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Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community.

PURPOSE: The purpose of this study was to evaluate the use of an AI conversational agent during the postoperative recovery of patients undergoing elective hip arthroscopy. METHODS: Patients undergoing hip arthroscopy were enrolled in a prospective cohort for their first 6 weeks following surgery. Patients used standard SMS text messaging to interact with an artificial intelligence (AI) chatbot (“Felix”) used to initiate automated conversations regarding elements of postoperative recovery. Patient satisfaction was measured at 6 weeks after surgery using a Likert scale survey. Accuracy was determined by measuring the appropriateness of chatbot responses, topic recognition, and examples of confusion. Safety was measured by evaluating the chatbot’s responses to any questions with potential medical urgency. RESULTS: Twenty-six patients were enrolled with a mean age of 36 years, and 58% (n = 15) were male. Overall, 80% of patients (n = 20) rated the helpfulness of Felix as good or excellent. In the postoperative period, 12/25 (48%) patients reported being worried about a complication but were reassured by Felix and, thus, did not seek medical attention. Of a total of 128 independent patient questions, Felix handled 101/128 questions appropriately (79%), either by addressing them independently, or facilitating contact with the care team. Felix was able to adequately answer the patient question independently 31% of the time (n = 40/128). Of 10 patient questions that were thought to potentially represent patient complications, in 3 cases Felix did not adequately address or recognize the health concern—none of these situations resulted in patient harm. CONCLUSION: The results of this study demonstrate that the use of a chatbot or conversational agent can enhance the postoperative experience for hip arthroscopy patients, as demonstrated by high levels of patient satisfaction. LEVELS OF EVIDENCE: Level IV, therapeutic case series.

Summary Oculocutaneous albinism (OCA) encompasses a set of autosomal recessive genetic conditions that affect pigmentation in the eye, skin, and hair. OCA patients display reduced best-corrected visual acuity, reduced to absent ocular pigmentation, abnormalities in fovea development, and/or abnormal decussation of optic nerve fibers. It has been hypothesized that improving eye pigmentation could prevent or rescue some of the vision defects. The goal of the present study was to develop an in vitro model for studying pigmentation defects in human retinal pigment epithelium (RPE). We developed a “disease in a dish” model for OCA1A and OCA2 types using induced pluripotent stem cells to generate RPE. The RPE is a monolayer of cells that are pigmented, polarized, and polygonal in shape, located between the neural retina and choroid, with an important role in vision. Here we show that RPE tissue derived in vitro from OCA patients recapitulates the pigmentation defects seen in albinism, while retaining the apical-basal polarity and normal polygonal morphology of the constituent RPE cells., Graphical abstract, Highlights • We established a human iPSC-based in vitro model for oculocutaneous albinism (OCA) • iRPE derived from OCA-iPSC retains apical-basal polarity and polygonal morphology • OCA-iRPE recapitulates the pigmentation defect seen in albinism • Excess pre-melanosomes and scarce mature melanosomes are found in OCA-iRPE, In this article, Brooks and colleagues establish an iPSC-derived retinal pigment epithelium (iRPE) model of two forms of oculocutaneous albinism, OCA1A and OCA2. Both OCA-iRPE monolayers are morphologically normal, albeit with differences in cellular phenotypes. Pigmentation and melanosome content are abnormal. OCA-iRPE models will help with dissecting the pathways underlying abnormalities in visual system development in albinism and devising novel treatments.

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × ∼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

