The design and use of a simple device for the MRI assessment of changes in cardiovascular function by lower-body negative-pressure-simulated reduction of central blood volume.

AIM: To use a locally designed and simple lower-body negative-pressure (LBNP) device and 1.5 T magnetic resonance imaging (MRI) to demonstrate the ability to assess changes in cardiovascular function during preload reduction. These effects were evaluated on ventricular volumes and great vessel flow in healthy volunteers, for which there are limited published data. MATERIAL AND METHODS: After ethical review, 14 volunteers (mean age 33.9 ± 7 years, mean body mass index [BMI] 23.1 ± 2.5) underwent LBNP prospectively at 0, -5, -10, and -20 mmHg pressure, using a locally designed LBNP box. Expiratory breath-hold biventricular volumes, and free-breathing flow imaging of the ascending aorta and main pulmonary artery were acquired at each level of LBNP. RESULTS: At -5 mmHg, there was no change in aortic flow or left ventricular volumes versus baseline. Right ventricular output (p=0.013) and pulmonary net flow (p=0.026) decreased. At -20 mmHg, aortic and pulmonary net flow (p<0.001) decreased, as were left and right ventricular end diastolic volume (p<0.001) and left and right end systolic volumes (p=0.038 and p=0.003 respectively). CONCLUSIONS: Use of a MRI-compatible LBNP device is feasible to measure changes in ventricular volume and great arterial flow in the same experiment. This may enhance further research into the effects of preload reduction by MRI in a wide range of important cardiovascular pathologies.

Why is the temperature of the universe 2.726 Kelvin?

The Cosmic Background Explorer satellite has recently made the most accurate measurement of the temperature of the universe, determining it to be 2.726 +/- 0.01 kelvin. In trying to understand why the temperature has this value, one is led to discover the most fundamental features of the universe-an early, radiation-dominated epoch, enormous entropy per nucleon, synthesis of the light elements around 3 minutes after the bang, and a small excess of matter over antimatter-as well as some of the most pressing issues in cosmology today-the development of structure in the universe and the identification of the nature of the ubiquitous dark matter.

The Case for a Hubble Constant of 30 km s-1 Mpc-1.

Although recent determinations of the distance to the Virgo cluster based on Cepheid variable stars represent an important step in pinning down the Hubble constant, after 65 years a definitive determination of the Hubble constant still eludes cosmologists. At present, most of the observational determinations place the Hubble constant between 40 and 90 kilometers per second per megaparsec (km s(-1) Mpc(-1)). The case is made here for a Hubble constant that is even smaller than the lower bound of the accepted range on the basis of the great advantages, all theoretical in nature, of a Hubble constant of around 30 kilometers per second per megaparsec. Such a value for the Hubble cures all of the ills of the current theoretical orthodoxy, that is, a spatially flat universe composed predominantly of cold dark matter.

Big-bang nucleosynthesis and the baryon density of the universe.

For almost 30 years, the predictions of big-bang nucleosynthesis have been used to test the big-bang model to within a fraction of a second of the bang. The agreement between the predicted and observed abundances of deuterium, helium-3, helium-4, and lithium-7 confirms the standard cosmology model and allows accurate determination of the baryon density, between 1.7 x 10(-31) and 4.1 x 10(-31) grams per cubic centimeter (corresponding to about 1 to 15 percent of the critical density). This measurement of the density of ordinary matter is pivotal to the establishment of two dark-matter problems: (i) most of the baryons are dark, and (ii) if the total mass density is greater than about 15 percent of the critical density, as many determinations indicate, the bulk of the dark matter must be "non-baryonic," composed of elementary particles left from the earliest moments.

Two-point heterogeneous connections in a continuum neural field model.

