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Data preprocessing is an integral step prior to analyzing data in psychological science, with implications for its potentially guiding policy. This article reports how psychological researchers address data preprocessing or quality concerns, with a focus on aberrant responses and missing data in self-report measures. 240 articles were sampled from four journals: Psychological Science, Journal of Personality and Social Psychology, Developmental Psychology, and Abnormal Psychology from 2012 to 2018. Nearly half of the studies did not report any missing data treatment (111/240; 46.25%), and if they did, the most common approach was listwise deletion (71/240; 29.6%). Studies that remove data due to missingness removed, on average, 12% of the sample. Likewise, most studies do not report any aberrant responses (194/240; 80%), but if they did, they classified 4% of the sample as suspect. Most studies are either not transparent enough about their data preprocessing steps or may be leveraging suboptimal procedures. Recommendations can improve transparency and data quality.

In the treatment of native shoulder septic arthritis, the optimal irrigation and débridement modality-arthroscopic versus open-is a matter of controversy. We aim to compare revision-free survival (RFS), complications, and resource utilization between these approaches.The National Readmission Database was queried from 2016 to 2019 to identify patients using International Classification of Diseases, 10th revision, diagnostic and procedure codes. Days to revision irrigation and débridement (ID) were calculated for patients during index admission or subsequent readmissions. Multivariate regression was used for healthcare utilization analysis. Survival analysis was done using Kaplan-Meier analysis and Cox proportional hazard regression.A total of 4,113 patients with native shoulder septic arthritis undergoing ID were identified, 2,775 arthroscopic (67.5%) and 1,338 open (32.5%). The median follow-up was 170 days (interquartile range 79 to 265). A total of 341 patients (8.3%) underwent revision ID at a median of 9 days. On multivariate analysis, arthroscopic ID was associated with a reduction in hospital costs of $4,154 ( P0.001) and length of stay of 0.78 days ( P = 0.030). Arthroscopic ID was associated with reduced blood transfusions (odds ratio 0.69, P = 0.001) and wound complications (odds ratio 0.30, P0.001). RFS was 96.4%, 94.9%, 93.3%, and 92.6% for arthroscopic ID and 94.1%, 92.6%, 90.4%, and 89.0% for open ID at 10, 30, 90 and 180 days, respectively ( P = 0.00043). On multivariate Cox modeling, arthroscopic ID was associated with improved survival (hazard ratio 0.67, P = 0.00035). On stratified analysis, arthroscopic ID was associated with improved RFS in patients aged 65 years or older ( P0.001), but RFS was similar in those younger than 65 years ( P = 0.17).Risk of revision ID was markedly lower after arthroscopic ID compared with open, although the protective benefit was limited to patients aged 65 years or older. Arthroscopy was also associated with decreased costs, length of stay, and complications. Although surgeons must consider specific patient factors, our results suggest that arthroscopic ID is superior to open ID.III.

In the treatment of native knee bacterial septic arthritis, the optimal irrigation and débridement modality-arthroscopic versus open-is a matter of controversy. We aim to compare revision-free survival, complications, and resource utilization between these approaches.The National Readmission Database was queried from 2016 to 2019 to identify patients using International Classification of Diseases, 10th revision, diagnostic and procedure codes. Days to revision irrigation and débridement (ID), if any, were calculated for patients during index admission or subsequent readmissions. Multivariate regression was used for healthcare utilization analysis. Survival analysis was done using Kaplan-Meier analysis and Cox proportional hazard regression.A total of 14,365 patients with native knee septic arthritis undergoing ID were identified, 8,063 arthroscopic (56.1%) and 6,302 open (43.9%). The mean follow-up was 148 days (interquartile range 53 to 259). A total of 2,156 patients (15.0%) underwent revision ID. On multivariate analysis, arthroscopic ID was associated with a reduction in hospital costs of $5,674 and length of stay of 1.46 days (P0.001 for both). Arthroscopic ID was associated with lower overall complications (odds ratio [OR] 0.63, P0.001), need for blood transfusion (OR 0.58, P0.001), and wound complications (OR 0.32, P0.001). Revision-free survival after index ID was 95.3% at 3 days, 91.0% at 10 days, 88.3% at 30 days, 86.0% at 90 days, and 84.5% at 180 days. No statistically significant difference was observed between surgical approaches on Cox modeling.Risk of revision ID did not differ between arthroscopic and open ID; however, arthroscopy was associated with decreased costs, length of stay, and complications. Additional study is necessary to confirm these findings and characterize which patients require an open ID.III.

