The effect of electro-anatomical mapping on the success rate and fluoroscopy time in supra-ventricular tachycardia ablation in children: single centre retrospective study.

AIMS: To evaluate the effect of electro-anatomical mapping on success rate and fluoroscopy time in ablation of supraventricular tachycardia substrates in a large group of children. METHODS: Patients referred from multiple centres in the Netherlands and who received a first ablation for supraventricular tachycardia substrates in the Leiden University Medical Center between 2014 and 2020 were included in this retrospective cohort study. They were divided in procedures in patients with fluoroscopy and procedures in patients using electro-anatomical mapping. RESULTS: Outcomes of ablation of 373 electro-anatomical substrates were analysed. Acute success rate in the fluoro-group (n = 170) was 95.9% compared to 94.5% in the electro-anatomical mapping group (n = 181) (p = 0.539); recurrence rate was 6.1% in the fluoro-group and 6.4% in the electro-anatomical mapping group (p = 0.911) after a 12-months follow-up. Redo-ablations were performed in 12 cases in the fluoro-group and 10 cases in the electro-anatomical mapping group, with a success rate of 83.3% versus 80.0%, resulting in an overall success rate of 95.9% in the fluoro-group and 92.8% in the electro-anatomical mapping group (p = 0.216) after 12 months. Fluoroscopy time and dose area product decreased significantly from 16.00 ± 17.75 minutes (median ± interquartile range) to 2.00 ± 3.00 minutes (p = 0.000) and 210.5 µGym2 ± 249.3 to 32.9 µGym2 ± 78.6 (p = 0.000), respectively. In the fluoro-group, four complications occurred (2.0%) and in the electro-anatomical mapping group no complications occurred. CONCLUSION: These results demonstrate that ablations of supraventricular tachycardia substrates in children remain a highly effective and safe treatment after the introduction of electro-anatomical mapping as a standard of care, while significantly reducing fluoroscopy time and dose area product.

Gelatin device for the delivery of growth factors involved in endochondral ossification.

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo.

High-resolution mapping of sources contributing to urban air pollution using adjoint sensitivity analysis: benzene and diesel black carbon.

The adjoint of the Community Multiscale Air Quality (CMAQ) model at 1 km horizontal resolution is used to map emissions that contribute to ambient concentrations of benzene and diesel black carbon (BC) in the San Francisco Bay area. Model responses of interest include population-weighted average concentrations for three highly polluted receptor areas and the entire air basin. We consider both summer (July) and winter (December) conditions. We introduce a novel approach to evaluate adjoint sensitivity calculations that complements existing methods. Adjoint sensitivities to emissions are found to be accurate to within a few percent, except at some locations associated with large sensitivities to emissions. Sensitivity of model responses to emissions is larger in winter, reflecting weaker atmospheric transport and mixing. The contribution of sources located within each receptor area to the same receptor's air pollution burden increases from 38-74% in summer to 56-85% in winter. The contribution of local sources is higher for diesel BC (62-85%) than for benzene (38-71%), reflecting the difference in these pollutants' atmospheric lifetimes. Morning (6-9am) and afternoon (4-7 pm) commuting-related emissions dominate region-wide benzene levels in winter (14 and 25% of the total response, respectively). In contrast, afternoon rush hour emissions do not contribute significantly in summer. Similar morning and afternoon peaks in sensitivity to emissions are observed for the BC response; these peaks are shifted toward midday because most diesel truck traffic occurs during off-peak hours.

Toward an improved prediction of human in vivo brain penetration.

The penetration of drugs into the central nervous system is a composite of both the rate of drug uptake across the blood-brain barrier and the extent of distribution into brain tissue compartments. Clinically, positron emission tomography (PET) is the primary technique for deriving information on drug biodistribution as well as target receptor occupancy. In contrast, rodent models have formed the basis for much of the current understanding of brain penetration within pharmaceutical Drug Discovery. Linking these two areas more effectively would greatly improve the translation of candidate compounds into therapeutic agents. This paper examines two of the major influences on the extent of brain penetration across species, namely plasma protein binding and brain tissue binding. An excellent correlation was noted between unbound brain fractions across species (R(2) > 0.9 rat, pig, and human, n = 21), which is indicative of the high degree of conservation of the central nervous system environment. In vitro estimates of human brain-blood or brain-plasma ratios of marketed central nervous system drugs and PET tracers agree well with in vivo values derived from clinical PET and post-mortem studies. These results suggest that passive diffusion across the blood-brain barrier is an important process for many drugs in humans and highlights the possibility for improved prediction of brain penetration across species.

