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"Burns, Brian"
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Our America : a photographic history
\"From one of our most treasured filmmakers, a pictorial history of America-a stunning and moving collection of Ken Burns's favorite photographs\"-- Provided by publisher.
Book
Atlas of tissue- and developmental stage specific gene expression for the bovine insulin-like growth factor (IGF) system
The insulin-like growth factor (IGF) axis is fundamental for mammalian growth and development. However, no comprehensive reference data on gene expression across tissues and pre- and postnatal developmental stages are available for any given species. Here we provide systematic promoter- and splice variant specific information on expression of IGF system components in embryonic (Day 48), fetal (Day 153), term (Day 277, placenta) and juvenile (Day 365-396) tissues of domestic cow, a major agricultural species and biomedical model. Analysis of spatiotemporal changes in expression of IGF1, IGF2, IGF1R, IGF2R, IGFBP1-8 and IR genes, as well as lncRNAs H19 and AIRN, by qPCR, indicated an overall increase in expression from embryo to fetal stage, and decrease in expression from fetal to juvenile stage. The stronger decrease in expression of lncRNAs (average -16-fold) and ligands (average -12.1-fold) compared to receptors (average -5.7-fold) and binding proteins (average -4.3-fold) is consistent with known functions of IGF peptides and supports important roles of lncRNAs in prenatal development. Pronounced overall reduction in postnatal expression of IGF system components in lung (-12.9-fold) and kidney (-13.2-fold) are signatures of major changes in organ function while more similar hepatic expression levels (-2.2-fold) are evidence of the endocrine rather than autocrine/paracrine role of IGFs in postnatal growth regulation. Despite its rapid growth, placenta displayed a more stable expression pattern than other organs during prenatal development. Quantitative analyses of contributions of promoters P0-P4 to global IGF2 transcript in fetal tissues revealed that P4 accounted for the bulk of transcript in all tissues but skeletal muscle. Demonstration of IGF2 expression in fetal muscle and postnatal liver from a promoter orthologous to mouse and human promoter P0 provides further evidence for an evolutionary and developmental shift from placenta-specific P0-expression in rodents and suggests that some aspects of bovine IGF expression may be closer to human than mouse.
Journal Article
Perfusion decellularization of a human limb: A novel platform for composite tissue engineering and reconstructive surgery
Muscle and fasciocutaneous flaps taken from autologous donor sites are currently the most utilized approach for trauma repair, accounting annually for 4.5 million procedures in the US alone. However, the donor tissue size is limited and the complications related to these surgical techniques lead to morbidities, often involving the donor sites. Alternatively, recent reports indicated that extracellular matrix (ECM) scaffolds boost the regenerative potential of the injured site, as shown in a small cohort of volumetric muscle loss patients. Perfusion decellularization is a bioengineering technology that allows the generation of clinical-scale ECM scaffolds with preserved complex architecture and with an intact vascular template, from a variety of donor organs and tissues. We recently reported that this technology is amenable to generate full composite tissue scaffolds from rat and non-human primate limbs. Translating this platform to human extremities could substantially benefit soft tissue and volumetric muscle loss patients providing tissue- and species-specific grafts. In this proof-of-concept study, we show the successful generation a large-scale, acellular composite tissue scaffold from a full cadaveric human upper extremity. This construct retained its morphological architecture and perfusable vascular conduits. Histological and biochemical validation confirmed the successful removal of nuclear and cellular components, and highlighted the preservation of the native extracellular matrix components. Our results indicate that perfusion decellularization can be applied to produce human composite tissue acellular scaffolds. With its preserved structure and vascular template, these biocompatible constructs, could have significant advantages over the currently implanted matrices by means of nutrient distribution, size-scalability and immunological response.
Journal Article
Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow-up of eight patients
Cluster headache is a form of primary headache that features repeated attacks of excruciatingly severe headache usually occurring several times a day. Patients with chronic cluster headache have unremitting illness that necessitates daily preventive medical treatment for years. When medically intractable, the condition has previously been treatable only with cranially invasive or neurally destructive methods.
Eight patients with medically intractable chronic cluster headache were implanted in the suboccipital region with electrodes for occipital nerve stimulation. Other than the first patient, who was initially stimulated unilaterally before being stimulated bilaterally, all patients were stimulated bilaterally during treatment.
