Noninvasive neuroimaging enhances continuous neural tracking for robotic device control.

Brain-computer interfaces (BCIs) utilizing signals acquired with intracortical implants have achieved successful high-dimensional robotic device control useful for completing daily tasks. However, the substantial amount of medical and surgical expertise required to correctly implant and operate these systems significantly limits their use beyond a few clinical cases. A noninvasive counterpart requiring less intervention that can provide high-quality control would profoundly impact the integration of BCIs into the clinical and home setting. Here, we present and validate a noninvasive framework utilizing electroencephalography (EEG) to achieve the neural control of a robotic device for continuous random target tracking. This framework addresses and improves upon both the "brain" and "computer" components by respectively increasing user engagement through a continuous pursuit task and associated training paradigm, and the spatial resolution of noninvasive neural data through EEG source imaging. In all, our unique framework enhanced BCI learning by nearly 60% for traditional center-out tasks and by over 500% in the more realistic continuous pursuit task. We further demonstrated an additional enhancement in BCI control of almost 10% by using online noninvasive neuroimaging. Finally, this framework was deployed in a physical task, demonstrating a near seamless transition from the control of an unconstrained virtual cursor to the real-time control of a robotic arm. Such combined advances in the quality of neural decoding and the practical utility of noninvasive robotic arm control will have major implications on the eventual development and implementation of neurorobotics by means of noninvasive BCI.

Association of mannose-binding lectin levels and invasive fungal disease in hematologic malignancy patients receiving myelosuppressive chemotherapy or allogeneic hematopoietic stem cell transplantation.

Several studies have suggested an association of mannose-binding lectin (MBL) deficiency with infections. In this study, we investigated the association between MBL deficiency and invasive fungal disease (IFD) in hematologic malignancy patients receiving myelosuppressive chemotherapy or hematopoietic stem cell transplant. MBL levels were quantified at the start of treatment in 152 patients who were followed for 6 months and scored as developing IFD or not. Forty-five patients (29.6%) developed IFD, of which 21 (46.7% of IFD cases and 13.8% of patients) were proven or probable IFD. Fifty-nine (38.8%) had MBL levels <1000 ng/mL. The rates of all IFD in patients with MBL levels below and above 1000 ng/mL were 33.9% and 26.9%, respectively (P=0.356). The rates of proven or probable IFD in patients with MBL levels below and above 1000 ng/mL were 11.9% and 15.1%, respectively (P=0.579). MBL levels <1000 ng/mL were not predictors of death (P=0.233). As expected, IFD was associated with death (P<0.0001). Our findings indicate that MBL levels <1000 ng/mL were not associated with an increased risk of developing IFD or overall survival.

Gender differences in variables related to B-natriuretic peptide, left ventricular ejection fraction and mass, and peak oxygen consumption, in patients with heart failure.

AIM AND METHODS: We assessed gender differences in variables related to B-natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), peak oxygen consumption (peak-VO2), and LV mass (LVM), among patients recently hospitalized for suspected heart failure (HF). RESULTS: Of 930 consecutive patients, 409 accepted follow-up after discharge, 221 of these had definite HF (90 women, mean age 74.5 [9.8]years). In 141 HF patients (61 women) with BNP data, women had lower BNP than men (43.9 [38.1] versus 76.3 [88.9]pmol/L, P=0.0193). LVEF (all HF patients) was higher in women (49.8 [13.4] versus 42.4 [13.9]%, P=0.0004). Peak-VO2 (147 HF patients, 48 women) was lower in women (13.9 [4.3] versus 16.3 [4.2]mL/kg/min, P=0.0093). LVM index (200 HF patients, 78 women) was lower in women (130.4 [46.5] versus 171.7 [57.6]g/m(2), P<0.0001). Among HF patients, variables independently related to BNP were body mass index (BMI) and peak-VO2 exclusively among men, mitral regurgitation, respiratory disease and angiotensin receptor blocker treatment only among women. Variables independently related to LVEF were resting heart rate, acetylic salicylic acid use and BNP exclusively among men. No variable was exclusive for women. Variables independently related to peak-VO2 were right ventricular size, BNP, resting and peak heart rate solely among men, BMI and stable angina pectoris exclusively among women. Variables independently related to LVM were left atrial diameter only among men, BMI exclusively among women. CONCLUSION: Among elderly HF patients, there were some important gender differences in BNP, LVEF, peak-VO2 and LVM, and in variables independently related to these factors.

Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African Americans.

The CYP3A locus encodes hepatic enzymes that metabolize many clinically used drugs. However, there is marked interindividual variability in enzyme expression and clearance of drugs metabolized by these enzymes. We utilized comparative genomics and computational prediction of transcriptional factor binding sites to evaluate regions within CYP3A that were most likely to contribute to this variation. We then used a haplotype tagging single-nucleotide polymorphisms (htSNPs) approach to evaluate the entire locus with the fewest number of maximally informative SNPs. We investigated the association between these htSNPs and in vivo CYP3A enzyme activity using a single-point IV midazolam clearance assay. We found associations between the midazolam phenotype and age, diagnosis of hypertension and one htSNP (141689) located upstream of CYP3A4. 141689 lies near the xenobiotic responsive enhancer module (XREM) regulatory region of CYP3A4. Cell-based studies show increased transcriptional activation with the minor allele at 141689, in agreement with the in vivo association study findings. This study marks the first systematic evaluation of coding and noncoding variation that may contribute to CYP3A phenotypic variability.

Gender aspects on survival among patients admitted to hospital with suspected or diagnosed heart failure.

OBJECTIVES AND DESIGN: There are conflicting data on gender differences in survival among heart failure (HF) patients. We prospectively assessed gender differences in survival among 930 consecutive patients (464 [49.9%] women, mean age 76.1+/-10.1 years), admitted to hospital with suspected or diagnosed HF. RESULTS: Overall, women had lower unadjusted mortality hazard ratio (HR) than men: HR 0.827; 95% confidence interval (CI) 0.690-0.992; p=0.040. Adjusted HR was 0.786; 95% CI 0.601-1.028; p=0.079. Unadjusted mortality was significantly higher among patients with a discharge HF diagnosis, compared to those without: HR 1.330; 95% CI 1.107-1.597; p=0.002; adjusted p=0.289. Women and men with a discharge HF diagnosis had similar survival: unadjusted HR 1.052; 95% CI 0.829-1.336; p=0.674; adjusted HR 0.875; 95% CI 0.625-1.225; p=0.437. Women had lower mortality risk among patients without a discharge HF diagnosis: HR 0.630, 95% CI 0.476-0.833, p=0.001; adjusted HR 0.611, p=0.036. CONCLUSION: Prognosis was poor among patients hospitalised with suspected or diagnosed HF. Among all patients, women had better survival, whereas both sexes had similar survival when the HF diagnosis was certified.

Modeling obsessive compulsive disorder.

A preliminary computational model for obsessive compulsive disorder is developed using neuro-circuitry information and systems biology principles. The model captures the salient features of the neuro-psychiatric disorder reported in the literature. Studies are on-going to model in more detail both the intra-cellular and extra-cellular features of the model, within the framework proposed.

The management of heart failure in Sweden.

Heart failure is a major concern to health care providers in Sweden due to its increasing prevalence and the rising health care costs. Heart failure affects more than 160000 Swedes, approximately 2% of the population. The costs for the management of heart failure have been calculated to be approximately SEK 2.500 million (Euro 275 million) which is 2% of the total health care budget. Most heart failure patients are managed by primary care physicians but hospitalisation is common and heart failure is the most common cause for hospitalisation in patients over 65 years of age. National diagnostic and treatment guidelines are not completely adhered to. Echocardiography is performed in a little more than 30% of patients in primary care probably due to poor access. In hospitals echocardiography is more easily available and routinely used for diagnosis. Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers appear to be under prescribed. Nurse-led heart failure clinics are being widely established in an attempt to curtail costs and improve management.

