Clinical Outcomes in 3343 Children and Adults with Rheumatic Heart Disease from 14 Low and Middle Income Countries: 2-Year Follow-up of the Global Rheumatic Heart Disease Registry (the REMEDY study)

BACKGROUND: -There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease (RHD) or information on their predictors. We report the two year follow-up of individuals with RHD from 14 low and middle income countries in Africa and Asia.

METHODS: -Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for two years to assess mortality, congestive heart failure (CHF), stroke or transient ischemic attack (TIA), recurrent acute rheumatic fever (ARF), and infective endocarditis (IE).

RESULTS: -Vital status at 24 months was known for 2960 (88.5%) patients. Two thirds were female. Although patients were young (median age 28 years, interquartile range 18 to 40), the two year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.80-3.11), CHF (HR 2.16, 95% CI 1.70-2.72), New York Heart Association functional class III/IV (HR 1.67, 95% CI 1.32-2.10), atrial fibrillation (AF) (HR 1.40, 95% CI 1.10-1.78) and older age (HR 1.02, 95% CI 1.01-1.02 per year increase) at enrolment. Post-primary education (HR 0.67, 95% CI 0.54-0.85) and female sex (HR 0.65, 95%CI 0.52-0.80) were associated with lower risk of death. 204 (6.9%) had new CHF (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or TIA (8.45/1000 patient-years), 19 (0.6%) had ARF (3.49/1000 patient-years), and 20 (0.7%) had IE (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/TIA or systemic embolism. Patients from low and lower-middle income countries had significantly higher age- and sex-adjusted mortality compared to patients from upper-middle income countries. Valve surgery was significantly more common in upper-middle income than in lower-middle- or low-income countries.

CONCLUSIONS: -Patients with clinical RHD have high mortality and morbidity despite being young; those from low and lower-middle income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and treatment of clinical RHD are required to improve outcomes.

Prosodic Characteristics of Skilled Reading: Fluency and Expressiveness in 8- 10-year-old Readers

Statistical methods of describing prosody were used to study fluency, expressiveness and their relationship among 8-10-year-old readers. There were robust relationships between expressiveness and variables associated with pitch mobility; and between fluency and measures associated with temporal organization. Interactions indicated that the relationships were not simple. Differences between groups depended on sentence content and position. Some measures offer a basis for rules aimed at assigning individuals to skill categories. The effects suggest psychological hypotheses about the underlying mechanisms.

A comparison of theoretical line intensity ratios for Ni XII with extreme ultraviolet observations from the JET tokamak

Recent R-matrix calculations of electron impact excitation rates in Ni XII are used to derive the emission line ratios R-1 = I(154.17 Angstrom)/I(152.15 Angstrom), R-2 = I(152.95 Angstrom)/I(152.15 Angstrom) and R-3 = 1(160.55 Angstrom)/I(152.15 Angstrom). This is the first time (to our knowledge) that theoretical emission line ratios have been calculated for this ion. The ratios are found to be insensitive to changes in the adopted electron density (N-e) when N-e greater than or equal to 5 x 10(11) cm(-3), typical of laboratory plasmas. However, they do vary with electron temperature (T-e), with for example R-1 and R-3 changing by factors of 1.3 and 1.8, respectively, between T-e = 10(5) and 10(6) K. A comparison of the theoretical line ratios with measurements from the Joint European Tents (JET) tokamak reveals very good agreement between theory and observation for R-1, with an average discrepancy of only 7%. Agreement between the calculated and experimental ratios for R-2 and R-3 is less satisfactory, with average differences of 30 and 33%, respectively. These probably arise from errors in the JET instrument calibration curve. However, the discrepancies are smaller than the uncertainties in the R-2 and R-3 measurements. Our results, in particular for R-1, provide experimental support for the accuracy of the Ni XIII line ratio calculations, and hence for the atomic data adopted in their derivation.

