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result(s) for
"Cardona, Charles A"
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Estimating the time of Highly Pathogenic Avian Influenza virus introduction into United States poultry flocks during the 2022/24 epizootic
Following confirmation of the first case of the ongoing U.S. HPAI H5N1 epizootic in commercial poultry on February 8, 2022, the virus has continued to devastate the U.S. poultry sector and the pathogen has since managed to cross over to livestock and a few human cases have also been reported. Efficient outbreak management benefits greatly from timely detection and proper identification of the pathways of virus introduction and spread. In this study, we used changes in mortality rates as a proxy for HPAI incidence in a layer, broiler and turkey flock together with diagnostic test results to infer within-flock HPAI transmission dynamics. Mathematical modeling techniques, specifically the Approximate Bayesian Computation algorithm in conjunction with a stochastic within-flock HPAI transmission model were used in the analysis. The time window of HPAI virus introduction into the flock (TOI) and the adequate contact rate (ACR) were estimated. Then, using the estimated TOI together with the day when the first HPAI positive sample was collected from the flock, we calculated the most likely time to first positive sample (MTFPS) which reflects the time to HPAI detection. The estimated joint (i.e., all species combined) median of the MTFPS for different flocks was six days, the joint median most likely ACR was 6.8 newly infected birds per infectious bird per day, the joint median R 0 was 13 and the joint median number of test days per flock was two. These results were also grouped by species and by epidemic phase and discussed accordingly. We conclude that this findings from this and other related studies are beneficial for the different stakeholders in outbreak management. We recommend that combining TOI analysis with complementary approaches such as phylogenetic analyses is critically important for improved understanding of disease transmission pathways. The estimated parameters can also be used to parametrize mathematical models that can guide the design of surveillance protocols, risk analyses of HPAI spread, and emergency preparedness for HPAI outbreaks.
Journal Article
Predicting the time to detect moderately virulent African swine fever virus in finisher swine herds using a stochastic disease transmission model
Background
African swine fever (ASF) is a highly contagious and devastating pig disease that has caused extensive global economic losses. Understanding ASF virus (ASFV) transmission dynamics within a herd is necessary in order to prepare for and respond to an outbreak in the United States. Although the transmission parameters for the highly virulent ASF strains have been estimated in several articles, there are relatively few studies focused on moderately virulent strains. Using an approximate Bayesian computation algorithm in conjunction with Monte Carlo simulation, we have estimated the adequate contact rate for moderately virulent ASFV strains and determined the statistical distributions for the durations of mild and severe clinical signs using individual, pig-level data. A discrete individual based disease transmission model was then used to estimate the time to detect ASF infection based on increased mild clinical signs, severe clinical signs, or daily mortality.
Results
Our results indicate that it may take two weeks or longer to detect ASF in a finisher swine herd via mild clinical signs or increased mortality beyond levels expected in routine production. A key factor contributing to the extended time to detect ASF in a herd is the fairly long latently infected period for an individual pig (mean 4.5, 95% P.I., 2.4 - 7.2 days).
Conclusion
These transmission model parameter estimates and estimated time to detection via clinical signs provide valuable information that can be used not only to support emergency preparedness but also to inform other simulation models of evaluating regional disease spread.
Journal Article
Octreoscan Versus FDG-PET for Neuroendocrine Tumor Staging: A Biological Approach
Background
Clinicians may order Octreoscan or positron emission tomography (PET) scan for staging patients with neuroendocrine tumors (NETs).
111
In-Octreoscan (Octreoscan) identifies tumors by radiolabeled targeting of somatostatin receptors, while 18F-fluorodeoxyglucose-positron emission tomography (
18
FDG-PET) measures differential tissue glucose transport. We assessed the sensitivity of both nuclear imaging modalities with pathologic correlation to define the best initial choice for NET staging after standard cross-sectional imaging.
Methods
We identified all patients diagnosed with NETs of gastrointestinal or pancreatic origin who underwent nuclear imaging staging by Octreoscan and/or PET from 2000 to 2013. Imaging results were correlated with tumor differentiation and grade of pathology specimens.
