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Prior evidence demonstrates the efficacy by which plyometric activities during warm-up conditions augment the subsequent performance in power-centric exercise. We investigated the acute effects of loaded jump squats incorporated into a standard sprinters' warm-up protocol on subsequent sprint performance in collegiate track athletes. Sprint times of 22 male and female collegiate track athletes were measured in 10-m intervals during a 30-m sprint trial following a standard sprinters' warm-up routine with or without plyometric exercise. Subjects were tested on two separate occasions, once with loaded jump squats as the experimental treatment (two sets of eight jumps, load = 13% bodyweight) (PLYO) and once with time-equated rest as the control treatment (CON). Treatments were implemented following a standard sprinters' warm-up routine familiar to the subjects. A dependent T-test was used for comparison of sprint interval times between conditions with a significant effect indicated by a p -value < 0.05. Sprint time did not differ between CON vs. PLYO at the 10 m (PLYO = 1.90 ± 0.12 s vs. CON = 1.90 ± 0.11 s, p = 0.66), 20 m (PLYO = 3.16 ± 0.21 s vs. CON = 3.15 ± 0.19 s, p = 0.53), and 30 m (PLYO = 4.32 ± 0.32 s vs. CON = 4.31 ± 0.28 s, p = 0.61) intervals. There was no interaction between treatment and sex, sex-specific ranking (above vs. below sex-specific mean), or sprint event (short vs. short-long vs. long) for 10 m, 20 m, or 30-m interval sprint times. At least within the limits of the current investigation, no evidence was provided to suggest that jump squats loaded at 13% bodyweight are an effective means to acutely potentiate sprint performance in collegiate track athletes. However, a further examination of responders indicates that the present loaded jump squat protocol may preferentially potentiate sprint performance in faster male athletes.

Background: We evaluated the effectiveness and cost-effectiveness of the Incredible Years® Teacher Classroom Management (TCM) programme as a universal intervention, given schools' important influence on child mental health., Methods: A two-arm, pragmatic, parallel group, superiority, cluster randomised controlled trial recruited three cohorts of schools (clusters) between 2012 and 2014, randomising them to TCM (intervention) or Teaching As Usual (TAU-control). TCM was delivered to teachers in six whole-day sessions, spread over 6 months. Schools and teachers were not masked to allocation. The primary outcome was teacher-reported Strengths and Difficulties Questionnaire (SDQ) Total Difficulties score. Random effects linear regression and marginal logistic regression models using Generalised Estimating Equations were used to analyse the outcomes., Trial Registration: ISRCTN84130388., Results: Eighty schools (2075 children) were enrolled; 40 (1037 children) to TCM and 40 (1038 children) to TAU. Outcome data were collected at 9, 18, and 30-months for 96, 89, and 85% of children, respectively. The intervention reduced the SDQ-Total Difficulties score at 9 months (mean (s.d.):5.5 (5.4) in TCM v. 6.2 (6.2) in TAU; adjusted mean difference = -1.0; 95% CI-1.9 to -0.1; p = 0.03) but this did not persist at 18 or 30 months. Cost-effectiveness analysis suggested that TCM may be cost-effective compared with TAU at 30-months, but this result was associated with uncertainty so no firm conclusions can be drawn. A priori subgroup analyses suggested TCM is more effective for children with poor mental health., Conclusions: TCM provided a small, short-term improvement to children's mental health particularly for children who are already struggling.

It is increasingly recognized that belowground responses to vegetation change are closely linked to plant functional traits. However, our understanding is limited concerning the relative importance of different plant traits for soil functions and of the mechanisms by which traits influence soil properties in the real world. Here we test the hypothesis that taller species, or those with complex rooting structures, are associated with high rates of nutrient and carbon (C) cycling in grassland. We further hypothesized that communities dominated by species with deeper roots may be more resilient to drought. These hypotheses were tested in a 3-yr grassland restoration experiment on degraded ex-arable land in southern England. We sowed three trait-based plant functional groups, assembled using database derived values of plant traits, and their combinations into bare soil. This formed a range of plant trait syndromes onto which we superimposed a simulated drought 2 yr after initial establishment. We found strong evidence that community weighted mean (CWM) of plant height is negatively associated with soil nitrogen cycling and availability and soil multifunctionality. We propose that this was due to an exploitative resource capture strategy that was inappropriate in shallow chalk soils. Further, complexity of root architecture was positively related to soil multifunctionality throughout the season, with fine fibrous roots being associated with greater rates of nutrient cycling. Drought resistance of soil functions including ecosystem respiration, mineralization, and nitrification were positively related to functional divergence of rooting depth, indicating that, in shallow chalk soils, a range of water capture strategies is necessary to maintain functions. Finally, after 3 yr of the experiment, we did not detect any links between the plant traits and microbial communities, supporting the finding that traits based on plant structure and resource foraging capacity are the main variables driving soil function in the early years of grassland conversion. We suggest that screening recently restored grassland communities for potential soil multifunctionality and drought resilience may be possible based on rooting architecture and plant height. These results indicate that informed assembly of plant communities based on plant traits could aid in the restoration of functioning in degraded soil., (© 2018 The Authors. Ecology published by Wiley Periodicals, Inc. on behalf of Ecological Society of America.)

Plant-soil feedbacks (PSFs) describe the effect of a plant species on soil properties, which affect the performance of future generations. Here we test the hypothesis that drought alters PSFs by reducing plant-microbe associations and nutrient uptake. We chose two grassland forb species, previously shown to respond differently to soil conditioning and drought, to test our hypothesis. We conditioned unsterilised grassland soil with one generation of each species, and left a third soil unconditioned. We grew a second generation consisting of each combination of plant species, soil, and drought in a full factorial design, and measured soil microbial community and nutrient availability. Scabiosa columbaria displayed negative PSF (smaller plants) under non-droughted conditions, but neutral under drought, suggesting that drought disrupts plant-soil interactions and can advantage the plant. Photosynthetic efficiency of S. columbaria was reduced under drought, but recovered on rewetting regardless of soil conditioning, indicating that PSFs do not impede resilience of this species. Sanguisorba minor showed positive PSFs (larger plants), probably due to an increase in soil N in conspecific soil, but neutral PSF under drought. PSF neutralisation appeared to occur through drought-induced change in the soil microbial community for this species. When S. minor was planted in conspecific soil, photosynthetic efficiency declined to almost zero, with no recovery following rewetting. We attributed this to increased demand for water through higher demand for nutrients with positive PSF. Here we show that drought neutralises PSFs of two grassland forbs, which could have implications for plant communities under climate change.

