Evaluating limited biopsy templates for men with markedly elevated PSAs.

INTRODUCTION: To define the smallest prostate needle biopsy (PNB) template necessary for accurate tissue diagnosis in men with markedly elevated PSA while decreasing procedural morbidity. MATERIALS AND METHODS: We performed a chart review of 80 men presenting with a newly elevated PSA > 100 ng/mL who underwent biopsy (PNB or metastatic site). For patients who underwent a full 12-core biopsy, simulated templates of 2- to 10-cores were generated by randomly drawing subsets of biopsies from their full-template findings. Templates were iterated to randomize core location and generate theoretical smaller template outcomes. Simulated biopsy results were compared to full-template findings to determine accuracy to maximal Grade Group (GG) diagnosis. RESULTS: Amongst those that underwent PNB, 93% had GG 4 or 5 disease. Twenty-two (40%) underwent a full 12-core biopsy, 20 (37%) a 6-core biopsy, and only 8 (15%) had fewer than six biopsy cores sampled at our hospital. Simulated templates with 2-, 4-, 6-, and 8-cores correctly diagnosed prostate cancer in all patients, and accurately identified the maximal GG in 82%, 91%, 95%, and 97% of patients, respectively. The biopsy locations most likely to detect maximal GG were medial mid and base sites bilaterally. A 4-core template of these sites would have accurately detected the maximal GG in 95% of patients relative to a full 12-core template. CONCLUSIONS: In men presenting with PSA > 100 ng/mL, decreasing from a 12-core to a 4-core prostate biopsy template results in universal cancer detection and minimal under-grading while theoretically decreasing procedural morbidity and cost.

Massed v. standard prolonged exposure therapy for PTSD in military personnel and veterans: 12-month follow-up of a non-inferiority randomised controlled trial.

BACKGROUND: The utilisation of massed therapy for treating posttraumatic stress disorder (PTSD) is gaining strength, especially prolonged exposure. However, it is unknown whether massed prolonged exposure (MPE) is non-inferior to standard prolonged exposure (SPE) protocols in the long term. The current study aimed to assess whether MPE was non-inferior to SPE at 12 months post-treatment, and to ascertain changes in secondary measure outcomes. METHODS: A multi-site non-inferiority randomised controlled trial (RCT) compared SPE with MPE in 12 clinics. The primary outcome was PTSD symptom severity (CAPS-5) at 12 months post-treatment commencement. Secondary outcome measures included symptoms of depression, anxiety, anger, disability, and quality of life at 12 weeks and 12 months post-treatment commencement. Outcome assessors were blinded to treatment allocation. The intention-to-treat sample included 138 Australian military members and veterans and data were analysed for 134 participants (SPE = 71, MPE = 63). RESULTS: Reductions in PTSD severity were maintained at 12 months and MPE remained non-inferior to SPE. Both treatment groups experienced a reduction in depression, anxiety, anger, and improvements in quality of life at 12 weeks and 12 months post-treatment commencement. Treatment effects for self-reported disability in the SPE group at 12 weeks were not maintained, with neither group registering significant effects at 12 months. CONCLUSIONS: The emergence of massed protocols for PTSD is an important advancement. The current study provides RCT evidence for the longevity of MPE treatment gains at 12 months post-treatment commencement and demonstrated non-inferiority to SPE. Promisingly, both treatments also significantly reduced the severity of comorbid symptoms commonly occurring alongside PTSD.

Nanomechanical Spectroscopy of 2D Materials.

We introduce a nanomechanical platform for fast and sensitive measurements of the spectrally resolved optical dielectric function of 2D materials. At the heart of our approach is a suspended 2D material integrated into a high Q silicon nitride nanomechanical resonator illuminated by a wavelength-tunable laser source. From the heating-related frequency shift of the resonator as well as its optical reflection measured as a function of photon energy, we obtain the real and imaginary parts of the dielectric function. Our measurements are unaffected by substrate-related screening and do not require any assumptions on the underling optical constants. This fast (τrise ∼ 135 ns), sensitive (noise-equivalent power = 90⁣pW√Hz), and broadband (1.2-3.1 eV, extendable to UV-THz) method provides an attractive alternative to spectroscopic or ellipsometric characterization techniques.

