Disease and its consequences result in social and economic impacts to the US animal livestock industry, ranging from losses in human capital to economic costs in excess of a billion dollars annually. ...Impacts would dramatically escalate if a devastating disease like Foot and Mouth Disease or African Swine Fever virus were to emerge in the United States. Investing in preventative biosecurity can reduce the likelihood of disease incursions and their negative impact on our livestock industry, yet uncertainty persists with regards to developing an effective biosecurity structure and culture. Here we show the implications of human behavior and decision making for biosecurity effectiveness, from the operational level to the owner/managerial level and finally to the systems level. For example, adjustments to risk messaging strategies could double worker compliance with biosecurity practices at the operational level. The improvement of our risk communication strategy may increase willingness to invest in biosecurity. Furthermore, the adaptation of policies could nudge behavior so that we observe a short disease outbreak followed by a quick eradication instead of a pandemic. Our research shows how the emergence of nowendemic diseases, such as Porcine Epidemic Diarrhea virus, cannot be adequately modeled without the use of a human behavioral component. Focusing solely on any one sector or level of the livestock system is not sufficient to predict emergent disease patterns and their social and economic impact on livestock industries. These results provide insight toward developing more effective risk mitigation strategies and ways to nudge behavior toward more disease resilient systems.
This article investigates the invisibility of Roma communities within Scottish census ethnic monitoring categories and broader empirical data. Consistent negative stereotyping as well as systematic ...oppression within social policy, dominant discourses, and data collection processes excludes Roma from participatorycitizenship. This article identifies precise forms of marginality and invisibility within official government data – permeated through social and education policy – that thereby limit the effective targeting of resources to marginalized communities. Specifically, the article argues that omitting Roma as an ethnic category from past data gathering processes limits understanding of the commonalities and differences within and amongScottish communities, rendering entire populations invisible within broader empirical data and therefore restricting both identification of needs and effective resource allocation. Thus, the article presents a timely argument for the inclusion of Roma as an ethnic category in the 2021 Scottish census, while addressingissues within the census approach to data collection – including the impending digitization of the process. Through discussing and advancing the case for the inclusion of Romani communities in the 2021 Scottish Census, the paper also seeks to establish the current social context by chronicling the history of Romanimigration and marginalization within Europe.
We searched for an optimized protocol for mapping observations from a point spectrometer onto a shape model composed of triangular facets, in the context of NASA's asteroid sample return mission, ...OSIRIS‐REx (Origins, Spectral Interpretation, Resource Identification, and Security‐Regolith Explorer). Our study was conducted before the spacecraft arrived at the mission target asteroid (101955) Bennu, and we used observational sequence plans of the OSIRIS‐REx Visible and InfraRed Spectrometer (OVIRS). We explored six methods of mapping data to shape model facets, using three spatial resolutions. We attempted to boost map fidelity by increasing the observational coverage of the surface. We find that increasing shape model resolution improves mapping quality. However, once the shape model's mean facet edge length is smaller than two‐fifths of the diameter of the instrument's field of view (FOV), the increase in quality tapers off. The six mapping methods can be broken into two categories: facets that (1) select or (2) combine (average) data from observations. The quality differences between similar averaging methods (clipped average, weighted average, etc.) are insignificant. Selecting the nearest observation to a facet best preserves an enclosed outcrop's shape and signal, but averaging spots are more conservative against errors in photometric modeling. A completely enclosed outcrop border expands into the surrounding region by 0.8–1.5 radii of the instrument's FOV. Regions smaller than the instrument's FOV are present in resulting maps; however, their signal strength is reduced as a function of their size relative to the instrument FOV.