Effects on quality of life, symptoms and daily activity 6 months after termination of an exercise training programme in heart failure patients.

BACKGROUND: Exercise training in heart failure patients improves exercise capacity, physical function, and quality-of-life. Prior studies indicate a rapid loss of these effects following termination of the training. We wanted to assess any sustained post-training effects on patients global assessment of change in quality-of-life (PGACQoL) and physical function. METHODS: Fifty-four stable heart failure patients were randomised to exercise or control. The 4-month exercise programme consisted of bicycle training at 80% of maximal intensity three times/week, and 49 patients completed the active study period. At 10 months (6 months post training) 37 patients were assessed regarding PGACQoL, habitual physical activity, and dyspnea-fatigue-index. RESULTS: Both post-training patients (n=17) and controls (n=20) deteriorated PGACQoL during the 6-month extended follow-up, although insignificantly. However, post-training patients improved PGACQoL slightly but significantly from baseline to 10 months (P=0.006), differing significantly (P=0.023) from controls who were unchanged. Regarding dyspnea-fatigue-index, post-training patients were largely unchanged and controls deteriorated insignificantly, during the extended follow-up as well as from baseline to 10 months. Both groups decreased physical activity insignificantly during the extended follow-up, and from baseline to 10 months post-training patients tended to decrease whereas controls significantly (P=0.007) decreased physical activity. CONCLUSION: There was no important sustained benefit 6 months after termination of an exercise training programme in heart failure patients. A small, probably clinically insignificant sustained improvement in PGACQoL was seen in post-training patients. Controls significantly decreased the habitual physical activity over 10 months and post-training patients showed a similar trend. Exercise training obviously has to be continuing to result in sustained benefit.

Quenching of singlet molecular oxygen (1O2) by azide anion in solvent mixtures.

The azide ion is a strong physical quencher of singlet molecular oxygen (1O2) and is frequently employed to show involvement of 1O2 in oxidation processes. Rate constants (k(q)) for the quenching of 1O2 by azide are routinely used as standards to calculate k(q) values for quenching by other substrates. We have measured k(q) for azide in solvent mixtures containing deuterium oxide (D2O), acetonitrile (MeCN), 1,4-dioxane, ethanol (EtOH), propylene carbonate (PC), or ethylene carbonate (EC), mixtures commonly used for many experimental studies. The rate constants were calculated directly from 1O2 phosphorescence lifetimes observed after laser pulse excitation of rose bengal (RB), used to generate 1O2. In aqueous mixtures with MeCN and carbonates, the rate constant increased nonlinearly with increasing volume of organic solvent in the mixtures. k(q) was 4.78 x 10(8) M(-1) s(-1) in D2O and increased to 26.7 x 10(8) and 27.7 x 10(8) M(-1) s(-1) in 96% MeCN and 97.7% EC/PC, respectively. However, in EtOH/D2O mixtures, k(q) decreased with increasing alcohol concentration. This shows that a higher solvent polarity increases the quenching efficiency, which is unexpectedly decreased by the proticity of aqueous and alcohol solvent mixtures. The rate constant values increased with increasing temperature, yielding a quenching activation energy of 11.3 kJ mol(-1) in D2O. Our results show that rate constants in most solvent mixtures cannot be derived reliably from k(q) values measured in pure solvents by using a simple additivity rule. We have measured the rate constants with high accuracy, and they may serve as a reliable reference to calculate unknown k(q) values.

Health-related quality of life in elderly patients with heart failure.

