Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality.

BACKGROUND: The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. MATERIALS AND METHODS: We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993-2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. RESULTS: Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths-with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths-with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. CONCLUSION: Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina

Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds

Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time-dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n =15) no typical granulation tissue had developed and no alpha-actin-positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha-smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occured. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases. The immunohistochemical detection of actin-positive cells, therefore, demonstrates whether an unknown skin wound is aged approximately 5 days or more. Even though a time-dependent decrease of myofibroblasts in human granulation tissue after 31 days in human wounds seems probable, the extended presence (up to about 2 months) of these cells allows no further exact age determination of older wounds

Internal and external cooling methods and their effect on body temperature, thermal perception and dexterity

© 2018 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0191416© 2018 Maley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective The present study aimed to compare a range of cooling methods possibly utilised by occupational workers, focusing on their effect on body temperature, perception and manual dexterity. Methods Ten male participants completed eight trials involving 30 min of seated rest followed by 30 min of cooling or control of no cooling (CON) (34C, 58% relative humidity). The cooling methods utilised were: ice cooling vest (CV0), phase change cooling vest melting at 14C (CV14), evaporative cooling vest (CVEV), arm immersion in 10C water (AI), portable water-perfused suit (WPS), heliox inhalation (HE) and ice slushy ingestion (SL). Immediately before and after cooling, participants were assessed for fine (Purdue pegboard task) and gross (grip and pinch strength) manual dexterity. Rectal and skin temperature, as well as thermal sensation and comfort, were monitored throughout. Results Compared with CON, SL was the only method to reduce rectal temperature (P = 0.012). All externally applied cooling methods reduced skin temperature (P0.05). Conclusion The present study observed that ice ingestion or ice applied to the skin produced the greatest effect on rectal and skin temperature, respectively. AI should not be utilised if workers require subsequent fine manual dexterity. These results will help inform future studies investigating appropriate pre-cooling methods for the occupational worker.This project is financially supported by the US Government through the Technical Support Working Group within the Combating Terrorism Technical Support Office.Published versio

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that "regrowth resistance" initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulfoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggests the taxanes may be useful in the treatment of platinum resistant SCLC. These novel cellular models of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC

Wavefunctions and the Point of E8 in F-theory

In F-theory GUTs interactions between fields are typically localised at points of enhanced symmetry in the internal dimensions implying that the coefficient of the associated operator can be studied using a local wavefunctions overlap calculation. Some F-theory SU(5) GUT theories may exhibit a maximum symmetry enhancement at a point to E8, and in this case all the operators of the theory can be associated to the same point. We take initial steps towards the study of operators in such theories. We calculate wavefunctions and their overlaps around a general point of enhancement and establish constraints on the local form of the fluxes. We then apply the general results to a simple model at a point of E8 enhancement and calculate some example operators such as Yukawa couplings and dimension-five couplings that can lead to proton decay.Comment: 46 page

Foot pain and foot health in an educated population of adults: results from the Glasgow Caledonian University Alumni Foot Health Survey

Abstract Background Foot pain is common amongst the general population and impacts negatively on physical function and quality of life. Associations between personal health characteristics, lifestyle/behaviour factors and foot pain have been studied; however, the role of wider determinants of health on foot pain have received relatively little attention. Objectives of this study are i) to describe foot pain and foot health characteristics in an educated population of adults; ii) to explore associations between moderate-to-severe foot pain and a variety of factors including gender, age, medical conditions/co-morbidity/multi-morbidity, key indicators of general health, foot pathologies, and social determinants of health; and iii) to evaluate associations between moderate-to-severe foot pain and foot function, foot health and health-related quality-of-life. Methods Between February and March 2018, Glasgow Caledonian University Alumni with a working email address were invited to participate in the cross-sectional electronic survey (anonymously) by email via the Glasgow Caledonian University Alumni Office. The survey was constructed using the REDCap secure web online survey application and sought information on presence/absence of moderate-to-severe foot pain, patient characteristics (age, body mass index, socioeconomic status, occupation class, comorbidities, and foot pathologies). Prevalence data were expressed as absolute frequencies and percentages. Multivariate logistic and linear regressions were undertaken to identify associations 1) between independent variables and moderate-to-severe foot pain, and 2) between moderate-to-severe foot pain and foot function, foot health and health-related quality of life. Results Of 50,228 invitations distributed, there were 7707 unique views and 593 valid completions (median age [inter-quartile range] 42 [31–52], 67.3% female) of the survey (7.7% response rate). The sample was comprised predominantly of white Scottish/British (89.4%) working age adults (95%), the majority of whom were overweight or obese (57.9%), and in either full-time or part-time employment (82.5%) as professionals (72.5%). Over two-thirds (68.5%) of the sample were classified in the highest 6 deciles (most affluent) of social deprivation. Moderate-to-severe foot pain affected 236/593 respondents (39.8%). High body mass index, presence of bunions, back pain, rheumatoid arthritis, hip pain and lower occupation class were included in the final multivariate model and all were significantly and independently associated with moderate-to-severe foot pain (p < 0.05), except for rheumatoid arthritis (p = 0.057). Moderate-to-severe foot pain was significantly and independently associated lower foot function, foot health and health-related quality of life scores following adjustment for age, gender and body mass index (p < 0.05). Conclusions Moderate-to-severe foot pain was highly prevalent in a university-educated population and was independently associated with female gender, high body mass index, bunions, back pain, hip pain and lower occupational class. Presence of moderate-to-severe foot pain was associated with worse scores for foot function, foot health and health-related quality-of-life. Education attainment does not appear to be protective against moderate-to-severe foot pain

