bluuebunny/crossref_metadata_2025_split huggingface dataset:
A web application for evaluating Phase I methods using a non-parametric optimal benchmark
Authors: Wages Nolan A , Varhegyi Nikole 
Published: June 2017

Background/aims: In evaluating the performance of Phase I dose-finding designs, simulation studies are typically conducted to assess how often a method correctly selects the true maximum tolerated dose under a set of assumed dose–toxicity curves. A necessary component of the evaluation process is to have some concept for how well a design can possibly perform. The notion of an upper bound on the accuracy of maximum tolerated dose selection is often omitted from the simulation study, and the aim of this work is to provide researchers with accessible software to quickly evaluate the operating characteristics of Phase I methods using a benchmark. Methods: The non-parametric optimal benchmark is a useful theoretical tool for simulations that can serve as an upper limit for the accuracy of maximum tolerated dose identification based on a binary toxicity endpoint. It offers researchers a sense of the plausibility of a Phase I method’s operating characteristics in simulation. We have developed an R shiny web application for simulating the benchmark. Results: The web application has the ability to quickly provide simulation results for the benchmark and requires no programming knowledge. The application is free to access and use on any device with an Internet browser. Conclusion: The application provides the percentage of correct selection of the maximum tolerated dose and an accuracy index, operating characteristics typically used in evaluating the accuracy of dose-finding designs. We hope this software will facilitate the use of the non-parametric optimal benchmark as an evaluation tool in dose-finding simulation.
Alignment Accuracy and Cost-Savings Threshold of Patient-Specific Instrumentation In Total Ankle Replacements
Authors: Hamid Kamran , Matson Andrew , Nwachukwu Benedict , Scott Daniel , Mather Richard , DeOrio James 
Published: June 2017

Category: Ankle Arthritis Introduction/Purpose: Traditional intraoperative referencing for total ankle replacements (TAR) involves multiple steps and fluoroscopic guidance to determine mechanical alignment. Recent adoption of patient-specific instrumentation (PSI) allows for referencing to be determined preoperatively, resulting in less steps and potentially decreased operative time. We hypothesize that usage of PSI will result in decreased operating room time that offsets the additional cost of PSI as compared to standard referencing (SR). Additionally, we aim to demonstrate similar postoperative radiographic alignment between PSI and SR. Methods: Between 2014 and 2015, 87 patients undergoing TAR were enrolled in a prospectively collected TAR database. Patients were divided into cohorts based on PSI versus SR and operative times were reviewed. Radiographic alignment parameters were retrospectively measured at 6 weeks postoperatively. Time-driven activity-based costing (TDABC) was utilized to derive direct costs. Cost versus operative time-savings were examined via two-way sensitivity analysis to determine cost-saving thresholds for PSI applicable to a range of institution types. Cost-saving thresholds defined the price of PSI below which PSI is cost-saving. Results: A total of 35 PSI and 52 SR cases were evaluated with no significant differences identified in patient characteristics. Operative time from incision to completion of casting in cases without adjunct procedures was 127 minutes with PSI and 161 minutes with SR (p < 0.05). PSI demonstrated similar postoperative accuracy to SR in coronal tibial-plafond alignment (1.1° vs. 0.3° varus, p=0.06) and tibial component sagittal alignment (0.7° vs. 0.9° plantarflexion, p=0.14). TDABC methodology estimated a PSI cost-savings threshold range at our institution of $863 - $1,026 below which PSI pricing will provide net cost-savings. Two-way sensitivity analysis generated a globally applicable cost-savings threshold model based on institution-specific costs and surgeon-specific time-savings. Conclusion: This study demonstrates equivalent post-operative TAR alignment with PSI and SR referencing systems but with a significant decrease in operative time with PSI. Based on TDABC and associated sensitivity analysis, a cost-savings threshold of $863 - $1,026 is identified for PSI pricing at our institution below which PSI is less costly than SR. Similar internal cost accounting may benefit healthcare systems for identifying cost drivers and obtaining leverage during price negotiations.
Time related effects of non-steroidal anti-inflammatory drugs on Achilles tendinopathy in a murine model
Authors: Bitterman Adam , Gao Shuguang , Trella Katie , Li Jun , Galante Jorge , Lee Simon , Holmes George , Lin Johnny , Plaas Anna 
Published: June 2017

