Establishing gaze markers of perceptual load during multi-target visual search

Highly-automated technologies are increasingly incorporated into existing systems, for instance in advanced car models. Although highly automated modes permit non-driving activities (e.g. internet browsing), drivers are expected to reassume control upon a 'take over' signal from the automation. To assess a person's readiness for takeover, non-invasive eye tracking can indicate their attentive state based on properties of their gaze. Perceptual load is a well-established determinant of attention and perception, however, the effects of perceptual load on a person's ability to respond to a takeover signal and the related gaze indicators are not yet known. Here we examined how load-induced attentional state affects detection of a takeover-signal proxy, as well as the gaze properties that change with attentional state, in an ongoing task with no overt behaviour beyond eye movements (responding by lingering the gaze). Participants performed a multi-target visual search of either low perceptual load (shape targets) or high perceptual load (targets were two separate conjunctions of colour and shape), while also detecting occasional auditory tones (the proxy takeover signal). Across two experiments, we found that high perceptual load was associated with poorer search performance, slower detection of cross-modal stimuli, and longer fixation durations, while saccade amplitude did not consistently change with load. Using machine learning, we were able to predict the load condition from fixation duration alone. These results suggest monitoring fixation duration may be useful in the design of systems to track users' attentional states and predict impaired user responses to stimuli outside of the focus of attention

Structural characterization of the closed conformation of mouse guanylate kinase

Guanylate kinase (GMPK) is a nucleoside monophosphate kinase that catalyzes the reversible phosphoryl transfer from ATP to GMP to yield ADP and GDP. In addition to phosphorylating GMP, antiviral prodrugs such as acyclovir, ganciclovir, and carbovir and anticancer prodrugs such as the thiopurines are dependent on GMPK for their activation. Hence, structural information on mammalian GMPK could play a role in the design of improved antiviral and antineoplastic agents. Here we present the structure of the mouse enzyme in an abortive complex with the nucleotides ADP and GMP, refined at 2.1 Angstrom resolution with a final crystallographic R factor of 0.19 (R-free = 0.23). Guanylate kinase is a member of the nucleoside monophosphate (NMP) kinase family, a family of enzymes that despite having a low primary structure identity share a similar fold, which consists of three structurally distinct regions termed the CORE, LID, and NMP-binding regions. Previous studies on the yeast enzyme have shown that these parts move as rigid bodies upon substrate binding. It has been proposed that consecutive binding of substrates leads to "closing" of the active site bringing the NMP-binding and LID regions closer to each other and to the CORE region. Our structure, which is the first of any guanylate kinase with both substrates bound, supports this hypothesis. It also reveals the binding site of ATP and implicates arginines 44, 137, and 148 (in addition to the invariant P-loop lysine) as candidates for catalyzing the chemical step of the phosphoryl transfer

Clinical characteristics, treatment patterns and outcomes of Hispanic hypertensive patients

Hispanics are the largest and fastest-growing minority population in the United States, currently comprising about 16.3% (52 million) of the total population. With an increased prevalence of metabolic risk factors in this population, the rate of uncontrolled hypertension (HTN) in Hispanics significantly exceeds the rates observed among non-Hispanic blacks and whites. Unfortunately, data on HTN in Hispanics remains limited due to the under-representation of Hispanics in clinical trials; with most of the data primarily restricted to observational and retrospective subgroup analyses. This article aims to review the available data on prevalence, awareness and control of HTN, risk factors and some of the challenges unique to the Hispanics population. We also discuss treatment strategies derived from large HTN trials that included Hispanics

Impact of echocardiographic left ventricular geometry on clinical prognosis

Abnormal left ventricular (LV) geometry, including LV hypertrophy (LVH), is associated with increased risk of major cardiovascular (CV) events and all-cause mortality and may be an independent predictor of morbid CV events. Patients with LVH have increased risk of congestive heart failure, coronary heart disease, sudden cardiac death and stroke. We review the risk factors for LVH and its consequences, as well as the risk imposed by concentric remodeling (CR). We also examine evidence supporting the benefits of LVH regression, as well as evidence regarding the risk of CR progressing to LVH, as opposed to normalization of CR. We also briefly review the association of abnormal LV geometry with left atrial enlargement and the combined effects of these structural cardiac abnormalities

Update on obesity and obesity paradox in heart failure

Obesity has reached epidemic proportions in most of the Westernized world. Overweightness and obesity adversely impact cardiac structure and function, including on both the right and, especially, left sides of the heart, with adverse affects on systolic and, especially, diastolic ventricular function. Therefore, it is not surprising that obesity markedly increases the prevalence of heart failure (HF). Nevertheless, many studies have documented an obesity paradox in large cohorts with HF, where overweight and obese have a better prognosis, at least in the short-term, compared with lean HF patients. Although weight loss clearly improves cardiac structure and function and reduces symptoms in HF, there are no large studies on the impact of weight loss on clinical events in HF, preventing definitive guidelines on optimal body composition in patients with HF

