The Long Road Home: Driving Performance and Ocular Measurements of Drowsiness Following Night Shift-Work

Because time-of-day effects on sleepiness interact with duration of prior waking, the commute home following a night shift is an especially vulnerable time for night shift workers. The current study aimed to explore the impact of night shift work on critical driving events as well as to explore physiological indices leading up to these events. Sixteen healthy night shift workers (18-65 years) each participated in two 2-hour driving sessions in an instrumented vehicle on a driving track. A baseline driving session was conducted following a night of rest, while another session was conducted following a night of shift work. Objective physiological measurements of drowsiness were monitored and collected continuously throughout the drive session as well as different measures of driving performance. Following the night-shift, drivers had higher Johns Drowsiness Scores (based on ocular measures) and were more likely to experience lane excursion events and investigator-initiated braking events than following a night’s rest. While they also reported increasing failures in lane keeping ability, the pattern was not always consistent with actual observed data. The implications for countermeasures are discussed

High risk of near-crash driving events following night-shift work

Night-shift workers are at high risk of drowsiness-related motor vehicle crashes as a result of circadian disruption and sleep restriction. However, the impact of actual night-shift work on measures of drowsiness and driving performance while operating a real motor vehicle remains unknown. Sixteen night-shift workers completed two 2-h daytime driving sessions on a closed driving track at the Liberty Mutual Research Institute for Safety: (i) a postsleep baseline driving session after an average of 7.6 ± 2.4 h sleep the previous night with no night-shift work, and (ii) a postnight-shift driving session following night-shift work. Physiological measures of drowsiness were collected, including infrared reflectance oculography, electroencephalography, and electrooculography. Driving performance measures included lane excursions, near-crash events, and drives terminated because of failure to maintain control of the vehicle. Eleven near-crashes occurred in 6 of 16 postnight-shift drives (37.5%), and 7 of 16 postnight-shift drives (43.8%) were terminated early for safety reasons, compared with zero near-crashes or early drive terminations during 16 postsleep drives (Fishers exact: P = 0.0088 and P = 0.0034, respectively). Participants had a significantly higher rate of lane excursions, average Johns Drowsiness Scale, blink duration, and number of slow eye movements during postnight-shift drives compared with postsleep drives (3.09/min vs. 1.49/min; 1.71 vs. 0.97; 125 ms vs. 100 ms; 35.8 vs. 19.1; respectively, P < 0.05 for all). Night-shift work increases driver drowsiness, degrading driving performance and increasing the risk of near-crash drive events. With more than 9.5 million Americans working overnight or rotating shifts and one-third of United States commutes exceeding 30 min, these results have implications for traffic and occupational safety

Biogeochemistry of a Southern Ocean plankton ecosystem: Using natural variability in community composition to study the role of metazooplankton in carbon and nitrogen cycles

The pelagic ecosystem around the island of South Georgia is subject to significant interannual variability, and changes in zooplankton community composition can be used as natural ecosystem experiments to examine biogeochemical cycles. The biomass of the large euphausiid Antarctic krill may range from ca. 2 to 150 g fresh mass (FM) m−2. When krill biomass is low, copepod biomass may be correspondingly higher and overall zooplankton biomass remains more or less unchanged. Krill are omnivorous, feeding facultatively either as grazers on microplankton or as predators on smaller zooplankton. This leads to complex feedbacks within the plankton. A simple model of the phytoplankton–copepod–krill system is used to simulate two scenarios of zooplankton composition. For the “low krill-high copepod” scenario, the model predicts higher phytoplankton biomass and production, lower mixed layer (ML) ammonium, nitrate and silicate concentrations, and higher detrital carbon production than in the “high krill-low copepod” scenario. Nitrogen cycling provides the most explicit demonstration of the differences between the scenarios. For the “low krill-high copepod” scenario, ML ammonium concentration decreased by 25% over 20 days, but excretion by metazooplankton supplied 30% of phytoplankton nitrogen demand. In the “high krill-low copepod” scenario, ML ammonium only declined by 10% over 20 days, but metazooplankton excretion was much lower, at 10% of phytoplankton N demand. These predictions are compared with data from several surveys covering krill biomass in the range 10–55 g FM m−2. Phytoplankton chlorophyll biomass is negatively related to krill biomass, and ML nutrients are positively correlated with krill biomass in these data. Both observations and model results suggest that variation in biogeochemical carbon and nitrogen cycles in the South Georgia pelagic ecosystem is determined largely by changes in zooplankton community composition and its impact on phytoplankton dynamics

Biogeochemistry of a Southern Ocean plankton ecosystem: Using natural variability in community composition to study the role of metazooplankton in carbon and nitrogen cycles

