As driving functions become increasingly automated, motorists run the risk of becoming cognitively removed from the driving process. Psychophysiological measures may provide added value not captured ...through behavioral or self-report measures alone. This paper provides a selective review of the psychophysiological measures that can be utilized to assess cognitive states in real-world driving environments. First, the importance of psychophysiological measures within the context of traffic safety is discussed. Next, the most commonly used physiology-based indices of cognitive states are considered as potential candidates relevant for driving research. These include: electroencephalography and event-related potentials, optical imaging, heart rate and heart rate variability, blood pressure, skin conductance, electromyography, thermal imaging, and pupillometry. For each of these measures, an overview is provided, followed by a discussion of the methods for measuring it in a driving context. Drawing from recent empirical driving and psychophysiology research, the relative strengths and limitations of each measure are discussed to highlight each measures' unique value. Challenges and recommendations for valid and reliable quantification from lab to (less predictable) real-world driving settings are considered. Finally, we discuss measures that may be better candidates for a near real-time assessment of motorists' cognitive states that can be utilized in applied settings outside the lab. This review synthesizes the literature on in-vehicle psychophysiological measures to advance the development of effective human-machine driving interfaces and driver support systems.
The sequencing of the first complete bacterial genome in 1995 heralded a new era of hope for antibacterial drug discoverers, who now had the tools to search entire genomes for new antibacterial ...targets. Several companies, including GlaxoSmithKline, moved back into the antibacterials area and embraced a genomics-derived, target-based approach to screen for new classes of drugs with novel modes of action. Here, we share our experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years, and look at what we learned and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.
The error negativity/error-related negativity (Ne/ERN) is one of the most well-studied event-related potential (ERP) components in the electroencephalography (EEG) literature. Peaking about 50 ms ...after the commission of an error, the Ne/ERN is a negative deflection in the ERP waveform that is thought to reflect error processing in the brain. While its relationships to trait constructs such as anxiety are well-documented, there is still little known about how the Ne/ERN may subsequently influence task-related behavior. In other words, does the occurrence of the Ne/ERN trigger any sort of error corrective process, or any other behavioral adaptation to avoid errors? Several theories have emerged to explain how the Ne/ERN may implement or affect behavior on a task, but evidence supporting each has been mixed. In the following manuscript, we review these theories, and then systematically discuss the reasons that there may be discrepancies in the literature. We review both the inherent biological factors of the neural regions that underlie error-processing in the brain, and some of the researcher-induced factors in analytic and experimental choices that may be exacerbating these discrepancies. We end with a table of recommendations for future researchers who aim to understand the relationship between the Ne/ERN and behavior.
Both anxiety and working memory capacity appear to predict increased (more negative) error-related negativity (ERN) amplitudes, despite being inversely related to one another. Until the interactive ...effects of these variables on the ERN are clarified, there may be challenges posed to our ability to use the ERN as an endophenotype for anxiety, as some have suggested. The compensatory error monitoring hypothesis suggests that high trait-anxiety individuals have larger ERN amplitudes because they must employ extra, compensatory efforts to override the working memory demands of their anxiety. Yet, to our knowledge, no ERN study has employed direct manipulation of working memory demands in conjunction with direct manipulations of induced (state) anxiety. Furthermore, little is known about how these manipulations affect other measures of error processing, such as the error-related pupil dilation response and post-error behavioral adjustments. Therefore, we manipulate working memory load and anxiety in a 2 × 2 within-subjects design to examine the interactive effects of working memory load and anxiety on ERN amplitude, error-related pupil dilation response amplitude, and post-error behavior. There were no effects of our manipulations on ERN amplitude, suggesting a strong interpretation of compensatory error-processing theory. However, our worry manipulation affected post-error behavior, such that worry caused a reduction in post-error accuracy. Additionally, our working memory manipulation affected error-related PDR magnitude and the amplitude of the error-related positivity (Pe), such that increased working memory load decreased the amplitude of these responses. Implications of these results within the context of the compensatory error processing framework are discussed.
Background. In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time ...reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). Methods. Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical record reviews, and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using 3 US Centers for Disease Control and Prevention serologic tests for detection of anti–MERS-CoV antibodies. Results. Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti–MERS-CoV antibodies by at least 2 of 3 serologic tests, in addition to 2 fatal cases identified by rRT-PCR. The case-fatality rate among the 9 total cases was 22%. Six subjects were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at 2 transfer hospitals having acceptable infection control practices. Conclusions. Novel serologic tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts in a Jordanian hospital-associated respiratory illness outbreak in April 2012, resulting in a total of 9 test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most subjects had no major, underlying medical conditions; none were on hemodialysis. Our observed case-fatality rate was lower than has been reported from outbreaks elsewhere.
Friedreich Ataxia (FA) is a rare and often fatal autosomal recessive disease in which a mitochondrial protein, frataxin (FXN), is severely reduced in all tissues. With loss of FXN, mitochondrial ...metabolism is severely disrupted. Multiple therapeutic approaches are in development, but a key limitation is the lack of biomarkers reflecting the activity of FXN in a timely fashion. We predicted this dysregulated metabolism would present a unique metabolite profile in blood of FA patients versus Controls (Con). Plasma from 10 FA and 11 age and sex matched Con subjects was analyzed by targeted mass spectrometry and untargeted NMR. This combined approach yielded quantitative measurements for 540 metabolites and found 59 unique metabolites (55 from MS and 4 from NMR) that were significantly different between cohorts. Correlation-based network analysis revealed several clusters of pathway related metabolites including a cluster associated with one‑carbon (1C) metabolism composed of formate, sarcosine, hypoxanthine, and homocysteine. Receiver operator characteristics analyses demonstrated an excellent ability to discriminate between Con and FA with AUC values >0.95. These results are the first reported metabolomic analyses of human patients with FA. The metabolic perturbations, especially those related to 1C metabolism, may serve as a valuable biomarker panel of disease progression and response to therapy. The identification of dysregulated 1C metabolism may also inform the search for new therapeutic targets related to this pathway.