Category: Basic Sciences/Biologics Introduction/Purpose: Tendinopathy has been identified to result from work and sports-related activities, in many patients. Common treatment for such degenerative tendon pathology includes non-steroidal anti-inflammatory drugs (NSAIDs). Although they provide pain relief, their mechanistic effects, on modulating inflammation associated with tendinopathy is poorly understood. Recent reports suggest impaired functional healing of rat rotator cuff tear repairs when treated in the early postoperative period with ibuprofen, while delayed treatment did not affect healing. We have now identified, using a murine model, a cascade of genes associated with innate inflammation, which influence premature fibrotic scarring without repair. The objective of this study was to evaluate the effects of orally administered ibuprofen on inflammation and wound-healing responses after initiation and during progression of Achilles tendinopathy in a murine model. Methods: All animal experimentation was carried out under IACUC approval. C57BL/6 wild-type male mice (12 wks) received two injections, two days apart, of 100ng rhTGF-β1 into the midportion of the Achilles tendon. Ibuprofen (IBU) was administered orally as described by Ezell et al5, for 7 days either 1 day (Early) or 8 days (Late) after the initiating injury. Experimental groups were 1) Tendinopathy + NO drug, 2) Tendinopathy + IBU Early, 3) Tendinopathy + IBU Late, 4) Naïve mice + IBU Early. Following sacrifice of the mice at 28 days post injury, Achilles tendons were harvested, and RNA was prepared as described by Trella et al6, for transcriptomic analyses using wound healing and NfKb target gene platforms (PAMM-121A, PAMM-225ZA Qiagen, Valencia, CA). Tendon histopathology was assessed on paraffin embedded thin sections using standard methods for HE and Safranin O staining. Results: Both early and late dosing times with ibuprofen prolonged the innate inflammation response genes (e.g., PGE Synthase, Interleukin1b, Interferon gamma, Cxcl3 chemokine), relative to untreated tendinopathy. Furthermore, early dosing also elevated collagen genes (Collagens 1, 3 and 5), and such a response has been associated with fibrotic scarring. Drug administration to naïve mice showed no significant effects on gene expression in the tendons. Conclusion: This study represents the first report of the time related effect of ibuprofen on mechanisms involved in healing of tendinopathy. If the drug is administered early after the initiating injury, a prolonged increase in inflammation and potential for scarring in the tendon was observed, whereas later administration resulted in persistent inflammation only. The data suggest that the anti-inflammatory action of such NSAID may occur outside of the tendon (such as the bone marrow) resulting in a dysregulated systemic mechanism that controls the innate (tendon) inflammation and healing pathways.
Hindfoot Alignment of Adult Acquired Flatfoot Deformity
Authors: de Cesar Netto Cesar , Demehri Shadpour , Chinanuvathana Apisan , Mousavian Alireza , Tan Eric , O’Daly Andres , Aynardi Michael , Fonseca Lucas , Thawait Gaurav , Ficke James , Schon Lew 
Published: June 2017

