Methods for increasing customization in rapid machining patient-specific bone implants

This research presents new methods for increasing the customization of the surface characteristics of rapid machined patient-specific bone implants. A bone implant is a medical device that is used for replacing missing or damaged bone tissue in a patient\u27s body. It is possible for a bone implant to have three different types of surfaces (articular, periosteal, fracture) which each require different surface characteristics to help provide biocompatibility. It is also desirable to manufacture implants that are customized specifically for an individual patient to increase the stability and fit of the implant, which has been shown to improve patient healing. A research project at Iowa State University involves developing methods for manufacturing implants using a subtractive rapid manufacturing process called CNC-RP, which combines the automated process planning of rapid prototyping (RP) technologies with the capabilities of 4-axis CNC machining. New methods are proposed for providing more effective setup planning for the CNC-RP process, and for isolating the individual surfaces from one another during machining with the goal of increasing customization while preserving biocompatibility of the implant. The methods were used for performing setup planning for machining a bone implant using a surrogate bone material. It was shown that the methods were effective at increasing the customization of the implant, showing a notable increase in the ability to customize the fracture surface

Turbidity-Based Sediment Monitoring in Northern Thailand: Hysteresis, Variability, and Uncertainty

Annual total suspended solid (TSS) loads in the Mae Sa River in northern Thailand, determined with an automated, turbidity-based monitoring approach, were approximately 62,000, 33,000, and 14,000 Mg during the three years of observation. These loads were equivalent to basin yields of 839 (603-1170), 445 (217-462), and 192 (108-222) Mg km-2 for the 74.16-km2 catchment during 2006, 2007, and 2008, respectively. The yearly uncertainty ranges indicate our loads may be underestimated by 38-43% or overestimated by 28-33%. In determining the annual loads, discharge (Q) and turbidity (T) values were compared against 333 hand-sampled total suspended solid concentrations (TSS) measured during 18 runoff events and other flow conditions across the three-year period. Annual rainfall varied from 1632 to 1934 mm; and catchment runoff coefficients (annual runoff/annual rainfall) ranged from 0.25 to 0.41. Measured TSS ranged from 8-15,900 mg l-1; the low value was associated with dry-season base flow; the latter, a wet-season storm. Storm size and location played an important role in producing clockwise, anticlockwise, and complex hysteresis effects in the Q-TSS relationship. Turbidity alone was a good estimator for turbidity ranges of roughly 10-2800 NTU (or concentrations approximately 25-4000 mg l-1). However, owing to hysteresis and high sediment concentrations that surpass the detection limits of the turbidity sensor during many annual storms, TSS was estimated best using a complex multiple regression equation based on high/low ranges of turbidity and Q as independent variables. Turbidity was not a good predictor of TSS fractions \u3e 2000 μm. Hysteresis in the monthly Q-TSS relationship was generally clockwise over the course of the monsoon season, but infrequent large dry-season storms disrupted the pattern in some years. The large decrease in annual loads during the study was believed to be related to depletion of fine sediment delivered to the stream by several landslides occurring the year prior to the study. The study indicated the importance of monitoring Q and turbidity at fine resolutions (e.g., sub-hourly) to capture the TSS dynamics and to make accurate load estimations in this flashy headwater stream where hysteresis in the Q-TSS signature varied at several time scales

Cost-Effectiveness Model Shows Superiority of Wireless Spinal Cord Stimulation Implantation Without a Separate Trial.