Geometrical dependence in photoionization of H-2(+) in high-intensity, high-frequency, ultrashort laser pulses

The ionization dynamics of H2 + exposed to high-intensity, high-frequency, ultrashort laser pulses is investigated with two theoretical approaches. The time-dependent Schrödinger equation is solved by a direct numerical method, and a simple two-center interference-diffraction model is studied. The energy and angular distributions of the photoelectron for various internuclear distances and relative orientations between the internuclear axis of the molecule and the polarization of the field are calculated. The main features of the photoelectron spectrum pattern are described well by the interference-diffraction model, and excellent quantitative agreement between the two methods is found. The effect of quantal vibration on the photoelectron spectrum is also calculated. We find that vibrational average produces some broadening of the main features, but that the patterns remain clearly distinguishable.

Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.

The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose–volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7–31.2% depending on the /ß ratio of prostate cancer (p

Intensity-modulated radiotherapy reduces lung irradiation in patients with carcinoma of the oesophagus.

The 2-year survival rate after conventional radiotherapy for carcinoma of the oesophagus is around 10–20% [8]. Concomitant chemoradiation schedules have produced survival figures of 25–30% at 5 years, and this is now considered standard treatment [1]. Conformal radiotherapy techniques offer the potential to deliver higher doses of radiation to oesophageal tumours [5], and this may improve local tumour control. However, concerns regarding late normal tissue damage to the lung parenchyma and spinal cord remain a concern. Intensitymodulated radiotherapy (IMRT) allows complex dose distributions to be produced, and can reduce the dose to radiosensitive organs close to the tumour [2]. The present study was designed to investigate the impact of beam intensity modulation on treatment planning for carcinoma of the oesophagus, by comparing a standard three-dimensional conformal radiotherapy (3DCRT) technique to an IMRT technique using the same number and orientation of treatment fields.

A comparison of conformal and intensity-modulated techniques for oesophageal radiotherapy.

Background and purpose: To investigate the potential of intensity-modulated radiotherapy (IMRT) to reduce lung irradiation in the treatment of oesophageal carcinoma with radical radiotherapy.Materials and methods: A treatment planning study was performed to compare two-phase conformal radiotherapy (CFRT) with IMRT in five patients. The CFRT plans consisted of anterior, posterior and bilateral posterior oblique fields, while the IMRT plans consisted of either nine equispaced fields (9F), or four fields (4F) with orientations equal to the CFRT plans. IMRT plans with seven, five or three equispaced fields were also investigated in one patient. Treatment plans were compared using dose-volume histograms and normal tissue complication probabilities.Results: The 9F IMRT plan was unable to improve on the homogeneity of dose to the planning target volume (PTV), compared with the CFRT plan (dose range, 16.9+/-4.5 (1 SD) vs. 12.4+/-3.9%; P=0.06). Similarly, the 9F IMRT plan was unable to reduce the mean lung dose (11.7+/-3.2 vs. 11.0+/-2.9 Gy; P=0.2). Similar results were obtained for seven, five and three equispaced fields in the single patient studied. The 4F IMRT plan provided comparable PTV dose homogeneity with the CFRT plan (11.8+/-3.3 vs. 12.4+/-3.9%; P=0.6), with reduced mean lung dose (9.5+/-2.3 vs 11.0+/-2.9 Gy; P=0.001).Conclusions: IMRT using nine equispaced fields provided no improvement over CFRT. This was because the larger number of fields in the IMRT plan distributed a low dose over the entire lung. In contrast, IMRT using four fields equal to the CFRT fields offered an improvement in lung sparing. Thus, IMRT with a few carefully chosen field directions may lead to a modest reduction in pneumonitis, or allow tumour dose escalation within the currently accepted lung toxicity.

Potential role of intensity-modulated radiotherapy in the treatment of tumors of the maxillary sinus.