Category: Hindfoot Introduction/Purpose: Assessment of hindfoot alignment in adult acquired flatfoot deformity (AAFD) can be challenging. Clinical judgment and radiograph studies while important may not represent the accurate valgus alignment of the affected patients. Weightbearing (WB) ConeBeam CT (CBCT) is an emerging imaging modality that may potentially better demonstrate the three-dimensional (3D) deformity, facilitating visualization of important soft-tissue and bony landmarks and helping in surgical planning. Based on the relative position of bone and soft-tissue axes, different measurements of hindfoot alignment can be obtained with CT images. Therefore, we compared clinical assessment of hindfoot valgus alignment in AAFD patients with different possible measurements performed on WB CBCT images. Methods: In this prospective, IRB-approved study, 20 patients (20 feet, 15 right and 5 left) with clinical diagnosis of flexible AAFD were included. There were 12 males and 8 females, with a mean age of 52.2 years (range, 20 – 88 years of age), and average BMI of 30.35 kg/m2 (range, 19.00 – 46.09 kg/m2). Patients underwent clinical assessment of hindfoot alignment as well as WB CBCT. Two independent and blinded foot and ankle board-certified surgeons performed different hindfoot alignment measurements on the WB CBCT images that included: 3D “clinical” alignment; Achilles tendon axis/calcaneal tuberosity angle; angles formed between the tibial axis and the calcaneal tuberosity, calcaneal axis and line connecting midpoint of subtalar joint and most inferior part of calcaneal tuberosity. Positive values were considered valgus alignment. Mean differences between the measurements modalities were compared by paired T-test. Intra- and Inter-observer reliability for the WB CBCT measurements were calculated using Pearson correlation. Results: The mean clinical hindfoot valgus measured was 15.15o (SD 7.7o). It was found to be significantly different from the mean values of all WB CBCT angles modalities: 3D “clinical” alignment (10.42o, p < 0.015); Achilles tendon/calcaneal tuberosity angle (2.96o, p < 0.0001); tibial axis/calcaneal tuberosity angle (5.42o, p < 0.0001); tibial axis/subtalar joint angle (7.52o, p < 0.0001) and tibial axis/calcaneal axis angle (20.39o, p < 0.017). We found an excellent intra-observer agreement for all WB CBCT 3D measurements (range, 0.8863 – 0.9713, p < 0.0001). There was also good to excellent inter-observer reliability, with the exception of the 3D “clinical” alignment (r=0.450, p < 0.04), that showed moderate correlation. Conclusion: The use of 3D WB CBCT imaging can help characterize the valgus hindfoot alignment in patients with adult acquired flatfoot deformity. We found the different CBCT measurements modalities to be reliable and repeatable, and to significantly differ from the clinical evaluation of hindfoot valgus alignment.
FAAM ADL Scores Correlate with PROMIS Physical Function, Pain Interference, and Depression Outcomes
Authors: Nixon Devon , McCormick Jeremy , Johnson Jeffrey , Klein Sandra 
Published: June 2017

Category: Midfoot/Forefoot Introduction/Purpose: Legacy patient-reported outcome instruments like the FAAM Activities of Daily Living (ADL) quantify patient disability but are often limited by responder burden and incomplete questionnaires. The Patient-Reported Outcome Measurement Information System (PROMIS) overcomes such obstacles through computer-adaptive technology to collect data on various health domains including Physical Function (PF), Pain Interference (PI), and Depression. Few reports, though, have examined PROMIS tools in lower extremity patients, and no study has examined PROMIS psychosocial outcomes like PI and Depression in foot and ankle conditions. We investigated the relationship between FAAM ADL and PROMIS measures, hypothesizing that FAAM ADL and PROMIS scores would correlate. Methods: All new patients with either a primary or secondary diagnosis of hallux valgus based on clinic billing codes from July, 2015 – February, 2016 were retrospectively identified. Patients with complete FAAM ADL paper-based surveys and electronic PROMIS questionnaires for PF, PI, and Depression were included. Spearman rho correlations were performed between FAAM ADL and PROMIS scores. Bivariate and multivariate analyses were then performed to identify differences in FAAM ADL and PROMIS PF measures based on select demographic variables (gender, comorbidities, marital status, employment status, prior foot and/or ankle surgery, and smoking status). Significant variables (P < 0.1) from bivariate and multivariate analyses were then entered into stepwise linear regressions to determine which variable(s) determined variance in FAAM ADL and PROMIS PF scores. Results: Eighty-five patients were identified (13 males, 72 females). FAAM scores significantly correlated with PROMIS PF (r = 0.70, P < 0.001), PI (r = 0.65, P < 0.001), and Depression (r = 0.35, P < 0.001) outcomes. Bivariate and multivariate analyses revealed significantly lower FAAM ADL scores in men (P = 0.02) and active smokers (P = 0.1). No significant group differences were detected for PROMIS PF scores (P > 0.1). Regression analyses demonstrated that PROMIS PI scores alone accounted for significant portions of the variance in FAAM ADL (R2 = 0.44, P < 0.001) and PROMIS PF (R2 = 0.57, P < 0.001) measures. Conclusion: PROMIS PF, PI, and Depression scores all correlated with FAAM ADL scores, highlighting the importance of understanding functional and psychosocial disability when assessing outcomes in lower extremity patients. Further, PROMIS PI results predicted significant portions of FAAM ADL and PROMIS PF scores, suggesting that function and pain are interrelated when measured by either traditional or modern outcomes instruments.
Headless Compression Screw Fixation of Jones Fractures
Authors: Ruta David , Ellis Robert , Grear Benjamin , Ishikawa Susan , Richardson David , Murphy Garnett 
Published: June 2017