Določanje benzodiazepinov v urinu preko benzofenonskih derivatov z uporabo tekočinske kromatografije sklopljene s tandemsko masno spektrometrijo

The aim of this study was to validate a new method for determining benzodiazepines in urine via their benzophenone derivatives, based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Selected benzodiazepines were analysed after acid hydrolysis of urine and extraction by ethyl acetate in the presence of an internal standard. Samples were analysed using electrospray ionization LC-MS/MS in a multiple reaction monitoring mode. The chromatographic run time on a reversed phase C18 analytical column was set for 9 min. This method was validated in 21 patients receiving methadone. Benzodiazepines intake was established in two out of three patients. LC-MS/MS results were also compared with the rapid immunoassay and the methods showed good agreement. However, in three cases benzodiazepines were detected by LC-MS/MS, but not by the immunoassay. The sensitivity of the developed LC-MS/MS method is comparable to or even higher than of previously reported methods, which makes it suitable as a confi rmatory method.Razvili smo selektivno in občutljivo metodo za določanje nekaterih benzodiazepinov v urinu preko določanja njihovih benzofenonov. Metoda temelji na tekočinski kromatografi ji, sklopljeni s tandemsko masno spektrometrijo (LC-MS/MS). Izbrane benzodiazepine smo analizirali po kisli hidrolizi urinskih vzorcev in ekstrakciji z etilacetatom v prisotnosti internega standarda. Vzorce smo analizirali z elektrorazprševalno ionizacijo z MRM načinom detekcije. Čas kromatografske ločbe na reverznofazni (C18) analitski koloni je bil 9 min. Metoda je bila validirana in preizkušena na 21 pacientih, ki so prejemali metadonsko terapijo. Pri dveh tretjinah primerov je bil vnos benzodiazepinov tudi potrjen. Vzorce smo testirali tudi s hitro imunokemijsko metodo in rezultate primerjali z rezultati pridobljenimi z LC-MS/MS metodo. Ugotovili smo dobro ujemanje med rezultati pridobljenimi z obe a metodama. Kljub temu smo v treh primerih določili prisotnost benzodiazepinov z LC-MS/MS metodo, ki je z imunokemijsko metodo nismo. Občutljivost razvite metode je primerljiva ali celo boljša od predhodno opisanih metod, zato jo lahko uporabimo kot potrditveno metodo

Improving hypertension control and patient engagement using digital tools

Hypertension is present in 30% of the adult US population and is a major contributor to cardiovascular disease. The established office-based approach yields only 50% blood pressure control rates and low levels of patient engagement. Available home technology now provides accurate, reliable data that can be transmitted directly to the electronic medical record. We evaluated blood pressure control in 156 patients with uncontrolled hypertension enrolled into a home-based digital-medicine blood pressure program and compared them with 400 patients (matched to age, sex, body mass index, and blood pressure) in a usual-care group after 90 days. Digital-medicine patients completed questionnaires online, were asked to submit at least one blood pressure reading/week, and received medication management and lifestyle recommendations via a clinical pharmacist and a health coach. Blood pressure units were commercially available that transmitted data directly to the electronic medical record. Digital-medicine patients averaged 4.2 blood pressure readings per week. At 90 days, 71% of digital-medicine vs 31% of usual-care patients had achieved target blood pressure control. Mean decrease in systolic/diastolic blood pressure was 14/5 mm Hg in digital medicine, vs 4/2 mm Hg in usual care (

The interaction of cardiorespiratory fitness with obesity and the obesity paradox in cardiovascular disease

Overweight and obesity are well-established risk factors for most cardiovascular diseases (CVD), including coronary heart disease (CHD), heart failure (HF), and atrial fibrillation. Despite the strong link between excess adiposity and risk of CVD, growing evidence has demonstrated an obesity paradox in patients with CVD. This phenomenon is characterized by a better prognosis in overweight and mildly obese CVD patients than their leaner counterparts. Moreover, the worst outcomes are often incurred by underweight CVD patients, followed by those of normal weight or severely obese. The obesity paradox is now a well-established phenomenon across different types of CVD, and it occurs regardless of age and ethnicity of patients, and severity of CVD. Physical inactivity and low cardiorespiratory fitness (CRF) have long been recognized as major risk factors for CVD. In contrast, high levels of physical activity (PA) and CRF largely neutralize the adverse effects of excess adiposity and other traditional CVD risk factors, including hypertension, metabolic syndrome, and type-2 diabetes. Higher CRF also results in better CVD outcomes across different BMI groups and significantly alters the obesity paradox in patients with HF and CHD. Prognostic benefits of overweight/obesity tend to be limited to unfit patients with HF and CHD, and the obesity paradox usually disappears with improved levels of CRF. Nevertheless, increased PA and exercise training, to maintain or improve CRF, are effective, safe, and proven strategies for primary and secondary prevention of CVD in all weight groups. In this review, we discuss the current concepts of individual and combined contributions of fatness and fitness to CVD risk and prognosis. We then examine the influence of fitness on the obesity paradox in individuals with CVD