Mental workload and driving

International audienceThe aim of this review is to identify the most representative measures of subjective and objective mental workload in driving, and to understand how the subjective and objective levels of mental workload influence the performance as a function of situation complexity and driving experience, i.e., to verify whether the increase of situation complexity and the lack of experience increase the subjective and physiological levels of mental workload and lead to driving performance impairments. This review will be useful to both researchers designing an experimental study of mental workload and to designers of drivers' training content. In the first part, we will broach the theoretical approach with two factors of mental workload and performance, i.e., situation complexity and driving experience. Indeed, a low complex situation (e.g., highways), or conversely a high complex situation (e.g., town) can provoke an overload. Additionally, performing the driving tasks implies producing a high effort for novice drivers who have not totally automated the driving activity. In the second part, we will focus on subjective measures of mental workload. A comparison of questionnaires usually used in driving will allow identifying the most appropriate ones as a function of different criteria. Moreover, we will review the empirical studies to verify if the subjective level of mental workload is high in simple and very complex situations, especially for novice drivers compared to the experienced ones. In the third part, we will focus on physiological measures. A comparison of physiological indicators will be realized in order to identify the most correlated to mental workload. An empirical review will also take the effect of situation complexity and experience on these physiological indicators into consideration. Finally, a more nuanced comparison between subjective and physiological measures will be established from the impact on situation complexity and experience

Spheroid-plug model as a tool to study tumor development, angiogenesis, and heterogeneity in vivo

Subcutaneous injection of the tumor cell suspension is a simple and commonly used tool for studying tumor development in vivo. However, subcutaneous models poorly resemble tumor complexity due to the fast growth not reflecting the natural course. Here, we describe an application of the new spheroid-plug model to combine the simplicity of subcutaneous injection with improved resemblance to natural tumor progression. Spheroid-plug model relies on in vitro formation of tumor spheroids, followed by injection of single tumor spheroid subcutaneously in Matrigel matrix. In spheroid-plug model, tumors grow slower in comparison to tumors formed by injection of cell suspension as assessed by 3D ultrasonography (USG) and in vivo bioluminescence measurements. The slower tumor growth rate in spheroid-plug model is accompanied by reduced necrosis. The spheroid-plug model ensures increased and more stable vascularization of tumor than classical subcutaneous tumor model as demonstrated by 3D USG Power Doppler examination. Flow cytometry analysis showed that tumors formed from spheroids have enhanced infiltration of endothelial cells as well as hematopoietic and progenitor cells with stem cell phenotype (c-Kit+ and Sca-1+). They also contain more tumor cells expressing cancer stem cell marker CXCR4. Here, we show that spheroid-plug model allows investigating efficiency of anticancer drugs. Treatment of spheroid-plug tumors with known antiangiogenic agent axitinib decreased their size and viability. The antiangiogenic activity of axitinib was higher in spheroid-plug model than in classical model. Our results indicate that spheroid-plug model imitates natural tumor growth and can become a valuable tool for cancer research