At a median follow-up of 20 months (range 6–27 months for bilateral stimulation), six of eight patients reported responses that were sufficiently meaningful for them to recommend the treatment to similarly affected patients with chronic cluster headache. Two patients noticed a substantial improvement (90% and 95%) in their attacks; three patients noticed a moderate improvement (40%, 60%, and 20–80%) and one reported mild improvement (25%). Improvements occurred in both frequency and severity of attacks. These changes took place over weeks or months, although attacks returned in days when the device malfunctioned (eg, with battery depletion). Adverse events of concern were lead migrations in one patient and battery depletion requiring replacement in four.
Occipital nerve stimulation in cluster headache seems to offer a safe, effective treatment option that could begin a new era of neurostimulation therapy for primary headache syndromes.
Journal Article
Improving access to extracorporeal membrane oxygenation for out of hospital cardiac arrest: pre-hospital ECPR and alternate delivery strategies
Background
The use of extracorporeal membrane oxygenation (ECPR) in refractory out-of-hospital cardiac arrest (OHCA) patients is usually implemented in-hospital. As survival in ECPR patients is critically time-dependent, alternative models in ECPR delivery could improve equity of access.
Objectives
To identify the best strategy of ECPR delivery to provide optimal patient access, to examine the time-sensitivity of ECPR on predicted survival and to model potential survival benefits from different delivery strategies of ECPR.
Methods
We used transport accessibility frameworks supported by comprehensive travel time data, population density data and empirical cardiac arrest time points to quantify the patient catchment areas of the existing in-hospital ECPR service and two alternative ECPR strategies: rendezvous strategy and pre-hospital ECPR in Sydney, Australia. Published survival rates at different time points to ECMO flow were applied to predict the potential survival benefit.
Results
With an in-hospital ECPR strategy for refractory OHCA, five hospitals in Sydney (Australia) had an effective catchment of 811,091 potential patients. This increases to 2,175,096 under a rendezvous strategy and 3,851,727 under the optimal pre-hospital strategy. Assuming earlier provision of ECMO flow, expected survival for eligible arrests will increase by nearly 6% with the rendezvous strategy and approximately 26% with pre-hospital ECPR when compared to the existing in-hospital strategy.
Conclusion
In-hospital ECPR provides the least equitable access to ECPR. Rendezvous and pre-hospital ECPR models substantially increased the catchment of eligible OHCA patients. Traffic and spatial modelling may provide a mechanism to design appropriate ECPR service delivery strategies and should be tested through clinical trials.
Journal Article
Alfentanil versus fentanyl for emergency department rapid sequence induction with ketamine: A-FAKT, a pilot randomized trial
Fentanyl is often administered during rapid sequence induction of anesthesia (RSI) in the emergency department (ED) to ameliorate the hypertensive response that may occur. Due to its more rapid onset, the use of alfentanil may be more consistent with both the onset time of the sedative and the commencement of laryngoscopy. As such, we compared the effect of alfentanil and fentanyl on post-induction hemodynamic changes when administered as part of a standardized induction regimen including ketamine and rocuronium in ED RSI.
This was a double-blind pilot randomized controlled trial of adult patients requiring RSI in the ED of three urban Australian hospitals. Patients were randomized to receive either alfentanil or fentanyl in addition to ketamine and rocuronium for RSI. Non-invasive blood pressure and heart rate were measured immediately before and at two, four, and six minutes after induction. The primary outcome was the occurrence of at least one post-induction systolic blood pressure outside the pre-specified range of 100-160mmHg (with adjustment for patients with baseline hypertension). Secondary outcomes included hypertension, hypotension, hypoxia, first-pass intubation success, 30-day mortality, and the pattern of hemodynamic changes.
A total of 61 patients were included in the final analysis (31 in the alfentanil group and 30 in the fentanyl group). The primary outcome was met in 58% of the alfentanil group and 50% of the fentanyl group (difference 8%, 95% confidence interval: -17% to 33%). The 30-day mortality rate, first-pass success rate, and incidences of hypertension, hypotension, and hypoxia were similar between the groups. There were no significant differences in systolic blood pressure or heart rate between the groups at any of the measured time-points.