Spin/Valley Coupled Dynamics of Electrons and Holes at the MoS2-MoSe2 Interface.

The coupled spin and valley degrees of freedom in transition metal dichalcogenides (TMDs) are considered a promising platform for information processing. Here, we use a TMD heterostructure MoS2-MoSe2 to study optical pumping of spin/valley polarized carriers across the interface and to elucidate the mechanisms governing their subsequent relaxation. By applying time-resolved Kerr and reflectivity spectroscopies, we find that the photoexcited carriers conserve their spin for both tunneling directions across the interface. Following this, we measure dramatically different spin/valley depolarization rates for electrons and holes, ∼30 and <1 ns-1, respectively, and show that this difference relates to the disparity in the spin-orbit splitting in conduction and valence bands of TMDs. Our work provides insights into the spin/valley dynamics of photoexcited carriers unaffected by complex excitonic processes and establishes TMD heterostructures as generators of spin currents in spin/valleytronic devices.

Laser-Induced Intersite Spin Transfer.

Laser pulses induce spin-selective charge flow that we show to generate dramatic changes in the magnetic structure of materials, including a switching of magnetic order from antiferromagnetic (AFM) to transient ferromagnetic (FM) in multisub-lattice systems. The microscopic mechanism underpinning this ultrafast switching of magnetic order is dominated by spin-selective charge transfer from one magnetic sublattice to another. Because this spin modulation is purely optical in nature (i.e., not mediated indirectly via the spin-orbit interaction) this is one of the fastest means of manipulating spin by light. We further demonstrate this mechanism to be universally applicable to AFM, FM, and ferri-magnets in both multilayer and bulk geometry and provide three rules that encapsulate early-time magnetization dynamics of multisub-lattice systems.

Mild Depression Predicts Long-Term Mortality After Acute Myocardial Infarction: A 25-Year Follow-Up.

BACKGROUND: Past studies have found that depression is an independent predictor of death in patients after acute myocardial infarction (AMI). Our aim was to investigate whether the adverse effect upon mortality of depression, including mild levels, persisted up to 25 years. METHODS: We used an historical design to study patients who had been consecutively admitted to hospital after transmural AMI during the 1980s and enrolled in an exercise training trial. The Beck Depression Inventory (BDI) was administered to 188 patients in the third week after hospital admission. Scores were trichotomised and classified as low (0-5), mild (6-9) or moderate to severe (≥10) depression. The Australian National Death Index was used to determine mortality status. Cox proportional-hazards modelling was undertaken to determine the relationship between the trichotomised BDI-I scores and all-cause mortality over five time periods up to 25 years. RESULTS: The mean age of patients was 54.15 years. One hundred fourteen (114) (60.4%) had low or no depression, 47 (25.2%) mild depression and 27 (14.3%) moderate to severe depression. The mortality status of 185 (98.4%) patients was established. Depression was a significant predictor of death, independently of age and severity of myocardial infarction, at 5, 10 and 15 years but not at 20 or 25 years. Patients with mild depression had greater mortality than those with low or moderate to severe depression. CONCLUSIONS: Early identification of depression, including milder levels, is important since patients remain at increased risk for many years. They require ongoing monitoring and appropriate treatment.

Healthcare utilization in men with poorer sexual and urinary function recovery following robot-assisted radical prostatectomy.

