Clinical and Genetic Features of Choroideremia in Childhood.

PURPOSE: To review the functional and anatomic characteristics of choroideremia in the pediatric population, aiming to describe the earliest features of the disease and to identify biomarkers useful for monitoring disease progression. DESIGN: Retrospective case series. PARTICIPANTS: Children diagnosed with choroideremia at a single institution. METHODS: Patients were identified using an electronic patient record system. Case notes and retinal imaging (color fundus photography [CFP], spectral-domain [SD] optical coherence tomography [OCT], and fundus autofluorescence [FAF]) then were reviewed. The results of genetic testing also were recorded. MAIN OUTCOME MEASURES: Presenting symptoms, visual acuity, fundus changes (CFP, SD OCT, FAF), and CHM sequencing results. RESULTS: Twenty-nine patients were identified with a mean age at referral of 9 years (range, 3-16 years). CHM mutations were identified in 15 of 19 patients tested. Nyctalopia was the predominant symptom (66%). Five of 29 patients were asymptomatic at presentation. At the final follow-up visit (mean age, 16 years; range, 7-26 years), most maintained excellent visual acuity (mean, 0.98±0.13 decimalized Snellen acuity). The first sign of retinopathy was widespread pigment clumping at the level of the retinal pigment epithelium (RPE). This later evolved to chorioretinal atrophy, most marked in the mid-peripheral retina. Peripapillary atrophy also was an early feature and was progressive in nature. Three different zones of FAF change were visible. Persistence of the inner retinal layers, detected by SD OCT, was visible at presentation in 15 of 27 patients. Subfoveal choroidal thickness decreased with age, whereas central retinal thickness increased over a similar interval. Four patients in whom visual acuity decreased over the follow-up period recorded a reduction in central retinal thickness. CONCLUSIONS: Progressive structural changes occur at a time when central visual function is maintained. Pigmentary changes at the level of the RPE occur early in the disease course. Peripapillary chorioretinal atrophy, central retinal thickness, and subfoveal choroidal thickness are likely to be valuable in monitoring disease progression and should be considered as potential biomarkers in future therapeutic trials

A note on a third order curvature invariant in static spacetimes

We consider here the third order curvature invariant $I=R_{\mu\nu\rho\sigma;\delta}R^{\mu\nu\rho\sigma;\delta}$ in static spacetimes ${\cal M}=R\times\Sigma$ for which $\Sigma$ is conformally flat. We evaluate explicitly the invariant for the $N$-dimensional Majumdar-Papapetrou multi black-holes solution, confirming that $I$ does indeed vanish on the event horizons of such black-holes. Our calculations show, however, that solely the vanishing of $I$ is not sufficient to locate an event horizon in non-spherically symmetric spacetimes. We discuss also some tidal effects associated to the invariant $I$.Comment: 5 pages, 3 figures. Extra material available at http://vigo.ime.unicamp.br/in

Limiar do Índice Homeostasis Model Assessment (HOMA) para Resistência à Insulina numa População de Doentes Admitidos Electivamente numa Enfermaria Portuguesa de Cardiologia