Field observations of canopy flows over complex terrain

The investigation of airflow over and within forests in complex terrain has been, until recently, limited to a handful of modelling and laboratory studies. Here, we present an observational dataset of airflow measurements inside and above a forest situated on a ridge on the Isle of Arran, Scotland. The spatial coverage of the observations all the way across the ridge makes this a unique dataset. Two case studies of across-ridge flow under near-neutral conditions are presented and compared with recent idealized two-dimensional modelling studies. Changes in the canopy profiles of both mean wind and turbulent quantities across the ridge are broadly consistent with these idealized studies. Flow separation over the lee slope is seen as a ubiquitous feature of the flow. The three-dimensional nature of the terrain and the heterogeneous forest canopy does however lead to significant variations in the flow separation across the ridge, particularly over the less steep western slope. Furthermore, strong directional shear with height in regions of flow separation has a significant impact on the Reynolds stress terms and other turbulent statistics. Also observed is a decrease in the variability of the wind speed over the summit and lee slope, which has not been seen in previous studies. This dataset should provide a valuable resource for validating models of canopy flow over real, complex terrain

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Carbon-13 Dynamic MRS and MRSI of Normal and Fasted Rat Liver with Hyperpolarized C-Pyruvate

BACKGROUND: The use of in vivo (13)C nuclear magnetic resonance spectroscopy in probing metabolic pathways to study normal metabolism and characterize disease physiology has been limited by its low sensitivity. However, recent technological advances have enabled greater than 50,000-fold enhancement of liquid-state polarization of metabolically active (13)C substrates, allowing for rapid assessment of (13)C metabolism in vivo. The present study applied hyperpolarized (13)C magnetic resonance spectroscopy to the investigation of liver metabolism, demonstrating for the first time the feasibility of applying this technology to detect differences in liver metabolic states. PROCEDURES: [1-(13)C]pyruvate was hyperpolarized with a dynamic nuclear polarization instrument and injected into normal and fasted rats. The uptake of pyruvate and its conversion to the metabolic products lactate and alanine were observed with slice-localized dynamic magnetic resonance spectroscopy and 3D magnetic resonance spectroscopic imaging (3D-MRSI). RESULTS: Significant differences in lactate to alanine ratio (P < 0.01) between normal and fasted rat liver slice dynamic spectra were observed. 3D-MRSI localized to the fasted livers demonstrated significantly decreased (13)C-alanine levels (P < 0.01) compared to normal. CONCLUSIONS: This study presents the initial demonstration of characterizing metabolic state differences in the liver with hyperpolarized (13)C spectroscopy and shows the ability to detect physiological perturbations in alanine aminotransferase activity, which is an encouraging result for future liver disease investigations with hyperpolarized magnetic resonance technology

The clinical and therapeutic uses of MDM2 and PSMA and their potential interaction in aggressive cancers

Prostate-specific membrane antigen (PSMA) overexpression is observed in the neovasculature of solid tumors, but not in the vasculature of normal tissues. Increased PSMA expression is positively associated with tumor stage and grade, although its function in cancer remains unclear. Mouse double minute 2 (MDM2) is a negative regulator of the p53 tumor suppressor and is reported to regulate VEGF expression and angiogenesis. Both proteins have been considered as biomarkers and therapeutic targets for advanced solid tumors. Our work and a recent microarray-based gene profiling study suggest there could be signaling interplay between MDM2 and PSMA. We herein review the mechanisms underlining the outgrowth of tumors associated with PSMA and MDM2, their potential interaction and how this may be applied to anticancer therapeutics