BACKGROUND: Students’ use of feedback is associated with improved learning. Yet how soon does this association become robust enough to make predictions about learning is not fully understood. Such knowledge has strong implications for early identification of students at-risk for underachievement via digital learning platforms.OBJECTIVES: We sought to understand how early in the academic year students’ end-of-year learning outcomes could be predicted by their performance and use of feedback administered through a digital learning platform. We analyzed data collected at different time points in the academic year and across different cohorts of students within the context of high school advanced placement (AP) Statistics courses. METHODS: High school students enrolled in AP Statistics spanning three academic years between 2017-2020 (N=726; Mage=16.72 years) completed 3-4 homework assignments, each 2-3 months apart. RESULTS AND CONCLUSIONS: Across the three cohorts, and even as early as the first assignment, a model consisting of demographic variables (gender, race/ethnicity, parental education), assignment performance, and interaction with the score report explained significant variation in students’ final course grades (R2=.314-.412) and AP exam scores (kappa=.583-.689). Students’ assignment performance was positively associated with end-of-year learning outcomes. Students who more frequently checked their score reports tended to receive better learning outcomes, though not consistently across cohorts. IMPLICATIONS: These findings further an understanding of how students’ early performance and use of feedback within a digital learning platform predict end-of-year learning outcomes.

Supplementary Data from Activation of Host Wound Responses in Breast Cancer Microenvironment

Purpose: Cancer progression is mediated by processes that are also important in wound repair. As a result, cancers have been conceptualized as overhealing wounds or wounds that do not heal, and gene expression signatures reflective of wound repair have shown value as predictors of breast cancer survival. Despite the widespread acknowledgment of commonalities between host responses to wounds and host responses to cancer, the gene expression responses of normal tissue adjacent to cancers have not been well characterized.Experimental Design: Using RNA extracted from histologically normal breast tissue from 107 patients, including 60 reduction mammoplasty patients and 47 cancer patients, we measured whole genome expression profiles and identified a gene expression signature that is induced in response to breast cancer.Results: This signature represents an in vivo wound response signature that is differentially expressed in the normal tissue of breast cancer patients compared with those without disease and is highly accurate (at least 92 sensitivity and 98 specificity) in distinguishing diseased and nondiseased. The in vivo wound response signature is highly prognostic of breast cancer survival, and there is a strong association between the groups identified by this signature and those identified using serum-treated fibroblasts and other microenvironment-derived or microenvironment-related signatures.Conclusions: The prevalence of the wound response signature in histologically normal tissue adjacent to breast cancer suggests that microenvironment response is an important variable in breast cancer progression and may be an important target for clinical interventions. (Clin Cancer Res 2009;15(22):70208)

Contraction of the human sarcomere is the result of interactions between myosin cross-bridges and actin filaments. Pathogenic variants in genes such asMYH7,TPM1, andTNNI3that encode parts of the cardiac sarcomere cause muscle diseases that affect the heart, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In contrast, pathogenic variants in homologous genesMYH2,TPM2, andTNNI2, that encode parts of the skeletal muscle sarcomere, cause muscle diseases affecting skeletal muscle, such as the distal arthrogryposis (DA) syndromes and skeletal myopathies. To date, there have been few reports of genes (e.g.,MYH7) encoding sarcomeric proteins in which the same pathogenic variant affects both skeletal and cardiac muscle. Moreover, none of the known genes underlying DA have been found to contain mutations that also cause cardiac abnormalities. We report five families with DA due to heterozygous missense variants in the geneactin, alpha, cardiac muscle 1(ACTC1).ACTC1encodes a highly conserved actin that binds to myosin in both cardiac and skeletal muscle.Mutations inACTC1have previously been found to underlie atrial septal defect, dilated cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction. Our discovery delineates a new DA condition due to mutations inACTC1and suggests that some functions ofactin, alpha, cardiac muscle 1are shared in cardiac and skeletal muscle.

