Enrichment and characterization of dendritic cells from human bronchoalveolar lavages

In the present study about 0.3% to 1.6% of human bronchoalveolar lavage (BAL) cells were identified as typical dendritic cells (DC), having an irregular outline, lobulated nucleus, and clear distinguishable acid phosphatase activity or EBM11 (anti-CD68) reactivity in a spot near the nucleus. After DC enrichment, using transient adherence to plastic, FcR-panning, and a density metrizamide gradient, a population containing 7-8% typical DC was obtained. This DC-enriched low density fraction, containing the highest percentages of DC, very strongly induced T cell proliferation in an allogeneic mixed leucocyte reaction (MLR), which was significantly higher than that induced by other partly (un)fractionated BAL cells. These data indicate that DC seem to be the major accessory cells in the BAL fluid, and therefore may be important in the regulation of T cell immune responses in the lung

Global forecasting of thermal health hazards: the skill of probabilistic predictions of the Universal Thermal Climate Index (UTCI)

Although over a hundred thermal indices can be used for assessing thermal health hazards, many ignore the human heat budget, physiology and clothing. The Universal Thermal Climate Index (UTCI) addresses these shortcomings by using an advanced thermo-physiological model. This paper assesses the potential of using the UTCI for forecasting thermal health hazards. Traditionally, such hazard forecasting has had two further limitations: it has been narrowly focused on a particular region or nation and has relied on the use of single ‘deterministic’ forecasts. Here, the UTCI is computed on a global scale,which is essential for international health-hazard warnings and disaster preparedness, and it is provided as a probabilistic forecast. It is shown that probabilistic UTCI forecasts are superior in skill to deterministic forecasts and that despite global variations, the UTCI forecast is skilful for lead times up to 10 days. The paper also demonstrates the utility of probabilistic UTCI forecasts on the example of the 2010 heat wave in Russia

The role of clothing in thermal comfort: how people dress in a temperate and humid climate in Brazil

Abstract Thermal insulation from clothing is one of the most important input variables used to predict the thermal comfort of a building's occupants. This paper investigates the clothing pattern in buildings with different configurations located in a temperate and humid climate in Brazil. Occupants of two kinds of buildings (three offices and two university classrooms) assessed their thermal environment through 'right-here-right-now' questionnaires, while at the same time indoor climatic measurements were carried out in situ (air temperature and radiant temperature, air speed and humidity). A total of 5,036 votes from 1,161 occupants were collected. Results suggest that the clothing values adopted by occupants inside buildings were influenced by: 1) climate and seasons of the year; 2) different configurations and indoor thermal conditions; and 3) occupants' age and gender. Significant intergenerational and gender differences were found, which might be explained by differences in metabolic rates and fashion. The results also indicate that there is a great opportunity to exceed the clothing interval of the thermal comfort zones proposed by international standards such as ASHRAE 55 (2013) - 0.5 to 1.0 clo - and thereby save energy from cooling and heating systems, without compromising the occupants' indoor thermal comfort

Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages

BACKGROUND: Investigations on pulmonary macrophages (MΦ) mostly focus on alveolar MΦ (AM) as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM), are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. METHODS: Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR) expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. RESULTS: IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG). Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6.CONCLUSION: AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response

An ecological time-series study of heat-related mortality in three European cities

BACKGROUND: Europe has experienced warmer summers in the past two decades and there is a need to describe the determinants of heat-related mortality to better inform public health activities during hot weather. We investigated the effect of high temperatures on daily mortality in three cities in Europe (Budapest, London, and Milan), using a standard approach. METHODS: An ecological time-series study of daily mortality was conducted in three cities using Poisson generalized linear models allowing for over-dispersion. Secular trends in mortality and seasonal confounding factors were controlled for using cubic smoothing splines of time. Heat exposure was modelled using average values of the temperature measure on the same day as death (lag 0) and the day before (lag 1). The heat effect was quantified assuming a linear increase in risk above a cut-point for each city. Socio-economic status indicators and census data were linked with mortality data for stratified analyses. RESULTS: The risk of heat-related death increased with age, and females had a greater risk than males in age groups > or =65 years in London and Milan. The relative risks of mortality (per degrees C) above the heat cut-point by gender and age were: (i) Male 1.10 (95%CI: 1.07-1.12) and Female 1.07 (1.05-1.10) for 75-84 years, (ii) M 1.10 (1.06-1.14) and F 1.08 (1.06-1.11) for > or = or =85 years in Budapest (> or =24 degrees C); (i) M 1.03 (1.01-1.04) and F 1.07 (1.05-1.09), (ii) M 1.05 (1.03-1.07) and F 1.08 (1.07-1.10) in London (> or =20 degrees C); and (i) M 1.08 (1.03-1.14) and F 1.20 (1.15-1.26), (ii) M 1.18 (1.11-1.26) and F 1.19 (1.15-1.24) in Milan (> or =26 degrees C). Mortality from external causes increases at higher temperatures as well as that from respiratory and cardiovascular disease. There was no clear evidence of effect modification by socio-economic status in either Budapest or London, but there was a seemingly higher risk for affluent non-elderly adults in Milan. CONCLUSION: We found broadly consistent determinants (age, gender, and cause of death) of heat related mortality in three European cities using a standard approach. Our results are consistent with previous evidence for individual determinants, and also confirm the lack of a strong socio-economic gradient in heat health effects currently in Europe