Background: Transcatheter aortic valve replacement (TAVR) is a minimally invasive cardiac surgical procedure that has revolutionized the treatment of aortic stenosis. This is the most common valvular heart condition in developed countries, affecting 3.4% of those ages 75 and above. Because there is no medical therapy that can arrest progression of the disease, valve replacement forms the cornerstone of therapy., Methods: Naval Medical Center San Diego and the VA San Diego Healthcare System have developed a unique collaborative TAVR program-a first in the Department of Defense-to offer this revolutionary procedure to their beneficiaries. Herein, we review development of the program and outcome for patients referred during the first 9 months., Findings: Development of the program was a multiyear process made successful because of administrative support, facility upgrades, and collaboration within the crossfacility and multispecialty heart valve team. In the first 9 months, 29 patients were referred for evaluation. Twenty-two (average age 80 years) underwent TAVR, whereas others were deemed nonoperable or were pending disposition at the time of this report. Patients who underwent TAVR had a predicted risk of procedural mortality from surgical aortic valve replacement of 7.7%, similar to other trials and registry studies. After mean follow-up of 5.6 months (range 30-355 days), zero deaths were recorded in the patients who underwent TAVR. Compared to other nonfederal local institutions, the program also realized a cost savings of approximately 17%, or nearly $10,000, per patient., Discussion: In the first 9 months, results were positive and consistent with expectations from national and international registries. Our hope is that this program may serve as an example for other federal facilities looking to start their own combined programs to improve health care quality and patient experience while simultaneously achieving considerable cost containment within a constrained national health care budget., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Twelve healthy swine were dosed with penicillin G intramuscularly. Fluids and tissues samples were collected at the end of two periods of general anesthesia, performed 24 h apart. Tissue samples were collected by minimally invasive laparoscopy under general anesthesia at 8 and 28 h postdose. Four nonanesthetized, penicillin-treated pigs were euthanized at 8 h postdose, and a second set of four similarly treated control pigs were sacrificed 28 h postdose. Liver penicillin tissue concentrations from animals that underwent anesthesia and laparoscopic tissue collection had tissue concentrations that were higher than nonanesthetized pigs at both time points. Urine, plasma, kidney, skeletal, and cardiac muscle showed no differences between the two groups. Laparoscopic tissue collection under general anesthesia in swine induces physiological changes that cause alterations in tissue pharmacokinetics not seen in conscious animals., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

Aim: Despite recent advances, outcomes for patients with stage III non-small cell lung cancer (NSCLC) with concurrent chemoradiotherapy (CRT) remain poor. We evaluated the combination of ciplatin/vinorelbine and concurrent thoracic radiotherapy followed by consolidation oral vinorelbine in this phase II study., Methods: Eligible patients with unresectable stage III NSCLC received cisplatin intravenous (IV) 40 mg/m 2 and vinorelbine IV 20 mg/m 2 on days 1, 8, 22 and 29 concurrent with thoracic radiotherapy of 60 Gy in 30 fractions. Four to eight weeks later, oral vinorelbine 60 mg/m 2 day 1 and 8 every 3 weeks was given for 3 cycles. The primary end point was overall response rate (ORR). Secondary end points were safety, quality of life, progression-free survival (PFS) and overall survival (OS)., Results: Twenty-seven eligible patients were enrolled from December 2007 to June 2010 before the trial was prematurely closed due to toxicity concerns. The median age was 63 years (range, 42-71), 56% were male, 52% ECOG 0 and 52% stage IIIa. The ORR was 81% (including 37% complete response rate) and disease control rate of 93%. The median PFS was 11 months and median OS was 26 months. Consolidation vinorelbine was associated with significant grade 3/4 toxicity (68%) including grade 3-5 febrile neutropenia (27%) and respiratory infections (36%) including two deaths in the consolidation phase (9%)., Conclusions: Consolidation oral vinorelbine after CRT was associated with significant toxicity. Overall, this regimen achieved a high ORR and survival results comparable to other CRT protocols but the significant toxicity precludes further evaluation of this approach., (© 2017 John Wiley & Sons Australia, Ltd.)

Background: The benefits of end-user involvement in health-care research are widely recognized by research agencies. There are few published evaluations of end-user involvement in systematic reviews., Objectives: (i) Describe end-user involvement in a complex mixed-methods systematic review of ADHD in schools, (ii) reflect on the impact of end-user involvement, (iii) highlight challenges and benefits experienced and (iv) provide suggestions to inform future involvement., Methods: End-users were involved in all stages of the project, both as authors and as members of an advisory group. In addition, several events were held with groups of relevant end-users during the project., Results: End-user input (i) guided the direction of the research, (ii) contributed to a typology of interventions and outcomes, (iii) contributed to the direction of data analysis and (iv) contributed to the robustness of the syntheses by demonstrating the alignment of interim findings with lived experiences. Challenges included (i) managing expectations, (ii) managing the intensity of emotion, (iii) ensuring that involvement was fruitful for all not just the researcher, (iv) our capacity to communicate and manage the process and (v) engendering a sense of involvement amongst end-users., Conclusions: End-user involvement was an important aspect of this project. To minimize challenges in future projects, a recognition by the project management team and the funding provider that end-user involvement even in evidence synthesis projects is resource intensive is essential to allow appropriate allocation of time and resources for meaningful engagement., (© 2015 The Authors. Health Expectations. Published by John Wiley & Sons Ltd.)

