jobs with likely exposure to the chemicals of interest, additional questions were asked by telephone interview using modified job specific modules. An expert allocated exposures using the information in the job histories and the interviews. Odds ratios were calculated for each exposure adjusting for age, sex, region and ethnic origin. Results: 694 cases and 694 controls (70% and 45% respectively of those potentially eligible) participated. The risk of NHL was increased by about 30% for exposure to any solvent with a dose response relationship, subgroup analysis showed the finding was restricted to solvents other than benzene. Exposure to wood dust also increased the risk of NHL slightly. Exposures to other organic dusts, metals, and PCBs were not strongly related to NHL. Conclusions: The risk of NHL appears to be increased by exposure to solvents other than benzene and possibly to wood dust

Properties of a Luttinger Liquid with Boundaries at Finite Temperature and Size

We use bosonization methods to calculate the exact finite-temperature single-electron Green's function of a spinful Luttinger liquid confined by open boundaries. The corresponding local spectral density is constructed and analyzed in detail. The interplay between boundary, finite-size and thermal effects are shown to dramatically influence the low-energy properties of the system. In particular, the well-known zero-temperature critical behavior in the bulk always crosses over to a boundary dominated regime in the vicinity of the Fermi level. Thermal fluctuations cause an enhanced depletion of spectral weight for small energies E, with the spectral density scaling as E^2 for E much less than the temperature. Consequences for photoemission experiments are discussed.Comment: 18 pages in revtex format including 5 embedded figures (using epsf). The latest complete postscript file is available from http://fy.chalmers.se/~eggert/papers/longlutt.ps or by request from [email protected]. To appear in Phys. Rev. B (Dec. 1997

Baseline Levels of Influenza-Specific CD4 Memory T-Cells Affect T-Cell Responses to Influenza Vaccines

BACKGROUND: Factors affecting immune responses to influenza vaccines have not been studied systematically. We hypothesized that T-cell and antibody responses to the vaccines are functions of pre-existing host immunity against influenza antigens. METHODOLOGY/PRINCIPAL FINDINGS: During the 2004 and 2005 influenza seasons, we have collected data on cellular and humoral immune reactivity to influenza virus in blood samples collected before and after immunization with inactivated or live attenuated influenza vaccines in healthy children and adults. We first used cross-validated lasso regression on the 2004 dataset to identify a group of candidate baseline correlates with T-cell and antibody responses to vaccines, defined as fold-increase in influenza-specific T-cells and serum HAI titer after vaccination. The following baseline parameters were examined: percentages of influenza-reactive IFN-gamma(+) cells in T and NK cell subsets, percentages of influenza-specific memory B-cells, HAI titer, age, and type of vaccine. The candidate baseline correlates were then tested with the independent 2005 dataset. Baseline percentage of influenza-specific IFN-gamma(+) CD4 T-cells was identified as a significant correlate of CD4 and CD8 T-cell responses, with lower baseline levels associated with larger T-cell responses. Baseline HAI titer and vaccine type were identified as significant correlates for HAI response, with lower baseline levels and the inactivated vaccine associated with larger HAI responses. Previously we reported that baseline levels of CD56(dim) NK reactivity against influenza virus inversely correlated with the immediate T-cell response to vaccination, and that NK reactivity induced by influenza virus depended on IL-2 produced by influenza-specific memory T-cells. Taken together these results suggest a novel mechanism for the homeostasis of virus-specific T-cells, which involves interaction between memory helper T-cells, CD56(dim) NK and DC. SIGNIFICANCE: These results demonstrate that assessment of baseline biomarkers may predict immunologic outcome of influenza vaccination and may reveal some of the mechanisms responsible for variable immune responses following vaccination and natural infection

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification

WHO non-Hodgkin's lymphoma classification by criterion-based report review followed by targetedpathology review: An effective strategy for epidemiology studies

