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Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
Grotesque and vulgar, the masked character Gongoli upends the codes of Mende decorum in his madcap pursuit of laughs. His impropriety goes so far as to allow his mask to fall, comically revealing the identity of his dancer and subverting the anonymity so elemental to his fellow spirits’ vaunted status. Yet despite such transgressions, he stands among the most beloved figures of Sierra Leone's rich performance traditions. Gongoli's popularity hinges on his irreverence towards the fundamental laws of masked dance, laws that also regulate the balance between individual agency and communal responsibility, between internal desire and external restraint. The only quality necessary to play Gongoli is shamelessness (ngufe baa), and the greatest performers are acrobats braving risks that are not physical, but social. This article follows Siloh, an itinerant performer whose celebrity inheres in his uncanny similarity to the Gongoli he often plays. The composite figure Siloh Gongoli exemplifies a comic aesthetic relished throughout Sierra Leone in storytelling, ritual, festivals, videos and radio shows. Although mobilized for different ends, each of these conventions undermines principles of self-effacement, gerontocratic privilege and esoteric power by shamelessly playing with and within the existential tensions between interior and exterior selves.
Daily acquisitions from satellite microwave sensors can be used to observe the spatial and temporal characteristics of the Arctic sea-ice snowmelt onset because the initial presence of liquid water in a dry snowpack causes a dramatic change in the active-and passive-microwave response. A daily sequence of backscatter coefficient images from the NASA scatterometer (NSCAT) clearly shows the spatially continuous progression of decreasing backscatter associated with snowmelt onset across the Arctic Ocean during spring 1997. A time series of the active NSCAT backscatter and a scattering index from the passive Special Sensor Microwave/Imager (SSM/I) show similar trends during the time of the melt onset. An NSCATsnowmelt-onset detection algorithm is developed using the derivative of the backscatter with respect to time to select a melt-onset date for each pixel, generating a melt map for the Arctic sea ice. Comparison between this melt map and one previously generated from an SSM/I scattering index shows the NSCAT algorithm predicts the onset occurs 1−10 days earlier than the SSM/I-based algorithm for most portions of multi-year ice.
Climate models suggest surface warming in the Arctic will be rapid and pronounced, implying substantial changes in snowmelt onset are likely. This research therefore examines spatial and temporal variability in passive-microwave derived snow-melt-onset dates over Arctic sea ice. The objectives are to understand better the regional characteristics of snowmelt and to document whether the snowmelt-onset record shows signs of climate change. Snowmelt-onset dates are derived with Scanning Multichannel Microwave Radiometer and Special Sensor Microwave/Imager brightness-temperature data, and they are subsequently stratified into 13 regions to analyze spatial and temporal variability. Results illustrate significant spatial variability in snowmelt onset, with the median annual snowmelt-onset date in one region of the Arctic typically being statistically different from most other regions. The examination of temporal variability also shows large interannual differences in the median snowmelt-onset date in most regions. Additionally, trends towards earlier snowmelt onset are documented in the West Central Arctic, Lincoln Sea, Beaufort Sea and Canadian Arctic Archipelago regions.
The snowmelt-onset date represents an important transitional point in the Arctic surface energy balance, when albedo decreases and energy absorption increases rapidly in response to the appearance of liquid water. Interannual variations in snowmelt onset are likely related to large-scale variations in atmospheric circulation, such as described by the Arctic Oscillation (AO). This research therefore examines the relationship between monthly-averaged AO values and mean annual snowmelt-onset dates over Arctic sea ice in 13 regions, from 1979 to 1998. The objective is to statistically relate variations in mean annual regional snowmelt-onset dates to variations in the AO. Additionally, monthly-averaged 500 hPa heights and 2 m air temperatures are used to illustrate a physical link between snow-melt onset and a positive AO phase. Regression analyses demonstrate that variations in the AO explain a significant portion of the variations in snowmelt onset in the West Central Arctic, Laptev Sea, East Siberian Sea, Hudson Bay and Baffin Bay. Synoptic analyses suggest earlier (later) than average snowmelt onset occurs where warm (cold) air advection and increased (decreased) cyclonic activity are present.
Planning for a response to threats like pandemics or mass casualty events is a national priority. The US blood supply system can be particularly vulnerable to such events. It is important to understand the impacts of emergency situations on blood availability and the resiliency of the US blood supply system.
On the basis of the Stock-and-Flow simulation model of the US blood supply system, we developed an inter-regional blood transfer system representing the action of multiple blood collectors and distributors to enable effective planning of strategies to minimize collection and donation disruptions to the blood supply system in the event of a national emergency.