We examine a novel heterogeneous connection scheme in a 1D continuum neural field model. Multiple two-point connections are added to a local connection function in order to model the "patchy" connections seen in, for example visual cortex. We use a numerical approach to solve the equations, choosing the locations of the two-point connections stochastically. We observe self-sustained persistent fluctuations of activity which can be classified into two types (one of which is similar to that seen in network models of discrete excitable neurons, the other being particular to this model). We study the effect of parameters such as system size and the range, number and strength of connections, on the probability that a particular realisation of the connections is able to exhibit persistent fluctuations.

Persistent fluctuations of activity in undriven continuum neural field models with power-law connections.

We study the effect of random inhomogeneous connections on a continuous field description of neural tissue. We focus on a regime in which persistent random fluctuations in activity arise spontaneously in the absence of either time-varying or spatially inhomogeneous input. While present in real tissue and network models of discrete neurons, such behavior has not been reported in continuum models of this type. The activity contains frequencies similar to those seen experimentally. We consider a power-law envelope r(-alpha) for the inhomogeneity and present evidence that the statistical coherence (a measure of two-point correlation) rapidly percolates across the system as alpha is reduced below alphac approximately 1,2 in one and two dimensions, respectively.

Volatile sulfur compounds produced by probiotic bacteria in the presence of cysteine or methionine.

AIMS: To investigate the abilities of various probiotic bacteria to produce volatile sulfur compounds (VSCs) relevant to food flavour and aroma. METHODS AND RESULTS: Probiotic strains (Lactobacillus acidophilus NCFM, Lactobacillus plantarum 299v, Lactobacillus rhamnosus GG, Lactobacillus reuteri ATCC55730 and L. reuteri BR11), Lactobacillus delbrueckii ATCC4797, L. plantarum ATCC14917 and Lactococcus lactis MG1363 were incubated with either cysteine or methionine. Volatile compounds were captured, identified and quantified using a sensitive solid-phase microextraction (SPME) technique combined with gas chromatography coupled to a pulsed flame photometric detector (SPME/GC/PFPD). Several VSCs were identified including H(2)S, methanethiol, dimethyldisulfide and dimethyltrisulfide. The VSC profiles varied substantially for different strains of L. plantarum and L. reuteri and it was found that L. reuteri ATCC55730 and L. lactis MG1363 produced the lowest levels of VSCs (P < 0.05). Levels of VSCs generated by bacteria were found to be equivalent to, or higher than, that found in commercial cheeses. CONCLUSIONS: Several probiotic strains are able to generate considerable levels of VSCs and substantial variations in VSC generating potential exists between different strains from the same species. SIGNIFICANCE AND IMPORTANCE OF THE STUDY: This study demonstrates that probiotic bacteria are able to efficiently generate important flavour and aroma compounds and therefore has implications for the development of probiotic containing foods.

Anisotropy in sickle hemoglobin fibers from variations in bending and twist.

We have studied the variations of twist and bend in sickle hemoglobin fibers. We find that these variations are consistent with an origin in equilibrium thermal fluctuations, which allows us to estimate the bending and torsional rigidities and effective corresponding material moduli. We measure bending by electron microscopy of frozen hydrated fibers and find that the bending persistence length, a measure of the length of fiber required before it starts to be significantly bent due to thermal fluctuations, is 130microm, somewhat shorter than that previously reported using light microscopy. The torsional persistence length, obtained by re-analysis of previously published experiments, is found to be only 2.5microm. Strikingly this means that the corresponding torsional rigidity of the fibers is only 6x10(-27)Jm, much less than their bending rigidity of 5x10(-25)Jm. For (normal) isotropic materials, one would instead expect these to be similar. Thus, we present the first quantitative evidence of a very significant material anisotropy in sickle hemoglobin fibers, as might arise from the difference between axial and lateral contacts within the fiber. We suggest that the relative softness of the fiber with respect to twist deformation contributes to the metastability of HbS fibers: HbS double strands are twisted in the fiber but not in the equilibrium crystalline state. Our measurements inform a theoretical model of the thermodynamic stability of fibers that takes account of both bending and extension/compression of hemoglobin (double) strands within the fiber.

Random fluctuations of the firing rate function in a continuum neural field model.

