Search

BACKGROUND: Access to inhaled nitric oxide (iNO) is limited in low resource settings due to non-availability and high cost. There is a need for research on low-cost alternative therapies for management of persistent pulmonary hypertension of the newborn (PPHN). We aimed to compare oral sildenafil and bosentan as monotherapy in the treatment of neonates with PPHN. STUDY DESIGN: In this single-centre open-label randomized controlled trial (RCT), term and late preterm neonates with PPHN, defined as pulmonary arterial systolic pressure (PASP) > 35 mmHg and requiring fraction of inspired oxygen (FiO2) > 0.21, were randomized to receive oral sildenafil and bosentan. The primary outcome was reduction of PASP by 25% within 48 h after start of drug. RESULTS: Thirty-six neonates were analyzed (18 in each group). Initial PASPs were similar in both groups. The median (IQR) time for the primary outcome (PASP to reduce by 25% within 48 h) was 36 (24-48) h and 96 (48-120) h in sildenafil and bosentan groups respectively (p = 0.008). There was also a higher need to add other pulmonary vasodilators in bosentan group as compared to sildenafil group (p = 0.006). CONCLUSION: Sildenafil was associated with quicker reduction of PASP and FiO2 in neonates with PPHN, as compared to bosentan. Large multicentre blinded trials to assess efficacy and safety of bosentan in comparison with other pulmonary vasodilators would help to get a clearer understanding of its role in the management of PPHN, particularly for use in resource-limited settings that lack iNO. CLINICAL TRIAL REGISTRATION: https://ctri.nic.in/Clinicaltrials/rmaindet.php? trialid=63997&EncHid=39716.16132&modid=1&compid=19[CTRI/2022/06/043328].

BACKGROUND AND STUDY DESIGN: Limited data exists on noradrenaline therapy in neonatal septic shock. We compared the efficacy of noradrenaline with adrenaline in neonatal septic shock. This single center, open label, pilot randomized controlled trial included neonates with clinical evidence of sepsis and shock. STUDY OUTCOMES: Primary outcomes were: 1) resolution of shock one hour after treatment, and 2) mortality during hospital stay. Secondary outcomes included: need for additional vasopressors; hemodynamic stability without further administration of vasopressors for ≥2 h; changes in blood pressure and heart rate after 1 h of vasopressor treatment; and morbidities during the hospital stay. RESULTS: Of 65 eligible neonates, 42 were randomized (21 each in adrenaline and noradrenaline treatment arms) between August 2020 and January 2022, at level III neonatal intensive care unit (NICU) of Bharati Vidyapeeth Deemed University Medical College and Hospital (BVDUMCH). The mean (SD) gestational age and mean (SD) birth weight were 36.1(4.2) weeks and 1.8 (0.2) kilograms birth weight for noradrenaline and 36.9 (4.1) weeks and 1.7 (0.7) kilograms for adrenaline. Shock resolved within 1 h of vasopressor therapy in 76.2% neonates in the noradrenaline arm and 61.9% in adrenaline arm (p value-0.53). Mortality during hospital stay was 28.6% (6/21) in noradrenaline group and 33.3% (7/21) in adrenaline group (p value- 0.58). Additional vasopressors were required in 23.8% neonates of the noradrenaline group compared to 38.1% neonates in adrenaline arm (p value-0.53). Median (SD) duration of intensive care stay was 6 (SD) days in the noradrenaline group and 10 (SD) days in the adrenaline group (p value-0.045). CONCLUSION: Among neonates with septic shock, the efficacy of noradrenaline was comparable to adrenaline in resolving septic shock after one hour of infusion and on the mortality during hospital stay. CLINICAL TRIAL REGISTRATION: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NDI2NTc=&Enc=&userName=noradrenaline, Clinical Trials Registry - India with identifier CTRI/2020/08/027185 (17/08/2020).