INTRODUCTION: Insulin resistance is the pathophysiological key to explain metabolic syndrome. Although clearly useful, the Homeostasis Model Assessment index (an insulin resistance measurement) hasn't been systematically applied in clinical practice. One of the main reasons is the discrepancy in cut-off values reported in different populations. We sought to evaluate in a Portuguese population the ideal cut-off for Homeostasis Model Assessment index and assess its relationship with metabolic syndrome. MATERIAL AND METHODS: We selected a cohort of individuals admitted electively in a Cardiology ward with a BMI < 25 Kg/m2 and no abnormalities in glucose metabolism (fasting plasma glucose < 100 mg/dL and no diabetes). The 90th percentile of the Homeostasis Model Assessment index distribution was used to obtain the ideal cut-off for insulin resistance. We also selected a validation cohort of 300 individuals (no exclusion criteria applied). RESULTS: From 7 000 individuals, and after the exclusion criteria, there were left 1 784 individuals. The 90th percentile for Homeostasis Model Assessment index was 2.33. In the validation cohort, applying that cut-off, we have 49.3% of individuals with insulin resistance. However, only 69.9% of the metabolic syndrome patients had insulin resistance according to that cut-off. By ROC curve analysis, the ideal cut-off for metabolic syndrome is 2.41. Homeostasis Model Assessment index correlated with BMI (r = 0.371, p < 0.001) and is an independent predictor of the presence of metabolic syndrome (OR 19.4, 95% CI 6.6 - 57.2, p < 0.001). DISCUSSION: Our study showed that in a Portuguese population of patients admitted electively in a Cardiology ward, 2.33 is the Homeostasis Model Assessment index cut-off for insulin resistance and 2.41 for metabolic syndrome. CONCLUSION: Homeostasis Model Assessment index is directly correlated with BMI and is an independent predictor of metabolic syndrome

Prevalence and Risk Factors of High Risk Human Papillomavirus Infections among Women Attending Gynaecology Clinics in Kano, Northern Nigeria

Cervical cancer is the most common female cancer in northern Nigeria, yet the pattern of infection with human papillomavirus, the principal aetiologic agent is unknown. This was a preliminary study conducted in two referral hospitals in order to establish base-line data on the prevalence and risk factors for the infection in Kano state, Nigeria. Fifty (50) randomly selected women aged 18 years and above were recruited from gynaecology clinics in Murtala Muhammad Specialist Hospital and Aminu Kano teaching Hospital. Relevant sexual and socio-demographic information were obtained from each subject using a questionnaire. Exfoliated cervical cells were harvested and processed using Polymerase Chain Reaction to identify the DNAs of high-risk HPV types 16 and 18. The prevalence rate of HPV infection was 76% [(38/50) at 95% CI=61.8-86.9] with 60.5% (23/38) having co-infections with both HPV type 16 and 18. Risk factors of the infection include low literacy level; living in rural settlements; low parity; early menarche (&lt;15 years of age); early onset of first sexual intercourse (≤16 years of age) and multiple sexual partners. There was however, no statistically significant association between oral contraceptive usage and acquisition of the infections. Findings of this study suggest a high prevalence of HPV types 16 and 18 among women attending gynaecology clinic in Kano and thus called for more elaborate community based study in order to establish the magnitude of the problem from wider perspective.Keywords: Human Papillomavirus; Prevalence; Risk Factors, Northern Nigeri

International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21st Project.

