Custom Biomedical FAIR Data Analysis in the Cloud Using CAVATICA.

The historically fragmented biomedical data ecosystem has moved towards harmonization under the findable, accessible, interoperable, and reusable (FAIR) data principles, creating more opportunities for cloud-based research. This shift is especially opportune for scientists across diverse domains interested in implementing creative, nonstandard computational analytic pipelines on large and varied datasets. However, executing custom cloud analyses may present difficulties, particularly for investigators lacking advanced computational expertise. Here, we present an accessible, streamlined approach for the cloud compute platform CAVATICA that offers a solution. We outline how we developed a custom workflow in the cloud, for analyzing whole genome sequences of case-parent trios to detect sex-specific genetic effects on orofacial cleft risk, which required several programming languages and custom software packages. The approach involves just three components: Docker to containerize software environments, tool creation for each analysis step, and a visual workflow editor to weave the tools into a Common Workflow Language (CWL) pipeline. Our approach should be accessible to any investigator with basic computational skills, is readily extended to implement any scalable high-throughput biomedical data analysis in the cloud, and is applicable to other commonly used compute platforms such as BioData Catalyst. We believe our approach empowers versatile data reuse and promotes accelerated biomedical discovery in a time of substantial FAIR data.

Implementation of a pharmacist-provided pharmacogenomics service in an executive health program.

PURPOSE: We describe the implementation of a pharmacist-provided pharmacogenomics (PGx) service in an executive health program (EHP) at an academic medical center. SUMMARY: As interest in genomic testing grows, pharmacists have the opportunity to advance the use of PGx in EHPs, in collaboration with other healthcare professionals. In November 2018, a pharmacist-provided PGx service was established in the EHP at the University of Colorado Hospital. The team members included 3 physicians, a pharmacist trained in PGx, a registered dietitian/exercise physiologist, a nurse, and 2 medical assistants. We conducted 4 preimplementation steps: (1) assessment of the patient population, (2) selection of a PGx test, (3) establishment of a visit structure, and (4) selection of a billing model. The PGx consultations involved two 1-hour visits. The first visit encompassed pretest PGx education, review of the patient's current medications and previous medication intolerances, and DNA sample collection for genotyping. After this visit, the pharmacist developed a therapeutic plan based on the PGx test results, discussed the results and plan with the physician, and created a personalized PGx report. At the second visit, the pharmacist reviewed the PGx test results, personalized the PGx report, and discussed the PGx-guided therapeutic plan with the patient. Overall, the strategy worked well; minor challenges included evaluation of gene-drug pairs with limited PGx evidence, communication of information to non-EHP providers, scheduling issues, and reimbursement. CONCLUSION: The addition of a PGx service within an EHP was feasible and provided pharmacists the opportunity to lead PGx efforts and collaborate with physicians to expand the precision medicine footprint at an academic medical center.

Decreased bacterial growth on titanium nanoscale topographies created by ion beam assisted evaporation.

Titanium is one of the most widely used materials for orthopedic implants, yet it has exhibited significant complications in the short and long term, largely resulting from poor cell-material interactions. Among these many modes of failure, bacterial infection at the site of implantation has become a greater concern with the rise of antibiotic-resistant bacteria. Nanostructured surfaces have been found to prevent bacterial colonization on many surfaces, including nanotextured titanium. In many cases, specific nanoscale roughness values and resulting surface energies have been considered to be "bactericidal"; here, we explore the use of ion beam evaporation as a novel technique to create nanoscale topographical features that can reduce bacterial density. Specifically, we investigated the relationship between the roughness and titanium nanofeature shapes and sizes, in which smaller, more regularly spaced nanofeatures (specifically 40-50 nm tall peaks spaced ~0.25 µm apart) were found to have more effect than surfaces with high roughness values alone.

Recent coating developments for combination devices in orthopedic and dental applications: A literature review.

Orthopedic and dental implants have been used successfully for decades to replace or repair missing or damaged bones, joints, and teeth, thereby restoring patient function subsequent to disease or injury. However, although device success rates are generally high, patient outcomes are sometimes compromised due to device-related problems such as insufficient integration, local tissue inflammation, and infection. Many different types of surface coatings have been developed to address these shortcomings, including those that incorporate therapeutic agents to provide localized delivery to the surgical site. While these coatings hold enormous potential for improving device function, the list of requirements that an ideal combination coating must fulfill is extensive, and no single coating system today simultaneously addresses all of the criteria. Some of the primary challenges related to current coatings are non-optimal release kinetics, which most often are too rapid, the potential for inducing antibiotic resistance in target organisms, high susceptibility to mechanical abrasion and delamination, toxicity, difficult and expensive regulatory approval pathways, and high manufacturing costs. This review provides a survey of the most recent developments in the field, i.e., those published in the last 2-3years, with a particular focus on technologies that have potential for overcoming the most significant challenges facing therapeutically-loaded coatings. It is concluded that the ideal coating remains an unrealized target, but that advances in the field and emerging technologies are bringing it closer to reality. The significant amount of research currently being conducted in the field provides a level of optimism that many functional combination coatings will ultimately transition into clinical practice, significantly improving patient outcomes.