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been considered a public health emergency, extensively investigated by researchers. Accordingly, the respiratory tract has been the main research focus, with some other studies outlining the effects on the neurological, cardiovascular, and renal systems. However, concerning SARS-CoV-2 outcomes on skeletal muscle, scientific evidence is still not sufficiently strong to trace, treat and prevent possible muscle impairment due to the COVID-19. Simultaneously, there has been a considerable amount of studies reporting skeletal muscle damage in the context of COVID-19. Among the detrimental musculoskeletal conditions associated with the viral infection, the most commonly described are sarcopenia, cachexia, myalgia, myositis, rhabdomyolysis, atrophy, peripheral neuropathy, and Guillain-Barré Syndrome. Of note, the risk of developing sarcopenia during or after COVID-19 is relatively high, which poses special importance to the condition amid the SARS-CoV-2 infection. The yet uncovered mechanisms by which musculoskeletal injury takes place in COVID-19 and the lack of published methods tailored to study the correlation between COVID-19 and skeletal muscle hinder the ability of healthcare professionals to provide SARS-CoV-2 infected patients with an adequate treatment plan. The present review aims to minimize this burden by both thoroughly exploring the interaction between COVID-19 and the musculoskeletal system and examining the cutting-edge 3D cell culture techniques capable of revolutionizing the study of muscle dynamics.

Sleep spindles are intermittent bursts of 11-15 Hz EEG waves that occur during non-rapid eye movement sleep. Spindles are believed to help maintain sleep and to play a role in sleep-dependent memory consolidation. Here we applied an automated sleep spindle detection program to our large longitudinal sleep EEG dataset (98 human subjects, 6-18 years old, >2000 uninterrupted nights) to evaluate maturational trends in spindle wave frequency, density, amplitude, and duration. This large dataset enabled us to apply nonlinear as well as linear age models, thereby extending the findings of prior cross-sectional studies that used linear models. We found that spindle wave frequency increased with remarkable linearity across the age range. Central spindle density increased nonlinearly to a peak at age 15.1 years. Central spindle wave amplitude declined in a sigmoidal pattern with the age of fastest decline at 13.5 years. Spindle duration decreased linearly with age. Of the four measures, only spindle amplitude showed a sex difference in dynamics such that the age of most rapid decline in females preceded that in males by 1.4 years. This amplitude pattern, including the sex difference in timing, paralleled the maturational pattern for δ (1-4 Hz) wave power. We interpret these age-related changes in spindle characteristics as indicators of maturation of thalamocortical circuits and changes in sleep depth. These robust age-effects could facilitate the search for cognitive-behavioral correlates of spindle waveforms and might also help guide basic research on EEG mechanisms and postnatal brain maturation.SIGNIFICANCE STATEMENT The brain reorganization of adolescence produces massive changes in sleep EEG. These changes include the morphology and abundance of sleep spindles, an EEG marker of non-rapid eye movement sleep believed to reflect offline memory processes and/or protection of the sleep state. We analyzed >2000 nights of longitudinal sleep EEG from 98 subjects (age 6-18 years old) to investigate maturational changes in spindle amplitude, frequency, density, and duration. The large dataset enabled us to detect nonlinear as well as linear age changes. All measures showed robust age effects that we hypothesize reflect the maturation of thalamocortical circuits and decreasing sleep depth. These findings could guide further research into the cognitive-behavioral correlates of sleep spindles and their underlying brain mechanisms.

The CUPID-Mo experiment at the Laboratoire Souterrain de Modane (France) is a demonstrator for CUPID, the next-generation ton-scale bolometric 0νββ experiment. It consists of a 4.2 kg array of 20 enriched Li_{2}^{100}MoO_{4} scintillating bolometers to search for the lepton-number-violating process of 0νββ decay in ^{100}Mo. With more than one year of operation (^{100}Mo exposure of 1.17  kg×yr for physics data), no event in the region of interest and, hence, no evidence for 0νββ is observed. We report a new limit on the half-life of 0νββ decay in ^{100}Mo of T_{1/2}>1.5×10^{24}  yr at 90% C.I. The limit corresponds to an effective Majorana neutrino mass ⟨m_{ββ}⟩

