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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.
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)
We report some preliminary results from the Massachusetts - Stony Brook CO survey of the first galactic quadrant using the 14-meter millimeterwave telescope of the Five College Radio Astronomy Observatory. The survey contains approximately 50 000 observations spaced every 3 arcminutes in 1 and b between longitudes 0° and 90° and latitudes −1° and 1°. We have mapped emission from giant molecular clouds (GMC) which we identified, in earlier more limited strip surveys of the galactic plane (Solomon, Sanders and Scoville 1979; Sanders 1981), on size scales from a few parsecs to hundreds of parsecs, in order to determine the degree of clustering and organization into large-scale features. In addition to the characteristic size of 20 – 60 pc for individual GMC, we find clustering of clouds on a scale of from 100 to 300 pc.
The CO Galactic Plane Survey consists of 40,572 spectral line observations in the region between 1 = 8° to 90° and b = −1°.05 to +1°.05 spaced every 3 arc minutes, carried out with the FCRAO 14-m antenna. The velocity coverage from −100 to +200 km/s includes emission from all galactic radii. This high resolution survey was designed to observe and identify essentially all molecular clouds or cloud components larger than 10 parsecs in the inner galaxy. There are two populations of molecular clouds which separate according to temperature. The warm clouds are closely associated with H II regions, exhibit a non-axisymmetric galactic distribution and are a spiral arm population. The cold clouds are a disk population, are not confined to any patterns in longitude-velocity space and must be widespread in the galaxy both in and out of spiral arms. The correlation between far infrared luminosities from IRAS, and molecular masses from CO is utilized to determine a luminosity to mass ratio for the clouds. A face-on picture of the galaxy locating the warm population is presented, showing ring like or spiral arm features at R ∼ 5, 7.5 and 9 kpc. The cloud size and mass spectrum will be discussed and evidence presented showing the presence of clusters of giant molecular clouds with masses of 106 to 107 M⊙. The two populations of clouds probably have different star forming luminosity functions. The implication of the two populations for star formation mechanisms will be discussed.
The use of millimeter wave CO emission as a tracer of molecular hydrogen in the Galaxy (Scoville and Solomon 1975) showed that most of the H2 unlike HI is concentrated in the inner part of the Galaxy in a “ring” between 4–8 kpc and in the inner 1 kpc. Subsequent surveys (Gordon and Burton 1976, Cohen and Thaddeus 1977, Solomon etal. 1979) confirmed this picture with more extensive data. The molecular interstellar medium was shown to be dominated by Giant Molecular Clouds with individual masses between 105 and 3·106M⊙ (Solomon etal. 1979, Solomon and Sanders 1980). The GMC's confined to a layer with a half thickness of only 60 pc are an important component of the galactic disk, and the most massive objects in the galaxy. They affect the dynamics of the disk by contributing significantly to the surface density and through their individual gravitational interactions with stars.
We propose a physical mechanism to explain the origin of the intense burst of massive-star formation seen in physically colliding/ merging, field, spiral galaxies. We consider the detailed evolution of a realistic, two-component interstellar medium (consisting of H2 and Hi) within each galaxy. Also note that, in a typical spiral galaxy - like our Galaxy, the Giant Molecular Clouds (GMCs) are in a near-virial equilibrium and form the current sites of massive-star formation, but the star formation rate is low. We show that this star formation rate is greatly increased following a collision between galaxies. During a collision between two field spiral galaxies, the Hi clouds from the two galaxies undergo collisions at a relative velocity of ∼ 300 km · s−1. However, the GMCs, with their lower volume filling factor, do not collide. The collisions among the Hi clouds lead to the formation of hot, high-pressure remnant gas. The overpressure due to this hot gas causes a radiative shock compression of the outer layers of pre-existing GMCs in the overlapping wedge region. This triggers a burst of massive-star formation in the initially barely stable GMCs. For details, see Jog and Solomon (1990).
Studies of the central parts of nearby galaxies as well as of distant luminous galaxies, made with the IRAM 30 m telescope, show that the CO 2−1/1−0 ratio is 0.6 ± 0.2. Many galaxies in the distant luminous sample are new detections. In contrast to the distant luminous sample, the galaxy NGC 3147, at cz = 2800 km/s, has a more modest infrared luminosity, but a large mass of molecular gas, which is not concentrated in the center of the galaxy.