To assess 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques to see whether doses to critical structures could be reduced while maintaining planning target volume (PTV) coverage in patients receiving conventional radiotherapy (RT) for carcinoma of the maxillary sinus because of the risk of radiation-induced complications, particularly visual loss. Six patients who had recently received conventional RT for carcinoma of the maxillary sinus were studied. Conventional RT, 3D-CRT, and step-and-shoot IMRT plans were prepared using the same 2-field arrangement. The effect of reducing the number of segments in the IMRT beams was investigated. 3D-CRT and IMRT reduced the brain and ipsilateral parotid gland doses compared with the conventional plans. IMRT reduced doses to both optic nerves; for the contralateral optic nerve, 15-segment IMRT plans delivered an average maximal dose of 56.4 Gy (range 53.9–59.3) compared with 65.7 Gy (range 65.3–65.9) and 64.2 Gy (range 61.4–65.6) for conventional RT and 3D-CRT, respectively. IMRT also gave improved PTV homogeneity and improved coverage, with an average of 8.5% (range 7.0–11.7%) of the volume receiving

Self-reported quality of life of 8-12 year old children with cerebral palsy: a cross-sectional European Study

Background

Little is known about the quality of life (QoL) of disabled children. We describe self-reported QoL of children with cerebral palsy, factors that influence it, and how it compares with QoL of the general population.

Methods

1174 children aged 8–12 years were randomly selected from eight population-based registers of children with cerebral palsy in six European countries and 743 (63%) agreed to participate; one further region recruited 75 children from multiple sources. Researchers visited these 818 children. 318 (39%) with severe intellectual impairment could not self-report; 500 (61%) reported their QoL using KIDSCREEN, an instrument with scores in ten domains, each with SD=10. Multivariable regression was used to relate QoL to impairments, pain, and sociodemographic characteristics. Comparisons were made with QoL data from the general population.

Findings

Impairments were not significantly associated with six KIDSCREEN domains. Comparison of least and most able groups showed that severely limited self-mobility was significantly associated with reduced mean score for physical wellbeing (7·6, 95% CI 2·7–12·4); intellectual impairment with reduced mean for moods and emotions (3·7, 1·5–5·9) and autonomy (3·3, 0·9–5·7); and speech difficulties with reduced mean for relationships with parents (4·5, 1·9–7·1). Pain was common and associated with lower QoL on all domains. Impairments and pain explained up to 3% and 7%, respectively, of variation in QoL. Children with cerebral palsy had similar QoL to children in the general population in all domains except schooling, in which evidence was equivocal, and physical wellbeing, in which comparison was not possible.

Interpretation

Parents can be reassured that most children aged 8–12 years with cerebral palsy will have similar QoL to other children. This finding should guide social and educational policy to ensure that disabled children participate fully in society. Because of its association with QoL, children's pain should be carefully assessed.

Optimisation of radiotherapy for carcinoma of the parotid gland: a comparison of conventional, three-dimensional conformal, and intensity-modulated techniques

Background and purpose: To compare external beam radiotherapy techniques for parotid gland tumours using conventional radiotherapy (RT), three-dimensional conformal radiotherapy (3DCRT), and intensity-modulated radiotherapy (IMRT). To optimise the IMRT techniques, and to produce an IMRT class solution.Materials and methods: The planning target volume (PTV), contra-lateral parotid gland, oral cavity, brain-stem, brain and cochlea were outlined on CT planning scans of six patients with parotid gland tumours. Optimised conventional RT and 3DCRT plans were created and compared with inverse-planned IMRT dose distributions using dose-volume histograms. The aim was to reduce the radiation dose to organs at risk and improve the PTV dose distribution. A beam-direction optimisation algorithm was used to improve the dose distribution of the IMRT plans, and a class solution for parotid gland IMRT was investigated.Results: 3DCRT plans produced an equivalent PTV irradiation and reduced the dose to the cochlea, oral cavity, brain, and other normal tissues compared with conventional RT. IMRT further reduced the radiation dose to the cochlea and oral cavity compared with 3DCRT. For nine- and seven-field IMRT techniques, there was an increase in low-dose radiation to non-target tissue and the contra-lateral parotid gland. IMRT plans produced using three to five optimised intensity-modulated beam directions maintained the advantages of the more complex IMRT plans, and reduced the contra-lateral parotid gland dose to acceptable levels. Three- and four-field non-coplanar beam arrangements increased the volume of brain irradiated, and increased PTV dose inhomogeneity. A four-field class solution consisting of paired ipsilateral coplanar anterior and posterior oblique beams (15, 45, 145 and 170o from the anterior plane) was developed which maintained the benefits without the complexity of individual patient optimisation.Conclusions: For patients with parotid gland tumours, reduction in the radiation dose to critical normal tissues was demonstrated with 3DCRT compared with conventional RT. IMRT produced a further reduction in the dose to the cochlea and oral cavity. With nine and seven fields, the dose to the contra-lateral parotid gland was increased, but this was avoided by optimisation of the beam directions. The benefits of IMRT were maintained with three or four fields when the beam angles were optimised, but were also achieved using a four-field class solution. Clinical trials are required to confirm the clinical benefits of these improved dose distributions.