The CUPID-Mo experiment at the Laboratoire Souterrain de Modane (France) is a demonstrator for CUPID, the next-generation ton-scale bolometric 0νββ experiment. It consists of a 4.2 kg array of 20 enriched Li_{2}^{100}MoO_{4} scintillating bolometers to search for the lepton-number-violating process of 0νββ decay in ^{100}Mo. With more than one year of operation (^{100}Mo exposure of 1.17  kg×yr for physics data), no event in the region of interest and, hence, no evidence for 0νββ is observed. We report a new limit on the half-life of 0νββ decay in ^{100}Mo of T_{1/2}>1.5×10^{24}  yr at 90% C.I. The limit corresponds to an effective Majorana neutrino mass ⟨m_{ββ}⟩

CUPID-Mo is a cryogenic detector array designed to search for neutrinoless double-beta decay (0νββ) of 100Mo. It uses 20 scintillating 100Mo-enriched Li2MoO4 bolometers instrumented with Ge light detectors to perform active suppression of α backgrounds, drastically reducing the expected background in the 0νββ signal region. As a result, pileup events and small detector instabilities that mimic normal signals become non-negligible potential backgrounds. These types of events can in principle be eliminated based on their signal shapes, which are different from those of regular bolometric pulses. We show that a purely data-driven principal component analysis based approach is able to filter out these anomalous events, without the aid of detector response simulations.

CUPID-Mo is a cryogenic detector array designed to search for neutrinoless double-beta decay (0νββ) of 100Mo. It uses 20 scintillating 100Mo-enriched Li2MoO4 bolometers instrumented with Ge light detectors to perform active suppression of α backgrounds, drastically reducing the expected background in the 0νββ signal region. As a result, pileup events and small detector instabilities that mimic normal signals become non-negligible potential backgrounds. These types of events can in principle be eliminated based on their signal shapes, which are different from those of regular bolometric pulses. We show that a purely data-driven principal component analysis based approach is able to filter out these anomalous events, without the aid of detector response simulations.

We report the measurement of the two-neutrino double-beta (2 νββ) decay of 100Mo to the ground state of 100Ru using lithium molybdate (Li2100MoO4) scintillating bolometers. The detectors were developed for the CUPID-Mo program and operated at the EDELWEISS-III low background facility in the Modane underground laboratory (France). From a total exposure of 42.235 kg× day, the half-life of 100Mo is determined to be T1/22ν=[7.12-0.14+0.18(stat.)±0.10(syst.)]×1018 years. This is the most accurate determination of the 2 νββ half-life of 100Mo to date.

We report the measurement of the two-neutrino double-beta (2 νββ) decay of 100Mo to the ground state of 100Ru using lithium molybdate (Li2100MoO4) scintillating bolometers. The detectors were developed for the CUPID-Mo program and operated at the EDELWEISS-III low background facility in the Modane underground laboratory (France). From a total exposure of 42.235 kg× day, the half-life of 100Mo is determined to be T1/22ν=[7.12-0.14+0.18(stat.)±0.10(syst.)]×1018 years. This is the most accurate determination of the 2 νββ half-life of 100Mo to date.

CUPID-Mo is a bolometric experiment to search for neutrinoless double-beta decay (0 νββ) of 100Mo. In this article, we detail the CUPID-Mo detector concept, assembly and installation in the Modane underground laboratory, providing results from the first datasets. The CUPID-Mo detector consists of an array of 20 100Mo -enriched 0.2 kg Li 2MoO 4 crystals operated as scintillating bolometers at ∼20mK. The Li 2MoO 4 crystals are complemented by 20 thin Ge optical bolometers to reject α events by the simultaneous detection of heat and scintillation light. We observe a good detector uniformity and an excellent energy resolution of 5.3 keV (6.5 keV) FWHM at 2615 keV, in calibration (physics) data. Light collection ensures the rejection of α particles at a level much higher than 99.9% – with equally high acceptance for γ/β events – in the region of interest for 100Mo 0 νββ. We present limits on the crystals’ radiopurity: ≤3μBq/kg of 226Ra and ≤2μBq/kg of 232Th. We discuss the science reach of CUPID-Mo, which can set the most stringent half-life limit on the 100Mo 0 νββ decay in half-a-year’s livetime. The achieved results show that CUPID-Mo is a successful demonstrator of the technology developed by the LUMINEU project and subsequently selected for the CUPID experiment, a proposed follow-up of CUORE, the currently running first tonne-scale bolometric 0 νββ experiment.