PURPOSE: Robotic radical prostatectomy focuses on oncologic cure, urinary continence and sexual function recovery. However, little is known about the effect of declines in urinary continence and sexual function on healthcare utilization. We aim to identify these factors. MATERIALS AND METHODS: From March 2011 to September 2013, all men undergoing robotic prostatectomy within our healthcare system were enrolled. Men completed the expanded prostate cancer index composite-26 survey at the time of diagnosis and 90 days post-operatively. Patients were stratified according to change in scores in the sexual function and urinary incontinence domains. Patient, treatment and post-op utilization patterns were examined for association with the extent of decline in sexual function and urinary continence. Multivariate linear regression was used to identify factors independently associated with decline in continence and sexual function. RESULTS: A total of 411 men who completed the baseline survey and at 90 days postoperatively were included. On multivariate linear regression, younger age (p < 0.01), higher preoperative sexual function (< 0.01), single marital status (p = 0.04) and more post-surgery email contacts (p = 0.04) were associated with higher declines in sexual function. For continence, no family history of prostate cancer (p = 0.01), higher baseline continence (p < 0.01) and more post-surgery physical therapy visits (p < 0.01) were associated with higher declines. CONCLUSIONS: Patients with the poorest quality of life outcomes at 90 days post-operatively were more likely to seek care via email and physical therapy encounters related to sexual function and urinary incontinence, respectively. This suggests that maximizing post-treatment quality of life can potentially reduce healthcare utilization.

Treatment Outcomes for Military Veterans With Posttraumatic Stress Disorder: Response Trajectories by Symptom Cluster.

Although effective posttraumatic stress disorder (PTSD) treatments are available, outcomes for veterans with PTSD are relatively modest. Previous researchers have identified subgroups of veterans with different response trajectories but have not investigated whether PTSD symptom clusters (based on a four-factor model) have different patterns of response to treatment. The importance of this lies in the potential to increase treatment focus on less responsive symptoms. We investigated treatment outcomes by symptom cluster for 2,685 Australian veterans with PTSD. We used Posttraumatic Stress Disorder Checklist scores obtained at treatment intake, posttreatment, and 3- and 9-month follow-ups to define change across symptom clusters. Repeated measures effect sizes indicated that arousal and numbing symptoms exhibited the largest changes between intake and posttreatment, dRM = -0.61 and dRM = -0.52, respectively, whereas avoidance and intrusion symptoms showed more modest reductions, dRM = -0.36 and dRM = -0.30, respectively. However, unlike the other symptom clusters, the intrusions cluster continued to show significant changes between posttreatment and 3-month follow-up, dRM = -0.21. Intrusion and arousal symptoms also showed continued changes between 3- and 9-month follow-ups although these effects were very small, dRM = -0.09. Growth curve model analyses produced consistent findings and indicated modest initial changes in intrusion symptoms that continued posttreatment. These findings may reflect the longer time required for emotional processing, relative to behavioral changes in avoidance, numbing, and arousal, during the program; they also reinforce the importance of prioritizing individual trauma-focused therapy directly targeting intrusions as the core component of programmatic treatment.

A Longitudinal Study of Financial Difficulties and Mental Health in a National Sample of British Undergraduate Students.

Previous research has shown a relationship between financial difficulties and poor mental health in students, but most research is cross-sectional. To examine longitudinal relationships over time between financial variables and mental health in students. A national sample of 454 first year British undergraduate students completed measures of mental health and financial variables at up to four time points across a year. Cross-sectional relationships were found between poorer mental health and female gender, having a disability and non-white ethnicity. Greater financial difficulties predicted greater depression and stress cross-sectionally, and also predicted poorer anxiety, global mental health and alcohol dependence over time. Depression worsened over time for those who had considered abandoning studies or not coming to university for financial reasons, and there were effects for how students viewed their student loan. Anxiety and alcohol dependence also predicted worsening financial situation suggesting a bi-directional relationship. Financial difficulties appear to lead to poor mental health in students with the possibility of a vicious cycle occurring.

Corrections to Thomas-Fermi densities at turning points and beyond.

Uniform semiclassical approximations for the number and kinetic-energy densities are derived for many noninteracting fermions in one-dimensional potentials with two turning points. The resulting simple, closed-form expressions contain the leading corrections to Thomas-Fermi theory, involve neither sums nor derivatives, are spatially uniform approximations, and are exceedingly accurate.

AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity.