Contraction in striated muscle is initiated by calcium binding to troponin complexes, but it is now understood that dynamic transition of myosin between resting, ordered OFF states on thick filaments and active, disordered ON states that can bind to thin filaments is critical in regulating muscle contractility. These structural OFF to ON transitions of myosin are widely assumed to correspond to transitions from the biochemically defined, energy-sparing, super-relaxed (SRX) state to the higher ATPase disordered-relaxed (DRX) state. Here we examined the effect of 2’-deoxy-ATP (dATP), a naturally occurring energy substrate for myosin, on the structural OFF to ON transitions of myosin motors in porcine cardiac muscle thick filaments. Small-angle X-ray diffraction revealed that titrating dATP in relaxation solutions progressively moves the myosin heads from ordered OFF states on the thick filament backbone to disordered ON states closer to thin filaments. Importantly, we found that the structural OFF to ON transitions are not equivalent to the biochemically defined SRX to DRX transitions and that the dATP-induced structural OFF to ON transitions of myosin motors in relaxed muscle are strongly correlated with submaximal force augmentation by dATP. These results indicate that structural OFF to ON transitions of myosin in relaxed muscle can predict the level of force attained in calcium-activated cardiac muscle. Computational modeling and stiffness measurements suggest a final step in the OFF to ON transition may involve a subset of DRX myosins that form weakly bound cross-bridges prior to becoming active force-producing cross-bridges.

Complex and coordinated dynamics are closely connected with protein functions, including the binding of antibodies to antigens. Knowledge of such dynamics could improve the design of antibodies. Molecular dynamics (MD) simulations provide a "computational microscope" that can resolve atomic motions and inform antibody design efforts.

A three-phase strategy was adopted for a deep-water reservoir development due to large uncertainties associated with fault compartmentalization and aquifer support. First phase started with primary production from several wells while water injection was implemented a few years later as second phase. Finally, the third phase involved infills. Data collected during drilling was utilized to improve reservoir characterization. This paper describes how a Surveillance, Analysis and Optimization (SA&O) plan was utilized to resolve key subsurface uncertainties and optimize the development plan, along with lessons learned and best practices. The development plan included adding five infill wells during the infill campaign. Two of those infills, Well1 and Well2, delineated the reservoir south of a major fault. Early reservoir characterization placed two sealing faults between the Well1 and Well2 wells, creating a separate fault compartment with a future infill well in the development plan. Steeply dipping beds below a thick salt canopy make seismic imaging a challenge and fault delineation uncertain. Although a future infill well was planned to recover the reserves from this compartment, the length and transmissibility of the faults, as well as reservoir heterogeneity between the Well1 and Well2 wells were highly uncertain. Prior to start-up of Well2, a pulse test and multiple pressure build-up tests were conducted as part of the SA&O plan to resolve fault uncertainties. The pulse test involved creating pressure pulses by shutting-in and starting-up the Well1 and monitoring at Well2 for pulse arrival. Test design was developed using Intersect and Saphir numerical simulations sensitizing on the fault extent and transmissibility uncertainties. The test was planned and executed successfully as a result of multi-functional collaboration between the asset development, reservoir management support, and operations teams. Analysis of all transient pressure data indicated very strong pressure communication without any detectable barrier between the Well1 and Well2 wells. Increased confidence in recent seismic imaging enhancements have since corroborated these results. Reservoir simulations without these compartmental faults, indicated that Well1 & Well2 can effectively drain most of the recoverable oil, with limited improvement from an additional well. Consequently, the development plan was optimized by removing the future infill well, translating to a significant capital cost saving.