OBJECTIVE: To assess health-related quality of life (HRQL) in elderly patients with congestive heart failure (CHF) and correlate these to clinical and demographic variables. PATIENTS AND METHODS: HRQL was evaluated in 191 patients with CHF, aged 65-84 years, using a self-administered questionnaire including the Nottingham Health Profile (NHP), Quality of Life Questionnaire in Heart Failure and Patients' Global Self-Assessment. RESULTS: HRQL was more impaired in women than to men (p < 0.05), New York Heart Association functional class correlated to HRQL (p < 0.01) and HRQL, as assessed by NHP, was impaired in CHF patients compared to a previously evaluated, age and sex matched, normal reference population. CONCLUSION: Measurement of HRQL in heart failure patients provides important information in addition to a clinical evaluation, and inclusion of HRQL assessments in clinical practice is feasible and warranted. Specific intervention should be aimed at improving HRQL in those most severely affected.

Angiotensin converting enzyme (ACE) inhibitors and heart failure. The consequences of underprescribing.

Heart failure (HF) is a common and expensive cardiovascular disease, in economic terms as well as in lives lost. Angiotensin converting enzyme (ACE) inhibitors have been shown to significantly reduce mortality and hospitalisation in HF. However, recent surveys show that the prescription rate of ACE inhibitors for HF is far below what is considered to be optimal. Furthermore, prescribed dosages are usually lower than those recommended based on evidence from clinical trials. This article estimates the consequences, both economic and human, of underprescribing ACE inhibitors in patients with HF. The indication for prescribing an ACE inhibitor varies, and clinical trials have included different categories of patients; it is inappropriate to assess costs in all eligible patients without taking these factors into account. Therefore, we analysed the data with respect to 4 different groups: (i) asymptomatic left ventricular systolic dysfunction (LVSD)--an early stage leading to chronic HF; (ii) chronic HF; and post-myocardial infarction (MI) LVSD differentiated into (iii) post-MI asymptomatic LVSD and (iv) post-MI chronic HF. We also estimated the cost effectiveness of adding an ACE inhibitor to the treatment of patients with HF for whom an ACE inhibitor is not currently prescribed. If only patient populations in which large trials have shown a significant effect of ACE inhibition on mortality are included in the analysis (i.e. excluding asymptomatic patients with LVSD), increasing the number of Swedish patients receiving an ACE inhibitor could save in excess of 3700 lives each year, in addition to reducing the annual number of hospitalisations by 8400. The additional cost would be 101.5 million Swedish kronor (SEK), a cost per life saved of SEK27 200. Chronic HF is the most cost-effective patient population to treat, generating cost savings under certain assumptions. A further 6700 hospitalisations can be avoided should the use of ACE inhibitors be extended to asymptomatic patients with LVSD. Increasing dosages to those used in the large clinical trials may generate additional savings in lives and hospitalisations. In conclusion, the use of ACE inhibitors in HF and LVSD has clearly been proven to be cost effective, and compares favourably with the cost effectiveness of treating hypertension or hypercholesterolaemia. At present, however, ACE inhibitors are not optimally utilised. Given the increasingly constrained resources for healthcare, every effort should be made to increase the use of cost-effective treatments, such as ACE inhibitors in chronic HF and post-MI LVSD.

Left atrioventricular plane displacement is related to both systolic and diastolic left ventricular performance in patients with chronic heart failure.

AIMS: Left atrioventricular plane displacement is proposed to reflect left ventricular systolic function and is strongly related to prognosis in patients with heart failure. Left atrioventricular plane displacement is a different measure of left ventricular function compared to ejection fraction, and the factors influencing left atrioventricular plane displacement are insufficiently characterized. We wanted to assess any relationship between left atrioventricular plane displacement and left ventricular diastolic performance. METHODS AND RESULTS: Left ventricular diastolic filling, left atrioventricular plane displacement, and fractional shortening were assessed by echocardiography/Doppler in 54 patients with chronic heart failure (age 64 +/- 7 years). Left atrioventricular plane displacement correlated significantly with Doppler variables of left ventricular filling, in particular the inverse logarithm of early transmitral flow deceleration time; log-1 Edt (r = -0.61, P < 0.0001, n = 54). Left atrioventricular plane displacement also correlated with fractional shortening (r = 0.49, P < 0.001, n = 50). However, fractional shortening did not correlate with any Doppler variable. Log-1 Edt, fractional shortening, age, heart rate, left ventricular and atrial size, and degree of mitral regurgitation were included in a multiple regression analysis. Only log-1 Edt (P = 0.001) and fractional shortening (P = 0.03) correlated independently with left atrioventricular plane displacement. Among patients with similar fractional shortening, those with more compromised diastolic performance had lower left atrioventricular plane displacement. CONCLUSION: Left atrioventricular plane displacement was related to both systolic and diastolic left ventricular performance, which may explain some of the discrepancies between left atrioventricular plane displacement and ejection fraction.