We incorporate a source of noise into a continuum neural field model by allowing the firing threshold to fluctuate noisily about a mean value, and examine traveling wave front solutions. Under certain conditions we are able to calculate the first and second moments of the distributions of the resulting time varying front speed and shape. This is then compared with more complete numerical solutions. Fluctuations in the wave front speed and in the shape (i.e., fluctuations in activity at particular coordinate positions across the wave front) were found to increase as the magnitude of the fluctuations in firing threshold increased. The mean speed was found to increase as the magnitude of the fluctuations increases. The role of the correlation time for the threshold variation is also investigated. We also study the role of threshold fluctuations in the failure of front propagation, both in the fast and slow varying noise limits.

Regulation of limbic information outflow by the subthalamic nucleus: excitatory amino acid projections to the ventral pallidum.

The subthalamic nucleus (STN), a component of the basal ganglia motor system, sends an excitatory amino acid (EAA)-containing projection to the ventral pallidum (VP), a major limbic system output region. The VP contains both NMDA and AMPA subtypes of EAA receptors. To characterize the physiology of the subthalamic pathway to the VP, and to determine the influence of EAA receptor subtypes, in vivo intracellular recordings, and in vivo extracellular recordings combined with microiontophoresis, were made from VP neurons in anesthetized rats. Of the intracellularly recorded neurons, 86% responded to STN stimulation, and these displayed EPSPs with an onset of 8.7 msec, consistent with a monosynaptic input. The EPSPs evoked in spontaneously firing neurons were nearly twice the amplitude of those in nonfiring cells (13.1 vs 6.8 mV, respectively). As neurons were depolarized by current injection, the latency for spiking decreased from 24.2 to 14.2 msec, although EPSP latency was unaffected. Eighty-seven percent of the extracellularly recorded VP neurons responded to STN stimulation with a rapid and robust enhancement of spiking; the response onset, like the EPSP onset, equaled 8.7 msec. Firing rate was enhanced by NMDA in 94% of the STN-excited cells, and AMPA increased firing in 94% as well. The NMDA-selective antagonist AP-5 attenuated 67% of the STN-evoked excitatory responses, and the AMPA-selective antagonist CNQX attenuated 52%. Both antagonists attenuated 33% of responses, and 78% were attenuated by at least one. This evidence suggests that a great majority of VP neurons are directly influenced by STN activation and that both NMDA and non-NMDA receptors are involved. Moreover, the VP response to STN stimulation appears to be strongly dependent on the depolarization state of the neuron.

Left ventricular pacing minimizes diastolic ventricular interaction, allowing improved preload-dependent systolic performance.

BACKGROUND: Left ventricular (LV) pacing improves hemodynamics in patients with heart failure. We hypothesized that at least part of this benefit occurs by minimization of external constraint to LV filling from ventricular interaction. METHODS AND RESULTS: We present median values (interquartile ranges) for 13 heart failure patients with LV pacing systems implanted for New York Heart Association class III/IV limitation. We used the conductance catheter method to measure LV pressure and volume simultaneously. External constraint was measured from the end-diastolic pressure-volume relation recorded during inferior vena caval occlusion, during LV pacing, and while pacing was suspended. External constraint to LV filling was reduced by 3.0 (4.6 to 0.6) mm Hg from 4.8 (0.6 to 7.5) mm Hg (P<0.01) in response to LV pacing; effective filling pressure (LV end-diastolic pressure minus external constraint) increased by 4.0 (2.2 to 5.8) mm Hg from 17.7 (13.3 to 22.6; P<0.01). LV end-diastolic volume increased by 10 (3 to 11) mL from 238 (169 to 295) mL (P=0.01), whereas LV end-systolic volume did not change significantly (-1 [-2 to 3] mL from 180 [124 to 236] mL, P=0.97), which resulted in an increase in stroke volume of 11 (5 to 13) mL from 49 (38 to 59) mL (P<0.01). LV stroke work increased by 720 (550 to 1180) mL . mm Hg from 3400 (2110 to 4480) mL . mm Hg (P=0.01), and maximum dP/dt increased by 120 (2 to 161) mm Hg/s from 635 (521 to 767) mm Hg/s (P=0.03). CONCLUSIONS: This study suggests a potentially important mechanism by which LV pacing may produce hemodynamic benefit. LV pacing minimizes external constraint to LV filling, resulting in an increase in effective filling pressure; the consequent increase in LV end-diastolic volume increases stroke volume via the Starling mechanism.