Tissue-mimicking materials (TMMs) can provide a convenient, stable, and reproducible means for testing high intensity focused ultrasound (HIFU) devices. When TMMs containing thermal sensors are used to measure ultrasound-induced temperature rise, it is important that measurement results reasonably represent those that occur in biological tissue. Therefore the aim of this paper is to compare the thermal behavior of the TMM under HIFU exposure to that of ex vivo tissue. This was accomplished using both a previously developed TMM and fresh ex vivo swine muscle that were instrumented with bare 50 µm thin wire thermocouples. HIFU at 825 kHz was focused at the thermocouple junction. 30 s exposures of increasing peak negative pressure (1 to 5 MPa) were applied and the temperature profile during and after sonication was recorded. B-mode imaging was used to monitor bubble activity during sonication. If bubble formation was noted during the sonication, the sonication was repeated at the same pressure levels two more times at 20 min intervals. Temperature traces obtained at various pressure levels demonstrated similar types of heating profiles in both the tissue and TMM, the exact nature of which depended on whether bubbles formed during the HIFU exposure. The onset of bubble activity occurred at lower ultrasonic pressures in the TMM, but the basic temperature rise features due to HIFU exposure were essentially the same for both materials.

Purpose: To develop and characterize radiopaque embolization microspheres capable of in vivo detection with intraprocedural fluoroscopy and computed tomography (CT) imaging and to evaluate their spatial distribution inside target tissues during and after transcatheter embolization., Materials and Methods: Polyvinyl alcohol hydrogel microspheres were loaded with Lipiodol and examined for iodine content, stability of loading, and conspicuity with fluoroscopy and CT in vitro. Transcatheter embolization of swine liver and kidney was performed with the radiopaque microspheres and spatial distribution was evaluated with intraprocedural fluoroscopy and CT. Ex vivo evaluation was performed with light microscopy and micro-CT., Results: In vitro analyses demonstrated that radiopaque microspheres could be loaded with sufficient iodine content to be detected with routine fluoroscopy and CT imaging and that such loading was relatively stable. Radiopaque microspheres were visible in vivo with fluoroscopy and CT during transcatheter embolization. CT imaging during embolization procedures demonstrated a dose-dependent relationship in the number and size of visualized embolized arteries. Imaging features of radiopaque microsphere distribution inside target tissues correlated well with ex vivo light microscopic and micro-CT evaluation of microsphere distribution., Conclusions: Radiopaque embolization microspheres are visualized during transcatheter embolization with routine intraprocedural fluoroscopy and CT. These radiopaque microspheres provided the three-dimensional spatial distribution of embolic material inside target organs during the procedure, and therefore can provide real-time intraprocedural feedback for the interventional radiologist. These microspheres may be useful for demonstrating the influence of material and technical variability in transcatheter embolization in addition to providing intraprocedural identification of tissue at risk of undertreatment., (Copyright (c) 2010 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate a surface conductive radiofrequency (RF) coagulation instrument (Tissuelink FB3.0) in laparoscopic and open partial nephrectomy (PN) in hereditary kidney cancer. The lesion depth and viability in the pathologic specimens from a surgical series and an acute porcine model were characterized under conditions of vascular perfusion and occlusion., Materials and Methods: A total of 19 patients underwent 20 laparoscopic and open procedures with the device. Data were acquired on tumor number, size, operative time, blood loss, length of stay, renal function, complications, pathologic diagnosis, and surgical-margin status. Renal lesions were created in pigs with the device, ultrasonic shears, and a standard electrocautery for specified time intervals and operative energy settings. These lesions were analyzed for depth, diameter, and tissue viability., Results: In 20 separate (14 laparoscopic; 6 open) procedures in 19 patients, a total of 112 tumors were removed (range 1-31 tumors per procedure). The median operative time, blood loss, and length of stay were 310 minutes, 250 mL, and 4 days, respectively. There were no positive surgical margins. Median preoperative and postoperative creatinine concentrations were similar (1.0 v 1.0 mg/dL). The average treatment margin depth was 3 mm. In the porcine experiments, the treatment depth in the unclamped vascular model was significantly less in than the clamped model (4.0 +/- 1.7 mm v 7.0 +/- 1.6 mm; P < 0.05). Lesion depth and diameter increased with treatment time. Viability depth correlated well with the depth of the visible thermal lesions (Pearson correlation 0.989)., Conclusions: This RF energy device can provided adequate and uniform hemostatic control without hilar clamping during laparoscopic and open PN for hereditary renal tumors. Gross measures of renal function after surgery appeared clinically unchanged. Coagulation depth is dependent on both tissue perfusion and time in the porcine model.

Event-related potentials can serve as an adjunct to reaction time in elucidating the effects of nicotine on rapid human information processing. We review the literature related to nicotine and event-related potentials. Although evidence indicates that, in the visual modality, nicotine enhances early perceptual processing and in certain instances speeding stimulus evaluation, the bulk of nicotine's effects seem to be on enhancing response preparation and response execution.

Rationale: Nicotine absorbed from cigarette smoke shortens reaction time (RT) in a wide variety of cognitive tasks. However, relatively few studies have tried to isolate the specific stage(s) of information processing affected by smoking/nicotine., Objective: The present study was designed to investigate the effect of smoking/nicotine on the short-term memory (STM) scanning stage of information processing in minimally abstaining smokers. Both RT and event-related potentials (ERPs) were measured., Methods: A Sternberg-type STM-scanning task was performed before and after smoking each of two cigarettes. One cigarette had a 0.05-mg nicotine yield ("denicotinized") and the other had a 1.1-mg yield ("nicotine-yielding"). On each trial, either 2, 3, or 4 consonants were displayed as a memory set. After a brief interval, a single probe consonant was displayed. If the probe was in the memory set (positive probe) a right button press was required, and if the probe was not in the memory set (negative probe) the left button was pressed., Results: Smoking the nicotine-yielding cigarette but not the denicotinized cigarette shortened RT. However, memory-scanning speed, as estimated from the increase in RT as a function of increasing set size, was not differentially affected by the two types of cigarettes. For the ERPs, smoking the nicotine-yielding but not the denicotinized cigarette (a) reduced N200 latency to both the memory-set stimuli and negative probes, (b) increased N200 amplitude to negative probes and P300 amplitude to both types of probes, and (c) produced a sustained negative shift in memory-set ERP amplitude beginning around 600 ms post-stimulus., Conclusion: While smoking/nicotine shortened probe RT, it did not affect the speed of STM scanning. Moreover, the ERP-latency effects obtained for the probes were small relative to the effects of smoking/nicotine on RT, suggesting that smoking/nicotine shortens RT primarily by affecting response-related processes.

