Today’s industry sectors are filled with machines developed years ago. Healthcare, manufacturing, sustainment operations, and many others have equipment that may be reliable, but lacks certain ...capabilities that the newest technology delivers. The digital environment is becoming a necessity for users who want greater insights into how to improve their processes. A solution to this problem would be to purchase the newest equipment that contains robust measures to generate, collect, and analyze data. However, this solution may not be financially feasible for some and for others may sacrifice machine downtime and reliability. To combat these issues, this research focuses on applying a digital transformation approach to legacy equipment. Collected and analyzed data is used to develop advanced digital tools such as augmented reality, virtual reality, artificial intelligence, and digital dashboards. A use case of Automated Fiber Placement (AFP) is used to showcase the benefits of the digital transformation approach compared to typical controls retrofit. While both approaches result in similar benefits, the owner of the equipment must decide which approach will ensure that the most optimized process. In addition, a use case of military maintenance programs is discussed to provide a logical way ahead for a larger scale implementation of digital transformation. Both use cases show the benefits of the digital transformation approach and help to crystallize what the future of product life cycle management will look like.
We describe a case of cerebral trichomoniasis in a neonate in whom seizures and multiorgan failure developed during treatment for staphylococcal sepsis. Brain abscesses were identified with cranial ...sonography, and Trichomonas vaginalis was isolated from cerebrospinal fluid samples. The patient died despite metronidazole therapy.
Soil dwelling microorganisms are essential components of numerous ecosystem processes and biogeochemical cycles. In particular, they are important actors in terrestrial carbon cycling, producing and ...turning over soil organic matter. Microbially mediated soil carbon cycling can be influenced by environmental conditions, with soil organic matter dynamics and carbon fate varying across biomes. Drastic alterations to soil habitat conditions brought about through anthropogenic changes to land-use (e.g. agriculture) can greatly influence these processes. However, we are limited in our understanding of how land-use regimes and other environmental conditions control microbially mediated soil carbon cycling. I took three approaches to explore this relationship. First, I examined how bacterial community assembly and composition differed across cropland, old-field, and forest soils. I found that homogeneous selection, whereby selection pressure causes bacterial communities to be more phylogenetically similar to each other than expected by random assembly from a metacommunity, was the dominant bacterial community assembly process across all three land-use types. However, I also found that land-use interacted with soil pH to drive the balance between stochastic and deterministic assembly processes. This result indicates a mechanism by which microbial communities may develop differently across land-use regimes. Second, I examined the overall organic matter turnover across land-use regimes and the identity of the bacterial taxa actively involved in this carbon processing. I found that the dynamics of organic matter turnover and the active bacterial populations involved were distinct across land-use regimes. From these patterns I developed a conceptual model explaining how initial microbial biomass, which is impacted by land-use, may control bacterial activities in organic matter turnover. Finally, I examined the genomic basis of bacterial life history strategies, specifically the copiotroph-oligotroph continuum. Life history strategy can explain both bacterial activity in soil carbon cycling and bacterial response to environmental change. I found that the abundance of transcription factor genes and genes encoding a secretion signal peptide were both genomic signatures of the copiotroph-oligotroph continuum. These signatures can be used to classify diverse microbes based on their life history strategy and may further explain the biological drivers of these strategies. I also developed a toolkit, MetaSIPSim, that simulates metagenomic DNA-stable isotope probing datasets. Such datasets can be used to improve metagenomic DNA-stable isotope probing methodologies and analyses, which in turn can be used to link microbial genes and genomes to in situ carbon cycling activity. Overall, this work advances our knowledge of, and ability to study the ecological and biological controls of bacterially mediated soil carbon cycling.
The concept of constitutional construction is of central importance to originalist theory but is both underdeveloped and controversial among originalists. Some object that its apparent open-endedness ...undermines the constraining virtues of originalism and exposes citizens to arbitrary judicial power. In this article, we respond to this challenge by presenting an originalist theory of constitutional construction that can guide and constrain judicial activity within the "construction zone." When combined with an originalist theory of constitutional interpretation, our approach yields a unified theory of originalism.
