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Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
Preserving of vision is the main goal in vision research. The presented research evaluates the preservation of visual function in Royal College of Surgeon (RCS) rats using a depth perception test. Rats were placed on a stage with one side containing an illusory steep drop (“cliff”) and another side with a minimal drop (“table”). Latency of stage dismounting and the percentage of rats that set their first foot on the “cliff” side were determined. Nondystrophic Long–Evans (LE) rats were tested as control. Electroretinogram and histology analysis were used to determine retinal function and structure. Four-week-old RCS rats presented a significantly shorter mean latency to dismount the stage compared with 6-week-old rats (mean ± standard error, 13.7 ± 1.68 vs. 20.85 ± 6.5 s, P = 0.018). Longer latencies were recorded as rats aged, reaching 45.72 s in 15-week-old rats (P < 0.00001 compared with 4-week-old rats). All rats at the age of 4 weeks placed their first foot on the table side. By contrast, at the age of 8 weeks, 28.6% rats dismounted on the cliff side and at the age of 10 and 15 weeks, rats randomly dismounted the stage to either table or cliff side. LE rats dismounted the stage faster than 4-week-old RCS rats, but the difference was not statistically significant (7 ± 1.58 s, P = 0.057) and all LE rats dismounted on the table side. The latency to dismount the stage in RCS rats correlated with maximal electroretinogram b-wave under dark and light adaptation (Spearman’s rho test = −0.603 and −0.534, respectively, all P < 0.0001), outer nuclear layer thickness (Spearman’s rho test = −0.764, P = 0.002), and number of S- and M-cones (Spearman’s rho test = −0.763 [P = 0.002], and −0.733 [P = 0.004], respectively). The cliff avoidance test is an objective, quick, and readily available method for the determination of RCS rats’ visual function.
Terrorism and natural catastrophes have made disaster preparedness a critical issue. Despite the documented vulnerabilities of children during and following disasters, gaps remain in health care systems regarding pediatric disaster preparedness. This research study examined changes in knowledge acquisition of pediatric disaster preparedness among medical and non-medical personnel at a children’s hospital who completed an online training course of five modules: planning, triage, age-specific care, disaster management, and hospital emergency code response.
A multi-disciplinary team within the Pediatric Disaster Resource and Training Center at Children’s Hospital Los Angeles (Los Angeles, California USA) developed an online training course. Available archival course data from July 2009 to August 2012 were analyzed through linear growth curve multi-level modeling, with module total score as the outcome (0 to 100 points), attempt as the Level 1 variable (any module could be repeated), role in the hospital (medical or non-medical) as the Level 2 variable, and attempt by role as the cross-level effect.
A total of 44,115 module attempts by 5,773 course participants (3,686 medical personnel and 2,087 non-medical personnel) were analyzed. The average module total score upon first attempt across all participants ranged from 60.28 to 80.11 points, and participants significantly varied in how they initially scored. On average in the planning, triage, and age-specific care modules: total scores significantly increased per attempt across all participants (average rate of change ranged from 0.59 to 1.84 points) and medical personnel had higher total scores initially and through additional attempts (average difference ranged from 13.25 to 16.24 points). Cross-level effects were significant in the disaster management and hospital emergency code response modules: on average, total scores were initially lower among non-medical personnel compared to medical personnel, but non-medical personnel increased their total scores per attempt by 3.77 points in the disaster management module and 6.40 points in the hospital emergency code response module, while medical personnel did not improve their total scores through additional attempts.
Medical and non-medical hospital personnel alike can acquire knowledge of pediatric disaster preparedness. Key content can be reinforced or improved through successive training in an online course.
PhamPK, BeharSM, BergBM, UppermanJS, NagerAL. Pediatric Online Disaster Preparedness Training for Medical and Non-Medical Personnel: A Multi-Level Modeling AnalysisPrehosp Disaster Med.2018;33(4):349–354.
Objectives: This study investigated the relationship between on-field, objective signs immediately following sport-related concussion and self-reported symptom endorsement within 1 day post injury. Methods: A retrospective case series of 237 concussed high school athletes was performed. On-field signs were evaluated immediately post injury. Self-reported symptoms (2 clusters) were collected within 1 day post injury. A two-step structural equation model and follow-up bivariate regression analyses of significant on-field signs and symptom clusters were performed. Results: Signs of immediate memory, β=0.20, p=.04, and postural instability, β=0.19, p < .01, significantly predicted a greater likelihood of endorsing the cognitive-migraine-fatigue symptom cluster within 1 day post injury. Regarding signs correlated with specific symptoms, immediate memory was associated with symptoms of trouble remembering, χ2=37.92, p < .001, odds ratio (OR)=3.89 (95% confidence interval (CI) [2.47, 6.13]), and concentration difficulties, χ2=10.84, p=.001, OR=2.13 (95% CI [1.37, 3.30]). Postural instability was associated with symptom endorsement of trouble remembering, χ2=12.08, p < .001, OR=1.76 (95% CI [1.29, 2.40]). Conclusions: Certain post-concussion on-field signs exhibited after injury were associated with specific symptom endorsement within 1 day post injury. Based on these associations, individualized education-based interventions and academic accommodations may help reduce unanticipated worry from parents, students, and teachers following a student-athlete’s sport-related concussion, especially in cases of delayed onset symptoms. (JINS, 2018, 24, 476–485)
Antimicrobial resistance (AMR) is a global public health threat. Emergence of AMR occurs naturally, but can also be selected for by antimicrobial exposure in clinical and veterinary medicine. Despite growing worldwide attention to AMR, there are substantial limitations in our understanding of the burden, distribution and determinants of AMR at the population level. We highlight the importance of population-based approaches to assess the association between antimicrobial use and AMR in humans and animals. Such approaches are needed to improve our understanding of the development and spread of AMR in order to inform strategies for the prevention, detection and management of AMR, and to support the sustainable use of antimicrobials in healthcare.
