Quantitative Analysis of Retinal Structure Using Spectral-Domain Optical Coherence Tomography in RPGR-Associated Retinopathy

PURPOSE: To quantify retinal structure and progression using spectral-domain optical coherence tomography (SDOCT) in patients with retinitis pigmentosa (RP) associated with retinitis pigmentosa GTPase regulator gene (RPGR) mutations. DESIGN: Retrospective observational case series. METHODS: Setting: Moorfields Eye Hospital, London, United Kingdom. Subjects: Both eyes of 32 patients. SDOCT follow-up period of >1 year (3.1 ± 1.4 years). Main Outcome Measures: Ellipsoid zone (EZ) width (EZW) and outer nuclear layer (ONL) and inner retinal layer (IRL) thickness measurements. Progression rates, interocular symmetry, and association with age and genotype were investigated. RESULTS: Significant differences were observed between baseline and final measurements of EZW and ONL thickness, but not for IRL thickness. Baseline and final EZWs were 2438 ± 1646 μm and 1901 ± 1423 μm for right eyes (P < .0001); 2420 ± 1758 μm and 1922 ± 1482 μm for left eyes (P < .0001). EZW constriction rates were 176.6 ± 130.1 μm/year and 173.1 ± 146.8 μm/year for right and left eyes. ONL thinning rates were 2.58 ± 2.85 μm/year and 2.52 ± 3.54 μm/year for right and left eyes. Interocular differences in EZW and ONL progression were not significant (P = .8609 and P = .6735, respectively). Strong correlations were found between EZW constriction rates of right and left eyes (rs = 0.627, P = .0002) and between EZW constriction and baseline EZW (rs = 0.714, P < .0001). There was moderate negative correlation between EZW constriction and age (rs = −0.532, P < .0001). Correlation between ONL thinning and age was not significant, as were differences between EZW and ONL progression rates with respect to genotype. CONCLUSIONS: This study provides SDOCT progression rates for RPGR-associated RP. There is overall interocular symmetry with implications for future treatment trials where 1 eye could serve as a control

Quantitative Analysis of Hyperautofluorescent Rings to Characterize the Natural History and Progression in Rpgr-associated Retinopathy

PURPOSE: Quantitative analysis of hyperautofluorescent rings and progression in subjects with retinitis pigmentosa associated with retinitis pigmentosa GTPase regulator (RPGR) gene mutations. METHODS: Prospective observational study of 46 subjects. Ring area, horizontal and vertical diameter measurements taken from outer and inner ring borders. Intraobserver repeatability, baseline measurements, progression rates, interocular symmetry, and association with age and genotype were investigated. RESULTS: Baseline ring area was 11.8 ± 13.4 mm and 11.4 ± 13.2 mm for right and left eyes, respectively, with very strong interocular correlation (r = 0.9398; P < 0.0001). Ring area constriction was 1.5 ± 2.0 mm/year and 1.3 ± 1.9 mm/year for right and left eyes, respectively, with very strong interocular correlation (r = 0.878, P < 0.0001). Baseline ring area and constriction rate correlated negatively with age (r = -0.767; P < 0.0001 and r = -0.644, P < 0.0001, respectively). Constriction rate correlated strongly with baseline area (r = 0.850, P < 0.0001). Age, but not genotype, exerted a significant effect on constriction rates (P < 0.0001), with greatest rates of progression seen in younger subjects. An exponential decline overall was found. CONCLUSION: This study provides disease-specific baseline values and progression rates together with a repeatability assessment of fundus autofluorescence metrics. Our findings can guide future treatment trials and contribute to the clinical care of patients with RPGR-associated retinitis pigmentosa

A Comparative Modeling and Analysis of Voltage Variation by Using Spectrogram

In this paper, the power quality (PQ) disturbance which is the voltage variations consist of voltage swell, sag and interruption are model and analyze. Different types of voltage variations PQ disturbances models are developed and created by using MATLAB/Simulink as well as mathematical models. The mathematical and Simulink model are used to compare in terms of time-frequency representation (TFR). The Simulink models include shutting down enormouscapacities from system to resemble voltage swell, large loads energizing and three-phase fault to simulate voltage sag as well as implementing permanent three-phase fault to simulate voltage interruption. The signals generated are analyzed by using linear time-frequency distribution (TFD). The signal parameters such as root mean square voltage (Vrms), total harmonic distortion (THD) and power value are estimated from the TFR to identify the characteristics of the voltage variation. The results of analysis on the PQ disturbance waveforms generated are identical to the actual real-time PQ signals and the models can be modified to any desired situation respectively. The PQ waveforms obtained are suitable to be further analyzed

Characterization of Retinal Function using Microperimetry-Derived Metrics in both Adults and Children with RPGR-Associated Retinopathy