The pelagic ecosystem around the island of South Georgia is subject to significant interannual variability, and changes in zooplankton community composition can be used as natural ecosystem experiments to examine biogeochemical cycles. The biomass of the large euphausiid Antarctic krill may range from ca. 2 to 150 g fresh mass (FM) m−2. When krill biomass is low, copepod biomass may be correspondingly higher and overall zooplankton biomass remains more or less unchanged. Krill are omnivorous, feeding facultatively either as grazers on microplankton or as predators on smaller zooplankton. This leads to complex feedbacks within the plankton. A simple model of the phytoplankton–copepod–krill system is used to simulate two scenarios of zooplankton composition. For the “low krill-high copepod” scenario, the model predicts higher phytoplankton biomass and production, lower mixed layer (ML) ammonium, nitrate and silicate concentrations, and higher detrital carbon production than in the “high krill-low copepod” scenario. Nitrogen cycling provides the most explicit demonstration of the differences between the scenarios. For the “low krill-high copepod” scenario, ML ammonium concentration decreased by 25% over 20 days, but excretion by metazooplankton supplied 30% of phytoplankton nitrogen demand. In the “high krill-low copepod” scenario, ML ammonium only declined by 10% over 20 days, but metazooplankton excretion was much lower, at 10% of phytoplankton N demand. These predictions are compared with data from several surveys covering krill biomass in the range 10–55 g FM m−2. Phytoplankton chlorophyll biomass is negatively related to krill biomass, and ML nutrients are positively correlated with krill biomass in these data. Both observations and model results suggest that variation in biogeochemical carbon and nitrogen cycles in the South Georgia pelagic ecosystem is determined largely by changes in zooplankton community composition and its impact on phytoplankton dynamics

High risk of near-crash driving events following night-shift work

Night-shift workers are at high risk of drowsiness-related motor vehicle crashes as a result of circadian disruption and sleep restriction. However, the impact of actual night-shift work on measures of drowsiness and driving performance while operating a real motor vehicle remains unknown. Sixteen night-shift workers completed two 2-h daytime driving sessions on a closed driving track at the Liberty Mutual Research Institute for Safety: (i) a postsleep baseline driving session after an average of 7.6 ± 2.4 h sleep the previous night with no night-shift work, and (ii) a postnight-shift driving session following night-shift work. Physiological measures of drowsiness were collected, including infrared reflectance oculography, electroencephalography, and electrooculography. Driving performance measures included lane excursions, near-crash events, and drives terminated because of failure to maintain control of the vehicle. Eleven near-crashes occurred in 6 of 16 postnight-shift drives (37.5%), and 7 of 16 postnight-shift drives (43.8%) were terminated early for safety reasons, compared with zero near-crashes or early drive terminations during 16 postsleep drives (Fishers exact: P = 0.0088 and P = 0.0034, respectively). Participants had a significantly higher rate of lane excursions, average Johns Drowsiness Scale, blink duration, and number of slow eye movements during postnight-shift drives compared with postsleep drives (3.09/min vs. 1.49/min; 1.71 vs. 0.97; 125 ms vs. 100 ms; 35.8 vs. 19.1; respectively, P < 0.05 for all). Night-shift work increases driver drowsiness, degrading driving performance and increasing the risk of near-crash drive events. With more than 9.5 million Americans working overnight or rotating shifts and one-third of United States commutes exceeding 30 min, these results have implications for traffic and occupational safety

Comparison of immunohistochemistry and gene expression profiling subtyping for diffuse large B-cell lymphoma in the phase III clinical trial of R-CHOP ± ibrutinib

We assessed the concordance between immunohistochemistry (IHC) and gene expression profiling (GEP) for determining diffuse large B-cell lymphoma (DLBCL) cell of origin (COO) in the phase III PHOENIX trial of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with or without ibrutinib. Among 910 of 1114 screened patients with non-germinal centre B cell-like (non-GCB) DLBCL by IHC, the concordance with GEP for non-GCB calls was 82·7%, with 691 (75·9%) identified as activated B cell-like (ABC), and 62 (6·8%) as unclassified. Among 746 of 837 enrolled patients with verified non-GCB DLBCL by IHC, the concordance with GEP was 82·8%, with 567 (76·0%) identified as ABC and 51 (6·8%) unclassified; survival outcomes were similar regardless of COO or treatment, whereas among patients with ABC DLBCL aged &lt;60 years, the overall and event-free survival were substantially better with ibrutinib versus placebo plus R-CHOP [hazard ratio (HR) 0·365, 95% confidence interval (CI) 0·147-0·909, P = 0·0305; HR 0·561, 95% CI 0·326-0·967, P = 0·0348, respectively]. IHC and GEP showed high concordance and consistent survival outcomes among tested patients, indicating centralised IHC may be used to enrich populations for response to ibrutinib plus R-CHOP.</p

Dysregulation at multiple points of the kynurenine pathway is a ubiquitous feature of renal cancer: implications for tumour immune evasion

Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Abstract: Background: Indoleamine 2,3-dioxygenase (IDO), the first step in the kynurenine pathway (KP), is upregulated in some cancers and represents an attractive therapeutic target given its role in tumour immune evasion. However, the recent failure of an IDO inhibitor in a late phase trial raises questions about this strategy. Methods: Matched renal cell carcinoma (RCC) and normal kidney tissues were subject to proteomic profiling. Tissue immunohistochemistry and gene expression data were used to validate findings. Phenotypic effects of loss/gain of expression were examined in vitro. Results: Quinolate phosphoribosyltransferase (QPRT), the final and rate-limiting enzyme in the KP, was identified as being downregulated in RCC. Loss of QPRT expression led to increased potential for anchorage-independent growth. Gene expression, mass spectrometry (clear cell and chromophobe RCC) and tissue immunohistochemistry (clear cell, papillary and chromophobe), confirmed loss or decreased expression of QPRT and showed downregulation of other KP enzymes, including kynurenine 3-monoxygenase (KMO) and 3-hydroxyanthranilate-3,4-dioxygenase (HAAO), with a concomitant maintenance or upregulation of nicotinamide phosphoribosyltransferase (NAMPT), the key enzyme in the NAD+ salvage pathway. Conclusions: Widespread dysregulation of the KP is common in RCC and is likely to contribute to tumour immune evasion, carrying implications for effective therapeutic targeting of this critical pathwa