Emergent behavioural phenotypes of swarming models revealed by mimicking a frustrated anti-ferromagnet.

Self-propelled particle (SPP) models are often compared with animal swarms. However, the collective animal behaviour observed in experiments often leaves considerable unconstrained freedom in the structure of a proposed model. Essentially, multiple models can describe the observed behaviour of animal swarms in simple environments. To tackle this degeneracy, we study swarms of SPPs in non-trivial environments as a new approach to distinguish between candidate models. We restrict swarms of SPPs to circular (periodic) channels where they polarize in one of two directions (like spins) and permit information to pass through windows between neighbouring channels. Co-alignment between particles then couples the channels (anti-ferromagnetically) so that they tend to counter-rotate. We study channels arranged to mimic a geometrically frustrated anti-ferromagnet and show how the effects of this frustration allow us to better distinguish between SPP models. Similar experiments could therefore improve our understanding of collective motion in animals. Finally, we discuss how the spin analogy can be exploited to construct universal logic gates, and therefore swarming systems that can function as Turing machines.

Possible therapeutic targets in cardiac myocyte apoptosis.

Since Kerr described programmed cell death (apoptosis) as a process distinct from necrosis, there have been many studies of apoptosis in disease, especially of immunological origin. Because cardiac myocytes are terminally differentiated cells, they have typically been assumed to die exclusively by necrosis. However, during the last decade this view has been challenged by several studies demonstrating that a significant number of cardiac myocytes undergo apoptosis in myocardial infarction, heart failure, myocarditis, arrhythmogenic right ventricular dysplasia, and immune rejection after cardiac transplantation, as well as in other conditions of stress. These are potentially relevant observations, because apoptosis--unlike necrosis--can be blocked or reversed at early stages. Specific inhibition of this process may confer a considerable degree of cardioprotection, but requires a thorough understanding of the underlying mechanisms. Recent progress includes a better understanding of the importance of mitochondria-initiated events in cardiac myocyte apoptosis, of factors inducing apoptosis in heart failure and during hypoxia, and of the dual pro-apoptotic and anti-apoptotic effects of hypertrophic stimuli such as beta-adrenoceptor agonists, angiotensin converting enzyme inhibitors, nitric oxide and calcineurin. The investigation of cytoprotective and apoptotic signal transduction pathways has revealed important new insights into the roles of the mitogen-activated protein kinases p38, extracellular signal regulated kinase and c-Jun N-terminal kinase in cardiac cell fate. Our present review focuses on the intracellular signal transduction pathways of cardiac myocyte apoptosis and the possibility of specific inhibition of the process.

Significance of serum creatinine values in new end-stage renal disease patients.

The appropriate use of serum creatinine level as a surrogate for time in the course of renal failure when dialysis commences requires it to be a significant predictor of mortality in incident patients with end-stage renal disease (ESRD). This study evaluated factors that account for variations in creatinine level before the initiation of dialysis and whether incident creatinine level after controlling for these factors was a risk factor for mortality. This is a retrospective cohort study of patients from Maryland and Virginia who initiated dialysis between April 1, 1995, and December 31, 1996, with data ascertained from the Health Care Financing Administration Form 2728. Multivariate models were used to evaluate both the factors that predict incident serum creatinine level and the association between creatinine level and mortality. There were 5, 388 patients followed up for an average of 23.6 +/- 0.2 months. Mean creatinine level was 9.2 +/- 0.1 mg/dL, with case-mix factors most predictive of serum creatinine level and accounting for 9% of its variance. Hematocrit and blood urea nitrogen levels as additional surrogates for progression of renal disease accounted for 7.4% of the variance, whereas the nutritional parameters, body mass index, and albumin level only explained an additional 1% of the total variance in creatinine level. Creatinine level was inversely correlated with mortality risk, and this relationship was sustained both with transformation into an estimated glomerular filtration rate and multivariate adjustment for confounders (relative risk = 0. 96; P < 0.0001). Creatinine values from an incident ESRD population have a weak relationship with the timing of dialysis initiation but represent a strong measure of health status.