Timescales of Multineuronal Activity Patterns Reflect Temporal Structure of Visual Stimuli

The investigation of distributed coding across multiple neurons in the cortex remains to this date a challenge. Our current understanding of collective encoding of information and the relevant timescales is still limited. Most results are restricted to disparate timescales, focused on either very fast, e.g., spike-synchrony, or slow timescales, e.g., firing rate. Here, we investigated systematically multineuronal activity patterns evolving on different timescales, spanning the whole range from spike-synchrony to mean firing rate. Using multi-electrode recordings from cat visual cortex, we show that cortical responses can be described as trajectories in a high-dimensional pattern space. Patterns evolve on a continuum of coexisting timescales that strongly relate to the temporal properties of stimuli. Timescales consistent with the time constants of neuronal membranes and fast synaptic transmission (5–20 ms) play a particularly salient role in encoding a large amount of stimulus-related information. Thus, to faithfully encode the properties of visual stimuli the brain engages multiple neurons into activity patterns evolving on multiple timescales

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Expression of endoglin (CD105) in cervical cancer

In this study, we have investigated the role of endoglin (CD105), a regulator of transforming growth factor (TGF)-β1 signalling on endothelial cells, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) in cervical cancer. We have measured the number and determined the location of both newly formed (CD105-positive) and the overall number of (CD31-positive) blood vessels, and bFGF and VEGF-A expression using immunohistochemistry in 30 cervical carcinoma specimens. Vascular endothelial growth factor-A mRNA expression was determined using RNA-in situ hybridisation. CD105- and CD31-positive vessels and bFGF- and VEGF-A-positive cells were predominantly present in the stroma. The presence of CD105- and CD31-positive vessels in the stroma did neither correlate with the number of VEGF-A-positive cells nor the number of bFGF-positive cells. However, the number of CD105- and CD31-positive vessels was associated with the expression of VEGF-A mRNA in the epithelial cell clusters (P=0.013 and P=0.005, respectively). The presence of CD105-positive and CD31-positive vessels was associated with the expression of αvβ6 (a TGF-β1 activator; P=0.013 and P=0.006, respectively). Clinically, the number of CD105-positive vessels associated with the number of lymph node metastasis (P<0.001). Furthermore, the presence of CD105-positive vessels within the epithelial cell clusters associated with poor disease-free survival (P=0.007)

The 2023 terahertz science and technology roadmap

Terahertz (THz) radiation encompasses a wide spectral range within the electromagnetic spectrum that extends from microwaves to the far infrared (100 GHz–∼30 THz). Within its frequency boundaries exist a broad variety of scientific disciplines that have presented, and continue to present, technical challenges to researchers. During the past 50 years, for instance, the demands of the scientific community have substantially evolved and with a need for advanced instrumentation to support radio astronomy, Earth observation, weather forecasting, security imaging, telecommunications, non-destructive device testing and much more. Furthermore, applications have required an emergence of technology from the laboratory environment to production-scale supply and in-the-field deployments ranging from harsh ground-based locations to deep space. In addressing these requirements, the research and development community has advanced related technology and bridged the transition between electronics and photonics that high frequency operation demands. The multidisciplinary nature of THz work was our stimulus for creating the 2017 THz Science and Technology Roadmap (Dhillon et al 2017 J. Phys. D: Appl. Phys. 50 043001). As one might envisage, though, there remains much to explore both scientifically and technically and the field has continued to develop and expand rapidly. It is timely, therefore, to revise our previous roadmap and in this 2023 version we both provide an update on key developments in established technical areas that have important scientific and public benefit, and highlight new and emerging areas that show particular promise. The developments that we describe thus span from fundamental scientific research, such as THz astronomy and the emergent area of THz quantum optics, to highly applied and commercially and societally impactful subjects that include 6G THz communications, medical imaging, and climate monitoring and prediction. Our Roadmap vision draws upon the expertise and perspective of multiple international specialists that together provide an overview of past developments and the likely challenges facing the field of THz science and technology in future decades. The document is written in a form that is accessible to policy makers who wish to gain an overview of the current state of the THz art, and for the non-specialist and curious who wish to understand available technology and challenges. A such, our experts deliver a 'snapshot' introduction to the current status of the field and provide suggestions for exciting future technical development directions. Ultimately, we intend the Roadmap to portray the advantages and benefits of the THz domain and to stimulate further exploration of the field in support of scientific research and commercial realisation