Inverted Linear Halbach Array for Separation of Magnetic Nanoparticles.

A linear array of Nd-Fe-B magnets has been designed and constructed in an inverted Halbach configuration for use in separating magnetic nanoparticles. The array provides a large region of relatively low magnetic field, yet high magnetic field gradient in agreement with finite element modeling calculations. The magnet assembly has been combined with a flow channel for magnetic nanoparticle suspensions, such that for an appropriate distance away from the assembly, nanoparticles of higher moment aggregate and accumulate against the channel wall, with lower moment nanoparticles flowing unaffected. The device is demonstrated for iron oxide nanoparticles with diameters of ~ 5 and 20 nm. In comparison to other approaches, the inverted Halbach array is more amenable to modeling and to scaling up to preparative quantities of particles.

Relative safety of 4 weeks of blood flow-restricted resistance exercise in young, healthy adults.

This study evaluated the effect of 4 weeks of low-load resistance exercise with blood flow restriction (BFRE) on increasing strength in comparison with high-load resistance exercise (HLE), and assessed changes in blood, vascular and neural function. Healthy adults performed leg extension BFRE or HLE 3 days/week at 30% and 80% of strength, respectively. During BFRE, a cuff on the upper leg was inflated to 30% above systolic blood pressure. Strength, pulse-wave velocity (PWV), ankle-brachial index (ABI), prothrombin time (PT) and nerve conduction (NC) were measured before and after training. Markers of coagulation (fibrinogen and D-dimer), fibrinolysis [tissue plasminogen activator (tPA)] and inflammation [high sensitivity C-reactive protein (hsCRP)] were measured in response to the first and last exercise bouts. Strength increased 8% with BFRE and 13% with HLE (P<0.01). No changes in PWV, ABI, PT or NC were observed following training for either group (P>0.05). tPA antigen increased 30-40% immediately following acute bouts of BFRE and HLE (P=0.01). No changes were observed in fibrinogen, D-dimer or hsCRP (P>0.05). These findings indicate that both protocols increase the strength without altering nerve or vascular function, and that a single bout of both protocols increases fibrinolytic activity without altering selected markers of coagulation or inflammation in healthy individuals.

Morphological and quantitative changes in paternal brood-pouch vasculature during embryonic development in two Syngnathus pipefishes.

Vascular corrosion casts of Syngnathus floridae and Syngnathus fuscus brood pouches were examined by scanning electron microscopy. Morphological and quantitative data on the vasculature of the paternal brood pouch during each stage of embryonic development were investigated to explore potential changes during brooding, to consider interspecific differences and to provide structural evidence for previously reported functional roles of the brood pouch. The brood pouches of both species are highly vascularized structures with cup-like arrangements of brood-pouch vasculature developing around each embryo shortly after fertilization and breaking down before fry release. The density and size of paternally derived blood vessels in contact with the embryos were found to be consistent for S. fuscus once this structure was established early in development. On the contrary, these vasculature measurements varied with early S. floridae brood stages when the embryo still relied heavily on the yolk sac. Diameter measurements of S. fuscus brood-pouch blood vessels were also comparatively smaller during these early developmental stages, suggesting that the structural stability and opportunity for greater transport via slower blood flow may contribute to greater paternal allocation. This is the first study to document changes in brood-pouch vasculature during specific stages of embryonic development, to show regression of this vasculature before fry release and to provide morphological data for two syngnathid species for which information on brood-pouch physiology is available.

The value of the post-take ward round: are new working patterns compromising junior doctor education?

This prospective observational study assessed the impact of the changes in junior doctors' working hours and waiting-time initiatives on teaching and learning opportunities for junior doctors in acute medicine. An audit cycle of post-take ward rounds including all medical admissions to an urban teaching hospital was conducted. During two seven-day periods in July 2006 and 2008, 317 and 354 patients were admitted respectively. In the two-year interval a number of changes were implemented resulting in a significant increase in patients reviewed by a consultant within 24 hours of admission. Target waiting times were being met but there were many missed learning opportunities for junior staff. Senior doctors continue to perform the majority of post-take reviews in the absence of the doctors who had admitted the patient. Similar patterns are likely to be found in other hospitals attempting to balance training with government targets for waiting times and junior doctors' working hours.

