The use of artificial light at night (ALAN) enables social and commercial activities for urban living. However, the excessive usage of lighting causes nuisance and waste of energy. Light is provided ...to illuminate target areas on the street level where activities take place, yet light can also cause trespass to residents at the floors above. While regulations are beginning to cover light design, simulation tools for the outdoor environment have also become more popular for assessing the design condition. Simulation tools allow visualisation of the impact of the selected light sources on those who are affected. However, this cause-and-effect relationship is not easy to determine in the complex urban environment. The current work offers a simple methodology that takes site survey results and correlates them with the simulation model to determine lighting impact on the investigated area in 3D. Four buildings in two mixed commercial and residential streets in Hong Kong were studied. Data collection from each residential building requires lengthy work and permission from each household. Therefore, a valid lighting simulation model could help determine the light pollution impact in the area. A light model using DIALux is developed and calibrated by correlating the simulated data with the actual measured data. The correlation value R
achieved ranged from 0.95 to 0.99, verifying the accuracy of this model and matched from 340 lx to 35 lx for the lower to higher floors of one building and 10 lx to 4 lx for floors of another building. This model can also be applied to human health research, by providing light-level data on residential windows in an area or determining the environmental impact of a development project.
A limited number of studies on long-term effects of particulate matter with aerodynamic diameter < 2.5 μm (PM2.5) on health suggest it can be an important cause of morbidity and mortality. In Asia ...where air quality is poor and deteriorating, local data on long-term effects of PM2.5 to support policy on air quality management are scarce.
We assessed long-term effects of PM2.5 on the mortality in a single Asian city.
For 10-13 years, we followed up a cohort of 66,820 participants ≥ 65 years of age who were enrolled and interviewed in all 18 Elderly Health Centres of the Department of Health, Hong Kong, in 1998-2001. Their residential addresses were geocoded into x- and y-coordinates, and their proxy exposures to PM2.5 at their addresses in 1 × 1 km grids were estimated from the U.S. National Aeronautics and Space Administration (NASA) satellite data. We used Cox regression models to calculate hazard ratios (HRs) of mortality associated with PM2.5.
Mortality HRs per 10-μg/m3 increase in PM2.5 were 1.14 (95% CI: 1.07, 1.22) for all natural causes, 1.22 (95% CI: 1.08, 1.39) for cardiovascular causes, 1.42 (95% CI: 1.16, 1.73) for ischemic heart disease, 1.24 (95% CI: 1.00, 1.53) for cerebrovascular disease, and 1.05 (95% CI: 0.90, 1.22) for respiratory causes.
Our methods in using NASA satellite data provide a readily accessible and affordable approach to estimation of a sufficient range of individual PM2.5 exposures in a single city. This approach can expand the capacity to conduct environmental accountability studies in areas with few measurements of fine particles.
Wong CM, Lai HK, Tsang H, Thach TQ, Thomas GN, Lam KB, Chan KP, Yang L, Lau AK, Ayres JG, Lee SY, Chan WM, Hedley AJ, Lam TH. 2015. Satellite-based estimates of long-term exposure to fine particles and association with mortality in elderly Hong Kong residents. Environ Health Perspect 123:1167-1172; http://dx.doi.org/10.1289/ehp.1408264.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
This phase III randomized study compared concurrent cisplatin–radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 ...patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m2 weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval CI = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio HR = 0.71 95% CI = 0.5 to 1.0). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 95% CI = 0.59 to 1.4), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 95% CI = 0.3 to 0.88), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.
Background
There is limited work on the impact of chemotherapy‐induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin‐cyclophosphamide (AC)–treated patients with breast cancer. The ...objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients’ QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC.
Materials and Methods
This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index–emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included “no significant nausea” (NSN), “significant nausea” (SN), “no vomiting” (NoV), “vomiting” (V), and complete response (CR).
Results
Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p < .0001), with lower scores indicating better QoL; the mean scores for the FLIE vomiting domain for patients who experienced NoV versus V were 1.44 versus 19.11, respectively (p < .0001), with similar results across subsequent cycles. Analysis of the effect of the QoL in cycle 1 on the QoL of subsequent cycles revealed the following: for the nausea domain, among patients who had cycle 1 FLIE scores ≥ versus < the mean, the corresponding scores in cycle 2 were 6.87 versus 36.71 (p < .0001); whereas those for cycle 3 were 7.07 versus 36.87 (p < .0001); and those for cycle 4 were 5.92 versus 21.48 (p < .0001). Similar findings were observed for the vomiting domain. Netupitant + palonosetron– or aprepitant/olanzapine–based antiemetics had significantly better QoL outcomes.