Key Points
Spectral map quality is controlled by shape model facet size, boresight spot size, and method of assigning spot data to facets
Shape models with facet edges smaller than 2/5 the boresight spot diameter cease to improve map fidelity
Data selection algorithms perform better than data combination methods for mapping distinct outcrops
Autism spectrum disorder (ASD) is a genetically heterogeneous condition, caused by a combination of rare de novo and inherited variants as well as common variants in at least several hundred genes. ...However, significantly larger sample sizes are needed to identify the complete set of genetic risk factors. We conducted a pilot study for SPARK (SPARKForAutism.org) of 457 families with ASD, all consented online. Whole exome sequencing (WES) and genotyping data were generated for each family using DNA from saliva. We identified variants in genes and loci that are clinically recognized causes or significant contributors to ASD in 10.4% of families without previous genetic findings. In addition, we identified variants that are possibly associated with ASD in an additional 3.4% of families. A meta-analysis using the TADA framework at a false discovery rate (FDR) of 0.1 provides statistical support for 26 ASD risk genes. While most of these genes are already known ASD risk genes,
has the strongest statistical support and reaches genome-wide significance as a risk gene for ASD (
-value = 2.3e-06). Future studies leveraging the thousands of individuals with ASD who have enrolled in SPARK are likely to further clarify the genetic risk factors associated with ASD as well as allow accelerate ASD research that incorporates genetic etiology.
Hybrid algorithms in quantum Monte Carlo Kim, Jeongnim; Esler, Kenneth P; McMinis, Jeremy ...
Journal of physics. Conference series,
01/2012, Letnik:
402, Številka:
1
Journal Article
Recenzirano
Odprti dostop
With advances in algorithms and growing computing powers, quantum Monte Carlo (QMC) methods have become a leading contender for high accuracy calculations for the electronic structure of realistic ...systems. The performance gain on recent HPC systems is largely driven by increasing parallelism: the number of compute cores of a SMP and the number of SMPs have been going up, as the Top500 list attests. However, the available memory as well as the communication and memory bandwidth per element has not kept pace with the increasing parallelism. This severely limits the applicability of QMC and the problem size it can handle. OpenMP/MPI hybrid programming provides applications with simple but effective solutions to overcome efficiency and scalability bottlenecks on large-scale clusters based on multi/many-core SMPs. We discuss the design and implementation of hybrid methods in QMCPACK and analyze its performance on current HPC platforms characterized by various memory and communication hierarchies.
Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not ...been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings,
fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- vs. SST-positive interneurons. We find that there are robust molecular differences in synapse-associated genes between these neuron types, and that individual presynaptic pyramidal neurons evoke postsynaptic responses with heterogeneous synaptic dynamics in different postsynaptic cell types. Using molecular identification with FISH and classifiers based on transcriptomically identified PVALB neurons analyzed by Patch-seq, we find that PVALB neurons typically show depressing synaptic characteristics, whereas other interneuron types including SST-positive neurons show facilitating characteristics. Together, these data support the existence of target cell-specific synaptic properties in human cortex that are similar to rodent, thereby indicating evolutionary conservation of local circuit connectivity motifs from excitatory to inhibitory neurons and their synaptic dynamics.
Key points
Night time/active phase food restriction for 6 h impaired glucose intolerance in young male and female mice.
Females displayed increased capacity for lipogenesis and triglyceride storage ...in response to a short daily fast.
Females had lower fasting insulin levels and an increased potential for utilizing fat for energy through β‐oxidation compared to males.
The need for the inclusion of both sexes, and the treatment of sex as an independent variable, is emphasized within the context of this fasting regime.
There is growing interest in understanding the mechanistic significance and benefits of fasting physiology in combating obesity. Increasing the fasting phase of a normal day can promote restoration and repair mechanisms that occur during the post‐absorptive period. Most studies exploring the effect of restricting food access on mitigating obesity have done so with a large bias towards the use of male mice. Here, we disentangle the roles of sex, food intake and food withdrawal in the response to a short‐term daily fasting intervention, in which food was removed for 6 h in the dark/active phase of young, 8‐week‐old mice. We showed that the removal of food during the dark phase impaired glucose tolerance in males and females, possibly due to the circadian disruption induced by this feeding protocol. Although both sexes demonstrated similar patterns of food intake, body composition and various metabolic markers, there were clear sex differences in the magnitude and extent of these responses. While females displayed enhanced capacity for lipogenesis and triglyceride storage, they also had low fasting insulin levels and an increased potential for utilizing available energy sources such as fat for energy through β‐oxidation. Our results highlight the intrinsic biological and metabolic disparities between male and female mice, emphasizing the growing need for the inclusion of both sexes in scientific research. Furthermore, our results illustrate sex‐specific metabolic pathways that regulate lipogenesis, obesity and overall metabolic health.
Key points
Night time/active phase food restriction for 6 h impaired glucose intolerance in young male and female mice.
Females displayed increased capacity for lipogenesis and triglyceride storage in response to a short daily fast.