To prospectively evaluate a treat and extend algorithm of ranibizumab with and without navigated laser to monthly dosing for center-involving diabetic macular edema.
This was a multicenter, ...randomized, clinical trial.
One hundred fifty eyes were randomized into 3 cohorts: monthly (n = 30), treat and extend without laser photocoagulation (TREX; n = 60), and treat and extend with angiography-guided laser photocoagulation (GILA; n = 60). Monthly cohort eyes received ranibizumab 0.3 mg every 4 weeks. TREX and GILA cohort eyes received 4 monthly injections of ranibizumab 0.3 mg followed by a treat and extend dosing strategy. GILA cohort eyes also received navigated focal laser at month 1 and again every 3 months as needed. The primary outcomes included the mean change in best-corrected visual acuity and central retinal thickness and the number of injections from baseline to 2 years.
At 2 years, mean best-corrected visual acuity and central retinal thickness improved by 7.5, 9.6, and 9.0 letters (P = .75) and 139, 140, and 175 μm (P = .09), in the monthly, TREX, and GILA cohorts, respectively. The mean number of injections was significantly reduced in both the TREX (18.9) and GILA (17.5) cohorts compared with the monthly cohort (24.7, P < .001). Between the TREX and GILA cohorts, there was no significant difference in the mean treatment interval, mean maximal treatment interval, or percentage of eyes extended to 12 weeks. The total 2-year incidence of Anti-Platelet Trialists' Collaboration events was 6.7%.
The treat and extend algorithm of ranibizumab in the TREX-DME trial resulted in significantly fewer injections and yielded visual and anatomic gains comparable to monthly dosing at 2 years.
Apoptosis has long been considered to be the prevailing mechanism of cell death in response to chemotherapy. Currently, a more heterogeneous model of tumor response to therapy is acknowledged wherein ...multiple modes of death combine to generate the overall tumor response. The resulting mechanisms of cell death are likely determined by the mechanism of action of the drug, the dosing regimen used, and the genetic background of the cells within the tumor. This study describes a nonapoptotic response to docetaxel therapy in human breast cancer cells of increasing cancer progression (MCF-10A, MCF-7, and MDA-mb-231). Docetaxel is a microtubule-stabilizing taxane that is being used in the clinic for the treatment of breast and prostate cancers and small cell carcinoma of the lung. The genetic backgrounds of these cells were characterized for the status of key pathways and gene products involved in drug response and cell death. Cellular responses to docetaxel were assessed by characterizing cell viability, cell cycle checkpoint arrest, and mechanisms of cell death. Mechanisms of cell death were determined by Annexin V binding and scoring of cytology-stained cells by morphology and transmission electron microscopy. The primary mechanism of death was determined to be mitotic catastrophe by scoring of micronucleated cells and cells undergoing aberrant mitosis. Other, nonapoptotic modes of death were also determined. No significant changes in levels of apoptosis were observed in response to docetaxel.
Purpose of Review
Cardiomyopathy is a significant complication of various cancer treatments and has been best studied in patients receiving anthracyclines and trastuzumab. This paper evaluates ...strategies to prevent chemotherapy-induced cardiotoxicity.
Recent Findings
Increasing cumulative anthracycline dose, use of ≥2 cardiotoxic therapies, extremes of age, and pre-existing cardiovascular risk factors, or established cardiovascular disease, heighten the risk of developing chemotherapy-induced cardiomyopathy. Continuous rather than bolus anthracycline infusions, liposomal doxorubicin, or concomitant dexrazoxane reduces chemotherapy-induced cardiotoxicity. Treatment with neurohormonal antagonists or statins and exercise training during chemotherapy are promising, but as yet unproven, cardioprotective strategies.
Summary
Identification of high-risk patients and optimization of their underlying cardiovascular risk factors/disease are essential to prevent cardiotoxicity. In patients requiring high-dose anthracyclines, continuous infusions, liposomal doxorubicin, or dexrazoxane should be considered to mitigate cardiotoxicity. Current data do not support the routine use of neurohormonal antagonists or statins as cardioprotective agents in patients treated with cardiotoxic chemotherapies.
Hydraulic microhabitat assessment is a category of environmental flow tools (e.g., Physical Habitat Simulation system and other methodologically similar software) that, at its core, uses habitat ...suitability criteria (HSC) to link values of point hydraulic variables (usually depth, velocity, and substrate/cover) to habitat values for target life stages. Although this assessment tool has been used worldwide for decades, the history of the HSC curve is relatively unknown because the foundational information is predominantly contained in obscure and often unpublished reports. We review the history of the HSC concept in applied aquatic ecology to clarify its scientific pedigree, ensure its proper use, and build a foundation for future research. We begin the review with the formative decades of the 1950's through the 1970's, when consumptive‐based western USA water law conflicted with conservation traditions and natural resource management objectives, although water allocation issues date back at least to the 19th century. By analysing the history of the HSC concept, we aim to establish the biological, hydrologic, and geomorphological conditions that must be met for the HSC concept to be successfully employed. In spite of its documented assumptions and limitations, the HSC concept will likely continue to be a useful tool to help address water resources allocation issues in defined hydrologic and geomorphic settings. We conclude that HSC‐based methodologies should be considered as one of several environmental flow approaches involved in sustainable water resources management.
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