Conclusion
CINV had a significant impact on the QoL of patients with breast cancer treated with AC over multiple cycles.
Implications for Practice
In this post‐hoc analysis of three prospective studies on chemotherapy‐induced nausea and vomiting (CINV), quality of life (QoL) using contemporary antiemetic regimens in Chinese breast cancer patients receiving doxorubicin‐cyclophosphamide (AC) was evaluated. During the first and subsequent AC cycles, QoL was significantly better for patients who did not experience vomiting or significant nausea. QoL in an earlier cycle affected the QoL in subsequent AC cycles. Furthermore, recent regimens involving olanzapine/aprepitant or netupitant‐palonosetron were associated with a positive impact in QoL. Antiemetic guideline‐consistent practice and higher clinician awareness of the impact of CINV on QoL can further mitigate the negative effects of CINV on QoL
This article focuses on chemotherapy‐induced nausea and vomiting and quality of life of breast cancer patients through multiple cycles of treatment.
The inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex etiology. IBD is thought to arise in genetically susceptible individuals in the context of aberrant ...interactions with the intestinal microbiota and other environmental risk factors. Recently, the pregnane X receptor (PXR) was identified as a sensor for microbial metabolites, whose activation can regulate the intestinal epithelial barrier. Mutations in NR1I2, the gene that encodes the PXR, have been linked to IBD, and in animal models, PXR deletion leads to barrier dysfunction. In the current study, we sought to assess the mechanism(s) through which the PXR regulates barrier function during inflammation. In Caco-2 intestinal epithelial cell monolayers, tumor necrosis factor-α/interferon-γ exposure disrupted the barrier and triggered zonula occludens-1 relocalization, increased expression of myosin light-chain kinase (MLCK), and activation of c-Jun N-terminal kinase 1/2 (JNK1/2). Activation of the PXR rifaximin and 3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenylethenylidenebis-phosphonic acid tetraethyl ester (SR12813); 10 μM protected the barrier, an effect that was associated with attenuated MLCK expression and JNK1/2 activation. In vivo, activation of the PXR pregnenolone 16α-carbonitrile (PCN) attenuated barrier disruption induced by toll-like receptor 4 activation in wild-type, but not Pxr-/-, mice. Furthermore, PCN treatment protected the barrier in the dextran-sulfate sodium model of experimental colitis, an effect that was associated with reduced expression of mucosal MLCK and phosphorylated JNK1/2. Together, our data suggest that the PXR regulates the intestinal epithelial barrier during inflammation by modulating cytokine-induced MLCK expression and JNK1/2 activation. Thus, targeting the PXR may prove beneficial for the treatment of inflammation-associated barrier disruption in the context of IBD.
Cumulative evidence supports a role for neutralizing antibodies contributing to spontaneous viral clearance during acute hepatitis C virus (HCV) infection. Information on the timing and specificity ...of the B cell response associated with clearance is crucial to inform vaccine design. From an individual who cleared three sequential HCV infections with genotypes 1b, 1a and 3a strains, respectively, we employed peripheral B cells to isolate and characterize neutralizing human monoclonal antibodies (HMAbs) to HCV after the genotype 1 infections. The majority of isolated antibodies, designated as HMAbs 212, target conformational epitopes on the envelope glycoprotein E2 and bound broadly to genotype 1-6 E1E2 proteins. Further, some of these antibodies showed neutralization potential against cultured genotype 1-6 viruses. Competition studies with defined broadly neutralizing HCV HMAbs to epitopes in distinct clusters, designated antigenic domains B, C, D and E, revealed that the selected HMAbs compete with B, C and D HMAbs, previously isolated from subjects with chronic HCV infections. Epitope mapping studies revealed domain B and C specificity of these HMAbs 212. Sequential serum samples from the studied subject inhibited the binding of HMAbs 212 to autologous E2 and blocked a representative domain D HMAb. The specificity of this antibody response appears similar to that observed during chronic infection, suggesting that the timing and affinity maturation of the antibody response are the critical determinants in successful and repeated viral clearance. While additional studies should be performed for individuals with clearance or persistence of HCV, our results define epitope determinants for antibody E2 targeting with important implications for the development of a B cell vaccine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
This study aimed to investigate changes of QoL during the first 5 years of survival among disease-free Chinese breast cancer survivors.
Methods
A prospective cohort study enrolled 1462 ...Chinese women with early-stage breast cancer, and longitudinally visited those patients at four time-points, namely baseline (T0), 18- (T1), 36- (T2), and 60-month (T3) after diagnosis. This study included 992 patients who were disease-free during the first 5 years of survival and who had completed QoL assessments at all four time-points.