Females had lower fasting insulin levels and an increased potential for utilizing fat for energy through β‐oxidation compared to males.
The need for the inclusion of both sexes, and the treatment of sex as an independent variable, is emphasized within the context of this fasting regime.
Abstract
OBJECTIVE
To evaluate the safety and feasibility of combining resection with immediate initiation of radiation and subsequent Stupp protocol in newly-diagnosed glioblastoma (GBM).
BACKGROUND
...Rapid early local progression (REP) after resection, prior to the initiation of EBRT+/-chemotherapy, occurs in 25-50%. This high-rate of REP supports initiation of an effective postoperative treatment as early as safely possible. Bio-resorbable collagen tiles with imbedded cesium-131 radiation sources (Gammatiles™) are FDA cleared for this use. Intraoperatively, tiles are placed within the resection bed, thus achieving an immediate initiation of surgically targeted radiation therapy (STaRT). DESIGN/
METHODS
GESTALT is a single-arm 61 patient multi-center trial. Consented adults with suspected or confirmed GBM undergo a maximum safe resection with Gammatile™ (STaRT). Patients with molecular GBM (WHO 2021 criteria) start concurrent EBRT/Temozolomide beginning 25±4 days post-surgery. Subsequent EBRT (20 fractions, 4 weeks) to low and high-risk PTV takes Gammatile™ dose into account to a combined biologically equivalent dose of 46 and 60 Gy delivered in 2Gy/fraction, respectively. Adjuvant TMZ (6 cycles) begins 28±7 days after EBRT/Temozolomide. TTF is allowed. IDH-mutated gliomas are followed for safety. Outcomes include feasibility of incorporating Gammatile™ without delay of Stupp protocol, consent/attrition rates, safety, performance status trajectory (ECOG, KPS), immune competence (absolute lymphocyte counts), local control, PFS, and OS.
RESULTS
The trial opened in Fall 2022 at 4 sites. 12 additional sites are onboarding (NCT05342883). 16 patients are on trial as of abstract submission. Currently, this trial appears feasible and without any unexpected intolerances/toxicities.
CONCLUSIONS
This is the first trial in newly diagnosed GBM patients to combine resection, Gammatile™, and the Stupp protocol, in an attempt to reduce REP, as well as possibly, improve other outcomes.
RESULTS
will inform the routine and investigational use of Gammatile™, and if suggestive, will form the basis for a subsequent randomized trial.
•Aneurysmal hemodynamics are helpful in treatment planning and prediction.•In vitro models can validate patient-specific computational simulations of aneurysms.•Dimensionally-accurate, ...optically-transparent phantoms can be done by 3D printing.•Such models may inform optimal patient-specific neurointerventional strategies.
Perianeurysmal hemodynamics play a vital role in the initiation, growth and rupture of intracranial aneurysms. In vitro investigations of aneurysmal hemodynamics are helpful to visualize and measure blood flow, and aiding surgical planning approaches. Improving in vitro model creation can improve the feasibility and accuracy of hemodynamic investigations and surgical planning, improving clinical value. In this study, in vitro models were created from three-dimensional rotational angiography (3DRA) of six patients harboring intracranial aneurysms using a multi-step process involving 3D printing, index of refraction matching and silicone casting that renders the models transparent for flow visualization. Each model was treated with the same commercially-available, patient-specific, endovascular devices (coils and/or stents). All models were scanned by synchrotron X-ray microtomography to obtain high-resolution imaging of the vessel lumen, aneurysmal sac and endovascular devices. Dimensional accuracy was compared by quantifying the differences between the microtomographic reconstructions of the fabricated phantoms and the original 3DRA obtained during patient treatment. True-scale in vitro flow phantoms were successfully created for all six patients. Optical transparency was verified by using an index of refraction matched working fluid that replicated the mechanical behavior of blood. Synchrotron imaging of vessel lumen, aneurysmal sac and endovascular devices was successfully obtained, and dimensional errors were found to be O(100 μm). The creation of dimensionally-accurate, optically-transparent flow phantoms of patient-specific intracranial aneurysms is feasible using 3D printing technology. Such models may enable in vitro investigations of aneurysmal hemodynamics to aid in treatment planning and outcome prediction to devise optimal patient-specific neurointerventional strategies.
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