Positive control materials for clinical diagnostic molecular genetic testing are in critically short supply. High-quality DNA that closely resembles DNA isolated from patient specimens can be ...obtained from Epstein-Barr virus (EBV)-transformed peripheral blood lymphocyte cell lines. Here we report the development of a process to (a) recover residual blood samples with clinically important mutations detected during routine medical care, (b) select samples likely to provide viable lymphocytes for EBV transformation, (c) establish stable cell lines and confirm the reported mutation(s), and (d) validate the cell lines for use as positive controls in clinical molecular genetic testing applications.
A network of 32 genetic testing laboratories was established to obtain anonymous, residual clinical samples for transformation and to validate resulting cell lines for use as positive controls. Three panel meetings with experts in molecular genetic testing were held to evaluate results and formulate a process that could function in the context of current common practices in molecular diagnostic testing.
Thirteen laboratories submitted a total of 113 residual clinical blood samples with mutations for 14 genetic disorders. Forty-one EBV-transformed cell lines were established. Thirty-five individual point and deletion mutations were shown to be stable after 20 population doublings in culture. Thirty-three cell lines were characterized for specific mutations and validated for use as positive controls in clinical diagnostic applications.
A process for producing and validating positive control cell lines from residual clinical blood samples has been developed. Sustainable implementation of the process could help alleviate the current shortage of positive control materials.
In vivo studies of jaw-muscle behavior have been integral factors in the development of our current understanding of the primate masticatory apparatus. However, even though it has been shown that ...food textures and mechanical properties influence jaw-muscle activity during mastication, very little effort has been made to quantify the relationship between the elicited masticatory responses of the subject and the mechanical properties of the foods that are eaten. Recent work on human mastication highlights the importance of two mechanical properties-toughness and elastic modulus (i.e., stiffness)-for food breakdown during mastication. Here we provide data on the toughness and elastic modulus of the majority of foods used in experimental studies of the nonhuman primate masticatory apparatus. Food toughness ranges from approximately 56.97 Jm-2 (apple pulp) to 4355.45 Jm-2 (prune pit). The elastic modulus of the experimental foods ranges from 0.07 MPa for gummy bears to 346 MPa for popcorn kernels. These data can help researchers studying primate mastication select among several potential foods with broadly similar mechanical properties. Moreover, they provide a framework for understanding how jaw-muscle activity varies with food mechanical properties in these studies.
Introduction The selection of an optimal pacing strategy during cycling largely influences the success or failure of the performance (Hettinga et al., 2012). Trained athletes are proposed to develop ...experience-primed, stable pacing schemas which are robust even in deceptive conditions (Beedie 2012; Mauger). However, pacing decisions made continuously during performance are informed by both internal and external factors (Renfree 2014), therefore unexpected environmental events (e.g. competitors’ behaviour) are likely to challenge the initially planned pacing strategy. This study aimed to explore 1) the accuracy of cyclists’ pacing strategy predictions prior to 16.1 km time trials (TT), and 2) whether the accuracy of these predictions differs between ride-alone and competitive conditions. Methods Twenty-seven trained male cyclists with 16.1 km TT experience performed three laboratory-based TTs on a CompuTrainer ergometer. Following a baseline TT, participants rode a ride-alone TT (ALONE) and a competitive TT (COMP) in a counterbalanced order. During COMP, participants performed against a simulated virtual avatar that depicted the speed profile of their baseline performance. Prior to each trial, participants used a pace forecasting tool to predict their speed profile over each distance quartile of the TT. Immediately post-trial, a retrospective account of their perceived speed profile was also recorded. Results COMP (M = 26.43 ± 1.32 mins) was performed in a significantly faster time than ALONE (M = 26.74 ± 1.61) (p = .005). There were no significant differences between predicted, actual and post-trial perceptions of speed profile at any distance quartile in the ALONE TT (Figure 1). In the COMP TT, both predicted (p = .012) and post-trial perceived pace (p = 0.001) were significantly slower than actual pace at 8 km. At 16.1 km, predicted pace was significantly faster than actual pace (p = .003) (Figure 2). Discussion When performing a ride-alone 16.1 km TT, trained cyclists are able to accurately predict their pacing strategy. They can also accurately perceive what strategy they performed following the TT. However, when performing a TT in the presence of a competitor, cyclists exerted a faster than predicted speed at 8 km and consequently performed slower than predicted in the final quartile, due to premature fatigue as a result of a faster mid-section. Furthermore, cyclists believed that this drop in pace at 8 km was greater than what it actually was in their retrospective perception. Despite pace deviating from the pre-trial planned strategy in COMP, this trial was performed faster than the ALONE trial suggesting that this deviation was beneficial for performance. These findings support the robustness of trained cyclists’ pacing schemas in individual performance conditions but the presence of a competitor results in a deviation from this schema. Pacing decisions are therefore influenced by external cues and a competitor may allow cyclists to tap into an otherwise unused reserve capacity to produce an enhanced performance.