A method is described for construction of an in vitro flow model based on in vivo measurements of the lumen geometry of the human carotid bifurcation. A large-scale physical model of the vessel lumen was constructed using fused deposition modeling (a rapid prototyping technique) based on magnetic resonance (MR) images of the carotid bifurcation acquired in a healthy volunteer. The lumen negative was then used to construct a flow model for experimental studies that examined the hemodynamic environment of subject-specific geometry and flow conditions. The physical model also supplements physician insight into the three-dimensional geometry of the arterial segment, complementing the two-dimensional images obtained by MR. Study of the specific geometry and flow conditions in patients with vascular disease may contribute to our understanding of the relationship between their hemodvnamic environment and conditions that lead to the development and progression of arterial disease.

Smoking generally affects the human EEG by reducing low-frequency activity and increasing higher-frequency activity. Using a double-blind design, we sought to determine if acute tolerance (tachyphylaxis) to this effect can be observed. EEG was recorded in overnight-abstaining participants before and after smoking three cigarettes at 40-min intervals in two separate sessions. In one session ('short interval'), all three cigarettes had 'typical' nicotine yields (1.1 mg, FTC method). In the other session ('long interval'), the second cigarette had a very low nicotine yield (0.05 mg; thus making the interval between 1.1-mg cigarettes 80 min). Eyes-closed alpha power decreased and eyes-open beta-2 power increased following smoking each of the 'typical-yield' cigarettes but not the low-yield cigarettes. The decrease in alpha power after smoking the 'typical-yield' cigarette at the 40- and 80-min intervals was less than that following the first cigarette of the day, indicating tachyphylaxis. In contrast, the increase in eyes-open beta-2 power did not differ among cigarettes regardless of the order or interval between 'typical-yield' cigarettes. EEG changes in other frequency bands produced by smoking the first cigarette of the day were not consistent across sessions, making interpretation in terms of tachyphylaxis somewhat problematic. Overall, lower-frequency alpha activity displayed patterns consistent with tachyphylaxis while beta-2 did not., (Copyright 2001 S. Karger AG, Basel.)

A recent article in this journal by Bell and colleagues (Bell SL, Taylor RC, Singleton EG, Henningfield JE, Heishman SJ, Nicotine & Tobacco Research 1:45-52, 1999) studied the effects of smoking on cognitive performance using an overnight smoking abstention design. They interpreted their results for a two-letter search task (poorer performance following abstention that was improved by smoking) as indicating 'nicotine withdrawal-induced cognitive impairment' (p. 50). However, in this commentary, we point out that overnight-abstention experimental designs cannot distinguish withdrawal relief from absolute facilitation of performance (or a combination of the two). We suggest two approaches to resolving the issue of the nature of smoking/nicotine's effects on human cognitive performance.

The question of nonlinearity in the human electroencephalogram (EEG) is important, since linear methods of EEG analysis are more well-developed and computationally faster than nonlinear methods. Furthermore, the presence or absence of nonlinearity has important theoretical implications for understanding the nature of the brain's oscillatory activity. Using a linear summary measure as a control, we report a failure to reject the null hypothesis of a (largely) stationary linear-Gaussian process for normal, resting, eyes-closed EEG from a single participant. We found significant evidence of nonlinearity at two occipital sites (O1 and O2) where the 8-12.5 Hz alpha rhythm was prominent. However, this element of nonlinear structure appeared trivial, as (1) we found no evidence of time irreversibility at these loci, and (2) best-fitting linear models accounted on-average for over 94% of the variance in the data with nonlinear modeling doing no better. Half of the remaining variance could be accounted for by nonstationarity. While our findings technically apply only to the one individual tested, his EEG was typical of those seen under the conditions that we employed.

Object: We applied a new test, nonlinear cross prediction (NLCP), to investigate whether or polymorphic delta activity (PDA) and frontal intermittent rhythmic delta activity (FIRDA) reflect linear or nonlinear brain dynamics. Furthermore realistic models were constructed to explain the dynamical properties of PDA and FIRDA., Methods: Forty-nine EEG time series with FIRDA and 40 time series with PDA were studied with the NLCP algorithm. This characterizes a time series in terms of its predictability, amplitude asymmetry, and time asymmetry, with the latter two measures reflecting nonlinearity. Parameters of an EEG model proposed by Lopes da Silva were adjusted to obtain time series resembling PDA and FIRDA., Results: FIRDA was more predictable than PDA. Most PDA segments could not be distinguished from linearly filtered noise. In contrast, FIRDA activity showed strong evidence of nonlinear dynamics. These dynamical properties of PDA and FIRDA could be reproduced by the Lopes da Silva model. PDA and FIRDA reflect a point attractor and a limit cycle attractor, respectively, perturbed by dynamical noise., Conclusion: Experimental analysis and modeling of the data suggest that PDA and FIRDA reflect fundamentally different types of brain dynamics. While PDA is filtered noise, reflecting low-level, random input to cortical networks, FIRDA may reflect limit-cycle oscillations due to increased excitation.