OBJECTIVE: We evaluated the cost-effectiveness of wireless spinal cord stimulation (Wireless SCS) with single stage direct to permanent implantation vs. screening with temporary electrodes and an external pulse generator followed by implantation of a system for long-term use (IPG SCS). MATERIALS AND METHODS: We created a cost model that takes a 2019 United States (U.S.) payer perspective and is based on IPG SCS cost models for subjects with chronic back and/or leg pain. Our six-month decision tree includes the screening trial period (success ≥50% relief) and leads to various levels of pain relief with or without complications for IPG SCS and Wireless SCS and without complications for conventional medical management (CMM). Every three months in the follow-on 15-year Markov model (with costs and quality-adjusted life years discounted 3.5% annually), subjects remain stable or transition to deteriorated health or death. Subjects who fail SCS receive CMM. After 60 Markov cycles, a 100,000-sample simulation reveals the impact of maximum willingness-to-pay (WTP) from $10,000 to$100,000 per quality-adjusted life year on net monetary benefit (NMB). Sensitivity analyses considered the impact of the Wireless SCS screening success rate, Wireless SCS device cost, and IPG SCS device longevity. RESULTS: Compared with IPG SCS, Wireless SCS offers higher clinical effectiveness at a lower cost and a higher NMB for our WTP thresholds and is, thus, dominant. Wireless SCS is also cost-effective compared with CMM. Results remain robust with 1) Wireless SCS screening success rates as low as 85% (dominant), 2) the cost of the Wireless SCS devices as high as $55,000 (cost-effective), and 3) IPG SCS devices lasting 12 years (dominant). CONCLUSIONS: In this model, compared with IPG SCS or with CMM, Wireless SCS is a superior strategy

Genomic and karyotypic variation in Drosophila parasitoids (Hymenoptera, Cynipoidea, Figitidae)

Abstract Drosophila melanogaster Meigen, 1830 has served as a model insect for over a century. Sequencing of the 11 additional Drosophila Fallen, 1823 species marks substantial progress in comparative genomics of this genus. By comparison, practically nothing is known about the genome size or genome sequences of parasitic wasps of Drosophila. Here, we present the first comparative analysis of genome size and karyotype structures of Drosophila parasitoids of the Leptopilina Förster, 1869 and Ganaspis Förster, 1869 species. The gametic genome size of Ganaspis xanthopoda (Ashmead, 1896) is larger than those of the three Leptopilina species studied. The genome sizes of all parasitic wasps studied here are also larger than those known for all Drosophila species. Surprisingly, genome sizes of these Drosophila parasitoids exceed the average value known for all previously studied Hymenoptera. The haploid chromosome number of both Leptopilina heterotoma (Thomson, 1862) and Leptopilina victoriae Nordlander, 1980 is ten. A chromosomal fusion appears to have produced a distinct karyotype for Leptopilina boulardi (Barbotin, Carton et Keiner-Pillault, 1979)(n = 9), whose genome size is smaller than that of wasps of the Leptopilina heterotoma clade. Like Leptopilina boulardi, the haploid chromosome number for Ganaspis xanthopoda is also nine. Our studies reveal a positive, but non linear, correlation between the genome size and total chromosome length in Drosophila parasitoids. These Drosophila parasitoids differ widely in their host range, and utilize different infection strategies to overcome host defense. Their comparative genomics, in relation to their exceptionally well-characterized hosts, will prove to be valuable for understanding the molecular basis of the host-parasite arms race and how such mechanisms shape the genetic structures of insectcommunities

Costs of preparing to implement a virtual reality job interview training programme in a community mental health agency: A budget impact analysis

Rational, aims and objectivesIndividual Placement and Support (IPS) is an evidence based strategy for facilitating employment among adults with severe mental illness (SMI) where staff may lead mock job interviews to prepare clients for real- world interviews (a method with limited scalability and cost effectiveness). A virtual reality job interview training program (VR- JIT)- delivered via the internet- has demonstrated efficacy for increasing employment among adults with SMI. Now, VR- JIT is being implemented with a community mental health agency (CMHA) and evaluated for its effectiveness within IPS. This study is a budget impact analysis, evaluating the costs of preparing a CMHA to implement VR- JIT.MethodImplementation preparation occurred over 7 months from October 1, 2016 to April 30, 2017. CMHA staff (n- =- 15) and external research partners (n- =- 3) tracked their hours completing implementation preparation activities. Salaries plus a 28% fringe benefit rate were used to derive a per- hour salary amount for each individual and applied to each activity. Non- labor equipment costs were obtained from purchase receipts. A budget impact analysis evaluated the expenditures associated with preparing the CMHA to implement VRJIT.ResultsThe total implementation preparation costs equaled $25,482. Labor costs equaled$22,882 and non- labor costs equaled $2,600. In total, 655 person- hours were spent preparing for VR- JIT implementation (e.g., preparing lab space, training, and supervising operations).ConclusionsThis study presents an initial evaluation of the budget impact of preparing to implement VR- JIT in a CMHA. Cost considerations for future implementation preparation will be discussed. Given that the cost to prepare to implement an intervention can hinder its adoption, results provide an important analysis for decision- makers that may enhance uptake. Future work will determine the cost- effectiveness of VR- JIT implemented within IPS. This study is registered at http://clinicaltrials.gov, NCT- =- 03049813, - Virtual Reality Job Interview Training: An Enhancement to Supported Employment in Severe Mental Illness.-Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156238/2/jep13292.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156238/1/jep13292_am.pd