Using the ongoing NIDDK-funded multicenter randomized clinical trial, Sphincterotomy for Acute Recurrent Pancreatitis (SHARP) as an example, this article discusses the rationale and key aspects of ...study design that need to be considered when conducting a clinical trial of endoscopic therapy in acute pancreatitis. SHARP, the first trial using a sham ERCP in the placebo group, is designed to address a decades long controversy in clinical pancreatology, i.e. whether minor papilla sphincterotomy benefits patients with idiopathic acute recurrent pancreatitis who also have pancreas divisum. Although the trial has already enrolled and randomized over 5 times the number of subjects enrolled in the only randomized trial in this area published in 1992 (107 vs. 19), recruitment has been challenging and we are at ∼46% of target recruitment. The review discusses the challenges in the execution of the trial and strategies the SHARP team has used to address these, which investigators planning or considering treatment trials in pancreatitis may find helpful. It will also inform the general gastroenterologists the importance of discussing and referring potentially eligible subjects to centers participating in clinical trials. Developing evidence-based treatment will provide a solid scientific basis for physicians to recommend evidence-based treatments for pancreatitis.
•Cyclic behavior of ZK60 Mg alloy cast prior to and after forging process is studied.•Microstructure modification after forging leads to better fatigue response.•Forged alloy asymmetric fatigue ...behavior is due to the induced sharp basal texture.•ZnZr2 and MgZn2 intermetallics are main source of crack initiation.•An energy-based fatigue life model closely estimated the cyclic life.
The fatigue behavior of as-cast and cast-forged ZK60 magnesium alloy was investigated via fully-reversed strain controlled fatigue tests at different strain amplitudes. Microstructure analysis, texture measurement, and SEM fracture surface characterization were performed to discern the reason of fatigue behavior improvement via forging, and also to explain the mechanism underlying crack initiation in both cast and cast-forged conditions. It was perceived that the forged alloy contains less amount of porosities and second phase particles in its microstructure. In general, the forged alloy showed longer fatigue life for all strain amplitudes, especially when the strain amplitude is lower than 0.4%. The forging process increased the fatigue strength at 107 cycles from 0.175% to 0.22% strain amplitude. The microstructure obtained after fatigue test showed that twinning can be activated in the cast-forged alloy, once strain amplitude is higher than 0.4%. The interaction of twin bands with the grain boundaries can also adversely affect the fatigue life of the forged alloy. Also, the residual twins can develop tensile mean stress which affects the fatigue life negatively. Finally, the Coffin-Manson fatigue model and an energy-based fatigue model were employed to model the life of as-cast and cast-forged materials. While some of the predicted lives by the former were out of the ±2× boundary bounds, the latter’s results were tightly clustered in ±1.5× bounds.
The rate of movement for 3- and 10-cm-high granule ripples was documented in September of 2006 at Great Sand Dunes National Park and Preserve during a particularly strong wind event. Impact creep ...induced by saltating sand caused ∼24 granules min
−1 to cross each cm of crest length during wind that averaged ∼9
m
s
−1 (at a height well above 1
m), which is substantially larger than the threshold for saltation of sand. Extension of this documented granule movement rate to Mars suggests that a 25-cm-high granule ripple should require from hundreds to thousands of Earth-years to move 1
cm under present atmospheric conditions.
We present the first multi-wavelength follow-up observations of two candidate gravitational-wave (GW) transient events recorded by LIGO and Virgo in their 2009-2010 science run. The events were ...selected with low latency by the network of GW detectors (within less than 10 minutes) and their candidate sky locations were observed by the Swift observatory (within 12 hr). Image transient detection was used to analyze the collected electromagnetic data, which were found to be consistent with background. Off-line analysis of the GW data alone has also established that the selected GW events show no evidence of an astrophysical origin; one of them is consistent with background and the other one was a test, part of a "blind injection challenge." With this work we demonstrate the feasibility of rapid follow-ups of GW transients and establish the sensitivity improvement joint electromagnetic and GW observations could bring. This is a first step toward an electromagnetic follow-up program in the regime of routine detections with the advanced GW instruments expected within this decade. In that regime, multi-wavelength observations will play a significant role in completing the astrophysical identification of GW sources. We present the methods and results from this first combined analysis and discuss its implications in terms of sensitivity for the present and future instruments.
Experiments conducted at the National Ignition Facility using shaped laser pulses with more than 1 MJ of energy have demonstrated the ability to control the implosion symmetry under ignition ...conditions. To achieve thermonuclear ignition, the low mode asymmetries must be small to minimize the size of the hotspot. The symmetry tuning experiments use symmetry capsules, "symcaps", which replace the DT fuel with an equivalent mass of CH to emulate the hydrodynamic behavior of an ignition capsule. The x-ray self-emission signature from gas inside the capsule during the peak compression correlates with the surrounding hotspot shape. By tuning the shape of the self-emission, the capsule implosion symmetry can be made to be "round." In the experimental results presented here, we utilized crossbeam energy transfer S. H. Glenzer, et al., Science 327, 1228 (2010) to change the ratio of the inner to outer cone power inside the hohlraum targets on the NIF. Variations in the ratio of the inner cone to outer cone power affect the radiation pattern incident on the capsule modifying the implosion symmetry.
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