Purpose: The most prevalent current view of the functional role of the P300 component of the event-related potential (ERP) is that it indexes strategic processing related to context updating. Using independent-components analysis (ICA), the present study examined the role of P300 in the tactical process of response selection., Methods: In a task crossing manipulations of perceptual difficulty (PD) and response-selection difficulty (R-SD), ICA was employed to measure not only P300 latency, but its onset and duration as well., Results: Increased PD delayed P300 latency and onset in parallel, while increased R-SD lengthened P300 duration., Conclusions: The latency and onset results suggest that the often-cited covariation of P300 latency with stimulus-evaluation time is secondary to effects on processing stages preceding P300. The results for duration indicate that P300 is involved in response selection, suggesting that it is not a unitary phenomenon. While P300's well-known relation to stimulus probability indicates a strategic role, our findings indicate a tactical role as well.

Careful consideration of the issues raised by Pezard and colleagues (in this issue of Psychophysiology) allows for the conclusion that spatial embedding may be valid as a method of dynamical reconstruction. However, two problems with the technique cannot be ignored. First, spatial embedding of EEG invariably involves linear cross-correlation among channels, which distorts the dynamical reconstruction due to compression toward the main state-space diagonal. Further, before spatially embedding across a set of channels, one must first check for at least "similar" dynamics among them, using, for example, a measure such as estimated mutual dimension. Measuring a "whole cortex" state via spatial embedding may also be possible in principle, except for the nontrivial obstacle of separating local dynamics that are heterogeneous across the cortex from activity reflecting the "unified field" of the cortex as a whole.

Rationale: Smoking following overnight abstention reliably increases heart rate (HR), an effect due to nicotine absorption. The effect of subsequent cigarettes on HR is less than that associated with the first cigarette of the day, an indication of tachyphylaxis (acute tolerance). To date, smoking/HR studies have not been conducted double-blind. Instead, control conditions have included non-smoking or some type of "sham" smoking (puffing on an unlit cigarette or a straw)., Objective: We investigated the HR response to smoking and its time course using double-blind methodology., Methods: HR was recorded in overnight-abstaining participants before and after smoking the first, second and third cigarette of the day (40 min between each cigarette) in two sessions. The experimental manipulation involved replacing the second cigarette of one session with a very low nicotine-yield cigarette (0.05 mg; FTC method) compared with the other five cigarettes (1.1-mg nicotine yield)., Results: Smoking increased HR by 15, 8 and 7 beats/min (bpm) in the session where all three cigarettes had the higher yield. The comparable values for the session in which the second cigarette had the lower yield were 15, -1 and 11 bpm., Conclusions: In the session where all three cigarettes had the higher yield, larger increase in HR after smoking the first than the second or third cigarettes indicates tachyphylaxis. The HR response in the other session was smaller for the third cigarette than the first cigarette, indicating that a period greater than 80 min would be needed before the HR response was fully restored.

Rationale: A substantial portion of cigarette smokers prefer menthol-flavored cigarettes. To date, however, no studies have examined whether menthol in cigarettes has central pharmacological effects., Objective: We investigated psychophysiological and subjective effects of smoking menthol versus non-menthol cigarettes in both menthol and non-menthol smokers. To assess these effects independently of the immediate effects of nicotine, all cigarettes employed were "denicotinized" (FTC nicotine yield = 0.06 mg)., Methods: The psychophysiological measures were EEG and heart rate (HR). The subjective measures assessed mental alertness, muscular relaxation, anxiety/nervousness, and how much a participant wanted to smoke one of his usual brand of cigarettes. Menthol and non-menthol smokers participated in a single session in which each participant smoked both a menthol and a non-menthol denicotinized cigarette (order balanced across participants). The psychophysiological and subjective measures were recorded before and after smoking each cigarette., Results: Out of 48 F-ratios spanning 22 analyses of variance involving the critical interaction between pre-/post-smoking and menthol/non-menthol cigarette, only one unambiguously fit a "pharmacological" pattern, a result indistinguishable from a type-I statistical error. We report evidence that menthol smokers may be chronically less aroused and more sensitive to the effects of nicotine than non-menthol smokers., Conclusions: We found little evidence that menthol in cigarettes has central pharmacological effects.

Hemodynamic regulation of the endothelial gap junction protein connexin43 (Cx43) was studied in a model of controlled disturbed flows in vitro. Cx43 mRNA, protein expression, and intercellular communication were mapped to spatial variations in fluid forces. Hemodynamic features of atherosclerotic lesion-prone regions of the vasculature (flow separation and recirculation) were created for periods of 5, 16, and 30 h, with laminar shear stresses ranging between 0 and 13.5 dynes/cm2. Within 5 h, endothelial Cx43 mRNA expression was increased in all cells when compared with no-flow controls, with highest levels (up to 6- to 8-fold) expressed in regions of flow recirculation corresponding to high shear stress gradients. At 16 h, Cx43 mRNA expression remained elevated in regions of flow disturbance, whereas in areas of fully developed, undisturbed laminar flow, Cx43 expression returned to control levels. In all flow regions, typical punctate Cx43 immunofluorescence at cell borders was disrupted by 5 h. After 30 h of flow, disruption of gap junctions persisted in cells subjected to flow separation and recirculation, whereas regions of undisturbed flow were substantially restored to normal. These expression differences were reflected in sustained inhibition of intercellular communication (dye transfer) throughout the zone of disturbed flow (84.2 and 68.4% inhibition at 5 and 30 h, respectively); in contrast, communication was fully reestablished by 30 h in cells exposed to undisturbed flow. Up-regulation of Cx43 transcripts, sustained disorganization of Cx43 protein, and impaired communication suggest that shear stress gradients in regions of disturbed flow regulate intercellular communication through the expression and function of Cx43.