Category: Sports Introduction/Purpose: There remains controversy over the ideal implant for intramedullary screw fixation of fifth metatarsal Jones fractures. Promising results have separately been reported for both indication-specific partially threaded screws and headless compression screws. The purpose of this study was to compare clinical and radiographic results between Jones fracture patients treated with indication-specific partially threaded screws to variable-pitched headless compression screws. We also evaluated the association of various patient and fracture characteristics with surgical failure. Methods: We performed a retrospective review and comparative analyses of all Jones fractures treated with primary intramedullary screw fixation by 4 foot and ankle fellowship-trained orthopaedic surgeons at a single institution from 1995 through 2015. Exclusion criteria included concomitant foot or ankle procedures and revision surgery. Charts were reviewed for patient and injury characteristics, implant, and postoperative course. Serial radiographs were examined for fracture classification (Torg and anatomic zone) and radiographic union. Primary endpoint was number of surgical failures, defined as delayed union, nonunion, or refracture. Secondary endpoints included time to each of radiographic union, weight bearing, and pain resolution. Data were analyzed using independent T test, one-way ANOVA, chi-square, and correlation analyses with significance defined as p < 0.05. Results: Fifty-nine feet were reviewed with mean age 30 years and follow-up 9.6 months. Forty-seven received a partially threaded screw (PT) and 12 feet a headless compression screw (HC). The PT group had more failures (10/47, 21.3% vs. 1/12, 8.3%; p=0.31) and more weeks to full weight (4.2 vs. 3.3, p=0.06), without significant differences in time to radiographic union or pain resolution. Most failures were delayed unions. Pooled union rate was 96.6%. Correlated with failure were age (r=0.469, p < 0.001), diabetes (r=0.390, p=0.002), and BMI (r=0.281, p=0.03), without significant correlation for tobacco, gender, or weight. Compared to Torg 1 and 2, Torg 3 fractures had greater time to pain resolution and radiographic union, age, weight, and BMI. No differences were found between zone II and III fractures. Conclusion: To our knowledge, this is the first reported clinical comparison between indication-specific partially threaded screws (PT) and headless compression screws (HC) for treating Jones fractures. This is also one of the largest clinical series on the subject. The two groups had similar clinical and radiographic results, both with high union rates. While most failures were delayed unions that ultimately healed, the 21% failure rate in the PT group is concerning and may warrant further investigation. Increasing patient age, diabetes, and BMI were associated with worse outcomes. These data support headless compression screw fixation as a viable treatment for Jones fractures.
Change is permanent: thoughts on the fading of cochineal-based watercolor pigments
Authors: Berrie Barbara H. , Strumfels Yoonjoo 
Published: June 2017

Abstract

Background
Color change in artworks has been commented on for centuries. Fading of watercolor pigments is a notable alteration. Pigments based on carminic acid are among those particularly prone to color loss, but the mechanism and factors are not well understood.