Interaction of High Intensity Picosecond Laser Pulses with Large Pre-formed Plasmas

The interaction of short (1-2 ps) laser pulses with solid targets at irradiances of over 1016 Wcm~2 , in the presence of a substantial prepulse has been investigated. High absorption of laser energy is found even at high angles of incidence, with evidence for a resonance absorption peak being found for S, P, and circular polarizations. It is considered that this may be a result of refraction and beam filamentation, which causes loss of distinct polarization. Measurements of hard X-ray emission (~ 100 keV) confirm a resonance absorption type peak at 45-50°, again for all three cases. Typically, 5-15% of the incident light is back-reflected by stimulated Brillouin scatter, with spatially resolved spectra showing evidence of beam hot-spots at high intensity. The possibility that filamentation and refraction of the beam can explain the lack of polarization dependence in the absorption and hard X-ray emission data is discussed.

Antennas for over-body-surface communication at 2.45 GHz

In this paper, the on-body performance of a range of wearable antennas was investigated by measuring vertical bar S-21 vertical bar path gain between two devices mounted on tissue-equivalent numerical and experimental phantoms, representative of human muscle tissue at 2.45 GHz. In particular, the study focused on the performance of a compact higher mode microstrip patch antenna (HMMPA) with a profile as low as lambda/20. The 5- and 10-mm-high HMMPA prototypes had an impedance bandwidth of 6.7% and 8.6%, respectively, sufficient for the operating requirements of the 2.45-GHz industrial, scientific, and medical (ISM) band and both antennas offered 11-dB higher path gain compared to a fundamental-mode microstrip patch antenna. It was also dernonstrated that a 7-dB improvement in path gain can be obtained for a fundamental-mode patch through the addition of a shortening wall. Notably, on-body HMMPA performance was comparable to a quarter wave monopole antenna on the same size of ground-plane, mounted normal to the tissue surface, indicating that the low-profile and physically more robust antenna is a promising solution for bodyworn antenna applications.

An experimental investigation into the influence of user state and environment on fading characteristics in wireless body area networks at 2.45 GHz

Using seven strategically placed, time-synchronized bodyworn receivers covering the head, upper front and back torso, and the limbs, we have investigated the effect of user state: stationary or mobile and local environment: anechoic chamber, open office area and hallway upon first and second order statistics for on-body fading channels. Three candidate models were considered: Nakagami, Rice and lognormal. Using maximum likelihood estimation and the Akaike information criterion it was established that the Nakagami-m distribution best described small-scale fading for the majority of on-body channels over all the measurement scenarios. When the user was stationary, Nakagami-m parameters were found to be much greater than 1, irrespective of local surroundings. For mobile channels, Nakagami-m parameters significantly decreased, with channels in the open office area and hallway experiencing the worst fading conditions.

Pattern Switching Compact Patch Antenna for On-body and Off-body Communications at 2.45 GHz

The ability to switch between propagating modes is important for body-centric applications such as medical body area networks where a single node may need to be able to optimise communications for either on-body sensor links or off-body links to the wider network. Therefore, we present a compact 2.45 GHz active mode-switching wearable antenna for both on-body and off-body wireless communications. The single-layer patch antenna was pattern-switched using shorting pins and had an impedance bandwidth of 253 MHz and 217 MHz for the on-body and off-body radiating modes, respectively. An efficiency of 57 % and 56.8 % was obtained for on-body and off-body mode respectively when placed in close proximity to a phantom that represents a muscle issue at 2.45 GHz.