The conduct of a clinical investigation of a medical device to determine the safety and effectiveness of the device is covered by the investigational device exemptions (IDE) regulation. The purpose of IDE regulation is "to encourage, to the extent consistent with the protection of public health and safety and with ethical standards, the discovery and development of useful devices intended for human use, and to that end to maintain optimum freedom for scientific investigators in their pursuit of this purpose" (Federal Food, Drug, and Cosmetic Act). Conducting a clinical investigation may require an approved IDE application. The US Food and Drug Administration encourages early interaction with the agency through the pre-IDE process during the development of a device or technology and during the preparation of an IDE application. This facilitates approval of the IDE application and progression into the clinical investigation. This paper reviews the terminology and applicability of the IDE regulation and the type of study that requires an IDE application to the Food and Drug Administration. The pre-IDE process and the development of an IDE application for a significant risk study of a cardiovascular device are discussed.

The conduct of a clinical investigation of a medical device to determine the safety and effectiveness of the device is covered by the investigational device exemptions (IDE) regulation. The purpose of IDE regulation is "to encourage, to the extent consistent with the protection of public health and safety and with ethical standards, the discovery and development of useful devices intended for human use, and to that end to maintain optimum freedom for scientific investigators in their pursuit of this purpose." Conducting a clinical investigation may require an approved IDE application. The US Food and Drug Administration encourages early interaction with the agency through the pre-IDE approval process during the development of a device or technology and during the preparation of an IDE application. This facilitates approval of the IDE application and progression into the clinical investigation. This paper reviews the terminology and applicability of the IDE regulation and the type of study that requires an IDE application to the Food and Drug Administration. The pre-IDE approval process and the development of an IDE application for a significant risk study of a cardiovascular device are discussed.

The recent decision by the U.S. Food and Drug Administration (FDA) to approve one ultrasound imaging system for use in making breast biopsy decisions prompted considerable interest in the radiology community about the regulatory process and the associated implications for the practice of medicine. In this report, the concepts and statutory authority guiding the FDA in the regulation of medical devices are summarized and discussed, including the device classification scheme, premarket approval, premarket notification, and investigational device exemptions. Also, the critical concepts of safety and effectiveness for a given indication for use, the roles of advisory panels, and examples of imaging and interventional devices are described to shed light on the approval process.

The large-amplitude, occipital alpha rhythm of the human electroencephalogram (EEG) is associated in normal subjects with a state of relaxed wakefulness. We analyzed resting eyes-open and eyes-closed human EEG data using three measures: power in the 8-12-Hz alpha frequency band, estimated correlation dimension (D2), and the Savit-Green S-statistic. At occipital loci, two groups of points were evident in the scatterplot of S vs. estimated D2. Group A was of higher dimension and consisted of predominantly eyes-open records. Group B was of lower dimension and consisted of more eyes-closed than eyes-open records. Furthermore, Group B had a broad range of alpha power, with alpha power being negatively correlated with estimated D2 (higher alpha power associated with lower dynamical complexity). In contrast, Group A had a very small range of low alpha power, and was positively correlated with estimated D2 (higher alpha power associated with increased dynamical complexity). Our results indicate that Group B EEG (the alpha rhythm) and Group A EEG (EEG containing 'other' alpha activity) have fundamentally different dynamical properties.

Dimensional complexity (estimated correlation dimension) was measured for two topographic EEG time series: (a) the time evolution of global field power (GFP) and (b) the time evolution of sequential dissimilarity (SQD) for resting, eyes-closed and eyes-open data. Eyes-closed GFP and eyes-closed/open SQD all had an element of nonlinearity in their dynamics as evidenced by increased dimensional complexity associated with the phase-angle randomization, Gaussian surrogate-data procedure. However, none of the three gave any evidence of being deterministic chaotic processes. Eyes-open GFP dimensional complexity could not be distinguished from a linear-stochastic process.

Electroencephalogram (EEG) and heart rate (HR) were recorded while individuals performed visual and auditory go/no-go reaction time (RT) tasks. Overnight-abstaining smokers smoked two types of cigarettes in a single morning session. The first type was smoked once and had a nicotine yield of 0.05 mg. Two cigarettes of the second type (1.1 mg) were smoked. Four recordings were made: presmoking, postsmoking 0.05 mg, and postsmoking each 1.1 mg. HR was increased only by the first 1.1-mg cigarette. Smoking both the 1.1-mg cigarettes decreased RT. Smoking the first 1.1-mg cigarette increased EEG power in the beta2 band. A flexible effect of smoking the first 1.1-mg cigarette on EEG dimensional complexity (DCx) was obtained at locus Cz. Specifically, DCx was (a) raised when the presmoking level was low, (b) not affected when the presmoking level was intermediate, and (c) lowered when the presmoking level was high. Surrogate-data testing indicated the presence of nonlinearity in the EEG data that was not affected by smoking. Decreased RT was associated with increased DCx in the visual task only.

Non-linear EEG analysis provides a possibility for studying the dynamical changes in cortical networks related to mental activity. In this study the correlation dimension D2 was used to study local changes in complexity, and the mutual dimension Dm was used to assess changes in the dynamical coupling between different brain areas. EEGs were recorded in 25 healthy subjects under three conditions: (1) eyes closed, (2) eyes open, and (3) mental arithmetic with eyes closed (serial subtraction of 7s from 1000). In the eyes-closed condition, D2 was lower at parieto-occipital sites. D2 increased during the eye-open and arithmetic conditions. Contrary to the D2, the Dm showed no regional differences in the eyes closed condition. A clear increase in Dm was seen during eyes open and arithmetic. We conclude that both the correlation dimension and the mutual dimension are very sensitive to EEG changes during simple visual information processing and during mental arithmetic. However, these measures seem to be relatively non-specific, and correlate only weakly with performance on the arithmetic task.