Results
The score of global health status/QoL improved gradually (T1, T2, T3 > T0;
P
< 0.001 for overall comparisons). Social functioning score significantly improved when compared to that of T0 (T1, T2, T3 > T0;
P
< 0.001 for overall comparisons). In contrast, cognitive functioning score decreased (T0 > T1, T2, T3;
P
< 0.001 for overall comparisons). Scores of physical functioning, role functioning and emotional functioning showed a fluctuated picture, with the highest score achieved at T1. In symptoms profile, most of them scored lowest at T1 (best QoL). Multivariate analysis showed that several characteristics significantly correlated to changes in QoL from T0 to T3. For instance, patients with higher education had better recovery of physical functioning, role functioning, and social functioning.
Conclusion
During the first 5 years of survival, patients’ global health status/QoL improved over time, social functioning consistently improved, but cognitive functioning steadily deteriorated. Most of functioning domains and symptoms improved at 18-month follow-up, but such improvements were not maintained and even deteriorated at 36- and 60-month post-diagnosis. This study suggested that some interventions should be investigated during such period.
The E2 envelope glycoprotein is the primary target of human neutralizing antibody response against hepatitis C virus (HCV), and is thus a major focus of vaccine and immunotherapeutics efforts. There ...is emerging evidence that E2 is a highly complex, dynamic protein with residues across the protein that are modulating antibody recognition, local and global E2 stability, and viral escape. To comprehensively map these determinants, we performed global E2 alanine scanning with a panel of 16 human monoclonal antibodies (hmAbs), resulting in an unprecedented dataset of the effects of individual alanine substitutions across the E2 protein (355 positions) on antibody recognition. Analysis of shared energetic effects across the antibody panel identified networks of E2 residues involved in antibody recognition and local and global E2 stability, as well as predicted contacts between residues across the entire E2 protein. Further analysis of antibody binding hotspot residues defined groups of residues essential for E2 conformation and recognition for all 14 conformationally dependent E2 antibodies and subsets thereof, as well as residues that enhance antibody recognition when mutated to alanine, providing a potential route to engineer E2 vaccine immunogens. By incorporating E2 sequence variability, we found a number of E2 polymorphic sites that are responsible for loss of neutralizing antibody binding. These data and analyses provide fundamental insights into antibody recognition of E2, highlighting the dynamic and complex nature of this viral envelope glycoprotein, and can serve as a reference for development and rational design of E2-targeting vaccines and immunotherapeutics.
Background The genetic factors that determine the risk of papillary thyroid carcinoma (PTC) among patients with multinodular goiter (MNG) remain undefined. Because thyroid transcription factor-1 ...(TTF-1) is important to thyroid development, we evaluated whether the gene that encodes it, TITF-1/NKX2.1, is a genetic determinant of MNG/PTC predisposition. Methods Twenty unrelated PTC patients with a history of MNG (MNG/PTC), 284 PTC patients without a history of MNG (PTC), and 349 healthy control subjects were screened for germline mutation(s) in TITF-1/NKX2.1 by sequencing of amplified DNA from blood. The effects of the mutation on the growth and differentiation of thyroid cells were demonstrated by ectopic expression of wild-type (WT) and mutant proteins in PCCL3 normal rat thyroid cells, followed by tests of cell proliferation, activation of cell growth pathways, and transcription of TTF-1 target genes. All statistical tests were two-sided. Results A missense mutation (1016C>T) was identified in TITF-1/NKX2.1 that led to a mutant TTF-1 protein (A339V) in four of the 20 MNG/PTC patients (20%). These patients developed substantially more advanced tumors than MNG/PTC or PTC patients without the mutation (P = .022, Fisher exact test). Notably, this germline mutation was dominantly inherited in two families, with some members bearing the mutation affected with MNG, associated with either PTC or colon cancer. The mutation encoding the A339V substitution was not found among the 349 healthy control subjects nor among the 284 PTC patients who had no history of MNG. Overexpression of A339V TTF-1 in PCCL3 cells, as compared with overexpression of WT TTF-1, was associated with increased cell proliferation including thyrotropin-independent growth (average A339V proliferation rate = 134.27%, WT rate = 104.43%, difference = 34.3%, 95% confidence interval = 12.0% to 47.7%, P = .010), enhanced STAT3 activation, and impaired transcription of the thyroid-specific genes Tg, TSH-R, and Pax-8. Conclusion This is the first germline mutation identified in MNG/PTC patients. It could contribute to predisposition for MNG and/or PTC and to the pathogenesis of PTC.
PDF