Results
We painted out three pigments prepared from the aqueous extract of carminic acid (CA) from Dactylopius coccus: the uncomplexed, and aluminium- and tin-complexed lakes. These were applied in a 2% gum Arabic solution to papers that were acidic, neutral or alkaline pH and exposed to accelerated light aging in a weatherometer. The comparative rate of fading was dependent on the complexation and on the pH of the substrate. On alkaline paper, the Al complex was least light stable, on neutral paper the three colorants responded similarly, and on acidic paper the tin complex was the least light stable. This is discussed in light of the published information on reactions and mechanism of color loss of CA.
Biological complications in implant-supported oral rehabilitation: as the pendulum swings back towards endodontics and tooth preservation
Authors: Nemcovsky Carlos E. , Rosen Eyal 
Published: June 2017

AbstractThe decision whether to retain a tooth by additional endodontic and restorative treatments or to extract it and replace it with an implant-supported restoration has been extensively debated, and the common approach to this clinical question has shifted back and forth many times. However, in recent years, it has become clear that implants are more prone to technical and biological complications, and require more postoperative treatments to maintain them than the natural dentition. A review of the currently available literature regarding the biological complications of implant-supported oral rehabilitation, and the ensuing effects on the clinical decision-making regarding the preservation of the teeth by endodontic treatments is presented.
Deletion analysis of AGD1 reveals domains crucial for plasma membrane recruitment and function in root hair polarity
Authors: Yoo Cheol-Min , Naramoto Satoshi , Sparks J. Alan , Khan Bibi Rafeiza , Nakashima Jin , Fukuda Hiroo , Blancaflor Elison B. 
Published: June 2017

ABSTRACT
AGD1, a plant ACAP-type ADP-ribosylation factor-GTPase activating protein (ARF-GAP), functions in specifying root hair polarity in Arabidopsis thaliana. To better understand how AGD1 modulates root hair growth, we generated full-length and domain-deleted AGD1-green fluorescent protein (GFP) constructs, and followed their localization during root hair development. AGD1-GFP localized to the cytoplasm and was recruited to specific regions of the root hair plasma membrane (PM). Distinct PM AGD1-GFP signal was first detected along the site of root hair bulge formation. The construct continued to mark the PM at the root hair apical dome, but only during periods of reduced growth. During rapid tip growth, AGD1-GFP labeled the PM of the lateral flanks and dissipated from the apical-most PM. Deletion analysis and a single domain GFP fusion revealed that the pleckstrin homology (PH) domain is the minimal unit required for recruitment of AGD1 to the PM. Our results indicate that differential recruitment of AGD1 to specific PM domains is an essential component of the membrane trafficking machinery that facilitates root hair developmental phase transitions and responses to changes in the root microenvironment.
Specialist palliative care nurses' management of the needs of patients with depression
Authors: Hayes Jessica Elizabeth , Hart Bethne , Phillips Jane 
Published: June 2017

Background: Depression is an important condition to consider if we are to optimise the care outcomes for patients with palliative care needs. Depression has a high incidence in palliative patients, with up to 15% diagnosed with major depression and 37% expressing some form of depressive symptoms ( O'Connor et al, 2010 ). The challenge is to ensure that palliative care patients with depression are identified in a timely manner and that their depression is effectively managed. Aim: To examine how Australian specialist inpatient palliative care nurses perceive, assess and respond to depression in a patient case study. Method: This descriptive pilot study is a replication of a United States study by Little et al (2005) , exploring contemporary Australian specialist palliative care nurses' screening, assessment and management of depression in people with a progressive life-limiting illness. A survey titled ‘Specialist palliative care nurses managing patients with complex care needs’ questioned the nursing assessment, knowledge and clinical care priorities related to a case vignette of a patient demonstrating signs of depression. Results: A total of 33 nurses completed this survey. Less than half (39.4%) of the participants identified depression as a major issue arising from the case vignette. Depression screening tools were not widely known. Functionality assessments measuring activities of daily living were the most recognised and widely used tools by participants. Conclusion: This small sample pilot study demonstrated that specialist palliative care nurses are still not confident in their screening and responding to a patient with depression. The available evidenced based depression screening tools were unfamiliar to these nurses and not widely used which can result in depression remaining undetected and undermanaged. The connections between physical health and mental health need stronger recognition and response within nursing care of palliative patients.