Background Outpatient peripherally inserted central catheters (PICC) use has grown without standardized protocols for their management. We assessed the impact of a mobile app strategy for outpatient CLABSI prevention using photo-monitoring, assessment, and response to lines with local inflammation/infection in a cohort of cancer clinic patients. Methods This prospective cohort study evaluated adults with PICCs at an academic cancer clinic at baseline (7/2015–12/2016) and after implementing the SAFER (Standardizing Assessment For Effective Response) Lines program (intervention 5/2017–11/2018). This included a mobile app enabling (1) clinic assessment of localized inflammation or infection defined as Central Line Insertion Site Assessment (CLISA) score 2 or 3, respectively (Table 1), (2) photo-documentation, and (3) score-based automated physician alerts for remote response. We assessed demographics, malignancy type, and line characteristics. Generalized linear mixed effects model assessed program impact on frequency of CLISA 2 or 3 lines, clustered by patient. Cox proportional hazards and Kaplan Meier models assessed days to line removal after CLISA 2 or 3 were identified. Results Among 4,894 assessments of 528 PICCs in 380 outpatients, there were 272 lines (199 patients) at baseline and 256 lines (181 patients) after SAFER program implementation. Mean age, gender, PICC dwell time, and history of prior PICC were similar at baseline and intervention. The proportion of inflamed (CLISA 2) and infected (CLISA 3) lines decreased 40% (from 26% to 16%, and 19% to 11%, respectively) during intervention compared to baseline. Lines with peeling dressings decreased 80% (from 46% to 9%). Mean days to removal of inflamed lines decreased 59% (from 19 to 8 days); removal of infected lines decreased 85% (from 11 to < 2 days). Intervention was associated with 46% lower risk of local inflammation/infection (OR 0.46, CI=0.26–0.83, p< 0.01, Table 2) and faster line removal when such lines were identified (HR 0.18, CI=0.12–0.27, p< 0.01). Conclusion The SAFER Lines mobile app and program decreased the frequency of locally inflamed or infected PICC insertion sites and increased the speed of removal when local inflammation/infection was found in cancer clinic patients. Disclosures Raheeb Saavedra, AS, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products|Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products|Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products Raveena D. Singh, MA, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products|Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products|Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products Susan S. Huang, MD, MPH, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products|Molnlyke: Conducted clinical studies in which hospitals received contributed antiseptic product|Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products|Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic product.

Aims As the peak of the COVID-19 pandemic passes, the challenge shifts to safe resumption of routine medical services, including elective orthopaedic surgery. Protocols including pre-operative self-isolation, COVID-19 testing, and surgery at a non-COVID-19 site have been developed to minimize risk of transmission. Despite this, it is likely that many patients will want to delay surgery for fear of contracting COVID-19. The aim of this study is to identify the number of patients who still want to proceed with planned elective orthopaedic surgery in this current environment. Methods This is a prospective, single surgeon study of 102 patients who were on the waiting list for an elective hip or knee procedure during the COVID-19 pandemic. Baseline characteristics including age, ASA grade, COVID-19 risk, procedure type, surgical priority, and admission type were recorded. The primary outcome was patient consent to continue with planned surgical care after resumption of elective orthopaedic services. Subgroup analysis was also performed to determine if any specific patient factors influenced the decision to proceed with surgery. Results Overall, 58 patients (56.8%) wanted to continue with planned surgical care at the earliest possibility. Patients classified as ASA I and ASA II were more likely to agree to surgery (60.5% and 60.0%, respectively) compared to ASA III and ASA IV patients (44.4% and 0.0%, respectively) (p = 0.01). In addition, patients undergoing soft tissue knee surgery were more likely to consent to surgery (90.0%) compared to patients undergoing primary hip arthroplasty (68.6%), primary knee arthroplasty (48.7%), revision hip or knee arthroplasty (0.0%), or hip and knee injections (43.8%) (p = 0.03). Conclusion Restarting elective orthopaedic services during the COVID-19 pandemic remains a significant challenge. Given the uncertain environment, it is unsurprising that only 56% of patients were prepared to continue with their planned surgical care upon resumption of elective services. Cite this article: Bone Joint Open 2020;1-6:267–271.

The CLEAR trial demonstrated that a multi-site body decolonization regimen reduced post-discharge infection and hospitalization in methicillin-resistant Staphylococcus aureus (MRSA) carriers. This report describes decolonization efficacy in clearing site-specific MRSA colonization during the trial.We performed a large, multi-center, randomized clinical trial of MRSA decolonization among adult patients after hospital discharge with MRSA infection or colonization. Participants were randomized 1:1 to either MRSA prevention education or education plus decolonization with 4% topical chlorhexidine daily, 0.12% oral chlorhexidine rinse twice daily, and 2% nasal mupirocin twice daily. The intervention was given for five consecutive days twice monthly. Participants were swabbed in the nares, throat, axilla/groin, and wound (if applicable) at baseline, 1, 3, 6, and 9 months after randomization. The primary outcomes of this report are follow-up colonization differences between groups.Among 2,121 participants, 1,058 were randomized to the decolonization group. By one month, MRSA colonization was lower in the decolonization group compared to the education only group (OR = 0.44 [95% Confidence Interval 0.36-0.54, p≤0.001). Similar magnitude of reduction was seen in the nares (OR = 0.34 [0.27-0.42], p 0.001) throat (OR = 0.55 [0.42-0.73], p 0.001), and axilla/groin (OR = 0.57 [0.43-0.75], p 0.001). These differences persisted through month 9 except at the wound site, which had a relatively small sample size. Higher regimen adherence was associated with lower MRSA colonization (p≤0.01).In a randomized clinical trial, a repeated post-discharge decolonization regimen for MRSA carriers reduced MRSA colonization overall and at multiple body sites. Higher treatment adherence was associated with greater reductions in MRSA colonization.

Background Nursing home (NH) residents are at high infection and hospital readmission risk. Colonization with multidrug-resistant organisms (MDROs) is common. In ICU and post-hospital discharge settings, decolonization has reduced infection rates. However, the effectiveness of this strategy in NHs is unclear. Methods We performed a cluster randomized trial of 1:1 universal decolonization (decol) vs standard of care bathing (control) in 28 California NHs. After an 18 month baseline evaluation of hospitalization rates due to infection and MDRO prevalence, NHs were randomized to decol or control. Decol consisted of 1) chlorhexidine bathing; 2) nasal povidone iodine bid on admission x 5d and then M-F biweekly x 18 mo. Primary outcome was the probability that a transfer to a hospital was due to infection. Secondary outcome was the probability that a NH discharge was to a hospital. Results Four of 28 NHs dropped from the trial (3 decol, 1 control). Mean facility baseline of hospital transfers due to infection was 58% and 57% in the control and decol groups. In the intervention period, proportions were 57% and 48% in the control and decol groups. When accounting for clustering within NHs, hospital transfers due to infection had an OR of 0.91 (95% CI: 0.82-1.02) in the control group and an OR of 0.73 (95% CI: 0.56-0.95) in the decol group when comparing intervention to baseline period. For the primary outcome, decol had a 18% greater impact v. control (P=0.005, Fig. A). Baseline proportion of NH discharges due to hospitalization was 37% and 39% in the control and decol groups. In the intervention period, proportions were 36% and 33%. When accounting for clustering within NHs, the proportion of discharges due to hospitalization had an OR of 1.14 (95% CI: 1.06-1.22) in the control group and 0.91 (CI: 0.77-1.07) in the decol group when comparing the intervention period to the baseline period. For the secondary outcome, decol had a 23% greater impact v. control (P< 0.0001, Fig. B). In this figure, each nursing home is represented by a circle. The size of the circle represents the amount of contributed patient days to the trial. The groups represent “as randomized” categories. Panel A) compares the probability that a transfer to a hospital was due to infection; panel B) compares the probability that a nursing home discharge was to a hospital. The y-axis represents the odds ratio of these probabilities comparing the baseline to the intervention period. The p values represent the significance of the difference between groups (the trial effect). Conclusion Universal NH decolonization with chlorhexidine and nasal iodophor significantly reduced the proportion of transfers to hospitals due to infection and discharges due to hospitalization. Our findings suggest that NH decolonization reduces serious infections and can decrease morbidity in this vulnerable population. Disclosures Loren G. Miller, MD, MPH, Medline (Grant/Research Support, Other Financial or Material Support, Contributed product) Stryker (Other Financial or Material Support, Contributed product) Xttrium (Other Financial or Material Support, Contributed product) James A. McKinnell, MD, Medline (Grant/Research Support) Raveena Singh, MA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Gabrielle Gussin, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Raheeb Saavedra, AS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Lauren Heim, MPH, Medline (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of personal epigenomes, for ∼25 tissues and >10 assays in four donors (>1500 open-access functional genomic and proteomic datasets, in total). Each dataset is mapped to a matched, diploid personal genome, which has long-read phasing and structural variants. The mappings enable us to identify >1 million loci with allele-specific behavior. These loci exhibit coordinated epigenetic activity along haplotypes and less conservation than matched, non-allele-specific loci, in a fashion broadly paralleling tissue-specificity. Surprisingly, they can be accurately modelled just based on local nucleotide-sequence context. Combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci and enables models for transferring known eQTLs to difficult-to-profile tissues. Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

Battery performance is strongly correlated with electrode microstructure. Electrode materials for lithium-ion batteries have complex microstructure geometries that require millions of degrees of freedom to solve the electrochemical system at the microstructure scale. A fast-iterative solver with an appropriate preconditioner is then required to simulate large representative volume in a reasonable time. In this work, a finite element electrochemical model is developed to resolve the concentration and potential within the electrode active materials and the electrolyte domains at the microstructure scale, with an emphasis on numerical stability and scaling performances. The block Gauss-Seidel (BGS) numerical method is implemented because the system of equations within the electrodes is coupled only through the nonlinear Butler–Volmer equation, which governs the electrochemical reaction at the interface between the domains. The best solution strategy found in this work consists of splitting the system into two blocks—one for the concentration and one for the potential field—and then performing block generalized minimal residual preconditioned with algebraic multigrid, using the FEniCS and the Portable, Extensible Toolkit for Scientific Computation libraries. Significant improvements in terms of time to solution (six times faster) and memory usage (halving) are achieved compared with the MUltifrontal Massively Parallel sparse direct Solver. Additionally, BGS experiences decent strong parallel scaling within the electrode domains. Last, the system of equations is modified to specifically address numerical instability induced by electrolyte depletion, which is particularly valuable for simulating fast-charge scenarios relevant for automotive application.

Uneven terrain in natural environments challenges legged locomotion by inducing instability and causing limb collisions. During the swing phase, the limb releases from the ground and arcs forward to target a secure next foothold. In natural environments leg-obstacle collisions may occur during the swing phase which can result in instability, and may require contact sensing and trajectory re-planning if a collision occurs. However, collision detection and response often requires computationally- and temporally-expensive control strategies. Inspired by low stiffness limbs that can pass past obstacles in small insects and running birds, we investigated a passive method for overcoming swing-collisions. We implemented virtual compliance control in a robot leg that allowed us to systematically vary the limb stiffness and ultimately its response to collisions with obstacles in the environment. In addition to applying a standard positional control during swing motion, we developed two virtual compliance methods: 1) an isotropic compliance for which perturbations in the $x$ and $y$ directions generated the same stiffness response, and 2) a vertical anisotropic compliance in which a decrease of the upward $y$ vertical limb stiffness enabled the leg to move upwards more freely. The virtual compliance methods slightly increased variability along the limb's planned pathway, but the anisotropic compliance control improved the successful negotiation of step obstacles by over 70\% compared to isotropic compliance and positional control methods. We confirmed these findings in simulation and using a self-propelling bipedal robot walking along a linear rail over bumpy terrain. While the importance of limb compliance for stance interactions have been known, our results highlight how limb compliance in the swing-phase can enhance walking performance in naturalistic environments.

Objective:To assess the impact of a newly developed Central-Line Insertion Site Assessment (CLISA) score on the incidence of local inflammation or infection for CLABSI prevention.Design:A pre- and postintervention, quasi-experimental quality improvement study.Setting and participants:Adult inpatients with central venous catheters (CVCs) hospitalized in an intensive care unit or oncology ward at a large academic medical center.Methods:We evaluated CLISA score impact on insertion site inflammation and infection (CLISA score of 2 or 3) incidence in the baseline period (June 2014–January 2015) and the intervention period (April 2015–October 2017) using interrupted times series and generalized linear mixed-effects multivariable analyses. These were run separately for days-to-line removal from identification of a CLISA score of 2 or 3. CLISA score interrater reliability and photo quiz results were evaluated.Results:Among 6,957 CVCs assessed 40,846 times, percentage of lines with CLISA score of 2 or 3 in the baseline and intervention periods decreased by 78.2% (from 22.0% to 4.7%), with a significant immediate decrease in the time-series analysis (P < .001). According to the multivariable regression, the intervention was associated with lower percentage of lines with a CLISA score of 2 or 3, after adjusting for age, gender, CVC body location, and hospital unit (odds ratio, 0.15; 95% confidence interval, 0.06–0.34; P < .001). According to the multivariate regression, days to removal of lines with CLISA score of 2 or 3 was 3.19 days faster after the intervention (P < .001). Also, line dwell time decreased 37.1% from a mean of 14 days (standard deviation [SD], 10.6) to 8.8 days (SD, 9.0) (P < .001). Device utilization ratios decreased 9% from 0.64 (SD, 0.08) to 0.58 (SD, 0.06) (P = .039).Conclusions:The CLISA score creates a common language for assessing line infection risk and successfully promotes high compliance with best practices in timely line removal.