A chest wall restrictor to study effects on pulmonary function and exercise. 1. Development and validation.

Chest wall-restrictive loading reduces a person's ability to expand the chest wall during inhalation and results in decrements in lung capacities, resting pulmonary function, and ultimately, exercise performance. Chest wall restriction is observed in some forms of skeletal and pulmonary diseases (e.g., scoliosis) as well as in occupational situations (e.g., bulletproof vests). We have designed a constant-pressure chest wall-restrictive device that provides a quantifiable and reproducible load on the chest. This paper describes the device and the initial pulmonary function tests conducted. Ten subjects participated in this study. Subjects wore the restrictive device while performing pulmonary function tests at four externally added restrictive loads on three separate occasions. A two-way repeated-measures multivariate analysis of variance revealed significant decreases in forced expiratory vital capacity (FVC) and forced expiratory volume in 1 s (FEV1.0) at each load while the ratio of FEV1.0 to FVC (FEV1.0%) was maintained. No significant differences in any variable were found across time or between the seated and standing position. These results indicate that this chest wall-restrictive device provides a quantifiable added inspiratory load in the breathing cycle that results in reproducible decrements in pulmonary function representative of those seen in some restrictive pulmonary disease and occupational situations.

Non-compliance and knowledge of prescribed medication in elderly patients with heart failure.

AIMS: To determine the extent of non-compliance to prescribed medication in elderly patients with heart failure and to determine to what extent patients recall information given regarding their medication. METHODS AND RESULTS: Non-compliance and knowledge of prescribed medication was studied in 22 elderly heart failure patients [mean age 79 +/- 6 (range 70-97); 14 (64%) male], using in-depth interviews performed 30 days after having been prescribed medication. All patients received standardised verbal and written information regarding their medication. Only 12 (55%) patients could correctly name what medication had been prescribed, 11 (50%) were unable to state the prescribed doses and 14 (64%) could not account for when the medication was to be taken, i.e. at what time of day and when in relation to meals the medication was to be taken. In the overall assessment six (27%) patients were found non-compliant and 16 (73%) patients were considered as possibly being compliant with their prescribed medication. CONCLUSIONS: Non-compliance was common in elderly heart failure patients, as were shortcomings in patients knowledge regarding prescribed medication, despite efforts to give adequate information. There exists a need for alternative strategies to improve compliance in these patients.

Exercise training in heart failure improves quality of life and exercise capacity.

AIMS: Benefit from exercise training in heart failure has mainly been shown in men with ischaemic disease. We aimed to examine the effects of exercise training in heart failure patients < or = 75 years old of both sexes and with various aetiology. METHODS AND RESULTS: Fifty-four patients with stable mild-to-moderate heart failure were randomized to exercise or control, and 49 completed the study (49% > or = 65 years; 29% women; 24% non-ischaemic aetiology; training, n = 22; controls, n = 27). The exercise programme consisted of bicycle training at 80% of maximal intensity over a period of 4 months. Improvements vs controls were found regarding maximal exercise capacity (6 +/- 12 vs -4 +/- 12% [mean +/- SD], P < 0.01) and global quality-of-life (2 [1] vs 0 [1] units [median ¿inter-quartile range¿], P < 0.01), but not regarding maximal oxygen consumption or the dyspnoea-fatigue index. All of these four variables significantly improved in men with ischaemic aetiology compared with controls (n = 11). However, none of these variables improved in women with ischaemic aetiology (n = 5), or in patients with non-ischaemic aetiology (n = 6). The training response was independent of age, left ventricular systolic function, and maximal oxygen consumption. No training-related adverse effects were reported. CONCLUSION: Supervised exercise training was safe and beneficial in heart failure patients < or = 75 years, especially in men with ischaemic aetiology. The effects of exercise training in women and patients with non-ischaemic aetiology should be further examined.