In a previous criterion-based pathology report review of 717 cases of non-Hodgkin's lymphoma in an Australian population-based epidemiologic study, a WHO category could be assigned in 91% of cases, but confidence in this classification was high in only 57.5%. Given this lack of confidence, a pathology review was done in a subset of 315 cases, with the aims of assigning a WHO classification category and the corresponding International Classification of Diseases for Oncology, Third Edition code in all cases previously unclassified or classified with low confidence and testing the accuracy of report review in assigning a confident WHO classification. After pathology review, 10 cases were ineligible (not non-Hodgkin's lymphoma, 3.2%) and 99% (301 of 305) of the remainder were assigned a WHO classification, with high confidence in 87% (261 of 301). There was 78% overall agreement between the WHO classification assigned by report review and pathology review, with 92% agreement when there was high confidence in the report review classification and 69% agreement when there was low confidence. Eighteen percent of follicular lymphomas and 23% of diffuse large B-cell lymphomas were reclassified. The pathology review increased the accuracy of WHO classification by an estimated 12.5% in the 694 cases who were still eligible in the study. Although a potential error rate of 7.5% remained, reviewing more cases, or not reviewing any cases classified with high confidence, would have produced only a small change in accuracy. Criterion-based pathology report review of all cases followed by selective pathology review in cases classified with low confidence is recommended as a cost-saving and accurate strategy for pathology review in large epidemiologic studies

Use of the WHO lymphoma classification in a population-based epidemiological study

Background: Non-Hodgkin's lymphoma (NHL) is pathologically diverse. Epidemiological investigations into its increasing incidence and aetiology require accurate subtype classification. Patients and methods: Available pathology reports of 717 cases aged from 20 to 74 years in an Australian, population-based epidemiological study of NHL were reviewed by one anatomical pathologist to assign a World Health Organization (WHO) classification category. High or low confidence was assigned to the diagnosis of NHL, cell phenotype and WHO category and reasons given for low confidence. Results: The most informative biopsy reports were from open tissue biopsy (79% of cases), tissue core biopsy (8%), cytology (4%) and bone marrow (9%); 8% of cases had inadequate biopsies for diagnostic purposes. Immunohistochemistry or flow cytometry reports were available for 96% of cases, gene rearrangement studies for 6% and cytogenetics for 3%. The reviewer assigned high confidence to the diagnosis of NHL in 93% of cases and also the phenotype in 88%. While a WHO classification could be assigned in 91% of cases, confidence was high in only 57.5%; insufficient immunophenotyping as the commonest reason for low confidence. Conclusions: Expert pathology review of a population-based sample of NHL can provide a WHO classification category for most cases. A high level of confidence in the classification, however, would require review of diagnostic material and additional phenotyping

Occupational exposure to pesticides and risk of non-Hodgkin's lymphoma

Pesticide exposure may be a risk factor for non-Hodgkin's lymphoma, but it is not certain which types of pesticides are involved. A population-based case-control study was undertaken in 2000-2001 using detailed methods of assessing occupational pesticid

Birth order, atopy, and risk of non-Hodgkin lymphoma

Background: Immune deficiency is a strong risk factor for non-Hodgkin lymphoma (NHL), but whether or not other forms of immune dysregulation are associated with NHL risk is unknown. We investigated associations between atopy, which is associated with a Th2-dominant immune response, and NHL risk. Because late birth order and childhood crowding are inversely associated with atopy, we also investigated their associations with NHL risk. Methods: We carried out a population-based case-control study among adults aged 20-74 years in New South Wales and the Australian Capital Territory, Australia. NHL patients without clinically apparent immune deficiency (N = 704) were selected from a cancer registry, and control subjects (N = 694) were randomly selected from state electoral rolls and frequency-matched to case patients by age, sex, and area of residence. Birth order, childhood crowding, and history of atopic conditions (hay fever, asthma, eczema, and specific allergies) were assessed by questionnaire and interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models that included the matching variables as covariates. Results: The odds ratios for developing NHL were 0.52 (95% CI = 0.32 to 0.84) for only children, 0.55 (95% CI = 0.40 to 0.75) for first-born children, 0.70 (95% CI = 0.51 to 0.96) for second-born children, and 0.81 (0.57 to 1.14) for third-born children (all compared with fourth- or later-born children) (Ptrend<.001). Indicators of crowding in later childhood, such as sharing a bed or bedroom, were not associated with NHL risk. A history of atopic conditions was associated with a reduced risk of NHL; this reduction was statistically significant for hay fever (OR = 0.65, 95% CI = 0.52 to 0.82) and food allergies (OR = 0.29, 95% CI = 0.20 to 0.42). Conclusions: Early birth order and its immunologic consequence, a Th2-dominated immune response, as reflected by a history of atopic disease, are associated with a reduced risk of NHL