CUPID-Mo is a bolometric experiment to search for neutrinoless double-beta decay (0 νββ) of 100Mo. In this article, we detail the CUPID-Mo detector concept, assembly and installation in the Modane underground laboratory, providing results from the first datasets. The CUPID-Mo detector consists of an array of 20 100Mo -enriched 0.2 kg Li 2MoO 4 crystals operated as scintillating bolometers at ∼20mK. The Li 2MoO 4 crystals are complemented by 20 thin Ge optical bolometers to reject α events by the simultaneous detection of heat and scintillation light. We observe a good detector uniformity and an excellent energy resolution of 5.3 keV (6.5 keV) FWHM at 2615 keV, in calibration (physics) data. Light collection ensures the rejection of α particles at a level much higher than 99.9% – with equally high acceptance for γ/β events – in the region of interest for 100Mo 0 νββ. We present limits on the crystals’ radiopurity: ≤3μBq/kg of 226Ra and ≤2μBq/kg of 232Th. We discuss the science reach of CUPID-Mo, which can set the most stringent half-life limit on the 100Mo 0 νββ decay in half-a-year’s livetime. The achieved results show that CUPID-Mo is a successful demonstrator of the technology developed by the LUMINEU project and subsequently selected for the CUPID experiment, a proposed follow-up of CUORE, the currently running first tonne-scale bolometric 0 νββ experiment.

The half-life of 100Mo relatively to the 2ν2β decay to the ground state of 100Ru was measured as T1/2 = (6.99±0.15) × 1018 yr with the help of enriched in 100Mo lithium molybdate scintillating bolometers in the EDELWEISS-III low background set-up at the Modane underground laboratory. This is the most accurate value of the 2ν2β half-life of 100Mo.

The half-life of 100Mo relatively to the 2ν2β decay to the ground state of 100Ru was measured as T1/2 = (6.99±0.15) × 1018 yr with the help of enriched in 100Mo lithium molybdate scintillating bolometers in the EDELWEISS-III low background set-up at the Modane underground laboratory. This is the most accurate value of the 2ν2β half-life of 100Mo.

This paper reports on the development of a technology involving 100Mo -enriched scintillating bolometers, compatible with the goals of CUPID, a proposed next-generation bolometric experiment to search for neutrinoless double-beta decay. Large mass ( ∼1kg ), high optical quality, radiopure 100Mo -containing zinc and lithium molybdate crystals have been produced and used to develop high performance single detector modules based on 0.2-0.4 kg scintillating bolometers. In particular, the energy resolution of the lithium molybdate detectors near the Q-value of the double-beta transition of 100Mo (3034 keV) is 4-6 keV FWHM. The rejection of the α -induced dominant background above 2.6 MeV is better than 8σ . Less than 10μBq/kg activity of 232Th(228Th) and 226Ra in the crystals is ensured by boule recrystallization. The potential of 100Mo -enriched scintillating bolometers to perform high sensitivity double-beta decay searches has been demonstrated with only 10kg×d exposure: the two neutrino double-beta decay half-life of 100Mo has been measured with the up-to-date highest accuracy as T1/2 = [6.90 ± 0.15(stat.) ± 0.37(syst.)] ×1018years . Both crystallization and detector technologies favor lithium molybdate, which has been selected for the ongoing construction of the CUPID-0/Mo demonstrator, containing several kg of 100Mo .