Time-resolved single-crystal X-ray crystallography

In this chapter the development of time-resolved crystallography is traced from its beginnings more than 30 years ago. The importance of being able to “watch” chemical processes as they occur rather than just being limited to three-dimensional pictures of the reactant and final product is emphasised, and time-resolved crystallography provides the opportunity to bring the dimension of time into the crystallographic experiment. The technique has evolved in time with developments in technology: synchrotron radiation, cryoscopic techniques, tuneable lasers, increased computing power and vastly improved X-ray detectors. The shorter the lifetime of the species being studied, the more complex is the experiment. The chapter focusses on the results of solid-state reactions that are activated by light, since this process does not require the addition of a reagent to the crystalline material and the single-crystalline nature of the solid may be preserved. Because of this photoactivation, time-resolved crystallography is often described as “photocrystallography”. The initial photocrystallographic studies were carried out on molecular complexes that either underwent irreversible photoactivated processes where the conversion took hours or days. Structural snapshots were taken during the process. Materials that achieved a metastable state under photoactivation and the excited (metastable) state had a long enough lifetime for the data from the crystal to be collected and the structure solved. For systems with shorter lifetimes, the first time-resolved results were obtained for macromolecular structures, where pulsed lasers were used to pump up the short lifetime excited state species and their structures were probed by using synchronised X-ray pulses from a high-intensity source. Developments in molecular crystallography soon followed, initially with monochromatic X-ray radiation, and pump-probe techniques were used to establish the structures of photoactivated molecules with lifetimes in the micro- to millisecond range. For molecules with even shorter lifetimes in the sub-microsecond range, Laue diffraction methods (rather than using monochromatic radiation) were employed to speed up the data collections and reduce crystal damage. Future developments in time-resolved crystallography are likely to involve the use of XFELs to complete “single-shot” time-resolved diffraction studies that are already proving successful in the macromolecular crystallographic field.</p

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

2019 ESC/EAS Guidelines for themanagement of dyslipidaemias: lipid modification to reduce cardiovascular risk

n/

The Combination of an Oral Appliance and Supplemental Oxygen Markedly Improves Obstructive Sleep Apnea Severity: A Randomized Controlled Trial

Introduction: Obstructive sleep apnea (OSA) is challenging to treat due to limited tolerance of the leading therapy, continuous positive airway pressure. A leading second line therapy, oral appliances, are well tolerated but have limited efficacy. On the basis that oral appliance efficacy is lowest in patients with a high chemoreflex "loop gain", the current study tested the hypothesis that administration of supplemental oxygen (to lower loop gain) in combination with an oral appliance provides greater OSA treatment efficacy compared to oral appliance therapy alone. Methods: In a multicentre randomized crossover trial, 41 patients with moderate-to-severe OSA (apnea-hypopnea index [AHI] >20 events/hr) underwent in-laboratory polysomnography to assess the impact of a night of supplemental oxygen (4 L/min), oral appliance, both therapies in combination, compared to sham (air) on AHI. For primary analysis, hypopneas were scored regardless of desaturation/arousal criteria. Mixed model analysis compared treatment efficacy (change in AHI from baseline) between combination therapy and oral appliance alone (primary outcome). Sensitivity analysis reported AHI changes using standard 3% desaturation or arousal criteria (AHI3pa). Key secondary outcomes were arousal index and visual analog scale for sleep quality (VASSQ); higher score reflects improved sleep (0-10 units). Results: Of the 41 randomized patients (14F:27M, baseline AHI = 49 [29, 62] events/hr; median [interquartile range]), 38 completed all four interventions. Compared to sham, AHI was lowered with oxygen (−33% [CI: −46, −17]), oral appliances (−53% [−64, −41]), and the combination (−67% [−77, −57]): the combination provided a greater reduction compared to oral appliance alone (difference = −14% [−23, −4], P=0.009) confirming the study hypothesis. Sensitivity analysis using AHI3pa yielded a −73% change with the combination vs. sham (difference vs. oral appliance = −17% [−25, −7]). In secondary analysis, arousal index was lowered with oxygen (−19% [−28, −9]), oral appliances (−29% [−37, −20]), and the combination (−36% [−43, −27]; difference vs. oral appliance = −7% [−14, 2], P=0.11). VASSQ increased with oxygen (0.52 [−0.08, 1.1], borderline change), oral appliances (0.71 [0.11, 1.30]), and with the combination (0.98 [0.39, 1.58]; difference vs. oral appliance = 0.28 [−0.31, 0.86]). Conclusion: In moderate-severe OSA, the combination of supplemental oxygen and oral appliance therapy provides a greater OSA treatment efficacy compared to oral appliances alone. Combining a loop gain intervention with oral appliances is a promising approach to markedly attenuate the severity of OSA