Inter- and Intra-annual Effects of Lethal Removal on Common Raven Abundance in Nevada and California, USA

Populations of common ravens (Corvus corax; ravens) have increased rapidly within sagebrush (Artemisia spp.) ecosystems between 1960 and 2020. Although ravens are native to North America, their population densities have expanded to levels that negatively influence the population dynamics of other wildlife species of conservation concern, such as greater sage-grouse (Centrocercus urophasianus) and desert tortoises (Gopherus agassizii). For this reason, lethal removal, such as the application of the avicide DRC-1339, has been used to manage raven numbers at local scales and under certain circumstances. Because the relative effectiveness of DRC-1339 in reducing raven populations densities is not thoroughly understood, we completed 2 case studies using a before-after-control-impact experimental design of density estimates generated from point count data within a Bayesian hierarchical distance sampling framework. Specifically, we analyzed \u3e16,000 point count surveys collected during 2009–2019 and split into 2 study designs covering multiple field sites within the Great Basin region. The first experiment evaluated intra-annual changes in density by comparing before and after treatment time periods within a single breeding season for multiple treatment regions compared to 2 control regions. The other experiment focused on inter-annual differences by comparing time periods across years before and after the onset of annual avicide application for a single treatment region compared to multiple control regions. Our models estimated a 100% probability of decline in density relative to control sites for both the intra- and inter-annual model designs. At treatment sites, expected densities of ravens varied but were reduced by 43% (95% CRI: 33–49%) and 54% (95% CRI: 24–71%) according to intra- and inter-annual analyses, respectively, whereas densities increased by 42% (95% CRI: 27–60%) and 15% (95% CRI: -17 to 58%) at control sites. Although population densities were reduced with treatments, trends indicated that sustained effort would likely be needed to maintain densities at acceptable levels within regions of interest. Effectively reducing the adverse effects of raven populations on other native species likely will depend on a variety of targeted management actions such as improving habitat quality for prey species, possibly reducing ravens’ population density, and treating the cause of increased raven abundance to reduce future carrying capacity and prevent rebounds

The marine fish food web is globally connected

The productivity of marine ecosystems and the services they provide to humans are largely dependent on complex interactions between prey and predators. These are embedded in a diverse network of trophic interactions, resulting in a cascade of events following perturbations such as species extinction. The sheer scale of oceans, however, precludes the characterization of marine feeding networks through de novo sampling. This effort ought instead to rely on a combination of extensive data and inference. Here we investigate how the distribution of trophic interactions at the global scale shapes the marine fish food web structure. We hypothesize that the heterogeneous distribution of species ranges in biogeographic regions should concentrate interactions in the warmest areas and within species groups. We find that the inferred global metaweb of marine fish—that is, all possible potential feeding links between co-occurring species—is highly connected geographically with a low degree of spatial modularity. Metrics of network structure correlate with sea surface temperature and tend to peak towards the tropics. In contrast to open-water communities, coastal food webs have greater interaction redundancy, which may confer robustness to species extinction. Our results suggest that marine ecosystems are connected yet display some resistance to perturbations because of high robustness at most locations.Using a global interaction dataset, the authors quantify the distribution of trophic interactions among marine fish, finding a high degree of geographic connectivity but low spatial modularity.C.A. was supported by a MELS-FQRNT Postdoctoral Fellowship and a Ressources Aquatique Québec (RAQ) fellowship during the conception and writing of this manuscript. T.P., D.G. and D.B.S. acknowledge financial support by the CIEE through their working group programme. M.B.A. is funded through FCT project No. PTDC/AAG-MAA/3764/2014. A.R.C. is funded by a Natural Sciences and Engineering Research Council of Canada (NSERC) PGS-D scholarship. D.G., T.P., M.-J.F., P.A. and S.J.L. are supported by NSERC Discovery Grants. T.P. also acknowledges a FRQNT New Investigator award and a Université de Montréal starting grant. D.B.S. acknowledges support from the Royal Society of New Zealand (via Marsden Fast-Start No. UOC-1101 and a Rutherford Discovery Fellowship)