In this study, satellite-based daily precipitation estimation data from precipitation estimation from remotely sensed information using artificial neural networks (PERSIANN)-climate data record (CDR) are being evaluated in Iran. This dataset (0.25°, daily), which covers over three decades of continuous observation beginning in 1983, is evaluated using rain-gauge data for the period of 1998–2007. In addition to categorical statistics and mean annual amount and number of rainy days, ten standard extreme indices were calculated to observe the behavior of daily extremes. The results show that PERSIANN-CDR exhibits reasonable performance associated with the probability of detection and false-alarm ratio, but it overestimates precipitation in the area. Although PERSIANN-CDR mostly underestimates extreme indices, it shows relatively high correlations (between 0.6316–0.7797) for intensity indices. PERSIANN-CDR data are also used to calculate the trend in annual amounts of precipitation, the number of rainy days, and precipitation extremes over Iran covering the period of 1983–2012. Our analysis shows that, although annual precipitation decreased in the western and eastern regions of Iran, the annual number of rainy days increased in the northern and northwestern areas. Statistically significant negative trends are identified in the 90th percentile daily precipitation, as well as the mean daily precipitation from wet days in the northern part of the study area. The positive trends of the maximum annual number of consecutive dry days in the eastern regions indicate that the dry periods became longer in these arid areas.

In the first part of this paper, monthly precipitation data from Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks–Climate Data Record (PERSIANN-CDR) and Tropical Rainfall Measuring Mission 3B42 algorithm Version 7 (TRMM-3B42V7) are evaluated over Iran using the Generalized Three-Cornered Hat (GTCH) method which is self-sufficient of reference data as input. Climate Data Unit (CRU) is added to the GTCH evaluations as an independent gauge-based dataset thus, the minimum requirement of three datasets for the model is satisfied. To ensure consistency of all datasets, the two satellite products were aggregated to 0.5° spatial resolution, which is the minimum resolution of CRU. The results show that the PERSIANN-CDR has higher Signal to Noise Ratio (SNR) than TRMM-3B42V7 for the monthly rainfall estimation, especially in the northern half of the country. All datasets showed low SNR in the mountainous area of southwestern Iran, as well as the arid parts in the southeast region of the country. Additionally, in order to evaluate the efficacy of PERSIANN-CDR and TRMM-3B42V7 in capturing extreme daily-precipitation amounts, an in-situ rain-gauge dataset collected by the Islamic Republic of the Iran Meteorological Organization (IRIMO) was employed. Given the sparsity of the rain gauges, only 0.25° pixels containing three or more gauges were used for this evaluation. There were 228 such pixels where daily and extreme rainfall from PERSIANN-CDR and TRMM-3B42V7 could be compared. However, TRMM-3B42V7 overestimates most of the intensity indices (correlation coefficients; R between 0.7648–0.8311, Root Mean Square Error; RMSE between 3.29mm/day-21.2mm/5day); PERSIANN-CDR underestimates these extremes (R between 0.6349–0.7791 and RMSE between 3.59mm/day-30.56mm/5day). Both satellite products show higher correlation coefficients and lower RMSEs for the annual mean of consecutive dry spells than wet spells. The results show that TRMM-3B42V7 can capture the annual mean of the absolute indices (the number of wet days in which daily precipitation >10 mm, 20 mm) better than PERSIANN-CDR. The results of daily evaluations show that the similarity of Empirical Cumulative Density Function (ECDF) of satellite products and IRIMO gauges daily precipitation, as well as dry spells with different thresholds in some selected pixels (include at least five gauges), are significant. The results also indicate that ECDFs become more significant when threshold increases. In terms of regional analyses, the higher SNR of the products on monthly (based on the GTCH method) and daily evaluations (significant ECDFs) is mostly consistent.

PurposeThe purpose of this study was to evaluate the diagnostic performance of a "simulated" abbreviated MRI (AMRI) protocol using diffusion-weighted imaging (DWI) and T1-weighted (T1w) imaging obtained at the hepatobiliary phase (HBP) post gadoxetic acid injection alone and in combination, compared to dynamic contrast-enhanced (CE)-T1w imaging for the detection of hepatocellular carcinoma (HCC).MethodsThis was an IRB approved HIPAA compliant retrospective single institution study including patients with liver disease who underwent gadoxetic acid-enhanced MRI for HCC diagnosis. Three independent observers assessed 2 sets of images (full CE-set and AMRI including DWI+T1w-HBP). Diagnostic performance of T1w-HBP and DWI alone and in combination was compared to that of CE-set. All imaging sets included unenhanced T1w and T2w sequences. A preliminary analysis was performed to assess cost savings of AMRI protocol compared to a full MRI study.Results174 patients including 62 with 80 HCCs were assessed. Equivalent per-patient sensitivity and negative predictive value (NPV) were observed for DWI (85.5% and 92.2%, pooled data) and T1w-HBP (89.8% and 94.2%) (P = 0.1-0.7), while these were significantly lower for the full AMRI protocol (DWI+T1w-HBP, 80.6% and 80%, P = 0.02) when compared to CE-set (90.3% and 94.9%). Higher specificity and positive predictive value were observed for CE-set vs. AMRI (P = 0.02). The estimated cost reduction of AMRI versus full MRI ranged between 30.7 and 49.0%.ConclusionAMRI using DWI and T1w-HBP has a clinically acceptable sensitivity and NPV for HCC detection. This could serve as the basis for a future study assessing AMRI for HCC screening and surveillance.

