The atypical IκB family member Bcl3 associates with p50/NF-κB1 or p52/NF-κB2 homodimers in the nucleus, and positively or negatively modulates transcription in a context-dependent manner. In mice lacking Bcl3 globally or specifically in CD11c+ cells, we previously reported that Toxoplasma gondii infection is uniformly fatal and is associated with an impaired Th1 immune response. Since Bcl3 expression in dendritic cells (DC) is pivotal for antigen presentation and since classical DCs (cDC) are major antigen presenting cells, we investigated the role of Bcl3 specifically in cDCs in vivo by crossing Zbtb46 cre mice with Bcl3flx/flx mice.
View Article and Find Full Text PDFT cell activation by antigen involves multiple sequential steps, including T cell receptor-microcluster TCR-(MC) formation, immunological synapse formation, and phosphorylation of mediators downstream of the TCR. The adaptor protein, Disc Large Homolog 1 (DLG1), is known to regulate proximal TCR signaling and, in turn, T cell activation, acting as a molecular chaperone that organizes specific kinases downstream of antigen recognition. In this study, we used knockdown and knockout technologies in human primary T cells and a human T cell line to demonstrate the role of DLG1 in proximal T cell signaling.
View Article and Find Full Text PDFBackground: Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide.
Methods: The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe.
Survivors of childhood cancer treated with cranial irradiation are at risk of cerebrovascular disease (CVD), but the risks beyond age 50 are unknown. In all, 13457 survivors of childhood cancer included in the population-based British Childhood Cancer Survivor Study cohort were linked to Hospital Episode Statistics data for England. Risk of CVD related hospitalisation was quantified by standardised hospitalisation ratios (SHRs), absolute excess risks and cumulative incidence.
View Article and Find Full Text PDFBackground: Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors.
Methods: This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries.
ZAP-70 is a tyrosine kinase that is essential for initiation of T cell antigen receptor (TCR) signaling. We have found that T cell p38 MAP kinase (MAPK), which is directly phosphorylated and activated by ZAP-70 downstream of the TCR, in turn phosphorylates Thr-293 in the interdomain B region of ZAP-70. Mutant T cells expressing ZAP-70 with an alanine substitution at this residue (ZAP-70) had enhanced TCR proximal signaling and increased effector responses.
View Article and Find Full Text PDFBackground: Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer.
Methods: We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer.
Background: Reorganisation of clinical follow-up care in England was proposed by the National Cancer Survivorship Initiative (NCSI), based on cancer type and treatment, ranging from Level 1 (supported self-management) to Level 3 (consultant-led care). The objective of this study was to provide an investigation of the risks of serious adverse health-outcomes associated with NCSI Levels of clinical care using a large population-based cohort of childhood cancer survivors.
Methods: The British Childhood Cancer Survivor Study (BCCSS) was used to investigate risks of specific causes of death, subsequent primary neoplasms (SPNs) and non-fatal non-neoplastic outcomes by NCSI Level.
Introduction: We investigate the risks of subsequent primary bone cancers after childhood and adolescent cancer in 12 European countries. For the first time, we satisfactorily address the risks beyond 40 years from diagnosis and beyond 40 years of age among all survivors.
Methods: This largest-ever assembled cohort comprises 69 460 five-year survivors of cancer diagnosed before age 20 years.
Background: Female survivors of childhood cancer treated with abdominal radiotherapy who manage to conceive are at risk of delivering premature and low-birthweight offspring, but little is known about whether abdominal radiotherapy may also be associated with additional complications during pregnancy and labor. We investigated the risk of developing pregnancy and labor complications among female survivors of childhood cancer in the British Childhood Cancer Survivor Study (BCCSS).
Methods: Pregnancy and labor complications were identified by linking the BCCSS cohort (n = 17 980) to the Hospital Episode Statistics (HES) for England.
Background: Survivors of teenage and young adult cancer are at risk of cerebrovascular events, but the magnitude of and extent to which this risk varies by cancer type, decade of diagnosis, age at diagnosis, and attained age remains uncertain. This is the largest-ever cohort study to evaluate the risks of hospitalization for a cerebrovascular event among long-term survivors of teenage and young adult cancer.
Methods: The population-based TYACSS (Teenage and Young Adult Cancer Survivor Study) (N=178,962) was linked to Hospital Episode Statistics data for England to investigate the risks of hospitalization for a cerebrovascular event among 5-year survivors of cancer diagnosed when 15 to 39 years of age.
Background: Survivors of teenage and young adult cancer are acknowledged as understudied. Little is known about their long-term adverse health risks, particularly of cardiac disease that is increased in other cancer populations where cardiotoxic treatments have been used.