We simulated a pandemic or mass casualty event on both a national and an inter-regional blood supply system. Differences in the estimated impacts demonstrated the importance of incorporating spatial and temporal variations of blood collection and utilization across US regions. The absence of blood shortage in both emergency scenarios highlighted the resilience of the inter-regional system to meet the potential associated blood demand.
Our inter-regional model considered complex factors and can be a valuable tool to assist regulatory decision-making and strategic planning for emergency preparedness to avoid and mitigate associated adverse health consequences. (Disaster Med Public Health Preparedness. 2018;12:201–210)
Objectives: This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. Methods: Participants were children with traumatic brain injury (N=82; 8–13 years of age), arterial ischemic stroke (N=36; 6–16 years of age), and brain tumor (N=74; 9–18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children’s Version (TEA-Ch) subtests: Creature Counting, Walk-Don’t-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. Results: As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. Conclusions: Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529–538)
Farming can be shown to have spread very rapidly across the British Isles and southern Scandinavia around 6000 years ago, following a long period of stasis when the agricultural ‘frontier’ lay further south on the North European Plain between northern France and northern Poland. The reasons for the delay in the adoption of agriculture on the north-west fringe of Europe have been debated by archaeologists for decades. Here, we present fresh evidence that this renewed phase of agricultural expansion was triggered by a significant change in climate. This finding may also have implications for understanding the timing of the expansion of farming into some upland areas of southern and mid-latitude Europe.
Although the formation and melt of sea ice are primarily functions of the
annual radiation cycle, atmospheric sensible-heat forcing does serve to
delay or advance the timing of such events. Additionally, if atmospheric
conditions in the Arctic were to vary due to climate change it may have
significant influence on ice conditions. Therefore, this paper investigates
a methodology to determine melt-onset dale distribution, both spatially and
temporally, in the Arctic Ocean and surrounding sea-ice covered regions.
Melt determination is made by a threshold technique using the spectral
signatures of the horizontal brightness temperatures (19 GHz horizontal
channel minus the 37 GHz horizontal channel) obtained from the Special
Sensor Microwave Imager (SSM/I) passive-microwave sensor. Passive-microwave
observations are used to identify melt because of the large increase in
emissivity that occurs when liquid water is present. Emissivity variations
are observed in the brightness temperatures due to the different scattering,
absorption and penetration depths of the snowpack from the available
satellite channels during melt. Monitoring the variations in the brightness
temperatures allows the determination of melt-onset dates.
Analysis of daily brightness temperature data allows spatial variations in
the date of the snow inch onset for sea ice to be detected. Since the data
are gridded on a daily basis, a climatology of daily melt-onset dates can be
produced for the Arctic region. From this climatology, progression of melt
can be obtained and compared inter-annually.
The ablation of sea ice is an important feature in the global climate system. During the melt season in the Arctic, rapid changes occur in sea-ice surface conditions and areal extent of ice. These changes alter the albedo and vary the energy budgets. Understanding the spatial and temporal variations of melt is critical in the polar regions. This study investigates the spring onset of melt in the seasonal sea-ice zone of the Arctic Basin through the use of a melt signature derived by Anderson and others from the Nimbus-7 Scanning Multichannel Microwave Radiometer (SMMR) data. The signature is recognized in the “gradient ratio” of the 18 and 37 GHz vertical brightness temperatures used to distinguish multi-year ice. A spuriously high fraction of multi-year ice appears rapidly during the initial melt of sea ice, when the snow-pack on the ice surface has started to melt. The brightness-temperature changes are a result of either enlarged snow crystals or incipient puddles forming at the snow/ice interface.
The timing of these melt events varies geographically and with time. Within the Arctic Basin, the melt signatures are observed first in the Chukchi and Kara/Barents Seas. As the melt progresses, the location of the melt signature moves westward from the Chukchi Sea and eastward from the Kara/Barents Seas to the Laptev Sea region. The timing of the melt signal also varies with year. For example, the melt signature occurred first in the Chukchi Sea in 1979, while in 1980 the signature was first observed in the Kara Sea.
There are also differences in the timing of melt for specific geographic locations between years. The melt signature varied almost 25 days in the Chukchi Sea region between 1979 and 1980. The other areas had changes in the 7–10 day range.
The occurrence of these melt signatures can be used as an indicator of climate variability in the seasonal sea-ice zones of the Arctic. The timing of the microwave melt signature has also been examined in relation to melt observed on short-wave imagery. The melt events derived from the SMMR data are also related to the large-scale climate conditions.