Thirty-two subjects were tested in five double-blind sessions (16 subjects in the morning following overnight smoking abstention, and 16 in the afternoon following ad-lib smoking). In each session, subjects smoked one of five experimental (EX) cigarettes having the following FTC nicotine/"tar' yields in mg: 0.08/8.5, 0.17/9.1, 0.37/9.8, 0.48/9.8, and 0.74/10.4. In a sixth session, subjects smoked a 0.71/8.6 commercial "light' (CL) cigarette that was their usual brand. Before and after smoking, subjects subjectively rated their desire to smoke a cigarette of their usual brand and had blood samples drawn. Following smoking, subjects rated the cigarette on a variety of sensory dimensions; they also rated smoking satisfaction. Analysis of variance indicated that nicotine played an important sensory role for a variety of dimensions related to cigarette taste and sensory impact but not perceived draw. Principal-components analyses indicated that sensory factors were at least as important as nicotine pharmacology (indirectly indexed by the pre-to post-smoking rise in blood nicotine concentration) when considering smoking's overall effects on satisfaction, product acceptance, and reduction in desire to smoke.

We demonstrate by using simulations that spatial embedding of single-variable time series data does not reliably reconstruct state-space dynamics. Instead, correlation dimension estimated from spatially embedded data is largely a measure of linear cross-correlation in the data set. For actual electroencephalographic (EEG) data, we demonstrate a high negative correlation between spatial correlation dimension and the average amount of lag-zero cross-correlation between "nearest-neighbor" embedding channels (the greater the cross-correlation, the lower the dimension). We also show that the essential results obtained from spatially embedding EEG data are also obtained when one spatially embeds across a set of highly cross-correlated stochastic (second-order autoregressive) processes. Although, with appropriate surrogate data, correlation dimension estimated from spatially embedded data detects nonlinearity, its use is not recommended because correlation dimension estimated from temporally embedded data both reconstructs state-space dynamics and, with appropriate surrogate data, detects nonlinearity as well.

Eight data sets relating usual-brand nicotine yield (FTC method or equivalent) to blood cotinine concentration are reviewed with respect to the so-called nicotine-"compensation" hypothesis, i.e., that all smokers achieve a specific level of nicotine in their blood, regardless of the FTC nicotine yield of the cigarette smoked. The data from the studies reviewed here indicate wide variability in blood cotinine concentrations over the range of FTC nicotine yields and that the nicotine-compensation hypothesis is not supported. On average, blood cotinine concentrations are found to be roughly midway between complete compensation (all smokers absorb equal amounts of nicotine regardless of FTC nicotine yield) and the value expected if there was no compensation (i.e., smokers absorb an amount of nicotine exactly equal to the FTC yield). As a result of individual smoking-behavior differences (number of cigarettes smoked, puff volume, puff frequency inhalation volume and depth, etc.), the data indicate that, on average, smokers achieve roughly 50% lower blood cotinine concentrations than predicted by the nicotine-compensation hypothesis.

In two separate experiments, P300 was recorded from overnight-abstaining smokers before and after smoking. In the first experiment, 32 subjects counted forward by ones and counted backwards by threes upon presentation of a rare tone burst (20%) in a stream of standard tones. There were no changes in P300 amplitude or latency pre- to post-smoking (1.1-mg FTC nicotine-yield cigarette). In the second experiment, 29 subjects completed auditory and visual oddball tasks before smoking, after smoking a low nicotine-yield cigarette (0.05 mg), after smoking a higher nicotine-yield cigarette (1.1-mg), and after smoking a second 1.1-mg cigarette. In the visual oddball task, P300 latency decreased after smoking the first higher-yield cigarette relative to both pre-smoking and post smoking the lower-yield cigarette. This effect was maintained after smoking the second higher-yield cigarette. In the visual task, P300 amplitude increased after smoking the first higher-yield cigarette (from a lower baseline level) in a group of subjects with larger changes in tidal-breath CO but not in a group with smaller changes in CO. There were no effects of smoking on P300 amplitude or latency in the auditory tasks of either the first or second experiment.

Thirty-two subjects were tested in five double-blind sessions-16 subjects in the morning (a.m.) following overnight smoking abstention, and 16 in the afternoon (p.m.) following ad lib smoking. In each session, subjects smoked 1 of 5 cigarettes having the following FTC nicotine/'tar' yields in mg: 0.08/8.5, 0.17/9.1, 0.37/9.8, 0.48/9.8, and 0.74/10.4. On a pre- to postsmoking basis, blood nicotine and heart rate increased with nicotine yield. The effect of nicotine yield on changes in self-rated anxiety was an inverted-U function, but this effect was possibly confounded by baseline differences. The following effects on EEG spectral-band magnitude were also obtained: (1) nicotine yields > or = 0.17 mg decreased delta; (2) nicotine yields of 0.37 and 0.48 mg decreased theta in a.m. subjects; (3) nicotine yields > or = 0.37 mg decreased alpha, the effect being greater in a.m. subjects; (4) no effect of yield on beta 1 was obtained; (5) nicotine yields of 0.48 and 0.74 mg increased the Cz-minus-T5 differential in beta 2. Pre- to postsmoking changes in this measure of beta 2 were not correlated with either blood nicotine or anxiety.

There is a correlation between the location of early atherosclerotic lesions and the hemodynamic characteristics at those sites. Circulating monocytes are key cells in the pathogenesis of atherosclerotic plaques and localize at sites of atherogenesis. The hypothesis that the distribution of monocyte adhesion to the vascular wall is determined in part by hemodynamic factors was addressed by studying monocyte adhesion in an in vitro flow model in the absence of any biological activity in the model wall. Suspensions of U937 cells were perfused (Re = 200) through an axisymmetric silicone flow model with a stenosis followed by a reverse step. The model provided spatially varying wall shear stress, flow separation and reattachment, and a three-dimensional flow pattern. The cell rolling velocity and adhesion rates were determined by analysis of videomicrographs. Wall shear stress was obtained by numerical solution of the equations of fluid motion. Cell adhesion patterns were also studied in the presence of chemotactic peptide gradients. The cell rolling velocity varied linearly with wall shear stress. The adhesion rate tended to decrease with increasing local wall shear stress, but was also affected by the radial component of velocity and the dynamics of the recirculation region and flow reattachment. Adhesion was increased in the vicinity of chemotactic peptide sources downstream of the expansion site. Results with human monocytes were qualitatively similar to the U937 experiments. Differences in the adhesion rates of U937 cells occurring solely as a function of the fluid dynamic properties of the flow field were clearly demonstrated in the absence of any biological activity in the model wall.