Maternal cradling and infant nipple preferences in rhesus monkeys (Macaca mulatta).

This study investigated lateral biases in nipple preferences, maternal cradling, carrying, and retrieval in 41 rhesus macaque (Macaca mulatta) mother-infant dyads living in two captive social groups. Observations were made during the first 6 weeks of infant life using a combination of scan sampling and ad-libitum sampling techniques. Infants exhibited a significant left-nipple preference in the first weeks of life but the bias decreased with infant age. Mothers showed a left-arm bias in carrying their infants but no significant lateral bias in cradling or retrieval. Our results suggest that the left-side cradling bias reported in studies of humans and some other primates reflects a bias in the infant's nipple preference rather than in maternal behavior. The infants' preference for the left nipple is consistent with both Salk's (1960) heartbeat hypothesis and with more recent hypotheses linking this lateral bias with brain asymmetry and hemispheric specialization for mother-infant communication.

Cost effective management programme for heart failure reduces hospitalisation.

OBJECTIVE: To study the effects of a management programme on hospitalisation and health care costs one year after admission for heart failure. DESIGN: Prospective, randomised trial. SETTING: University hospital with a primary catchment area of 250,000 inhabitants. PATIENTS: 190 patients (aged 65-84 years, 52.3% men) hospitalised because of heart failure. INTERVENTION: Two types of patient management were compared. The intervention group received education on heart failure and self management, with follow up at an easy access, nurse directed outpatient clinic for one year after discharge. The control group was managed according to routine clinical practice. MAIN OUTCOME MEASURES: Time to readmission, days in hospital, and health care costs during one year. RESULTS: The one year survival rate was 71.8% (n = 79) in the control group and 70.0% (n = 56) in the intervention group (NS). The mean time to readmission was longer in the intervention group than in the control group (141 (87) v 106 (101); p < 0.05) and number of days in hospital tended to be fewer (4.2 (7.8) v 8.2 (14.3); p = 0.07). There was a trend towards a mean annual reduction in health care costs per patient of US$1300 (US $1 = SEK 7.76) in the intervention group compared with costs in the controls (US$3594 v 2294; p = 0.07). CONCLUSIONS: A management programme for patients with heart failure discharged after hospitalisation reduces health care costs and the need for readmission.

Left ventricular atrioventricular plane displacement: an echocardiographic technique for rapid assessment of prognosis in heart failure.

OBJECTIVE: To assess the prognostic value of atrioventricular plane displacement in heart failure patients. DESIGN: Patients were followed prospectively for one year after atrioventricular plane displacement determination. SETTING: Malmö University Hospital, with a primary catchment area of 250,000 inhabitants. PATIENTS: 181 patients with a clinical diagnosis of heart failure; age 75.7 (SD 5.2) years, duration of heart failure 2.7 (5.7) years; 100 men, 81 women. MAIN OUTCOME MEASURES: Mortality in relation to atrioventricular plane displacement. RESULTS: Total mortality was 22.7% (41/181), and was highly significantly (P = 0.001) related to atrioventricular plane displacement. Mortality within prospectively defined categories of displacement was: > or = 10.0 mm, 0% (0/19); 8.2 to 9.9 mm, 10.3% (3/29); 6.4 to 8.1 mm, 19.4% (12/62); and < 6.4 mm, 36.6% (26/71). The groups were similar in age, sex, angiotensin converting enzyme inhibitor and beta blocker treatment, and cause and duration of heart failure. CONCLUSIONS: Mortality in heart failure is strongly related to atrioventricular plane displacement.