Alfentanil and fentanyl produced comparable post-induction hemodynamic changes when used as adjuncts to ketamine in ED RSI. Future studies could consider comparing different dosages of these opioids.
Journal Article
Towards multi-breed genomic evaluations for female fertility of tropical beef cattle
Developing accurate genomic evaluations of fertility for tropical beef cattle must deal with at least two major challenges 1) recording cow fertility traits in extensive production systems on large numbers of cows and 2) the genomic evaluations should work across the breeds, crossbreds and composites used in tropical beef production. Here we assess accuracy of genomic evaluations for a trait which can be collected on a large scale in extensive conditions, Corpus Luteum score (CLscore), which is 1 if ovarian scanning indicates a heifer has cycled by 600 days and 0 if not, in a multi-breed population. A total of 3696 heifers, including 979 Brahmans, 914 Droughtmasters and 1803 Santa Gertrudis in 7 herds across three year cohorts with CLscores were genotyped for 24,211 SNP. Genotypes were imputed to 728,785 SNP. GBLUP and BayesR were used to predict genomic estimated breeding values (GEBV). Accuracy of GEBV was evaluated with two validation strategies. In the first strategy, the last year cohort of heifers from each herd was used for validation, such that every herd had heifers in both reference and validation populations. In the second validation strategy, each herd in turn was removed in its entirety from the reference population, and was used for validation. For both validation strategies, accuracy of GEBV for single breed and multi-breed reference populations was assessed. For the first validation strategy, accuracy of GEBV ranged from 0.2 for Brahmans to 0.4 for Droughtmasters. Increasing marker density from 24K SNP to 728K SNP resulted in a small increase in accuracy, and including multiple-breeds in the reference did not help improve accuracy. These results suggest that provided a herd has animals in the reference population, the accuracy of the GEBV is largely determined by within herd (linkage) information. The situation was very different when entire herds were predicted in the second validation. In this case accuracy of GEBV using only 24K SNP and only a within breed reference, was close to zero for all breeds. Accuracy increased substantially when 728K SNP, BayesR, and a multi-breed reference was used, to 0.15 for Brahmans to 0.35 for Santa Gertrudis. Given the second validation strategy is more likely to reflect the situation for many herds in tropical beef production (no animals in the reference), genomic evaluations for fertility in tropical beef cattle should be based on high density markers (728K SNP) and should be multi-breed.
Journal Article
Use of whole-genome sequence data and novel genomic selection strategies to improve selection for age at puberty in tropically-adapted beef heifers
In tropically-adapted beef heifers, application of genomic prediction for age at puberty has been limited due to low prediction accuracies. Our aim was to investigate novel methods of pre-selecting whole-genome sequence (WGS) variants and alternative analysis methodologies; including genomic best linear unbiased prediction (GBLUP) with multiple genomic relationship matrices (MGRM) and Bayesian (BayesR) analyses, to determine if prediction accuracy for age at puberty can be improved.
Journal Article
Concurrently mapping quantitative trait loci associations from multiple subspecies within hybrid populations
Many of the world’s agriculturally important plant and animal populations consist of hybrids of subspecies. Cattle in tropical and sub-tropical regions for example, originate from two subspecies, Bos taurus indicus (Bos indicus) and Bos taurus taurus (Bos taurus). Methods to derive the underlying genetic architecture for these two subspecies are essential to develop accurate genomic predictions in these hybrid populations. We propose a novel method to achieve this. First, we use haplotypes to assign SNP alleles to ancestral subspecies of origin in a multi-breed and multi-subspecies population. Then we use a BayesR framework to allow SNP alleles originating from the different subspecies differing effects. Applying this method in a composite population of B. indicus and B. taurus hybrids, our results show that there are underlying genomic differences between the two subspecies, and these effects are not identified in multi-breed genomic evaluations that do not account for subspecies of origin effects. The method slightly improved the accuracy of genomic prediction. More significantly, by allocating SNP alleles to ancestral subspecies of origin, we were able to identify four SNP with high posterior probabilities of inclusion that have not been previously associated with cattle fertility and were close to genes associated with fertility in other species. These results show that haplotypes can be used to trace subspecies of origin through the genome of this hybrid population and, in conjunction with our novel Bayesian analysis, subspecies SNP allele allocation can be used to increase the accuracy of QTL association mapping in genetically diverse populations.
Journal Article