This paper reports on the development of a technology involving 100Mo -enriched scintillating bolometers, compatible with the goals of CUPID, a proposed next-generation bolometric experiment to search for neutrinoless double-beta decay. Large mass ( ∼1kg ), high optical quality, radiopure 100Mo -containing zinc and lithium molybdate crystals have been produced and used to develop high performance single detector modules based on 0.2-0.4 kg scintillating bolometers. In particular, the energy resolution of the lithium molybdate detectors near the Q-value of the double-beta transition of 100Mo (3034 keV) is 4-6 keV FWHM. The rejection of the α -induced dominant background above 2.6 MeV is better than 8σ . Less than 10μBq/kg activity of 232Th(228Th) and 226Ra in the crystals is ensured by boule recrystallization. The potential of 100Mo -enriched scintillating bolometers to perform high sensitivity double-beta decay searches has been demonstrated with only 10kg×d exposure: the two neutrino double-beta decay half-life of 100Mo has been measured with the up-to-date highest accuracy as T1/2 = [6.90 ± 0.15(stat.) ± 0.37(syst.)] ×1018years . Both crystallization and detector technologies favor lithium molybdate, which has been selected for the ongoing construction of the CUPID-0/Mo demonstrator, containing several kg of 100Mo .

PurposeThe purpose of this study was to evaluate the diagnostic performance of a "simulated" abbreviated MRI (AMRI) protocol using diffusion-weighted imaging (DWI) and T1-weighted (T1w) imaging obtained at the hepatobiliary phase (HBP) post gadoxetic acid injection alone and in combination, compared to dynamic contrast-enhanced (CE)-T1w imaging for the detection of hepatocellular carcinoma (HCC).MethodsThis was an IRB approved HIPAA compliant retrospective single institution study including patients with liver disease who underwent gadoxetic acid-enhanced MRI for HCC diagnosis. Three independent observers assessed 2 sets of images (full CE-set and AMRI including DWI+T1w-HBP). Diagnostic performance of T1w-HBP and DWI alone and in combination was compared to that of CE-set. All imaging sets included unenhanced T1w and T2w sequences. A preliminary analysis was performed to assess cost savings of AMRI protocol compared to a full MRI study.Results174 patients including 62 with 80 HCCs were assessed. Equivalent per-patient sensitivity and negative predictive value (NPV) were observed for DWI (85.5% and 92.2%, pooled data) and T1w-HBP (89.8% and 94.2%) (P = 0.1-0.7), while these were significantly lower for the full AMRI protocol (DWI+T1w-HBP, 80.6% and 80%, P = 0.02) when compared to CE-set (90.3% and 94.9%). Higher specificity and positive predictive value were observed for CE-set vs. AMRI (P = 0.02). The estimated cost reduction of AMRI versus full MRI ranged between 30.7 and 49.0%.ConclusionAMRI using DWI and T1w-HBP has a clinically acceptable sensitivity and NPV for HCC detection. This could serve as the basis for a future study assessing AMRI for HCC screening and surveillance.