An organoselenium compound inhibits Staphylococcus aureus biofilms on hemodialysis catheters in vivo.

Colonization of central venous catheters (CVCs) by pathogenic bacteria leads to catheter-related bloodstream infections (CRBSIs). These colonizing bacteria form highly antibiotic-resistant biofilms. Staphylococcus aureus is one of the most frequently isolated pathogens in CRBSIs. Impregnating CVC surfaces with antimicrobial agents has various degrees of effectiveness in reducing the incidence of CRBSIs. We recently showed that organoselenium covalently attached to disks as an antibiofilm agent inhibited the development of S. aureus biofilms. In this study, we investigated the ability of an organoselenium coating on hemodialysis catheters (HDCs) to inhibit S. aureus biofilms in vitro and in vivo. S. aureus failed to develop biofilms on HDCs coated with selenocyanatodiacetic acid (SCAA) in either static or flowthrough continuous-culture systems. The SCAA coating also inhibited the development of S. aureus biofilms on HDCs in vivo for 3 days. The SCAA coating was stable and nontoxic to cell culture or animals. This new method for coating the internal and external surfaces of HDCs with SCAA has the potential to prevent catheter-related infections due to S. aureus.

In vivo evaluation of hydroxyapatite coatings of different crystallinities.

PURPOSE: The influence of calcium phosphate (CaP) and hydroxyapatite (HA) crystallinity on bone-implant osseointegration is not well established. In this study, the effect of HA crystallinity and coating method on bone-implant osseointegration was investigated using a rat tibia model. MATERIALS AND METHODS: HA coatings 1 to 5 microm thick were produced using a supersonic particle acceleration (SPA) technology. The HA crystallinities used for this study were weight ratios of 30%, 50%, 70%, and 90%. A total of 128 HA-coated implants were placed into the tibiae of 64 male Sprague-Dawley rats. Bone-implant interfaces were evaluated using histology and push-out strength testing at 3 and 9 weeks after implantation. RESULTS: The 70% crystalline coatings exhibited significantly greater interfacial strength (5 implants/time point/treatment) than the 30%, 50%, and 90% crystalline coatings at 3 and 9 weeks following implantation. The implants with coatings of 70% crystallinity also had the greatest bone contact length. In addition, the HA coatings produced with SPA demonstrated greater interfacial strength and bone contact length than plasma-sprayed HA coatings (except for the HA coating with 30% crystallinity). DISCUSSION: HA coatings of different crystallinities exhibited different dissolution and re-precipitation properties which may enhance early bone formation and bone bonding. CONCLUSIONS: This study suggested that coating crystallinity and coating methods can influence the bone-implant interface.

Large bore catheters with surface treatments versus untreated catheters for vascular access in hemodialysis.

Infection, thrombosis, and stenosis are among the most frequent complications associated with blood-contacting catheters. Complications resulting from infection remain a major problem for hemodialysis catheters, with significant numbers of catheters being removed due to catheter-related sepsis. Numerous strategies have been employed to reduce the occurrence of infection and im-prove long-term outcomes, with varying degrees of success. The most important is the careful and sterile handling by the attending staff of the catheters during hemodialysis treatments to minimize or stop a microbial colonization of the skin and the catheter. Another approach is coating the external surface of the catheters with substances which are antibacterial like silver and/or substances with low thrombogenicity like silicone. This investigation reviews results of animal and clinical experiments conducted to assess the efficacy and biocompatibility of silver and silicone coated dialysis catheters. It is concluded that silver coatings can reduce bacterial colonization and occurrence of infection associated with these devices. The catheters employing ion implantation of silicone rubber showed low thrombogenicity. Results of the studies indicate that ion beam based processes can be used to improve thrombus and infection resistance of blood contacting catheters. A new development is the microdomain structured surface (PUR-SMA coated catheters). Preliminary results with these catheters are very encouraging.

Silver coating of dialysis catheters to reduce bacterial colonization and infection.

Complications resulting from infection remain a major problem for hemodialysis catheters, with significant numbers of catheters being removed due to catheter-related sepsis. Numerous strategies have been employed to reduce the occurrence of infection and improve long-term outcomes, with varying degrees of success. One promising approach is coating the external surface of catheters with silver using physical vapor deposition processes. This article reviews results of animal and clinical experiments conducted to assess efficacy and biocompatibility of silver-coated dialysis catheters. It is concluded that silver coatings can reduce bacterial colonization and occurrence of infection associated with these devices.