PURPOSE: To investigate microperimetry testing of RPGR-associated retinopathy in a cohort of children and adults. STUDY DESIGN: Prospective observational case series. METHODS: The coefficient of repeatability and intraclass correlation coefficient (ICC) of mean sensitivity (MS) were calculated for mesopic microperimetry. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), MS, total volume (VTOT), and central 3-degree field volume (V3) from volumetric and topographic analyses were acquired. RESULTS: Seventy-six RPGR subjects (53 adults, 23 children) were recruited. The mean follow-up period was 2.8 years. The ICC values for MS, VTOT and V3 were 0.982 dB (95% confidence intervals, CI 0.969 to 0.989), 0.970 dB-sr (95% CI -0.02658 to 0.03691) and 0.986 dB-sr (95% CI 0.978 to 0.991), respectively. The r values for interocular MS, VTOT and V3, were 0.97 (P<0.01), 0.97 (P<0.01) and 0.98 (P<0.01) respectively, indicating strong inter-ocular correlation. The interocular correlation of progression for MS, VTOT and V3 was 0.81 (P<0.01), 0.64 (P<0.01) and 0.81 (P<0.01), respectively. There was no statistically significant difference in the interocular progression rates for MS or VTOT. V3 did show a statistically significant difference. Most patients lost retinal sensitivity rapidly during their second and third decades of life. CONCLUSIONS: The high degree of reproducibility of results and the good interocular correlation lends this modality to accurately monitoring disease progression, as well as supporting validation of the use of MP in assessing the outcomes of gene therapy clinical treatment trials

Cellular Imaging Of The Tapetal-like Reflex In Carriers Of RPGR-associated Retinopathy

PURPOSE: To examine the features of the tapetal-like reflex (TLR) in female carriers of RPGR-associated retinopathy by means of adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography. METHODS: Nine molecularly confirmed RPGR carriers and three healthy controls underwent ocular examination and the following retinal imaging modalities: color photography, near-infrared reflectance, fundus autofluorescence, spectral domain optical coherence tomography, and AOSLO. After identifying TLR areas across all imaging modalities, normalized local contrast of outer retinal bands on spectral domain optical coherence tomography was calculated and AOSLO-acquired photoreceptor mosaic analysis was performed. RESULTS: Seven carriers had TLR areas, which colocalized with increased rod photoreceptor reflectivity on confocal AOSLO and reduced cone photoreceptor densities. Parafoveal TLR areas also exhibited reduced local contrast (i.e., increased reflectivity) of the outer retinal bands on spectral domain optical coherence tomography (inner segment ellipsoid zone and outer segment interdigitation zone). Healthy controls did not show TLR. CONCLUSION: The cellular resolution provided by AOSLO affords the characterization of the photoreceptor mosaic in RPGR carriers with a TLR. Features revealed include reduced cone densities, increased cone inner segment diameters, and increased rod outer segment reflectivity

Genetic Variability of the mTOR Pathway and Prostate Cancer Risk in the European Prospective Investigation on Cancer (EPIC)

The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p<0.01) and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (ORallele = 0.85, 95% CI 0.78–0.94, p = 1.3×10−3 for rs546950 and ORallele = 0.84, 95% CI 0.76–0.93, p = 5.6×10−4 for rs4955720). We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer

Relationship between blood lead concentration and nutritional status among Malay primary school children in Kuala Lumpur, Malaysia.

A cross-sectional study was conducted to identify the relationship between blood lead concentration and nutritional status among primary school children in Kuala Lumpur. A total of 225 Malay students, 113 male and 112 female, aged 6.3 to 9.8 were selected through a stratified random sampling method. The random blood samples were collected and blood lead concentration was measured by a Graphite Furnace Atomic Absorption Spectrophotometer. The nutrient intake was determined by the 24-hour Dietary Recall method and Food Frequency Questionnaire. An anthropometric assessment was reported according to growth indices (z-scores of weight-for-age, height-for-age, and weight-for-height). The mean blood lead concentration was low (3.4 ± 1.91 ug/dL) and was significantly different between gender. Only 14.7% of the respondents fulfilled the daily energy requirement. The protein and iron intakes were adequate for a majority of the children. However, 34.7% of the total children showed inadequate intake of calcium. The energy, protein, fat and carbohydrate intakes were significantly different by gender, that is, males had better intake than females. Majority of respondents had normal mean z-score of growth indices. Ten percent of the respondents were underweight, 2.8% wasted and 5.4% stunted. Multiple linear regression showed inverse significant relationships between blood lead concentration with children's age (β= -0.647, p<0.001) and per capita income (β=-0.001, p=0.018). There were inverse significant relationships between blood lead concentration with children's age (β=-0.877, p=0.001) and calcium intake (β= -0.011,p=0.014) and positive significant relationship with weight-for-height (β=0.326, p=0.041) among those with inadequate calcium intake. Among children with inadequate energy intake, children's age (β= -0.621, p< 0.001), per capita income (β= -0.001,p=0.025) and protein intake (β= -0.019, p=0.027) were inversely and significantly related with blood lead concentration. In conclusion, nutritional status might affect the children's absorption of lead and further investigation is required for confirmation

New targets for therapy in breast cancer: Mammalian target of rapamycin (mTOR) antagonists

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biologic functions such as transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In breast cancer this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. There is evidence suggesting that Akt promotes breast cancer cell survival and resistance to chemotherapy, trastuzumab, and tamoxifen. Rapamycin is a specific mTOR antagonist that targets this pathway and blocks the downstream signaling elements, resulting in cell cycle arrest in the G(1 )phase. Targeting the Akt/PI3K pathway with mTOR antagonists may increase the therapeutic efficacy of breast cancer therapy

Do Asian breast cancer patients have poorer survival than their western counterparts? A comparison between Singapore and Stockholm

10.1186/bcr2219Breast Cancer Research111-BCRR

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente