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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.

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.

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.

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.

BACKGROUND: Hospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge. METHODS: We conducted a multicenter, randomized, controlled trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence). RESULTS: In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval [CI], 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary out-comes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants. CONCLUSIONS: Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone. (Funded by the AHRQ Healthcare-Associated Infections Program and others; ClinicalTrials.gov number, NCT01209234.)

Objective Determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBLs), and carbapenem-resistant Enterobacteriaceae (CRE) among residents and in the environment of nursing homes (NHs). Design Point prevalence sampling of residents and environmental sampling of high-touch objects in resident rooms and common areas. Setting Twenty-eight NHs in Southern California from 2016 to 2017. Participants NH participants in Project PROTECT, a cluster-randomized trial of enhanced bathing and decolonization vs routine care. Methods Fifty residents were randomly sampled per NH. Twenty objects were sampled, including 5 common room objects plus 5 objects in each of 3 rooms (ambulatory, total care, and dementia care residents). Results A total of 2797 swabs were obtained from 1400 residents in 28 NHs. Median prevalence of multidrug-resistant organism (MDRO) carriage per NH was 50% (range: 24%-70%). Median prevalence of specific MDROs were as follows: MRSA, 36% (range: 20%-54%); ESBL, 16% (range: 2%-34%); VRE, 5% (range: 0%-30%); and CRE, 0% (range: 0%-8%). A median of 45% of residents (range: 24%-67%) harbored an MDRO without a known MDRO history. Environmental MDRO contamination was found in 74% of resident rooms and 93% of common areas. Conclusions and Implications In more than half of the NHs, more than 50% of residents were colonized with MDROs of clinical and public health significance, most commonly MRSA and ESBL. Additionally, the vast majority of resident rooms and common areas were MDRO contaminated. The unknown submerged portion of the iceberg of MDRO carriers in NHs may warrant changes to infection prevention and control practices, particularly high-fidelity adoption of universal strategies such as hand hygiene, environmental cleaning, and decolonization.

It is well-known that the standard Galerkin formulation, which is often the formulation of choice under the finite element method for solving self-adjoint diffusion equations, does not meet maximum principles and the non-negative constraint for anisotropic diffusion equations. Recently, optimization-based methodologies that satisfy maximum principles and the non-negative constraint for steady-state and transient diffusion-type equations have been proposed. To date, these methodologies have been tested only on small-scale academic problems. The purpose of this paper is to systematically study the performance of the non-negative methodology in the context of high performance computing (HPC). PETSc and TAO libraries are, respectively, used for the parallel environment and optimization solvers. For large-scale problems, it is important for computational scientists to understand the computational performance of current algorithms available in these scientific libraries. The numerical experiments are conducted on the state-of-the-art HPC systems, and a single-core performance model is used to better characterize the efficiency of the solvers. Our studies indicate that the proposed non-negative computational framework for diffusion-type equations exhibits excellent strong scaling for real-world large-scale problems. This figure shows the fate of chromium after 180 days using the single-field Galerkin formulation. The white regions indicate the violation of the non-negative constraint.

Primary cilia are sensory organelles that protrude from the cell membrane. Cilia defects 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 RPE maturation defects in ciliopathies precede photoreceptor development. Pharmacologically enhanced ciliogenesis in wildtype induced pluripotent stem cells (iPSCs)-RPE leads to fully-mature and functional cells. Whereas, ciliopathy patient-derived iPSCs-RPE and wildtype iPSC-RPE with a knockdown of ciliary-trafficking protein remain immature, with defective apical processes, reduced functionality, and reduced adult-specific gene expression. Primary cilia proteins regulate RPE maturation by simultaneously suppressing canonical-WNT and activating PKC-δ pathways. A similar cilia-dependent maturation pathway exists in lung epithelium. Our results provide novel 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.

The objective of this paper is twofold. First, we propose two composable block solver methodologies to solve the discrete systems that arise from finite element discretizations of the double porosity/permeability (DPP) model. The DPP model, which is a four-field mathematical model, describes the flow of a single-phase incompressible fluid in a porous medium with two distinct pore-networks and with a possibility of mass transfer between them. Using the composable solvers feature available in PETSc and the finite element libraries available under the Firedrake Project, we illustrate two different ways by which one can effectively precondition these large systems of equations. Second, we employ the recently developed performance model called the Time-Accuracy-Size (TAS) spectrum to demonstrate that the proposed composable block solvers are scalable in both the parallel and algorithmic sense. Moreover, we utilize this spectrum analysis to compare the performance of three different finite element discretizations (classical mixed formulation with H(div) elements, stabilized continuous Galerkin mixed formulation, and stabilized discontinuous Galerkin mixed formulation) for the DPP model. Our performance spectrum analysis demonstrates that the composable block solvers are fine choices for any of these three finite element discretizations. Sample computer codes are provided to illustrate how one can easily implement the proposed block solver methodologies through PETSc command line options.

Important computational physics problems are often large-scale in nature, and it is highly desirable to have robust and high performing computational frameworks that can quickly address these problems. However, it is no trivial task to determine whether a computational framework is performing efficiently or is scalable. The aim of this paper is to present various strategies for better understanding the performance of any parallel computational frameworks for solving PDEs. Important performance issues that negatively impact time-to-solution are discussed, and we propose a performance spectrum analysis that can enhance one's understanding of critical aforementioned performance issues. As proof of concept, we examine commonly used finite element simulation packages and software and apply the performance spectrum to quickly analyze the performance and scalability across various hardware platforms, software implementations, and numerical discretizations. It is shown that the proposed performance spectrum is a versatile performance model that is not only extendable to more complex PDEs such as hydrostatic ice sheet flow equations, but also useful for understanding hardware performance in a massively parallel computing environment. Potential applications and future extensions of this work are also discussed.

Marjolin’s ulcer, a form of squamous cell carcinoma, is a rare complication of a chronic wound infection. To date, there have not been any detailed reports of lymphatic spread of Marjolin’s ulcer from an extremity. This report describes a 44-year old male with a history of an open tibia fracture at age 15, who presented with chronic osteomyelitis, increasing bloody wound drainage, and an enlarging vascular exophytic masses in the region of drainage. Biopsy of the mass showed squamous cell carcinoma. Initial staging with computed tomography (CT) was negative for metastatic disease. Six months after undergoing a below-knee amputation (BKA), the patient developed an enlarged lymph node in the left inguinal area. His re-staging CT and biopsy of inguinal node confirmed the presence of metastatic squamous cell carcinoma. The patient was subsequently treated with inguinal node dissection and adjuvant radiation therapy. At 2.5 years follow-up, the patient remains disease-free. Our case illustrates the importance suspecting squamous cell carcinoma in patients with chronic infections and diligent follow up for patients with Marjolin’s ulcers.

The J-sign is defined as lateral patellar translation over the anterolateral femur proximal to the trochlear groove during active leg extension. Dynamic magnetic resonance imaging (MRI) techniques allow for quantification of the J-sign using a variety of published indices. However, to date, clinical quantification of the J-sign has not been reliably described. The purpose of the present study is to assess the accuracy of clinically quantifying the J-sign compared with objective MRI data.All patients in this case series were indicated for Fulkerson osteotomy due to recurrent lateral patellar instability and examined preoperatively for the presence of J-sign. The J-sign was estimated by placing a finger on the lateral edge of the trochlea and estimating the lateral translation of the patella while the patient actively extended the knee from 30 degrees of flexion to maximum extension. Independent preoperative measurements were obtained by both the senior author and a resident and compared to dynamic MRI measurements read by independent investigators.Preoperative physical examination for the presence of the J-sign was conducted on 10 patients (10 knees). The average difference between clinical and MRI J-sign measurement was 4.32 mm (range 0.2 - 10.4 mm). There was no significant difference between the clinical and MRI J-sign measurements (p = 0.2579). Clinical measurements of the J-sign differed by an average of 2.2 mm between the two examiners (range 0 - 5 mm).Clinical quantification of the Jsign showed relative imprecision when compared with MRI measurements of the modified lateral patellar edge (LPE), though in several patients we did achieve accurate J-sign assessment. If further research can validate this technique as accurate and consistent using larger patient populations, it could aid in the development of surgical treatment plans for patients presenting with patellar instability, and serve as an objective assessment of alignment in the postoperative period.

Evidence-based guidelines have recently been published for the nonarthroplasty treatment of osteoarthritis of the hip and knee and are becoming an expected part of comprehensive patient care. To understand how current treatment practices correlate with these guidelines, a survey was administered to 50 consecutive hip replacement and 50 consecutive knee replacement patients immediately before arthroplasty for osteoarthritis in one group practice. This article is a compilation of patients' usage of the modalities suggested in two such exemplary guidelines and demonstrates that patient and surgeon preferences, as well as factors such as preoperative Oxford score, body mass index, age, and joint involved, affect usage of one or more of the commonly employed preoperative modalities. This information provides orthopaedic surgeons and administrators with a compilation of responses that reflects surgeon and patient preferences for treatment before surgery.

Author(s): Gohil, Shruti K; Yim, Jennifer; AQuan, Kathleen; Espinoza, Maurice; Thompson, Deborah; Kong, Allen P; Tjoa, Thomas; Bahadori, Bardia; Paiji, Christopher; Rashid, Syma; Hong, Suzie S; Dickey, Linda; Alsharif, Mohamad N; Amin, Alpesh N; Chang, Justin; Khusbu, Usme; Huang, Susan S

PURPOSE The purpose of this study was to determine publication rates of all abstracts submitted for presentation at the annual conference of the Pediatric Orthopaedic Society of North America (POSNA) comparing papers accepted for presentation with those that were not accepted and to determine the median times to publication and the mean impact factor of journals that published papers from the 2 groups. METHODS The titles and authors of all abstracts submitted for presentation to the POSNA for the years 2003 to 2005 were identified. To determine publication status, we conducted a computerized Pubmed search using the first author's name. If multiple publications were identified, the Boolean search operator AND was used to combine author names with key words. The title of each located published article was compared with the title of the abstract. If differences were noted, the abstract content was compared with the final publication. The journals, impact factor was determined using the journal citation report. The median time from conference presentation to publication was determined using a Kaplan-Meier survival analysis. RESULTS Of 1191 abstracts submitted to the annual meetings of POSNA from the years 2003 through 2005, 440 (37%) were accepted for presentation. Acceptance of submitted abstracts increased from 30% in 2003 to 40% in 2005. Of the 1191 abstracts 599 (50%) were subsequently published by August 2009. The mean publication rate for abstracts accepted for presentation was 58.9% (259 of 440) compared with 45% (339 of 751) for rejected abstracts. The median time to publication of accepted abstracts was not significantly different when compared with that of rejected abstracts. The mean journal impact factor for accepted articles was 2.2 compared with 1.5 for rejected abstracts. CONCLUSIONS The publication rates of abstracts submitted to POSNA is high compared with those of other international orthopaedic associations. The mean publication rate for accepted abstracts and rejected abstracts has increased substantially from 45% and 38% in 1991 to 1994 to 58.9% and 45% in 2003 to 2005, respectively. The journal in which most of the abstracts are ultimately published is the Journal of Pediatric Orthopaedics[corrected]. SIGNIFICANCE A significant proportion of abstracts not accepted for presentation at POSNA meetings are published in peer-reviewed journals. Nonacceptance of a study for presentation should not be a hindering factor for researchers in attempting to publish their study in peer-reviewed journals. LEVEL OF EVIDENCE Not applicable.

Objective: The prevalence of adverse respiratory outcomes among children has been frequently associated with measurements of traffic-related exposures, and other data suggest asthma severity is worsened with residence near heavy traffic. We examined the association between neighbourhood traffic burden and repeated acute respiratory illnesses that required emergency department visits and/or hospitalisation for children with a primary or secondary diagnosis of asthma (89% acute bronchitis or pneumonia). Methods: This is a hospital-based longitudinal study of a southern California urban catchment area around two adjacent children’s hospitals. Subjects’ home addresses were geocoded and linked to nearby traffic data. Recurrent event proportional hazard analysis was used to estimate the hazard of repeated hospital encounters. Results: We found living within 300 metres of arterial roads or freeways increased risk of repeated hospital encounters in 3297 children age 18 years or less. At highest risk were children in the top quintile of traffic density (HR = 1.21; 95% CL 0.99 to 1.49) and those who had 750 metres or more of arterial road and freeway length within 300 metres of their residence (HR = 1.18; 95% CL 0.99 to 1.41). Associations between repeated hospital encounters and residence near heavy traffic were stronger in females than males and in children without insurance or who required government sponsored insurance than children with private insurance. The gender disparity was most notable among infants (age 0) and children ages 6–18 years. Conclusions: Results suggest exposure to traffic-related air pollution increases asthma severity as indicated by hospital utilisation. The finding in infants suggests this is an especially vulnerable population, although the validity of asthma diagnosis at this age is unknown. Females and children who do not have private insurance may also be more vulnerable to air pollution from traffic.

The paper presents the design and implementation of an intelligent transportation Web service (ITWS) and studies various QoS requirements for the Web service infrastructure. In particular, we pay attention to the performance issues on ITWS data transmission and compression. Since SOAP message is a textual document, we can improve the data transmission time by compressing data on transmission. In our experiment, compressing data before or after SOAP serialization both can reduce the size of transmitted message down to as little as 2% and cut the response time to a quarter of the original message.