In this work, we propose a multi-sensor platform where sensors are stacked over one another (3D stacked) each offering a unique functionality. The technique involves the use of Polyurethane (PU) sponge and PVDF/graphene (Gr) /ZnO composites for various sensing applications. The sponge was made conductive by dipping it in different weight percentages of pencil lead dispersed in ethanol through ultrasonication. Large area Gr/PVDF films were fabricated by simple solution mixing and casting method which also served as a substrate for the 3D stacked sensor. ZnO was grown hydrothermally over Gr/PVDF film by masking a portion of Gr/PVDF film to form a p-n junction. Silver paste and copper tape were used as contact pads. All the three fabricated devices were stacked with PU sponge sandwiched between Gr/PVDF/ZnO (top) and large area Gr/PVDF (bottom) as substrate. Performance of individual sensors and 3D stacked sensor was compared and no notable change was observed. The 3D stacked sensor array platform with its multifunctionality would be a step ahead in wearable electronics which can be integrated on human and can function as an e-skin for burn and acid victims, robotics and human-machine interactions.
Rest-frame 0.48–1.1 μm emission line strengths and molecular gas mass (H2) upper limits for three luminous infrared sources – the hyperluminous infrared galaxies (HyLIGs: Lir ≥ 1013L⊙ where Lir ~ L(8 – 1000μm) IRAS F09105+4108 (z = 0.4417), IRAS F15307+3252 (z = 0.926), and the optically-selected QSO PG 1634+706 (z = 1.338) - are presented. Diagnostic emission-line ratios ([O III] λ5007/Hβ, [S II] λ6724/Hα, [N II] λ6583/Hα, and [S III] λλ9069+9532/Hα) indicate a Seyfert 2-like spectrum for both infrared galaxies, consistent with previously published work. Upper limits on the molecular gas mass for all three sources are M(H2) < 1 - 3 × 1010h−2M⊙ (q0 = 0.5, H0 = 100h km s−1 Mpc−1), less than the H2 mass of the most gas-rich infrared galaxies in the local Universe. All three sources have Lir/L′CO ~ 1300 – 2000, the most extreme values for extragalactic sources measured to date. Given the relatively warm far-infrared colors for all three objects, much of their infrared luminosity may emanate from a relatively small quantity of hot dust near an AGN.
The number of identified high-redshift far-infrared hyperluminous sources (LFIR ≥ 1013L⊙) is now approaching ~20 (see e.g. Rowan-Robinson 1996). In about half of them, at z > 3.5, evidence for strong far-infrared emission has been obtained from its redshifted detection in the mm continuum. Most of the latter are bright radio-quiet QSOs (Omont et al. 1996b). The most prominent one, BR1202-0725 at z = 4.7, was first detected at 1.25mm with the IRAM 30m telescope (McMahon et al. 1994) with a flux of ∼ 10-15 mJy. Its submm detection at JCMT (Isaak et al. 1994) supports dust emission because of a submm-mm spectral index ≥ 3.
During the MEDOC campaign #4 (October 1999), we observed an active region filament with the SUMER/SoHO spectrometer using the 584.33 Å HeI line. After a description of the HeI line profile in the filament, we present a Fourier analysis of SUMER long time observations. This analysis allows to detect oscillations in several ranges of periodicities: 6–20 min, 40–90 min. We discuss these periodicities in terms of Alfvén and magnetoacoustic waves obtained with a filament model developed by Joarder & Roberts (1993).