Drought is one of the most relevant natural disasters, especially in arid regions such as Iran. One of the requirements to access reliable drought monitoring is long-term and continuous high-resolution precipitation data. Different climatic and global databases are being developed and made available in real time or near real time by different agencies and centers; however, for this purpose, these databases must be evaluated regionally and in different local climates. In this paper, a near real-time global climate model, a data assimilation system, and two gridded gauge-based datasets over Iran are evaluated. The ground truth data include 50 gauges from the period of 1980 to 2010. Drought analysis was carried out by means of the Standard Precipitation Index (SPI) at 2-, 3-, 6-, and 12-month timescales. Although the results show spatial variations, overall the two gauge-based datasets perform better than the models. In addition, the results are more reliable for the western portion of the Zagros Range and the eastern region of the country. The analysis of the onsets of the 6-month moderate drought with at least 3 months’ persistence indicates that all datasets have a better performance over the western portion of the Zagros Range, but display poor performance over the coast of the Caspian Sea. Base on the results of this study, the Modern-Era Retrospective Analysis for Research and Applications (MERRA) dataset is a preferred alternative for drought analysis in the region when gauge-based datasets are not available.

Background and purposeFractional flow may identify hemodynamic effects and ischemic risk beyond percent stenosis of an artery. We hypothesized that diminished TOF-MRA signal intensity distal to an intracranial stenosis predicts stroke risk.MethodsTOF-MRA was acquired prospectively in the SONIA-WASID trials. The distal/proximal signal intensity ratio (SIR) was calculated from 3 mm regions of interest, blinded to outcome. Univariate and multivariate analyses included clinical variables, SIR, and invasive angiography measures to identify predictors for risk of stroke in the territory.Results189 patients with 50-99% symptomatic intracranial stenosis in SONIA-WASID had TOF-MRA available. In univariate analysis, the hazard ratio (HR) for stroke in the territory of the symptomatic artery with SIR < .9 was 5.2 (1.8, 15.3; P < .001) as compared to SIR ≥ .9. Multivariate analysis correcting for baseline systolic blood pressure, LDL, centrally measured percent stenosis, recency of symptoms, TICI and downstream collaterals, the HR for SIR < .9 was 10.9 (2.0, 58.9; P < .001). In those with

Precipitation in semi-arid countries such as Iran is one of the most important elements for all aspects of human life. In areas with sparse ground-based precipitation observation networks, the reliable high spatial and temporal resolution of satellite-based precipitation estimation might be the best source for meteorological and hydrological studies. In the present study, four different satellite rainfall estimates (CMORPH, PERSIANN, adjusted PERSIANN, and TRMM-3B42 V6) are evaluated using a relatively dense Islamic Republic of Iran's Meteorological Organization (IRIMO) rain-gauge network as reference. These evaluations were done at daily and monthly time scales with a spatial resolution of 0.25° × 0.25° latitude/longitude. The topography of Iran is complicated and includes different, very diverse climates. For example, there is an extremely wet (low-elevation) Caspian Sea coastal region in the north, an arid desert in the center, and high mountainous areas in the west and north. Different rainfall regimes vary between these extremes. In order to conduct an objective intercomparison of the various satellite products, the study was designed to minimize the level of uncertainties in the evaluation process. To reduce gauge uncertainties, only the 32 pixels, which include at least five rain gauges, are considered. Evaluation results vary by different areas. The satellite products had a Probability of Detection (POD) greater than 40% in the southern part of the country and the regions of the Zagros Mountains. However, all satellite products exhibited poor performance over the Caspian Sea coastal region, where they underestimated precipitation in this relatively wet and moderate climate region. Seasonal analysis shows that spring precipitations are detected more accurately than winter precipitation, especially for the mountainous areas all over the country. Comparisons of different satellite products show that adj-PERSIANN and TRMM-3B42 V6 have better performance, and CMORPH has poor estimation, especially over the Zagros Mountains. The comparison between PERSIANN and adj-PERSIANN shows that the bias adjustment improved the POD, which is a daily scale statistic.