Our theory of constitutional construction draws upon a familiar common-law concept long used in contract and fiduciary law to handle the problem of opportunistic abuse of discretion: the duty of good faith. We contend that judges who take an oath to "support this Constitution" enter into a fiduciary relationship with private citizens-a relationship characterized by discretionary powers in the hands of judges and a corresponding vulnerability in the citizenry. As fiduciaries, judges are morally and legally bound to follow the instructions given to them in "this Constitution" in good faith. This means that judges engaging in constitutional construction (or "implementation") must seek to give legal effect to both the Constitution's "letter" (its original public meaning) and its "spirit" (the original function or purpose of the particular clauses and general structure of the text). Therefore, when interpretation of original meaning is not sufficient to resolve a controversy, judges have a duty to employ good-faith construction. Good-faith construction consists of (a) accurately identifying the spirit - or "original function" - of the relevant constitutional provision at the time it was enacted and (b) devising implementing rules that are calculated to give effect to both the letter and the spirit of the text in the case at hand and in future cases. Conversely, bad-faith construction consists in opportunistically using the discretion inherent in implementing the Constitution to evade its original letter or spirit in pursuit of the judge's own extraconstitutional preferences.
Growth differentiation factor 15 (GDF15) is a cytokine that reduces food intake through activation of hindbrain GFRAL-RET receptors and has become a keen target of interest for anti-obesity ...therapies. Elevated endogenous GDF15 is associated with energy balance disturbances, cancer progression, chemotherapy-induced anorexia, and morning sickness. We hypothesized that GDF15 causes emesis and that its anorectic effects are related to this function. Here, we examined feeding and emesis and/or emetic-like behaviors in three different mammalian laboratory species to help elucidate the role of GDF15 in these behaviors. Data show that GDF15 causes emesis in Suncus murinus (musk shrews) and induces behaviors indicative of nausea/malaise (e.g., anorexia and pica) in non-emetic species, including mice and lean or obese rats. We also present data in mice suggesting that GDF15 contributes to chemotherapy-induced malaise. Together, these results indicate that GDF15 triggers anorexia through the induction of nausea and/or by engaging emetic neurocircuitry.
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•Chemotherapy-induced sickness involves GDF15•GDF15-GFRAL signaling causes emesis and nausea that precede the onset of anorexia•Anorexia triggered by GDF15 is associated with sickness in both lean and obese rats•GDF15-induced anorexia cannot be dissociated from GDF15-induced sickness
This work assesses whether or not GDF15 produces emesis and/or emetic-like behaviors in the vomiting shrew (Suncus murinus) and non-vomiting rat. The results suggest that exogenous delivery of GDF15 produces either emesis or emetic-like behavior (i.e., pica) prior to the induction of anorexia in shrews and rats, respectively.
To use decision modeling to compare the costs associated with robotic, laparoscopic, and open hysterectomy for the treatment of endometrial cancer.
Three separate models were used, each with ...sensitivity analysis: 1) a societal perspective model, which included inpatient hospital costs, robotic expenses, and lost wages and caregiver costs; 2) a hospital perspective plus robot costs model, which was identical to the societal perspective model but excluded lost wages and caregiver costs; and 3) a hospital perspective without robot costs model, which was identical to the hospital perspective plus robot costs model except that it excluded initial cost of the robot.
The societal perspective model predicted laparoscopy ($10,128) as the least expensive approach followed by robotic and ($11,476) and open hysterectomy ($12,847). Societal perspective model sensitivity analyses predicted robotic hysterectomy to be least expensive when robotic disposable equipment cost less than $1,046 per case (baseline cost $2,394). In the hospital perspective plus robot costs model, laparoscopy was least expensive ($6,581) followed by open ($7,009) and robotic hysterectomy ($8,770); however, if hospital stay after open surgery was less than 2.9 days, open hysterectomy was least expensive. In the hospital perspective without robot costs model, laparoscopy remained least expensive, but robotic surgery became least expensive if the cost of robotic disposable equipment was reduced to less than $1,496 per case.
Laparoscopy is the least expensive surgical approach for the treatment of endometrial cancer. Robotic is less costly than abdominal hysterectomy when the societal costs associated with recovery time are accounted for and is most economically attractive if disposable equipment costs can be minimized.
III.
Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506) administration has been shown to ...hasten recovery and improve functional outcomes after PNI repair. Unfortunately, high systemic levels of FK506 can result in adverse side effects. The localized administration of FK506 could provide the neuroregenerative benefits of FK506 while avoiding systemic, off-target side effects. This study investigates the utility of a novel FK506-impregnated polyester urethane urea (PEUU) nerve wrap to treat PNI in a previously validated rat infraorbital nerve (ION) transection and repair model. ION function was assessed by microelectrode recordings of trigeminal ganglion cells responding to controlled vibrissae deflections in ION-transected and -repaired animals, with and without the nerve wrap. Peristimulus time histograms (PSTHs) having 1 ms bins were constructed from spike times of individual single units. Responses to stimulus onsets (ON responses) were calculated during a 20 ms period beginning 1 ms after deflection onset; this epoch captures the initial, transient phase of the whisker-evoked response. Compared to no-wrap controls, rats with PEUU-FK506 wraps functionally recovered earlier, displaying larger response magnitudes. With nerve wrap treatment, FK506 blood levels up to six weeks were measured nearly at the limit of quantification (LOQ ≥ 2.0 ng/mL); whereas the drug concentrations within the ION and muscle were much higher, demonstrating the local delivery of FK506 to treat PNI. An immunohistological assessment of ION showed increased myelin expression for animals assigned to neurorrhaphy with PEUU-FK506 treatment compared to untreated or systemic-FK506-treated animals, suggesting that improved PNI outcomes using PEUU-FK506 is mediated by the modulation of Schwann cell activity.
Summary Background Bilateral perisylvian polymicrogyria (BPP), the most common form of regional polymicrogyria, causes the congenital bilateral perisylvian syndrome, featuring oromotor dysfunction, ...cognitive impairment, and epilepsy. The causes of BPP are heterogeneous, but only a few genetic causes have been reported. The aim of this study was to identify additional genetic causes of BPP and characterise their frequency in this population. Methods Children (aged ≤18 years) with polymicrogyria were enrolled into our research programme from July, 1980, to October, 2015, at two centres (Florence, Italy, and Seattle, WA, USA). We obtained samples (blood and saliva) throughout this period at both centres and did whole-exome sequencing on DNA from eight trios (two parents and one affected child) with BPP in 2014. After the identification of mosaic PIK3R2 mutations in two of these eight children, we performed targeted screening of PIK3R2 by two methods in a cohort of 118 children with BPP. First, we performed targeted sequencing of the entire PIK3R2 gene by single molecule molecular inversion probes (smMIPs) on 38 patients with BPP with normal to large head size. Second, we did amplicon sequencing of the recurrent PIK3R2 mutation (Gly373Arg) in 80 children with various types of polymicrogyria including BPP. One additional patient had clinical whole-exome sequencing done independently, and was included in this study because of the phenotypic similarity to our cohort. Findings We identified a mosaic mutation (Gly373Arg) in a regulatory subunit of the PI3K-AKT-mTOR pathway, PIK3R2 , in two children with BPP. Of the 38 patients with BPP and normal to large head size who underwent targeted next-generation sequencing by smMIPs, we identified constitutional and mosaic PIK3R2 mutations in 17 additional children. In parallel, one patient had the recurrent PIK3R2 mutation identified by clinical whole-exome sequencing. Seven of these 20 patients had BPP alone, and 13 had BPP in association with features of the megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome. 19 patients had the same mutation (Gly373Arg), and one had a nearby missense mutation (Lys376Glu). Mutations were constitutional in 12 patients and mosaic in eight patients. In patients with mosaic mutations, we noted substantial variation in alternate (mutant) allele levels, ranging from ten (3%) of 377 reads to 39 (37%) of 106 reads, equivalent to 5–73% of cells analysed. Levels of mosaicism varied from undetectable to 37 (17%) of 216 reads in blood-derived DNA compared with 2030 (29%) of 6889 reads to 275 (43%) of 634 reads in saliva-derived DNA. Interpretation Constitutional and mosaic mutations in the PIK3R2 gene are associated with developmental brain disorders ranging from BPP with a normal head size to the MPPH syndrome. The phenotypic variability and low-level mosaicism, which challenge conventional molecular methods, have important implications for genetic testing and counselling. Funding US National Institutes of Health.
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