Factors affecting survival in advanced chronic kidney disease patients who choose not to receive dialysis.

INTRODUCTION: Non-dialytic treatment (NDT) has become a recognized and important modality of treatment in end stage renal disease (ESRD) in certain groups of chronic kidney disease (CKD) patients. However, little is known about the prognosis of these NDT patients in terms of hospitalization rates and survival. We analyzed our experience in managing these NDT with a multidisciplinary team (MDT) approach over a three-year period. PATIENTS AND METHODS: The Renal Unit at the Royal Liverpool University Hospital set up a dedicated MDT clinic to manage NDT patients in January 2003. Patients approaching end stage chronic kidney disease who chose not to dialyse were recruited from other nephrologists. The study group was classified according to age band (<70 years, 71-80 years, and >80 years), estimated glomerular filtration rate (eGFR) (<10 ml/min, 11-20 ml/min, and >20 ml/min) according to the Modified Diet In Renal Disease formula and Stoke comorbidity grade (SCG). The SCG is a validated scoring system for the survival of patients on renal replacement therapy. We also used the ERA-EDTA primary renal diagnosis codes. As there are no existing standards for NDT patients, we used the U.K. national set for haemodialysis patients as a reference and target for our NDT patients. Data was collected prospectively. RESULTS: The median age was 79 years and the male: female ratio was approximately 1. The most common primary cause of kidney disease in the NDT study population was chronic renal failure of unknown cause n = 22 (31%), but the most common identifiable cause was diabetic nephropathy, n = 20 (28%). The most common comorbidity was ischaemic heart disease n = 25 (34%). Those achieving the standards for anaemia were 78% at referral. Only 30% of the NDT patients achieved the standard for blood pressure (<130/80 mmHg) at referral. Forty-three patients (60%) had no admissions at all. There were a total of 30 patients admitted on 58 occasions. Thirty-one (53%) of these were due to a non-renal cause. The median length of stay for the other NDT patients was 10 days. The median overall survival (life expectancy) was 1.95 years. The one-year overall survival was 65%. SCG was an independent prognostic factor in predicting survival in NDT patients studied (p = 0.005), the hazard ratio being 2.53, for each incremental increase in the SCG. At one year, the survival for comorbidity grade 0, 1 and 2 were 83%, 70% and 56% respectively. Of the 28 patients who died, 20 did so at home (71%). DISCUSSION: The NDT of ESRD has become an important alternative modality in renal replacement therapy. With the emergence of epidemic proportions of CKD, more elderly patients with progressive renal disease will need to make informed decisions regarding renal replacement therapy. There is likely to be increasing number of elderly patients that will tolerate dialysis badly and who will be very dependent on others. We believe that there should be a multidisciplinary approach to assist the ESRD patients in choosing their modality of renal replacement therapy, and with an agreed care plan to support these patients in managing their chosen modality to achieve the best possible quality of life. There should be integrated services with primary care, community nurses, and palliative care teams to enable the majority of the patient's treatment to be carried out at home and to allow a dignified death. However. there was a statistically significant trend for shorter survival among those with greater comorbidities, as determined by the SCG. This is the first report of the potential importance of SCG as an independent prognostic factor in NDT patients. This will help us to counsel our patients in the future about their prognosis if they choose NDT as their modality of renal replacement therapy. CONCLUSION: Our prospective study is the first and currently the largest observational study of a multidisciplinary approach in the management of NDT patients. SCG was an independent prognostic factor in predicting survival. In those patients who chose not to dialyse, SCG provides a potentially useful indication of expected prognosis.

A data analysis algorithm for programmed field-flow fractionation.

An algorithm that employs numerical integration for analysis of field-flow fractionation (FFF) data is presented. The algorithm utilizes detector response, field strength, and channel flow rate data, monitored at discrete time intervals during sample elution to generate a distribution of sample components according to particle size or molecular weight. The field strength and channel flow rate may either be held constant or programmed as functions of time, and it is not necessary for these programs to follow specific mathematical functions. If experimental conditions are monitored during a run, the algorithm can account for any deviation from nominal set conditions. The algorithm also allows calculation of fractionating power for the actual conditions as monitored during the run. The method provides greatly increased flexibility in the application of the FFF family of techniques. It removes the limitations on experimental conditions incurred by adherence to analytically available solutions to FFF theory, allowing ad hoc variation of field strength and other experimental parameters as necessary to increase sensitivity and specificity of the method. An implementation of the algorithm is described that is independent of the FFF technique (i.e., independent of field type) and mode of operation. To reduce computation time, it uses mathematical techniques to reduce the required number of numerical integrations. This is of particular importance when the perturbations to ideal FFF theory, such as those due to the effects of hydrodynamic lift forces, particle-wall or particle-particle interactions, and secondary relaxation, necessitate relatively lengthy numerical calculations.