Within-center correlation in dialysis adequacy.

The purpose of this study was to determine whether patients with end stage renal disease treated with hemodialysis were correlated in dialysis adequacy within facilities. This was a retrospective analysis of dialysis adequacy based on urea reduction ratio (URR) values from 6969 patients dialyzed at 154 facilities. The within-center correlation was quantified using the between-center variation and the parameter p that was derived using ANOVA tables and mixed effects models. The variation in center means for URR was wider than expected for independent observations (52.9-76.1 versus 60.7-73.8, respectively). Furthermore, there was a significant within-center correlation in URR values across all facilities (p = 0.136, P<0.0001), which persisted after adjusting for patient specific covariates, facility characteristics, and state. In conclusion, there was a substantial within-center correlation in dialysis adequacy that reflected important center effects on the outcome of ESRD patients.

Extrusion of a Raimondi peritoneal catheter from the thigh.

A case of extrusion of a peritoneal shunt catheter from the thigh is reported. The literature is reviewed and the frequent involvement of Raimondi catheters in extrusion is discussed.

Measuring the diabetes knowledge of nurses in long-term care facilities.

A knowledge test was developed by a local diabetes educators' group to evaluate the diabetes knowledge base of 59 nurses currently employed in four long-term care facilities in eastern North Carolina. The test contained items in the following categories: monitoring, medication, hypoglycemia, hyperglycemia, illness care, diet, exercise, foot care, and patient/family education. The results of the diabetes knowledge test were analyzed according to overall test scores as well as scores in each of the selected categories. The overall scores ranged from 42% to 89%, with a group mean of 67% (passing = 70% or higher). The scores in the individual categories ranged from 18.6% for monitoring and 23.8% for medications to 91.5% for patient/family education.

Interactions between proteins bound to biomembranes.

We study a physical model for the interaction between general inclusions bound to fluid membranes that possess finite tension gamma, as well as the usual bending rigidity kappa. We are motivated by an interest in proteins bound to cell membranes that apply forces to these membranes, due to either entropic or direct chemical interactions. We find an exact analytic solution for the repulsive interaction between two similar circularly symmetric inclusions. This repulsion extends over length scales approximately sqrt[kappa/gamma] and contrasts with the membrane-mediated contact attraction for similar inclusions on tensionless membranes. For noncircularly symmetric inclusions we study the small, algebraically long-ranged, attractive contribution to the force that arises. We discuss the relevance of our results to biological phenomena, such as the budding of caveolae from cell membranes and the striations that are observed on their coats. These, and other, "gnarly buds" may prove fascinating to study further.

The effect of tibial torsion of the pathology of the knee.

Measurements of tibial torsion using a tropometer were made in more than 1200 consecutive patients attending an adult knee clinic. In total 1672 readings from 836 patients in 11 diagnostic categories were analysed. Patients with either patellofemoral instability or Osgood-Schlatter disease had a significant increase in lateral tibial torsion. The most important finding was a significant reduction in this torsion in patients with panarticular disease.

The treatment of hydrocephalus: a brief guide to shunt selection.

The placement of a cerebrospinal fluid shunt system is a procedure that most neurosurgeons feel comfortable performing. The procedure is fraught with many pitfalls and the choices of equipment are staggering. We review the recent literature on shunt systems. We describe the newer shunt systems and procedures and identify possible roles for them in shunt procedures by the neurosurgeon in practice.