AMP-activated protein kinase (AMPK) is a metabolic fuel gauge conserved along the evolutionary scale in eukaryotes that senses changes in the intracellular AMP/ATP ratio. Recent evidence indicated an important role for AMPK in the therapeutic benefits of metformin, thiazolidinediones and exercise, which form the cornerstones of the clinical management of type 2 diabetes and associated metabolic disorders. In general, activation of AMPK acts to maintain cellular energy stores, switching on catabolic pathways that produce ATP, mostly by enhancing oxidative metabolism and mitochondrial biogenesis, while switching off anabolic pathways that consume ATP. This regulation can take place acutely, through the regulation of fast post-translational events, but also by transcriptionally reprogramming the cell to meet energetic needs. Here we demonstrate that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD+-dependent type III deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD+ levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets that include the peroxisome proliferator-activated receptor-gamma coactivator 1alpha and the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors. The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism.

Longitudinal relationships between financial difficulties and eating attitudes in undergraduate students.

OBJECTIVE: Previous research has shown a relationship between financial difficulties and poor mental health in students, but there has been no research examining such a relationship for eating attitudes. METHOD: A group of 444 British undergraduate students completed the Index of Financial Stress and the Eating Attitudes Test (26-item version) at up to four time points across a year at university. RESULTS: Higher baseline financial difficulties significantly predicted higher eating attitudes scores at Times 3 and 4 (up to a year), after adjusting for demographic variables and baseline eating attitudes score. Lower family affluence also predicted higher eating attitudes scores at Time 4 (up to a year). A higher eating attitudes score at baseline also significantly predicted greater financial difficulties at Time 2 (3-4 months). When considering these relationships by gender, they were significant for women only. DISCUSSION: Greater financial difficulties and lower family affluence predict a worsening in eating attitudes over time in female students. The relationship appears to be partially bi-directional, with financial difficulties driving poorer eating attitudes in the shorter term.

A phase II, randomized, placebo-controlled, double-blind, multi-dose study of SRT2104, a SIRT1 activator, in subjects with type 2 diabetes.

AIM: SRT2104 is a selective activator of SIRT1. In animal models, SRT2104 improves glucose homeostasis and increases insulin sensitivity. We evaluated the tolerability and pharmacokinetics of SRT2104, and its effects on glycaemic control, in adults with type 2 diabetes mellitus. METHOD: Type 2 diabetics with glycosylated haemoglobin (HbA1c) ≥ 7.5% and ≤10.5%, fasting glucose ≥160 and ≤240 mg dl(-1) , and on stable doses of metformin were evenly randomized to placebo or SRT2104 0.25 g, 0.5 g, 1.0 g or 2.0 g, administered orally once daily for 28 days. Changes in fasting and post-prandial glucose and insulin were analyzed. RESULTS: Safety evaluation found no major differences between groups in the frequency of adverse events. SRT2104 concentrations did not increase in a dose-proportional fashion. Significant variability in exposure was observed. Treatment with SRT2104 did not lead to any consistent, dose-related changes in glucose or insulin. Day 28 change from baseline (mean (SD)): fasting glucose (mmol l(-1) ) = -1.17 (2.42), -1.11 (3.45), -0.52 (2.60), -0.97 (2.83) and -0.15 (2.38) for placebo, 0.25 g, 0.5 g, 1.0 g and 2.0 g, respectively. Day 28 change from baseline (mean (SD)): fasting insulin (mmol l(-1) ) = 1.0 (51.66), 8.9 (95.04), -6.9 (41.45), 4.1 (57.16) and 15.2 (138.79) for placebo, 0.25 g, 0.5 g, 1.0 g and 2.0 g, respectively) Treatment with SRT2104 was associated with improvement in lipid profiles. CONCLUSION: Treatment with SRT2104 for 28 days did not result in improved glucose or insulin control which is likely due to the observed pharmacokinetics which were not dose proportional and had large between subject variability.

Kinetic and interaction components of the exact time-dependent correlation potential.