Dissipative exponentially-fitted methods for the numerical solution of the Schrödinger equation.

The first dissipative exponentially fitted method for the numerical integration of the Schrödinger equation is developed in this paper. The technique presented is a nonsymmetric multistep (dissipative) method. An application to the bound-states problem and the resonance problem of the radial Schrödinger equation indicates that the new method is more efficient than the classical dissipative method and other well-known methods. Based on the new method and the method of Raptis and Allison (Comput. Phys. Commun. 14 (1978) 1-5) a new variable-step method is obtained. The application of the new variable-step method to the coupled differential equations arising from the Schrödinger equation indicates the power of the new approach.

New insights in the development of Numerov-type methods with minimal phase-lag for the numerical solution of the Schrödinger equation.

Explicit Numerov-type methods with minimal phase-lag are developed in this paper. These methods are of algebraic order five and have phase-lag order eight and ten. The methods have new features; namely that they are dissipative, i.e. they are not symmetric and they have no interval of periodicity. Numerical illustrations using (i) the radial Schrödinger equation and (ii) coupled differential equations arising from the Schrödinger equation, indicate that these new methods are more efficient than older ones. It is seen that the property of the phase-lag is more important than the non-empty interval of periodicity in constructing numerical methods for the solution of the Schrödinger equations and related problems.

Aspirin for vascular dementia.

BACKGROUND: For patients with a diagnosis of vascular dementia there is evidence that aspirin is widely prescribed - in one study, completed by geriatricians and psychiatrists in the UK, 80% of patients with cognitive impairment (with vascular risk factors) were prescribed aspirin. However, a number of queries remain unanswered: Is there convincing evidence that aspirin benefits patients with vascular dementia? Does aspirin affect cognition or improve prognosis? In addition, does the risk of cerebral or gastric haemorrhage outweigh any benefit? OBJECTIVES: To assess the evidence of effectiveness of the use of aspirin for vascular dementia. SEARCH STRATEGY: Computerized databases were searched independently by two reviewers. In addition, relevant websites were searched and some journals were handsearched. Specialists in the field were approached for unpublished material and any publications found were searched for additional references. The most recent search for trials was carried out in February 2000. SELECTION CRITERIA: All randomized controlled trials investigating the effect of aspirin for vascular dementia are included. Inclusion/exclusion of studies comprised systematic assessment of the quality of study design and the risk of bias. DATA COLLECTION AND ANALYSIS: Data were extracted independently by both reviewers, using a previously tested data extraction form and, where required, authors were contacted for data not provided in the papers. The aim is to evaluate data recorded via tools assessing cognitive and behavioural changes along with mortality, morbidity and institutionalization data. MAIN RESULTS: No trials are eligible for inclusion in this review. REVIEWER'S CONCLUSIONS: There is no evidence that aspirin is effective in treating patients with a diagnosis of vascular dementia. Further research is needed to assess the effect of aspirin on cognition, and on other outcomes such as behaviour, and quality of life. At present there is no evidence relating to other queries about the use of aspirin for dementia (these are described in the Background section of this review). The most recent search for references to relevant research was carried out in February 2000, but no new evidence was found.

Aspirin for vascular dementia.