The use of 12CO as a mass tracer of H2 in molecular clouds is based on three independent calibrations, all of which agree. The physical basis for an approximately constant molecular (H2) mass to CO luminosity ratio is the origin of the CO emission from gravitationally bound molecular clouds. We discuss the size-line width and virial mass-CO luminosity relations derived from the Massachusetts-Stony Brook CO Survey. The criticisms of the size-line width relation by the Wolfendale group are wrong. Their tests were not self consistent, and were constrained by the properties of the real clouds, not independent of them, as was implied. We show that the virial masses are a reliable measure of the true cloud masses. The CO to H2 conversion factor depends only weakly on molecular cloud parameters, and its value in other spiral galaxies should not be very different from that in the Milky Way. The H2 masses in the centers of galaxies are not overestimated, since the CO excitation is observed to be normal there, and the brightness temperatures not much different from those in the Milky Way. The effect of metallicity on the conversion factor is also briefly discussed.
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.
The contribution of protected areas to biodiversity conservation is well attested but many taxa in many regions remain dependent on the unprotected wider landscape. To develop conservation plans for large mammals such as the Endangered pygmy hippopotamus Choeropsis liberiensis of West Africa's Upper Guinea Forests it is critical to understand the importance of unprotected land. Despite being a conservation priority, little is known about the habitat associations of this species, or its distribution across its range. Through a combination of field surveys, species distribution models and community questionnaires we investigated the use of unprotected areas by the pygmy hippopotamus in the Sierra Leone–Liberia border region. We found signs of the species in 128 of 525 1-km2 cells surveyed. Our analysis suggested that the species is reasonably widespread in this region and is associated with major rivers. It occurred close to, but rarely within, large areas of intact forest, and 80.4% of pygmy hippopotamus signs were recorded outside protected areas. The expansion of the protected area network in this area is unrealistic in Sierra Leone and to some extent in Liberia, mainly because of anthropogenic pressure and the overlap of proposed protected areas with mining and logging concessions. Thus pygmy hippopotamus conservation activities in the region need to include programmes on community lands while maintaining a robust network of protected forests. Community-based conservation of the pygmy hippopotamus may prove valuable for other threatened and endemic species that are not confined to protected areas in this region.
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 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.
We have mapped an extensive molecular cloud in Perseus in the 115 GHz line of 12CO. Observations were made every 10′ in right ascension and declination over most of the cloud, and every 2′ in the regions of most intense emission, near the open cluster IC 348 and near the reflection nebula NGC 1333. We also obtained 110 GHz 13CO data every 2′ in the latter regions, as well as every 10′ in several long strips across the cloud. A total of 812 positions were observed in 12CO, and 200 in 13CO. This work was done using the 5 m antenna of the Millimeter Wave Observatory of the University of Texas. The half-power beam size was 2!6.
The dominant photodissociation process for H2 under interstellar conditions is absorption in the lines of the ultraviolet Lyman bands at 912 Å < λ < 1108 Å and re-emission into the continuum at λ ~ 1600 Å. It is shown that 40% of all upward transitions in this band lead to emission into the continuum of the ground state and therefore dissociation of the molecule. The photodissociation rate is calculated and the theory is developed for the abundance of interstellar H2. It is shown that interstellar space will be divided into atomic and molecular regions in a manner analogous to the division between Hii and Hi regions. The molecular regions will exist only where the rate of formation of H2 is sufficiently great to build up a self-shielding layer. This is expected in cold clouds with number densities greater than 100 atoms cm−3. Normal regions of interstellar space will have an extremely small abundance of molecular hydrogen.
Observations of CO emission at ℓ=0 to 70°, |b| ≤ 1° are analyzed to give a map of the molecular cloud distribution in the galaxy as viewed from the galactic pole. From the fact that this distribution shows no obvious spiral pattern we conclude that the giant molecular clouds sampled in the CO line are situated in both arm and interarm regions and they must last more than 108 years. A similar age estimate is deduced from the large mass fraction of H2 in the interstellar medium in the interior of the galaxy. An implication of this longevity is that the great masses of these clouds may be accumulated through cloud-cloud collisions of originally smaller clouds.