Methods: The Teenage and Young Adult Cancer Survivor Study cohort comprises 200 945 5-year survivors of cancer diagnosed at 15 to 39 years of age in England and Wales from 1971 to 2006, and followed to 2014.
Purpose: Survivors of Wilms tumor (WT) are at risk for adverse health and social outcomes but risks beyond 30 years from diagnosis remain uncertain. We investigated the risks of adverse outcomes among 5-year survivors of WT, in particular, those between 30 and 50 years from diagnosis.
Patients And Methods: The British Childhood Cancer Survivor Study includes 1,441 5-year survivors of WT.
An aim of the EURO-URHIS 2 project was to collect standardised data on urban health indicators (UHIs) relevant to the health of adults resident in European urban areas. This article details development of the survey instruments and methodologies to meet this aim. 32 urban areas from 11 countries conducted the adult surveys.
View Article and Find Full Text PDFMeasuring health and its determinants in urban populations is essential to effectively develop public health policies maximizing health gain within this context. Adolescents are important in this regard given the origins of leading causes of morbidity and mortality develop pre-adulthood. Comprehensive, accurate and comparable information on adolescent urban health indicators from heterogeneous urban contexts is an important challenge.
View Article and Find Full Text PDFBackground: With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study.
Methods: Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors.
We have studied the recombination of O atoms on an anodized Al surface in an oxygen plasma, using a new "spinning wall" technique. With this method, a cylindrical section of the wall of the plasma reactor is rotated and the surface is periodically exposed to an oxygen plasma and then to a differentially pumped mass spectrometer (MS). By varying the substrate rotation frequency (r), we vary the reaction time (t(r)), that is, the time between exposure of the surface to O atoms in the plasma and MS detection of desorbing O(2) (t(r) = 1/2r).
View Article and Find Full Text PDFWe report a new method for studying surface reactions and kinetics at moderately high pressures (<10 Torr) in near real time. A cylindrical substrate in a reactor wall is rotated at up to 200,000 rpm, allowing the surface to be periodically exposed to a reactive environment and then analyzed by a triple-differentially pumped mass spectrometer in as little as 150 micros thereafter. We used this method to study oxygen plasma reactions on anodized aluminum.
View Article and Find Full Text PDFThis paper illustrates a real environmental concern and draws attention to the fact that natural processes can mobilize thallium (Tl), a highly toxic metal, which may enter the food chain as a "hidden health killer" with severe health impacts on local human population. Natural processes may be exacerbated by human activities such as mining and farming, and may cause enrichment of Tl in the environment. In geochemically anomalous areas with concentrated levels of Tl in the surface environment (bedrocks, waters, soils, and crops), such as the Lanmuchang area in southwestern Guizhou Province, China, it is essential to establish base-level values and to pay heed to the geological context of "natural contamination," as high concentrations of Tl in bedrocks/ores (6-35,000 mg/kg) can lead to enrichment of Tl in the aquatic system (0.
View Article and Find Full Text PDFThallium (Tl) contamination in soils poses a significant threat to human health due to the high toxicity of Tl and its ready assimilation by crops. This study is focused on high concentrations of Tl in soils in the Lanmuchang area of southwest Guizhou, China, which is related to natural processes of Tl-rich sulfide mineralization. Thallium contents range from 40 to 124 mg/kg in soils originating from the mining area, from 20 to 28 mg/kg in slope wash materials, from 14 to 62 mg/kg in alluvial deposits downstream, from 1.
View Article and Find Full Text PDFExperiments were performed on a CO(2) laser with an annular resonator. The objective of these experiments was to control the polarization in an annular laser and to verify computer code predictions. A Mylar pellicle was placed in the annular leg, and its angular orientation with respect to the optical axis was varied.
View Article and Find Full Text PDFFor precision optical systems, the focus and tilt errors caused by coating thickness nonuniformity can be a serious concern. These errors are wavelength dependent and hence cannot be compensated in an IR optical system by aligning and focusing with an auxiliary visible alignment laser. It is shown here that the coating design can be modified so as to make the aberrations caused by coating thickness nonuniformity approximately equal at the IR design wavelength and the wavelength of the auxiliary laser.
View Article and Find Full Text PDFPrevious measurements of electric field induced second harmonic generation indicated that the confocal parameter for a laser beam as calculated from the second harmonic intensity profile was in disagreement with that calculated from the measured beam diameter. In this paper, we show that this discrepancy is caused by the departure of the beam from the pure TEM(00) mode. We expand a distorted beam in terms of the component modes by using the experimental beamscan and calculate the second harmonic profile using this expansion.
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