BACKGROUND: For patients with a diagnosis of vascular dementia there is evidence that aspirin is widely prescribed - in one study, completed by geriatricians and psychiatrists in the UK, 80% of patients with cognitive impairment (with vascular risk factors) were prescribed aspirin. However, a number of queries remain unanswered: Is there convincing evidence that aspirin benefits patients with vascular dementia? Does aspirin affect cognition or improve prognosis? In addition, does the risk of cerebral or gastric haemorrhage outweigh any benefit? The aim of this review is to assess the evidence of effectiveness of aspirin in those with a diagnosis of vascular dementia. OBJECTIVES: To assess the evidence of effectiveness of the use of aspirin for vascular dementia. SEARCH STRATEGY: Computerised databases were searched independently by two reviewers. In addition, relevant websites were searched and some journals were handsearched. Specialists in the field were approached for unpublished material and also any publications found were searched for additional references. SELECTION CRITERIA: All randomised controlled trials investigating the effect of aspirin for vascular dementia are included. Inclusion/exclusion of studies comprised systematic assessment of the quality of study design and the risk of bias. DATA COLLECTION AND ANALYSIS: Data were extracted independently by both reviewers, using a previously tested data extraction form and, where required, authors were contacted for data not provided in the papers. The aim was to evaluate data recorded via tools assessing cognitive and behavioural changes along with mortality, morbidity and institutionalisation data. MAIN RESULTS: One randomised controlled trial ( approximately approximately Meyer 1989 approximately approximately ) was included, and yielded data for analysis on a total of 70 patients. The only relevant outcome assessed in this trial was cognition. Change in cognitive outcome was towards being in favour of treatment. REVIEWER'S CONCLUSIONS: There is very limited evidence that aspirin is effective in treating patients with a diagnosis of vascular dementia. Further research is needed to assess the effect of aspirin on cognition, and also on additional outcomes such as behaviour, and quality of life. At present it is not possible to provide evidence for other queries regarding the use of aspirin for dementia (these are described in the Background section of this review).

Flow rate optimization for the quadrupole magnetic cell sorter.

The quadrupole magnetic cell sorter is a form of split-flow thin-channel (SPLITT) separation device. It employs a quadrupole magnetic field and annular channel geometry. Immunomagnetic labels are used to bind to specific receptors on the surface of the cells of interest. It is the interaction of these labels with the magnetic field that brings about the selective isolation of these cells. The SPLITT separation devices have generally been based on parallel-plate geometry, usually with effectively constant field strength applied across the channel thickness. The nonconstant field strength and annular channel geometry of the magnetic cell sorter require that a new strategy be developed for optimization of inlet and outlet flow rates. We present such a strategy here based on a consideration of certain specific cell trajectories within the system.

Quantification of cellular properties from external fields and resulting induced velocity: cellular hydrodynamic diameter.

An experimental technique is discussed in which the size distribution of a population of cells is determined by calculating each cell's settling velocity. The settling velocity is determined from microscopically obtained images which were recorded on SVHS tape. These images are then computer imaged and processed, and the cell's location and velocity are determined using a computer algorithm referred to as cell tracking velocimetry (CTV). Experimental data is presented comparing the distribution of human lymphocytes and a human breast cancer cell line, MCF-7, determined using a Coulter counter and the CTV approach.

Quantification of cellular properties from external fields and resulting induced velocity: magnetic susceptibility.

An experimental technique is discussed in which the magnetic susceptibility of immunomagnetically labeled cells can be determined on a cell-by-cell basis. This technique is based on determining the magnetically induced velocity that an immunomagnetically labeled cell has in a well-defined magnetic energy gradient. This velocity is determined through the use of video recordings of microscopic images of cells moving in the magnetic energy gradient. These video images are then computer digitized and processed using a computer algorithm, cell tracking velocimetry, which allows larger numbers (>10(3)) of cells to be analyzed.

Numerical simulation of band-broadening during hydrodynamic relaxation in frit-inlet field-flow fractionation channels.

The frit-inlet technique is a promising implementation of hydrodynamic relaxation of samples in field-flow fractionation (FFF). The optimization of the process is of great importance in order to maximize overall system efficiency. The mechanism of band-broadening that takes place during hydrodynamic relaxation has been examined using a three-dimensional simulation of the flow inside the triangular end-piece of the channel. This is the first time this contribution to band-broadening has been considered and studied. Particle trajectories in the absence of a transverse field were numerically calculated, thereby isolating this effect from the familiar field-driven relaxation effect. As a first step towards an optimization of the system, the influence of the length of frit element was examined. Band-broadening was examined by determining the number of particles passing through the triangular end-piece as a function of transit time for a uniform particle distribution at the injection point. Due to the complexity of the flow patterns within the system, it is concluded that such numerical simulations are necessary for the optimization of the design and operation of this type of channel.