Results
Imaging and pathology results were identified for 153 patients. Of these, 131 underwent Octreoscan, 43 underwent PET, and 21 patients had both performed. Overall sensitivity of Octreoscan and PET for NET detection was similar (77 vs. 72 %;
p
= not significant). For well-differentiated NETs, Octreoscan (
n
= 124) demonstrated sensitivity of 80 vs. 60 % (
p
= 0.28) for PET (
n
= 30). For poorly-differentiated NETs, Octreoscan (
n
= 7) proved significantly less sensitive than PET (
n
= 13) (57 vs. 100 %;
p
= 0.02). The sensitivity of Octreoscan versus PET varied similarly when analyzed by WHO tumor grade: Grade 1 (79 vs. 52 %;
p
= 0.16), Grade 2 (85 vs. 86 %;
p
= not significant), and Grade 3 (57 vs. 100 %;
p
= 0.02).
Conclusions
Tumor differentiation can be used to guide selection of nuclear imaging modalities for staging gastrointestinal and pancreatic NETs. Octreoscan appears more sensitive than
18
FDG-PET for well-differentiated NETs, whereas
18
FDG-PET demonstrates superior sensitivity for poorly-differentiated NETs.
Journal Article
Life cycle assessment of integrated additive–subtractive concrete 3D printing
A life cycle assessment (LCA) was conducted on an innovative concrete 3D printing system, offering the following main advantages: (1) additive and subtractive capabilities, allowing for the automated post-processing of printed parts, including operations such as surface polishing, grooving and drilling and (2) the use of a cable robot, which is less expensive, lighter, more transportable, more energy-efficient and more easily reconfigurable than alternatives such as gantry-type systems. The production of a 4-m height structural pillar was assessed, comparing it to production with traditional methods, namely, using a mould. The study included the entire supply chain of the 3D printing equipment, operation and end-of-life, based on real data from the design and operation of a demonstration plant installed in Spain. Data for traditional construction was based on literature and expert judgement. The 3D production process included printing the pillar perimeter in four pieces with 3D printing concrete, transporting to the construction site and reinforcing and casting with conventional concrete. Traditional production involved reinforcing and casting with the mould on-site. The results show that when only one pillar needs to be produced, 3D printing has a lower environmental impact in all the environmental indicators assessed when compared to using a mould that is discarded after a single use. As an example, GHG emissions are lower by 38%. It was also found that the contribution of 3D printing to the environmental impact of producing a pillar is almost negligible, representing less than 1% of the pillar’s total GHG emissions. However, when the same pillar needs to be produced in higher numbers, the results show that 3D printing and conventional production have a similar environmental impact, given that the mould used in conventional production can be reused, becoming a comparatively efficient option.
Journal Article
Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma
Genetically engineered mouse models that employ site-specific recombinase technology are important tools for cancer research but can be costly and time-consuming. The CRISPR-Cas9 system has been adapted to generate autochthonous tumours in mice, but how these tumours compare to tumours generated by conventional recombinase technology remains to be fully explored. Here we use CRISPR-Cas9 to generate multiple subtypes of primary sarcomas efficiently in wild type and genetically engineered mice. These data demonstrate that CRISPR-Cas9 can be used to generate multiple subtypes of soft tissue sarcomas in mice. Primary sarcomas generated with CRISPR-Cas9 and Cre recombinase technology had similar histology, growth kinetics, copy number variation and mutational load as assessed by whole exome sequencing. These results show that sarcomas generated with CRISPR-Cas9 technology are similar to sarcomas generated with conventional modelling techniques and suggest that CRISPR-Cas9 can be used to more rapidly generate genotypically and phenotypically similar cancers.
Site-specific recombination and CRISPR-Cas9 have been used to generate genetically engineered mouse models of cancer. Here the authors compare sarcomas generated using both systems and see similar genetic and cellular phenotypes, suggesting CRISPR-Cas9 can be used to rapidly generate sarcoma models.