Surrogate-data testing has recently been proposed as one way to detect the presence of nonlinearity and low-dimensional chaos in experimental time series. Such testing involves estimating correlation dimension for both the original data and surrogate data from which nonlinearity has been removed. We applied such testing to the same resting, eyes-closed, and eyes-open electroencephalogram (EEG) data set that was originally analyzed using dimension estimation applied only to the original data (Pritchard & Duke, 1992). Two kinds of surrogate-data sets had higher estimated dimension and poorer saturation. This indicates that the normal resting human EEG is nonlinear and therefore not a linear-stochastic system. Because nearly complete saturation at some loci was not differently affected by the surrogate-data procedures, our results also indicate that the normal resting human EEG is high dimensional and does not represent low-dimensional chaos.

The Gaussian surrogate-date procedure was applied to the measurement of the effect of cigarette smoking on the dimensional complexity of normal, resting EEG. Evidence of significant nonlinearity in the EEG was obtained, replicating previous results. However, unlike EEG dimensional complexity, EEG nonlinearity (difference between original and surrogate data) was not affected by smoking. This indicates that, under resting conditions, smoking/nicotine may have a modulating effect on input from the reticular activating system, with such input having a global, linearizing effect on cortical dynamics. Nonlinear dynamics resulting from intracortical processes appear not to be affected.

The technique of dimension estimation is currently a leading application of nonlinear dynamics (popularly termed "chaos theory") to EEG analysis. A tutorial review of this technique is presented along with some elementary background concepts from nonlinear dynamics. Practical aspects of applying dimension estimation to EEG data are also reviewed, and the possible role of deterministic chaos in brain function is discussed.

The effects of caffeine and smoking on cognitive performance, subjective variables, heart rate, and EEG were assessed in two sessions. In one session, subjects received caffeine (2.5 mg/kg bodyweight), while in the other they received placebo. In both sessions they smoked a cigarette (8 cued puffs) having a nicotine yield of 1.2 mg. Caffeine produced an increase in self-reported muscular tension and tended to increase anxiety and delta magnitude. Smoking facilitated performance of a paper-and-pencil math task and increased heart rate. Smoking also appeared to produce cortical activation as indexed by decreased right frontal delta, decreased right centro-parietal theta, globally increased alpha, and increased centro-occipital/decreased posterior-temporal beta 1. Smoking also increased central/decreased posterior-temporal beta 2. Smoking and caffeine did not interact for any measure, suggesting that the epidemiological link between smoking and coffee drinking may have a non-pharmacological basis.

Attempts to classify Alzheimer's disease (AD) subjects versus controls using spectral-band measures of electroencephalographic (EEG) data typically achieve around 80% success. This study assessed the ability of adding non-linear EEG measures and using a neural-net classification procedure to improve this performance level. The non-linear EEG measures were estimated correlation dimension ("dimensional complexity," or DCx) and saturation (degree of leveling-off of DCx with increasing embedding dimension). In a sample of 39 subjects (14 ADs, 25 controls), it was found that (a) the addition of non-linear EEG measures improved the classification accuracy of the AD/control status of subjects, and (b) a back-percolation neural net predictively classified the subjects much better than the standard linear techniques of multivariate discriminant analysis or nearest-neighbor discriminant analysis.

A quantified smoke delivery system (QSDS) was used to experimentally control the administration of inhaled cigarette smoke to 28 male smokers. One puff (2 s, 35 cc) was taken every 30 s on a cigarette (nicotine yield 1.0 mg) until the char line reached 3 mm from the filter wrap. The smoke was inhaled for 5 s. Resting eyes-closed and eyes-open EEG was recorded from F3, F4, P3, and P4 before and after quantified smoke delivery (QSD). EEG dimensional complexity (DCx, a measure derived from chaos theory) was computed using the Takens-Ellner method. QSD appeared to have a 'flexible' effect on EEG DCx, primarily lowering it in subjects whose pre-smoking level was high, not affecting it in subjects whose pre-smoking level was intermediate, and tending to raise it in subjects whose pre-smoking level was low. This replicates previous results obtained with ad libitum smoking, suggesting the hypothesis that smoking may have an "optimizing" effect on the complexity of brain dynamics.

"1/f-like" power spectrum scaling is a ubiquitous feature of complex systems. In such scaling, the power spectrum of a given time series is dominated by an inverse power law, resulting in an inverse linear relation between log power and log frequency. The 1/f-like power spectrum scaling properties of human, resting eyes-closed and eyes-open EEG were examined. For both eyes-closed and eyes-open EEG, log power had a significant inverse linear relation with log frequency. The slope of this relation was not correlated with previously-calculated Grassberger-Procaccia dimension estimates for the same data, indicating that the EEG is not a 1/f-like stochastic process. Further, the degree of deviation from perfect log power versus log frequency linearity was related to power in the 8-12 Hz alpha frequency band. It is speculated that this deviation may be related to the low dimension of a chaotic alpha rhythm relative to other EEG rhythms.

AIDS is often accompanied by progressive encephalopathy and 'subcortical' dementia, but there is uncertainty regarding how early the brain involvement may begin in the course of HIV infection. This study used a cognitive auditory 'oddball' paradigm to elicit sensory and cognitive event related potential (ERP) components from healthy controls and from patients at different stages of HIV infection. Sensory component latencies did not differ between groups, but cognitive components showed progressive delays corresponding to increasingly severe clinical stages of HIV infection. The earliest changes were found among asymptomatic HIV + patients, suggesting that this test is a sensitive indicator of early subclinical CNS damage. In contrast, neither frequency analysis nor nonlinear dynamical analysis of the EEG showed differences between healthy controls and patients.