A Phase 1 Study of TRC102, An Inhibitor of Base Excision Repair, and Pemetrexed in Patients with Advanced Solid Tumors

Introduction TRC102 potentiates the activity of cancer therapies that induce base excision repair (BER) including antimetabolite and alkylating agents. TRC102 rapidly and covalently binds to apurinic/apyrimidinic (AP) sites generated during BER, and TRC102-bound DNA causes topoisomerase II-dependent irreversible strand breaks and apoptosis. This study assessed the safety, maximum-tolerated dose (MTD), pharmacokinetics and pharmacodynamics of TRC102 alone and in combination with pemetrexed. Purpose Patients with advanced solid tumors received oral TRC102 daily for 4 days. Two weeks later, patients began standard-dose pemetrexed on day 1 in combination with oral TRC102 on days 1 to 4. The pemetrexed-TRC102 combination was repeated every 3 weeks until disease progression. Methods Twenty-eight patients were treated with TRC102 at 15, 30, 60 or 100 mg/m2/d. The MTD was exceeded at 100 mg/m2/d due to grade 3 anemia in 50 % of patients. TRC102 exposure increased in proportion to dose with a mean t1/2 of 28 h. A pharmacodynamic assay confirmed that TRC102 binds to pemetrexed-induced AP sites at all doses studied. Stable disease or better was achieved in 15 of 25 patients evaluable for response (60 %), including one patient with recurrent metastatic oropharyngeal carcinoma that expressed high levels of thymidylate synthase, who achieved a partial response and was progression free for 14 months. Conclusions When administered with pemetrexed, the maximum tolerated dose of oral TRC102 is 60 mg/m2/d for 4 days. Randomized controlled studies are planned to evaluate the clinical benefit of adding TRC102 to pemetrexed and other agents that induce BER. © 2012 Springer Science+Business Media, LLC

Scraping the bottom of the barrel: are rare high throughput sequences artifacts?

Metabarcoding data generated using next-generation sequencing (NGS) technologies are overwhelmed with rare taxa and skewed in Operational Taxonomic Unit (OTU) frequencies comprised of few dominant taxa. Low frequency OTUs comprise a rare biosphere of singleton and doubleton OTUs, which may include many artifacts. We present an in-depth analysis of global singletons across sixteen NGS libraries representing different ribosomal RNA gene regions, NGS technologies and chemistries. Our data indicate that many singletons (average of 38 % across gene regions) are likely artifacts or potential artifacts, but a large fraction can be assigned to lower taxonomic levels with very high bootstrap support (~32 % of sequences to genus with ≥90 % bootstrap cutoff). Further, many singletons clustered into rare OTUs from other datasets highlighting their overlap across datasets or the poor performance of clustering algorithms. These data emphasize a need for caution when discarding rare sequence data en masse: such practices may result in throwing the baby out with the bathwater, and underestimating the biodiversity. Yet, the rare sequences are unlikely to greatly affect ecological metrics. As a result, it may be prudent to err on the side of caution and omit rare OTUs prior to downstream analyses