Management of anterior cruciate ligament (ACL) injuries in adults aged40 years has received increased attention in the literature because of an increase in the functional demands of aging athletes. Multiple structural and biomechanical age-dependent changes exist in the ACL, for example, fewer mesenchymal stem cells, decreased healing potential, decreased structural organization, decreased stiffness, and a decreased load to failure with age. As in younger patients, ACL insufficiency can predispose an older patient to the same risks of recurrent instability, meniscal and chondral injury, and osteoarthritis. The role of nonsurgical versus surgical management in these patients remains controversial. Lower-demand patients may be able to cope with ACL deficiency. Higher-demand patients may have functional instability, and the limited studies available suggest good functional outcomes with surgical reconstruction of the ACL in this population.

SUMMARY Primary cilia are sensory organelles that protrude from the cell membrane. Defects in the primary cilium cause ciliopathy disorders, with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation and that RPE maturation defects in ciliopathies precede photoreceptor degeneration. Pharmacologically enhanced ciliogenesis in wild-type induced pluripotent stem cells (iPSC)-RPE leads to fully mature and functional cells. In contrast, ciliopathy patient-derived iPSC-RPE and iPSC-RPE with a knockdown of ciliary-trafficking protein remain immature, with defective apical processes, reduced functionality, and reduced adult-specific gene expression. Proteins of the primary cilium regulate RPE maturation by simultaneously suppressing canonical WNT and activating PKCδ pathways. A similar cilium-dependent maturation pathway exists in lung epithelium. Our results provide insights into ciliopathy-induced retinal degeneration, demonstrate a developmental role for primary cilia in epithelial maturation, and provide a method to mature iPSC epithelial cells for clinical applications., Graphical Abstract, In Brief May-Simera et al. show that primary cilia regulate the maturation and polarization of human iPSC-RPE, mouse RPE, and human iPSC-lung epithelium through canonical WNT suppression and PKCδ activation. RPE cells derived from ciliopathy patients exhibit defective structure and function. These results provide insights into ciliopathy-induced retinal degeneration.

Key Points Question Which multidrug-resistant organism (MDRO) intervention is best to implement in a set of health care facilities to reduce the spread of MDROs regionwide? Findings In this computational simulation modeling study of 102 facilities in Orange County, California, the use of an agent-based model indicated that, after 3 years, increasing contact precaution effectiveness and implementing decolonization procedures in 42 target facilities would yield countywide relative decreases in the prevalence of methicillin-resistant Staphylococcus aureus of 1% and 24% and countywide relative decreases in the prevalence of carbapenem-resistant Enterobacteriaceae of 2% and 40%, respectively, but varied with effectiveness. Increasing interfacility communication produced no changes in prevalence or transmission. Meaning This study’s findings suggest that modeling can inform the design of real-world regional interventions to control MDROs when intervening in a set of health care facilities., Importance Multidrug-resistant organisms (MDROs) can spread across health care facilities in a region. Because of limited resources, certain interventions can be implemented in only some facilities; thus, decision-makers need to evaluate which interventions may be best to implement. Objective To identify a group of target facilities and assess which MDRO intervention would be best to implement in the Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County, a large regional public health collaborative in Orange County, California. Design, Setting, and Participants An agent-based model of health care facilities was developed in 2016 to simulate the spread of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae (CRE) for 10 years starting in 2010 and to simulate the use of various MDRO interventions for 3 years starting in 2017. All health care facilities (23 hospitals, 5 long-term acute care hospitals, and 74 nursing homes) serving adult inpatients in Orange County, California, were included, and 42 target facilities were identified via network analyses. Exposures Increasing contact precaution effectiveness, increasing interfacility communication about patients’ MDRO status, and performing decolonization using antiseptic bathing soap and a nasal product in a specific group of target facilities. Main Outcomes and Measures MRSA and CRE prevalence and number of new carriers (ie, transmission events). Results Compared with continuing infection control measures used in Orange County as of 2017, increasing contact precaution effectiveness from 40% to 64% in 42 target facilities yielded relative reductions of 0.8% (range, 0.5%-1.1%) in MRSA prevalence and 2.4% (range, 0.8%-4.6%) in CRE prevalence in health care facilities countywide after 3 years, averting 761 new MRSA transmission events (95% CI, 756-765 events) and 166 new CRE transmission events (95% CI, 158-174 events). Increasing interfacility communication of patients’ MDRO status to 80% in these target facilities produced no changes in the prevalence or transmission of MRDOs. Implementing decolonization procedures (clearance probability: 39% in hospitals, 27% in long-term acute care facilities, and 3% in nursing homes) yielded a relative reduction of 23.7% (range, 23.5%-23.9%) in MRSA prevalence, averting 3515 new transmission events (95% CI, 3509-3521 events). Increasing the effectiveness of antiseptic bathing soap to 48% yielded a relative reduction of 39.9% (range, 38.5%-41.5%) in CRE prevalence, averting 1435 new transmission events (95% CI, 1427-1442 events). Conclusions and Relevance The findings of this study highlight the ways in which modeling can inform design of regional interventions and suggested that decolonization would be the best strategy for the Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County., This computational simulation modeling study uses an agent-based model to identify target facilities and assess the optimal intervention to reduce the regional spread of multidrug-resistant organisms across health care facilities in Orange County, California.