The exact exchange-correlation (xc) potential of time-dependent density functional theory has been shown to have striking features. For example, step and peak features are generically found when the system is far from its ground-state, and these depend nonlocally on the density in space and time. We analyze the xc potential by decomposing it into kinetic and interaction components and comparing each with their exact-adiabatic counterparts, for a range of dynamical situations in model one-dimensional two-electron systems. We find that often, but not always, the kinetic contribution is largely responsible for these features that are missed by the adiabatic approximation. The adiabatic approximation often makes a smaller error for the interaction component, which we write in two parts, one being the Coulomb potential due to the time-dependent xc hole. Non-adiabatic features of the kinetic component were also larger than those of the interaction component in cases that we studied when there is negligible step structure. In ground-state situations, step and peak structures arise in cases of static correlation, when more than one determinant is essential to describe the interacting state. We investigate the time-dependent natural orbital occupation numbers and find the corresponding relation between these and the dynamical step is more complex than for the ground-state case.

Resumption of work after acute coronary syndrome or coronary artery bypass graft surgery.

BACKGROUND: Return to work is an important indicator of recovery after acute cardiac events. This study aimed to determine rates of work resumption and identify predictors of non-return to work and delayed resumption of work. METHODS: 401 currently employed patients consecutively admitted after acute coronary syndrome or to undergo coronary artery bypass graft surgery were recruited. Patient characteristics, perceptions and occupational outcomes were investigated via interviews and self-report questionnaires. RESULTS: Twenty-three patients were lost to follow-up. Of the 378 completers, 343 (90.7%) patients resumed work, while 35 (9.3%) did not. By four months, 309 (91.1%) patients had returned to work. At 12 months, 302 (79.9%) of the 378 patients were employed, 32 (8.5%) unemployed and 20 (5.3%) retired. The employment status of 24 (6.3%) patients was unknown. Non-return to work was significantly more likely if patients were not intending to return to work or were uncertain, had a negative perception of health, had a comorbidity other than diabetes and reported financial stress. Significant predictors of delayed return to work were cardiac rehabilitation attendance, longer hospital stay, past angina, having a manual job, physically active work, job dissatisfaction, no confidante and depression. CONCLUSIONS: Patients at risk of poor occupational outcomes can be identified early. Strategies to improve vocational rehabilitation require further investigation.

Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man.

AIM: SRT2104 is a novel, first-in-class, highly selective small molecule activator of the NAD + dependent deacetylase SIRT1. SRT2104 was dosed to healthy male and female volunteers in a series of phase 1 clinical studies that were designed to elucidate tolerability and pharmacokinetics associated with oral dosing to aid in dose selection for subsequent clinical trials. METHODS: In the first-in-human study, there was both a single dose phase and 7 day repeat dose phase. Doses used ranged from 0.03 to 3.0 g. A radioactive microtracer study was subsequently conducted to determine systemic clearance, bioavailability and preliminary metabolism, and a crossover study was conducted to determine the effect of gender, formulation and feeding state on SRT2104 pharmacokinetics. RESULTS: SRT2104 was well tolerated in all of these studies, with no serious adverse reactions observed. SRT2104 displayed a dose-dependent, but sub-proportional increase in exposure following single dose and repeated dose administration. Accumulation of three-fold or less occurs after 7 days of repeat dosing. The mean bioavailability was circa 14% and the mean clearance was circa 400 ml min(-1). Although there were no substantial effects on exposure resulting from gender or formulation differences, a notable food effect was observed, manifested as up to four-fold increase in exposure parameters. CONCLUSIONS: In the absence of an optimized formulation of SRT2104, the food effect can be used to maximize exposure in future clinical studies. Combined with the good tolerability of all doses demonstrated in these studies, the favourable selectivity profile of SRT2104 allows for the use of this SIRT1 modulator for target validation in the clinic.

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes.

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.

THz induced giant spin and valley currents.

