Tumor-infiltrating CD8 + T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8 + T-cell infiltration is robust in only 4%-18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer + CD8 + T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry. TCRβ (TRB) sequencing was performed on tetramer + cells from PBMC or TIL (n = 14) and matched tumors (n = 12). Functional avidity of T-cell clones was determined by IFNγ production. We identified KLL tetramer + T cells in 14% of PBMC and 21% of TIL from MCC patients. TRB repertoires were diverse (mean of 12 and 29 clonotypes/patient in PBMC and TIL, respectively) and mostly private. An increased fraction of KLL-specific TIL (> 1.9%) was associated with significantly increased MCC-specific survival P = 0.0009). Forty-two
Nighttime light emissions are increasing in most countries worldwide, but which types of lighting are responsible for the increase remains unknown. Also unknown is what fraction of outdoor light emissions and associated energy use are due to public light sources (i.e. streetlights) or various types of private light sources (e.g. advertising). Here we show that it is possible to measure the contribution of street lighting to nighttime satellite imagery using ‘smart city’ lighting infrastructure. The city of Tucson, USA, intentionally altered its streetlight output over 10 days, and we examined the change in emissions observed by satellite. We find that streetlights operated by the city are responsible for only 13% of the total radiance (in the 500–900 nm band) observed from Tucson from space after midnight (95% confidence interval 10–16%). If Tucson did not dim their streetlights after midnight, the contribution would be 18% (95% confidence interval 15–23%). When streetlights operated by other actors are included, the best estimates rise to 16% and 21%, respectively. Existing energy and lighting policy related to the sustainability of outdoor light use has mainly focused on street lighting. These results suggest an urgent need for consideration of other types of light sources in outdoor lighting policy.
In outdoor environments after dark, pedestrians may experience discomfort from glare caused by lighting. Several models to predict discomfort from glare have been proposed or extended for pedestrian applications; these models use different luminous and geometrical quantities to predict discomfort. Consistent measurements and reporting in studies of discomfort from glare are important for identifying best performing models; however, previous studies proposing a new model tended to only report the performance of the new model and its quantities. This practice makes it difficult to evaluate how a new model performs compared to other existing models. To promote more consistent and complete reporting, this research note proposes measuring and reporting all relevant quantities that are used in existing models. This can make it easier for researchers to use a study dataset to compare the performance of several models or to combine datasets from several studies to address between-study variance.
Flicker has been an important lighting system consideration for over a century. More precise terms are temporal light modulation (TLM) as the stimulus, and responses to TLM as the unwanted visual, cognitive, or physiological consequences. As lighting technology evolved, different forms of TLM emerged, and so did responses to them. Today, some LED systems – encompassing the LED, driver, and control – can result in TLM causing severe unwanted effects, while other LED systems produce no unwanted effects at all. LED systems can deliver a much wider range of luminous waveforms than conventional lighting systems, some exhibiting very high modulation depths. More than any light source before, they can elicit perceptions of the phantom array. Direct flicker effects at modulation frequencies less than about 80 Hz and the stroboscopic effect at frequencies greater than 80 Hz are fairly well understood, but the phantom array effect needs more exploration and characterisation. This review focuses on the technology and research history that led to current metrics for quantifying TLM and human responses to TLM. Visually impaired individuals may exhibit alterations in their response to TLM, but such a discussion is beyond the intent of this review. Thus, the focus is on individuals with normal visual function.
After dark, pedestrians may experience discomfort from glare caused by outdoor lighting. While several models for measuring discomfort have been proposed, there is no consensus as to which model should be used. The performances of different models were investigated using datasets from four independent studies, comparing the degree of association between model predictions and subjective ratings, and the ability of a model to distinguish between discomfort and non-discomfort situations. The models tested are those proposed by Petherbridge and Hopkinson in 1950, Schmidt-Clausen and Bindels in 1974, Bullough et al. in 2008 and Lin et al. in 2014 and 2015. They also include two quantities: direct illuminance at the eye from the glare source and average source luminance. Of the models tested, the best performance was found using either the model proposed by Bullough et al. in 2008 or by direct illuminance at the eye.
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