'Progressive' versus 'indolent' idiopathic membranous glomerulonephritis.

There is still controversy about safe and effective therapy for idiopathic membranous glomerulonephritis (MGN). Over 20 years, we have simply observed our patients clinically after diagnosis, and only used aggressive therapy with steroids in high dosage and azathioprine for 21 patients with progressive renal failure. The other 42 were thus classified as 'indolent' MGN. Those with 'progressive' MGN had heavier proteinuria and worse renal function on presentation, but the overlap was considerable. Patients with progressive MGN were treated after 1-4 years. All responded promptly, and 5 years after presentation all were alive, and only one was on dialysis. By 10 years, most were still alive, and of these most were off dialysis. In five patients, dialysis was delayed by several years. There were two deaths on dialysis, and three other deaths, mostly in older patients. All but one patient with indolent MGN remained stable on symptomatic treatment only, for at least 5 years after presentation. In many, proteinuria fell to insignificant levels over 4 years. In these remitting patients, there was a prevalence of thyroid disease (7), rheumatoid disease (3) and nephrotic presentation in pregnancy (4). After 6-10 years three patients developed worsening proteinuria and renal failure. Five older patients died from unrelated causes.

Colloid characterization by sedimentation field-flow fractionation: correction for particle-wall interaction.

The effect of particle-wall interaction on retention ratios in sedimentation field-flow fractionation (FFF) is shown to be describable in terms of a semiempirical parameter δ(w) having units of length. A method of experimentally determining the value of this parameter for a given system is presented. It requires the determination of retention ratios for a set of particle standards over a range of field strengths. The value of δ(w) is simply obtained from the slope of a certain straight line plot of the retention data. Once determined, this parameter may be incorporated into the procedure for the determination of particle diameters from measured retention times to take account of the effects of particle-wall interaction. In principle, δ(w) is independent of field strength and is the same for different FFF instruments providing they employ the same carrier liquid and channel wall material. Therefore, δ(w) values have the potential to be universal system constants transferable from one instrument to another.

Theory of field-programmed field-flow fractionation with corrections for steric effects.

This paper deals with the principal perturbation to ideal normal-mode elution of particles in field-flow fractionation (FFF). This perturbation is due to the finite size of particles undergoing migration in the FFF channel. The effects of a first-order correction for particle size are examined. Equations are derived for retention time, fractionating power, and steric inversion diameter for operation at constant field strength, as well as under conditions of both exponential and power programmed field decay. Useful limiting equations for fractionating power are derived and their validity is confirmed for typical experimental conditions. The derived equations are necessary for the future development of a systematic optimization strategy for the selection of operating conditions for particle size analysis by FFF. Calculations confirm our previous conclusion that the fractionating power for exponential field programming varies strongly with particle size; this variation is only slightly reduced by steric perturbations. The uniform fractionating power of power programming is slightly disturbed by steric effects although fractionating power remains much more uniform than for exponential programming. It is shown that a higher uniformity in fractionating power can be gained by manipulating the parameters of power programming but that no improvement is possible with exponential programming. Phenomena giving rise to higher order perturbations and to secondary relaxation are discussed and the conditions identified under which these effects are minimized.

Rapid breakthrough measurement of void volume for field-flow fractionation channels.

A peak breakthrough technique is described and evaluated for measuring the void volume of field-flow fractionation (FFF) channels, particularly those used for flow FFF. This technique uses a high-molecular-mass macromolecular or particulate probe that can be displaced rapidly by flow through the FFF channel with minimal transverse diffusion. The particles that emerge first are those carried through the entire length near the channel centerline at the apex of the parabolic flow profile. These particles generate a sharp breakthrough profile. The measured breakthrough time is two thirds of the void time, thus making it possible to calculate both the void time and the associated void volume. This method, although applicable to all FFF channels (and capable of extension to open tubes), is particularly useful for flow FFF because conventional low-molecular-mass void probes can diffuse into the permeable walls and thus distort void measurements. The theoretical basis of the breakthrough technique and an explanation for the sharpness of the breakthrough front are given. A method for compensating for deviations from perfect sharpness is developed in which the breakthrough time is identified with the time needed to reach 85-88% of the breakthrough peak maximum. Preliminary experimental results are shown using various protein probes in four different FFF channel systems.