Precipitation in semi-arid countries such as Iran is one of the most important elements for all aspects of human life. In areas with sparse ground-based precipitation observation networks, the reliable high spatial and temporal resolution of satellite-based precipitation estimation might be the best source for meteorological and hydrological studies. In the present study, four different satellite rainfall estimates (CMORPH, PERSIANN, adjusted PERSIANN, and TRMM-3B42 V6) are evaluated using a relatively dense Islamic Republic of Iran's Meteorological Organization (IRIMO) rain-gauge network as reference. These evaluations were done at daily and monthly time scales with a spatial resolution of 0.25° × 0.25° latitude/longitude. The topography of Iran is complicated and includes different, very diverse climates. For example, there is an extremely wet (low-elevation) Caspian Sea coastal region in the north, an arid desert in the center, and high mountainous areas in the west and north. Different rainfall regimes vary between these extremes. In order to conduct an objective intercomparison of the various satellite products, the study was designed to minimize the level of uncertainties in the evaluation process. To reduce gauge uncertainties, only the 32 pixels, which include at least five rain gauges, are considered. Evaluation results vary by different areas. The satellite products had a Probability of Detection (POD) greater than 40% in the southern part of the country and the regions of the Zagros Mountains. However, all satellite products exhibited poor performance over the Caspian Sea coastal region, where they underestimated precipitation in this relatively wet and moderate climate region. Seasonal analysis shows that spring precipitations are detected more accurately than winter precipitation, especially for the mountainous areas all over the country. Comparisons of different satellite products show that adj-PERSIANN and TRMM-3B42 V6 have better performance, and CMORPH has poor estimation, especially over the Zagros Mountains. The comparison between PERSIANN and adj-PERSIANN shows that the bias adjustment improved the POD, which is a daily scale statistic.

ObjectiveMutations in the Valosin-containing protein (VCP) gene cause a unique disorder characterized by classic Paget disease of bone (PDB), inclusion body myopathy, and frontotemporal dementia (IBMPFD). Our objective was to analyze the radiographic features of PDB associated with VCP mutations since there is a dearth of literature on the PDB component of VCP disease.Materials and methodsRadiographic bone surveys were examined in 23 individuals with VCP mutation and compared with their unaffected relatives. Laboratory testing relevant for VCP disease was performed in all individuals.ResultsOf the 17 affected individuals with clinical manifestations of VCP disease, 16 of whom had myopathy, radiographic analysis revealed classic PDB in 11 individuals (65%). The mean age of diagnosis for myopathy was 43.8 years and for PDB was 38.1 years of age. Radiological evidence of PDB was seen in one individual (16%) amongst six clinically asymptomatic VCP mutation carriers. Alkaline phosphatase was a useful marker for diagnosing PDB in VCP disease.ConclusionsRadiographic findings of classic PDB are seen in 52% of individuals carrying VCP mutations at a significantly younger age than conventional PDB. Screening for PDB is warranted in at-risk individuals because of the benefit of early treatment with the new powerful bisphosphonates that hold the potential for prevention of disease.

The CDMS and EDELWEISS collaborations have combined the results of their direct searches for dark matter using cryogenic germanium detectors. The total data set represents 614kg•days equivalent exposure. A straightforward method of combination was chosen for its simplicity before data were exchanged between experiments. The results are interpreted in terms of limits on spin-independent weakly interacting, massive particle (WIMP)-nucleon cross section. For a WIMP mass of 90GeV/c2, where this analysis is most sensitive, a cross section of 3.3×10-44cm2 is excluded at 90% C.L. At higher WIMP masses, the combination improves the individual limits, by a factor 1.6 above 700GeV/c2. Alternative methods of combining the data provide stronger constraints for some ranges of WIMP masses and weaker constraints for others. © 2011 American Physical Society.

The CDMS and EDELWEISS collaborations have combined the results of their direct searches for dark matter using cryogenic germanium detectors. The total data set represents 614kg•days equivalent exposure. A straightforward method of combination was chosen for its simplicity before data were exchanged between experiments. The results are interpreted in terms of limits on spin-independent weakly interacting, massive particle (WIMP)-nucleon cross section. For a WIMP mass of 90GeV/c2, where this analysis is most sensitive, a cross section of 3.3×10-44cm2 is excluded at 90% C.L. At higher WIMP masses, the combination improves the individual limits, by a factor 1.6 above 700GeV/c2. Alternative methods of combining the data provide stronger constraints for some ranges of WIMP masses and weaker constraints for others. © 2011 American Physical Society.