BACKGROUND: Reference values for umbilical artery Doppler indices are used clinically to assess fetal well-being. However, many studies that have produced reference charts have important methodologic limitations, and these result in significant heterogeneity of reported reference ranges. OBJECTIVES: To produce international gestational age-specific centiles for umbilical artery Doppler indices based on longitudinal data and the same rigorous methodology used in the original Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. STUDY DESIGN: In Phase II of the INTERGROWTH-21st Project (the INTERBIO-21st Study), we prospectively continued enrolling pregnant women according to the same protocol from 3 of the original populations in Pelotas (Brazil), Nairobi (Kenya), and Oxford (United Kingdom) that had participated in the Fetal Growth Longitudinal Study. Women with a singleton pregnancy were recruited at <14 weeks' gestation, confirmed by ultrasound measurement of crown-rump length, and then underwent standardized ultrasound every 5±1 weeks until delivery. From 22 weeks of gestation umbilical artery indices (pulsatility index, resistance index, and systolic/diastolic ratio) were measured in a blinded fashion, using identical equipment and a rigorously standardized protocol. Newborn size at birth was assessed using the international INTERGROWTH-21st Standards, and infants had detailed assessment of growth, nutrition, morbidity, and motor development at 1 and 2 years of age. The appropriateness of pooling data from the 3 study sites was assessed using variance component analysis and standardized site differences. Umbilical artery indices were modeled as functions of the gestational age using an exponential, normal distribution with second-degree fractional polynomial smoothing; goodness of fit for the overall models was assessed. RESULTS: Of the women enrolled at the 3 sites, 1629 were eligible for this study; 431 (27%) met the entry criteria for the construction of normative centiles, similar to the proportion seen in the original fetal growth longitudinal study. They contributed a total of 1243 Doppler measures to the analysis; 74% had 3 measures or more. The healthy low-risk status of the population was confirmed by the low rates of preterm birth (4.9%) and preeclampsia (0.7%). There were no neonatal deaths and satisfactory growth, health, and motor development of the infants at 1 and 2 years of age were documented. Only a very small proportion (2.8%-6.5%) of the variance of Doppler indices was due to between-site differences; in addition, standardized site difference estimates were marginally outside this threshold in only 1 of 27 comparisons, and this supported the decision to pool data from the 3 study sites. All 3 Doppler indices decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age for each of the 3 indices are provided, as well as equations to allow calculation of any value as a centile and z scores. The mean pulsatility index according to gestational age = 1.02944 + 77.7456*(gestational age)-2 - 0.000004455*gestational age3. CONCLUSION: We present here international gestational age-specific normative centiles for umbilical artery Doppler indices produced by studying healthy, low-risk pregnant women living in environments with minimal constraints on fetal growth. The centiles complement the existing INTERGROWTH-21st Standards for assessment of fetal well-being

Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.

Abstract OBJECTIVE: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. METHODS: Multicenter retrospective study of 16 children with NMO/NMOSD receiving 652 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 6510 7 10(6) cells/L). RESULTS: The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 7 10(6) cells/L, 10 had inadequate monitoring ( 641 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. CONCLUSION: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses

Capacity Gaps in Post Disaster Waste Management: Case Study in Sri Lanka

Disaster waste is one of the major consequences aftermath of any disaster, impacts on public and environment, rescue and emergency services, provision of lifeline support and socio-economic recovery of affected areas. Thus, management of wastes created by disasters has become an increasingly important issue to be addressed in responding to a disaster. This chapter intends to present the prevailing gaps in disaster waste management and approaches to minimize the impacts on disaster management at developing countries with special emphasis to Sri Lankan context. Findings revealed that, unavailability of single point responsibility and provisions for disaster waste in existing policies and capacity constraints of the prevailing peace time solid waste management practices as major capacity gaps. Establishment of a regulatory body and enforceable rules and regulations with necessary levels of capacities were identified with seven areas for capacity building for post disaster waste management. The research enabled to attain sustainable post disaster waste management for future resilience

Positron spectra from internal pair conversion observed in {238}U + {181}Ta collisions

We present new results from measurements and simulations of positron spectra, originating from 238U + 181Ta collisions at beam energies close to the Coulomb barrier. The measurements were performed using an improved experimental setup at the double-Orange spectrometer of GSI. Particular emphasis is put on the signature of positrons from Internal-Pair-Conversion (IPC) processes in the measured e+ energy spectra, following the de-excitation of electromagnetic transitions in the moving Ta-like nucleus. It is shown by Monte Carlo simulations that, for the chosen current sweeping procedure used in the present experiments, positron emission from discrete IPC transitions can lead to rather narrow line structures in the measured energy spectra. The measured positron spectra do not show evidence for line structures within the statistical accuracy achieved, although expected from the intensities of the observed $\gamma$ transitions (E$_{\gamma}~1250-1600$ keV) and theoretical conversion coefficients. This is due to the reduced detection efficiency for IPC positrons, caused by the limited spatial and momentum acceptance of the spectrometer. A comparison with previous results, in which lines have been observed, is presented and the implications are discussed.Comment: LaTeX, 20 pages including 5 EPS figures; Accepted by Eur. Phys.Jour.