Spin and valley indices represent the key quantum labels of quasi-particles in a wide class of two-dimensional materials and form the foundational elements of the fields of spintronics and valleytronics. Control over these degrees of freedom, therefore, remains the central challenge in these fields. Here, we show that femtosecond laser light combining optical frequency circularly polarized pulse and a terahertz (THz) frequency linearly polarized pulse, a so-called "hencomb" pulse, can generate precisely tailored and 90% pure spin currents for the dichalcogenide WSe2 and >75% pure valley currents for bilayer graphene with gaps greater than 120 millielectron volts (dephasing time, 20 femtoseconds). The frequency of the circular light component and the polarization vector of the THz light component are shown to represent the key control parameters of these pulses. Our results thus open a route toward light control over spin/valley current states at ultrafast times.

Cognitive Behavioral Therapy Enhances Survival in Cardiac Patients Aged Under 60: 14-YEAR OUTCOMES OF THE BEATING HEART PROBLEMS PROGRAM TRIAL.

PURPOSE: To optimize recovery and improve prognosis, people who have had an acute cardiac event (ACE) need support to manage their cardiac risk. In 2008, we conducted a randomized controlled trial (RCT) of Beating Heart Problems (BHP) , an 8-wk group program based on cognitive behavioral therapy (CBT) and motivational interviewing (MI), designed to improve behavioral and mental health. This study investigated 14-yr mortality status for RCT participants in order to evaluate the survival impact of the BHP program. METHODS: In 2021, mortality data on 275 participants from the earlier RCT were obtained from the Australian National Death Index. Survival analysis was undertaken to investigate differences in survival for participants in the treatment and control groups. RESULTS: Over the 14-yr follow-up period, there were 52 deaths (18.9%). For those aged <60 yr, there was a significant survival benefit to program participation, with 3% deaths in the treatment group and 13% deaths in the control group ( P = .022). For those aged ≥60 yr, the death rate was identical in both groups (30%). Other significant predictors of mortality included older age, higher 2-yr risk score, lower functional capacity, lower self-rated health, and having no private health insurance. CONCLUSIONS: Participation in the BHP conferred a survival benefit for patients aged <60 yr but not for participants overall. The findings highlight the long-term benefit of behavioral and psychosocial management of cardiac risk through CBT and MI for those who are younger at the time of their first ACE.

The hemodynamic and respiratory effects of cuirass ventilation in healthy volunteers: Part 1.

OBJECTIVE: Negative-pressure ventilation (NPV) by external cuirass (RTX; Deminax Medical Instruments Limited, London, UK) in intubated patients after cardiac surgery improves hemodynamics measured by pulmonary artery catheter (PAC)-based methods, with an increased cardiac output (CO) and stroke volume (SV), without changing the heart rate (HR). The less-invasive pressure recording analytical method (PRAM) (Mostcare; Vytech Health srl, Padova, Italy) allows radial artery-based monitoring of the CO, SV, SV variation, and cardiac cycle efficiency (CCE). The authors investigated the hypothesis that NPV improves PRAM-based hemodynamics and arterial blood gas analysis in spontaneously breathing subjects. DESIGN: A clinical investigation. SETTING: A teaching hospital. PARTICIPANTS: Ten healthy volunteers. INTERVENTIONS: Subjects underwent 5 consecutive experimental ventilation modalities lasting 5 minutes: (1) baseline (no cuirass ventilation), (2) mode 1: cuirass ventilation with a continuous negative pressure of -20 cmH(2)O, (3) first rest period (no cuirass ventilation), (4) mode 2: cuirass ventilation in control mode of 12 breaths/min at -20 cmH(2)O, and (5) second rest period. MEASUREMENTS AND MAIN RESULTS: PRAM parameters were analyzed throughout the final minute of each experimental modality, which concluded with arterial blood gas sampling. Both NPV modes significantly reduced HR without changing CO or systemic vascular resistance. Mode 1 significantly increased CCE and decreased SVV. PO(2) decreased in both rest modes compared with baseline. This was prevented by NPV. In 5 smokers, PO(2) significantly increased in the control mode compared with first rest period. The control mode NPV improved oxygenation with a reduced PCO(2) and reciprocally increased pH. CONCLUSIONS: Five minutes of NPV improves hemodynamics and oxygenation in healthy subjects.