The development of DSM-III through DSM-5 has relied heavily on expert consensus. In this essay, we provide an historical and critical perspective on this process. Over the last 40 years, medicine has struggled to find appropriate methods for summarizing research results and making clinical recommendations. When such recommendations are issued by authorized organizations, they can have widespread influence (i.e. DSM-III and its successors). In the 1970s, expert consensus conferences, led by the NIH, reviewed research about controversial medical issues and successfully disseminated results. However, these consensus conferences struggled with aggregating the complex available evidence. In the 1990s, the rise of evidence-based medicine cast doubt on the reliability of expert consensus. Since then, medicine has increasingly relied on systematic reviews, as developed by the evidence-based medicine movement, and advocated for their early incorporation in expert consensus efforts. With the partial exception of DSM-IV, such systematic evidence-based reviews have not been consistently integrated into the development of the DSMs, leaving their development out of step with the larger medical field. Like the recommendations made for the NIH consensus conferences, we argue that the DSM process should be modified to require systematic evidence-based reviews before Work Groups make their assessments. Our suggestions – which would require leadership and additional resources to set standards for appropriate evidence hierarchies, carry out systematic reviews, and upgrade the group process – should improve the objectivity of the DSM, increase the validity of its results, and improve the reception of any changes in nosology.
Digital tonometry is designed to non-invasively screen for endothelial dysfunction by the detection of impaired flow-induced reactive hyperaemia in the fingertip. We determined whether digital reactive hyperaemia correlated with risk factors for atherosclerosis in two groups of children at increased risk for endothelial dysfunction.
A total of 15 obese children and 23 non-obese, dyslipidaemic children, 8–21 years of age, were enrolled, and their medical histories, anthropometric measurements, carotid wall thickness by means of ultrasonography, and fasting blood samples for cardiovascular risk factors were obtained. The standard endoPAT index of digital reactive hyperaemia was modified to reflect the true peak response or the integrated response of the entire post-occlusion period. In each group, age, sex, pubertal status, carotid wall thickness, and multiple cardiovascular risk factors were tested as predictors of endothelial dysfunction.
In the non-obese, dyslipidaemic group, but not in the obese group, both indices strongly correlated with height (r=0.55, p=0.007, by peak response) followed by weight, waist circumference, and age. In both groups, neither index of reactive hyperaemia significantly correlated with any other cardiovascular risk factor.
Contrary to the known age-related increase in atherosclerosis, digital reactive hyperaemia increased with age and its correlates in non-obese, dyslipidaemic children and was not related to other cardiovascular risk factors in either group. The reason for the lack of this relationship with age in obese children is unknown. The age-dependent physiology of digital microvascular reactivity and the endothelium-independent factors controlling the peak hyperaemic response need further study in children with a wide age range.
Restricted and repetitive behaviors (RRBs) are hallmark symptoms of autism spectrum disorders (ASDs); however, it has proven difficult to understand the mechanisms underlying these behaviors. One hypothesis suggests that RRBs are the result of a core deficit in attention. Alternatively, abnormalities of the motor system may constitute the central mechanism underlying RRBs, given motor deficits observed in ASDs. In this experiment, we investigated the etiology of RRBs and the relationship between attention and motor deficits. Movement impairments (a) may be indirectly related to attention deficits, (b) may result from a shared compromised process, or (c) may be independent. Twenty-two adolescents with ASD and 20 typically developing participants performed a spatial attention task. Movement impairments were assessed with a rhythmic tapping task. Attentional orienting and motor control were found to be related and supported the hypothesis that these impairments in ASD arise from a shared process. In contrast, measures of attention switching and motor control were found to be independent. Stereotyped behaviors, as assessed by parental ratings, were related more to the degree of motor impairment than to deficits of attention. These results suggest that both attentional orienting deficits and stereotyped RRBs are related to a compromised motor system.
We focus our analysis on an event which occurred at the W-limb on May 30, 2003. The dynamical behavior of the filament, including damped oscillations, was investigated with the CDS and EIT (SoHO) experiments, as well as with Hα filtergrams (movies). The eruptive phase is analyzed taking into account the approximate phasing with other eruptive phenomena occurring at the same time or before, called homologous flares and eruptions.
Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However, because studies examining the associations of all three chronic conditions with circulating 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) are limited, we examined these associations in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian PLCO participants selected as controls in previous nested case–control studies of 25(OH)D and 1,25(OH)2D were included in this analysis. Diabetes, CHD and hypertension prevalence, risk factors for these conditions and intake of vitamin D and Ca were collected from a baseline questionnaire. Results indicated that serum levels of 25(OH)D were low ( < 50 nmol/l) in 29 % and very low ( < 37 nmol/l) in 11 % of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30 and 10 %, respectively. After adjustment for confounding by sex, geographical location, educational level, smoking history, BMI, physical activity, total dietary energy and vitamin D and Ca intake, only diabetes was significantly associated with lower 25(OH)D and 1,25(OH)2D levels. Caucasians who had 25(OH)D ≥ 80 nmol/l were half as likely to have diabetes (OR 0·5 (95 % CI 0·3, 0·9)) compared with those who had 25(OH)D < 37 nmol/l. Those in the highest quartile of 1,25(OH)2D ( ≥ 103 pmol/l) were less than half as likely to have diabetes (OR 0·3 (95 % CI 0·1, 0·7)) than those in the lowest quartile ( < 72 pmol/l). In conclusion, the independent associations of 25(OH)D and 1,25(OH)2D with diabetes prevalence in a large population are new findings, and thus warrant confirmation in larger, prospective studies.