Predictive simulations are crucial for the success of many subsurface applications, and it is highly desirable to obtain accurate non-negative solutions for transport equations in these numerical simulations. To this end, optimization-based methodologies based on quadratic programming (QP) have been shown to be a viable approach to ensuring discrete maximum principles and the non-negative constraint for anisotropic diffusion equations. In this paper, we propose a computational framework based on the variational inequality (VI) which can also be used to enforce important mathematical properties (e.g., maximum principles) and physical constraints (e.g., the non-negative constraint). We demonstrate that this framework is not only applicable to diffusion equations but also to non-symmetric advection–diffusion equations. An attractive feature of the proposed framework is that it works with any weak formulation for the advection–diffusion equations, including single-field formulations, which are computationally attractive. A particular emphasis is placed on the parallel and algorithmic performance of the VI approach across large-scale and heterogeneous problems. It is also shown that QP and VI are equivalent under certain conditions. State-of-the-art QP and VI solvers available from the PETSc library are used on a variety of steady-state 2D and 3D benchmarks, and a comparative study on the scalability between the QP and VI solvers is presented. We then extend the proposed framework to transient problems by simulating the miscible displacement of fluids in a heterogeneous porous medium and illustrate the importance of enforcing maximum principles for these types of coupled problems. Our numerical experiments indicate that VIs are indeed a viable approach for enforcing the maximum principles and the non-negative constraint in a large-scale computing environment. Also provided are Firedrake project files as well as a discussion on the computer implementation to help facilitate readers in understanding the proposed framework.

Background: The accuracy of correction has been shown to be an important determinant in long-term outcomes of patients who were treated with a medial open-wedge high tibial osteotomy (HTO) who suffer from unicompartmental osteoarthritis (OA). Computer navigation systems have the potential to improve surgical precision. The purpose of this study was to compare radiographic outcomes between patients treated with a navigation system and those treated through conventional methods of assessing alignment intra-operatively. The null hypothesis was that the method of assessing the alignment intra-operatively would make no difference in the accuracy of correction. Methods: In this retrospective study, 107 patients with medial varus OA who were managed by open-wedge HTO were included. Of the 107 patients, 41 were treated using an intraoperative navigation system and 66 were treated using conventional methods. Pre-operative and postoperative single-leg, long-leg standing alignment films were used to determine the extent of pre-operative varus deformity and the post-surgical correction achieved compared to the predetermined target range. Results: The navigational system had eight instances of software malfunction (19.5%) intraoperatively and correction was determined using the cable method. These results were analyzed as part of the conventional group. Post-operative radiographic differences were significant between the two groups. In the navigation group, 75.8% of the patients were corrected within the target range compared to 66.2% in the conventional group. More patients were also under corrected (to the point of remaining in varus) using conventional methods compared to a navigation system. There was no statistically significant difference in the degree of correction in the sagittal plane between the two groups. Regardless of the method used for checking alignment intra-operatively, there was a statistically significant difference in post-operative weight-bearing measurements when the surgeon had intra-operative axial loading versus when they did not. Conclusion: For coronal plane corrections, the navigation system was shown to have greater success in achieving the desired correction value and in having fewer patients who were under corrected. Despite the measurement technique a surgeon chooses to assess the accuracy of correction, axial loading the extremity in order to simulate the weight-bearing film alignment postoperatively is important to maximize the accuracy of correction needed.