Development of a combined microPET-MR system.

As evidenced by the success of PET-CT, there are many benefits from combining imaging modalities into a single scanner. The combination of PET and MR offers potential advantages over PET-CT, including improved soft tissue contrast, access to the multiplicity of contrast mechanisms available to MR, simultaneous imaging and fast MR sequences for motion correction. In addition, PET-MR is more suitable than PET-CT for cancer screening due to the elimination of the radiation dose from CT. A key issue associated with combining PET and MR is the fact that the performance of the photomultiplier tubes (PMTs) used in conventional PET detectors is degraded in the magnetic field required for MR. Two approaches have been adopted to circumvent that issue: retention of conventional, magnetic field-sensitive PMT-based PET detectors by modification of other features of the MR or PET system, or the use of new, magnetic field-insensitive devices in the PET detectors including avalanche photo-diodes (APDs) and silicon photomultipliers (SiPMs). Taking the former approach, we are assembling a modified microPET Focus 120 within a gap in a novel, 1T superconducting magnet. The PMTs are located in a low magnetic field (approximately 30mT) through a combination of magnet design and the use of fiber optic 'bundles'. Two main features of the modified PET system have been tested, namely the effect of using long fiber optic bundles in the PET detector, and the impact of magnetic field upon the performance of the position sensitive PMTs. The design of a modified microPET-MR system for small animal imaging is completed, and assembly and testing is underway.

A randomised, double blind, placebo-controlled study to determine the efficacy of immune modulation therapy in the treatment of patients suffering from peripheral arterial occlusive disease with intermittent claudication.

OBJECTIVES: this study examined the effect of immune modulation therapy (IMT) on claudication distances. MATERIALS AND METHODS: a double-blind placebo controlled trial was performed on patients with disabling intermittent claudication with randomisation stratified for short and long distance IC. For IMT, following exposure to UV light, oxidisation and 42.5 degrees C, 10 ml of citrated autologous blood was administered by intra-muscular injection. One course consisted of 6 injections in 3-weeks followed by 3-weeks rest. Patients received 2, 3 or 4 courses depending on response. The primary end-point was the number of responders (>50% increase in initial claudication distance (ICD)) in each group. Secondary end-points included percentage changes in ICD and change in quality of life. RESULTS: at week 24, there were more responders in the IMT group (20/31, 65%) compared to placebo (16/39, 41%) (p=0.06). In the subgroup of short distance claudicants this difference reached significance (IMT 17/26, 65%) (Placebo 12/33, 36%) (p=0.04). The median increase in ICD was significantly greater in the IMT group (81%) compared to placebo (44%, p=0.04). These results were supported by quality of life measurements. CONCLUSIONS; IMT is a safe and apparently effective treatment for patients with short distance claudication.

Pore geometry information via pulsed field gradient NMR.

Studies of echo attenuation at long diffusion times in pulsed field gradient NMR experiments on a variety of rock core samples are interpreted in the light of recent theoretical analysis of the effect of pore geometry and surface relaxation. This study is motivated by the need to test the applicability of that theory to real rock systems.

3D autocorrelation for the determination of large pore sizes.

A data analysis methodology is used to process 3D NMR image data acquired for porous systems. The method extracts the mean size of those repeating elements in the image data which are largely compared with the image voxel dimensions. In this work we extend the two-dimensional (2D) image analysis method described by others to three spatial dimensions (3D). 3D image data were acquired at a magnetic field strength of 7 T using NMR microscopy hardware. The 3D autocorrelation function obtained from the data reveals a characteristic pore size in each dimension.

Strategies for overcoming linewidth limitations in quantitative petrophysical NMR measurements.