Journal Article
Effect of Minimally Invasive Gastrectomy on Return to Intended Oncologic Therapy for Gastric Cancer
Background
Adjuvant chemotherapy offers survival benefit to patients with gastric cancer. Only 50–65% of patients who undergo neoadjuvant chemotherapy and gastrectomy are able to receive adjuvant therapy. It is optimal to start adjuvant therapy within 8 weeks after gastrectomy. We compared the rate of return to intended oncologic therapy (RIOT) between minimally invasive gastrectomy (MIG) and open gastrectomy (OG).
Method
Retrospectively, we analyzed patients who underwent gastrectomy within a multi-hospital university-based health system (2019–2022). Data on patient demographics, comorbid conditions, operative approach, and postoperative outcomes were assessed with univariate analysis and multivariable analysis (MVA) to determine the association with RIOT.
Results
Among 87 eligible patients, 33 underwent MIG and 54 underwent OG. There were no differences in demographics, performance status, comorbid conditions, or type of gastrectomy between the two groups. MIG patients were significantly more likely to RIOT compared with OG patients (87.9% vs. 63%,
p
= 0.003), with 73.1% of MIG patients starting adjuvant therapy within 8 weeks compared with 53.1% of OG patients. Factors associated with higher odds of RIOT included MIG and age <65 years, while major postoperative complications (Clavien–Dindo grade ≥IIIa) was associated with lower odds of RIOT. On MVA, MIG was independently associated with higher odds of RIOT compared with OG (odds ratio 6.05, 95% confidence interval 1.47–24.78,
p
= 0.008).
Conclusion
The minimally invasive approach may benefit patients undergoing gastrectomy, irrespective of the extent of gastric resection for adenocarcinoma. MIG is associated with a higher likelihood of (1) RIOT and (2) starting adjuvant therapy within the optimal time period after gastrectomy.
Journal Article
Maternal control of triploid seed development by the TRANSPARENT TESTA 8 (TT8) transcription factor in Arabidopsis thaliana
The balance between parental genome dosage is critical to offspring development in both animals and plants. In some angiosperm species, despite the imbalance between maternally and paternally inherited chromosome sets, crosses between parental lines of different ploidy may result in viable offspring. However, many plant species, like
Arabidopsis thaliana
, present a post-zygotic reproductive barrier, known as triploid block which results in the inability of crosses between individuals of different ploidy to generate viable seeds but also, in defective development of the seed. Several paternal regulators have been proposed as active players in establishing the triploid block. Maternal regulators known to be involved in this process are some flavonoid biosynthetic (FB) genes, expressed in the innermost layer of the seed coat. Here we explore the role of selected flavonoid pathway genes in triploid block, including
TRANSPARENT TESTA 4
(
TT4
)
, TRANSPARENT TESTA 7
(
TT7
)
, SEEDSTICK
(
STK
)
, TRANSPARENT TESTA 16
(
TT16
)
, TT8
and
TRANSPARENT TESTA 13
(
TT13
). This approach allowed us to detect that
TT8
, a bHLH transcription factor, member of this FB pathway is required for the paternal genome dosage, as loss of function
tt8
, leads to complete rescue of the triploid block to seed development.
Journal Article
Simulated Flock-Level Shedding Characteristics of Turkeys in Ten Thousand Bird Houses Infected with H7 Low Pathogenicity Avian Influenza Virus Strains
Understanding the amount of virus shed at the flock level by birds infected with low pathogenicity avian influenza virus (LPAIV) over time can help inform the type and timing of activities performed in response to a confirmed LPAIV-positive premises. To this end, we developed a mathematical model which allows us to estimate viral shedding by 10,000 turkey toms raised in commercial turkey production in the United States, and infected by H7 LPAIV strains. We simulated the amount of virus shed orally and from the cloaca over time, as well as the amount of virus in manure. In addition, we simulated the threshold cycle value (Ct) of pooled oropharyngeal swabs from birds in the infected flock tested by real-time reverse transcription polymerase chain reaction. The simulation model predicted that little to no shedding would occur once the highest threshold of seroconversion was reached. Substantial amounts of virus in manure (median 1.5×108 and 5.8×109; 50% egg infectious dose) were predicted at the peak. Lastly, the model results suggested that higher Ct values, indicating less viral shedding, are more likely to be observed later in the infection process as the flock approaches recovery.
Journal Article