The simple pulse-acquire experiment has been used to evaluate the level of accuracy and precision achievable in NMR fluid saturation measurements for a range of rock core samples saturated with either brine or hydrocarbons. For a set of more than 70 cores measured at 0.66 T the mean error in the NMR measurement is only 0.35% porosity when the sample linewidths are less than 50 ppm. However, for a significant portion of cores, those with very broad NMR linewidths (> 50 ppm), difficulties associated with nonuniform excitation are encountered. The magnetic susceptibility difference between pore fluid and rock matrix translates into relatively broad NMR linewidths, and this feature of petrophysical samples is the major difficulty in performing quantitative NMR experiments. Numerical simulations are used to complement the experimental results in order to develop strategies for obtaining accurate NMR results with these difficult samples.

Quantitative longitudinal fluid saturation profiles with a slice-selected CPMG sequence.

A technique for obtaining quantitative longitudinal saturation/porosity profiles of rock cores which are longer than the NMR coil has been developed. The slice-selected experiment uses a prefocused pulse in conjunction with a magnetic field gradient for the localization and a CPMG sequence to sample the data. A variety of rock core samples has been studied ranging from limestones to shaly sandstones. Comparison of the relaxation decay curves obtained from these experiments and the bulk experiments show that reliable localized relaxation data are obtained.

The intercostal-to-phrenic inhibitory reflex in the human fetus near term.

Human fetal breathing movements (FBM) differ from neonatal breathing in that they are predominantly paradoxical and are not present all the time. Respiratory pauses are common in the fetus while prolonged apneas are life-threatening in the neonate. In the latter they occur during state 2 (active sleep) when paradoxical breathing is more frequent. Then the inward movement of the thoracic wall causes spreading of the caudal ribs which may elicit an intercostal-to-phrenic inhibitory reflex (IPIR) leading to apnea. This is not the case in state 1 (quiet sleep). In the fetus similar sleep states, state 2F and 1F respectively, have been identified and we investigated if the IPIR is already present before birth and if so, if the response is different between 1F and 2F. In 21 healthy fetuses between 37 and 40 weeks, two real time scanners and a cardiotocograph were used to asses the fetal behavioural state. If FBM were present, the caudo-lateral part of the fetal thoracic wall was shortly compressed manually and the period that FBM ceased measured. During the same epoch moments of sham-stimulation, i.e. control periods without actual compression were also carried out. In 15 out of 16 fetuses with FBM in 1F, and in 19 out of 19 fetuses in 2F, compressions were immediately followed by an apnea. In contrast, moments of sham-stimulation never induced apnea, indicating that the IPIR is indeed present in both behavioural states.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality control of manual visual field examination by computer simulation.

Quality control of manual visual field examination is impaired because the process is difficult to monitor, and because examiners have minimal formal training and supervision, and are subject to rapid turnover. Computer simulation can be used both to teach perimetry and to provide a reference standard against which performance may be measured.

Microcomputer-based testing of proficiency with the visual field examination.

A system for computer-assisted instruction in performing ophthalmic visual field examinations is presented. The system is implemented on a microcomputer making use of specially developed algorithms to summarize the information contained in a visual field in a very compact, efficient manner and to determine cursor position relative to stored visual field landmarks. The computer program presents a challenging testing situation by using visual fields, based on those of actual patients, of differing degrees of complexity. It is particularly well suited for trainees as well as for the physicians and ophthalmic technicians who frequently perform this examination.

Acceptability of the cytopipette in a general hospital.

Altogether 2,798 cytopipette smears have been taken by patients entering the general medical and surgical wards of a hospital. Twelve unsuspected positive smears were found, a rate of 4 per 1,000. Biopsy of these patients has shown five pre-malignant lesions, one invasive carcinoma of cervix, and one carcinoma of corpus uteri. Five patients await biopsy.The cytopipette is both acceptable to the patient (62% acceptance) and a feasible laboratory technique and can produce good cytological smears. Only 30% of patients entering the hospital had already had the opportunity to obtain a smear before, and most of them welcomed the opportunity for the test.Though the self-pipette may be criticized for its inaccuracy we feel that any test, if it can detect cervical abnormality at the rate of 4 women per 1,000, is better than no test at all. It should have a place in routine cytological testing of women second only to the use of Ayre's spatula.