OBJECTIVE: Rearranged ROS1, present in 1%-2% of non-small cell lung cancer (NSCLC) patients, usually young, never or light smokers, is assessed by fluorescence in situ hybridization (FISH) to determine eligibility for tyrosine kinase inhibitors (TKI). Immunohistochemistry (IHC) for the protein product of ROS1 rearrangement, a cost-effective alternative, is validated on cytology and small biopsy samples.METHODS: From 1 March to 31 December 2019, cytology cell blocks and small biopsy samples from a selected cohort of NSCLC patients were concurrently tested for ROS1 gene rearrangement by Vysis 6q22 Break Apart FISH probe and IHC using Cell Signalling D4D6 antibody. Mismatch cases were tested by an RNA fusion next generation sequencing (NGS) panel.RESULTS: In a prospective population of 95 cases, 91 were negative and two were positive by both FISH and IHC. Both dual positive cases were female never smokers and benefited from TKI treatment. Another two cases were positive by FISH but negative by IHC and repeat by NGS showed one to be negative but one failed. Turnaround time for IHC was 0 to 8 days from request to authorisation, whilst that of FISH was 9 to 42 days at a cost of £51 and £159 respectively.CONCLUSION: IHC to assess for the protein product of ROS1 gene rearrangement on cytology cell blocks and small biopsy samples in a routine setting is a promising screening method to assess eligibility for TKI treatment with positive and indeterminate cases confirmed by FISH or NGS as it has good negative predictive value, faster turnaround time and is cost effective, with proven technical and clinical validation.

Robotic-arm assisted systems are increasingly used for knee arthroplasty, however introduction of new systems can involve a learning curve. We aimed to define the learning curve in terms of operative time and component placement/sizing of a robotic system for total knee arthroplasty (TKA) in a team of experienced surgeons, and to investigate mid-term patient outcomes.A total of 101 consecutive patients underwent primary robotic-arm assisted TKA by three surgeons (mean 2 year follow-up). Operative times, component placement, implant sizing and reoperations were recorded. Cumulative Summation (CUSUM) was used to analyse learning curves. Patient outcomes were compared between learning and proficiency phases.The learning curve was 16 cases, with a 12-min increase in operative time (P 0.01). Once proficiency was achieved, the greatest time reductions were seen for navigation registration (P = 0.003) and bone preparation (P 0.0001). A learning curve was found with polyethylene (PE) insert sizing (P = 0.01). No differences were found between learning and proficiency groups in terms of implant survival (100% and 97%, respectively, NS) or patient-reported outcome measures at 2 years (NS).Introduction of a robotic-arm assisted system for TKA led to increased operative times for navigation registration and bone preparation, and a learning curve with PE insert sizing. No difference in patient outcomes between learning and proficiency groups at 2 years was found. These findings can inform surgeons' expectations when starting to use robotic-assisted systems.

In the last few years, we have witnessed an explosive growth of fake content on the Internet which has significantly affected the veracity of information on many social platforms. Much of this disruption has been caused by the proliferation of advanced machine and deep learning methods. In turn, social platforms have been using the same technological methods in order to detect fake content. However, there is understanding of the strengths and weaknesses of these detection methods. In this article, we describe examples of machine and deep learning approaches that can be used to detect different types of fake content. We also discuss the characteristics and the potential for adversarial attacks on these methods that could reduce the accuracy of fake content detection. Finally, we identify and discuss some future research challenges in this area.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification., Nature Communications, 11 (1), ISSN:2041-1723

Inpatient ward placements are rich with practical learning opportunities for medical students; however, many such opportunities go overlooked and underused. Newly qualified doctors often feel underprepared for work on wards; improving student experience on ward placements can address this. Although this requires an active effort from both students and clinical educators, it is not arduous and has mutual benefit: improving medical education while simultaneously reducing staff workload. Here, we present a guide for both teachers and students highlighting three key areas of ward learning that may be improved: strategies to drive active learning, integration of students into the ward team and underutilised resources to develop a patient-centred approach.

Multiple genetic association studies have correlated a common allelic block linked to the BAG3 gene with a decreased incidence of heart failure, but the molecular mechanism for such protection remains elusive. One of the variants in this allele block is coding, changing cysteine to arginine at position 151 of BAG3 (rs2234962-BAG3C151R). Here, we use induced pluripotent stem cells (iPSC) to test if the BAG3C151Rvariant alters protein and cellular function in human cardiac myocytes. Quantitative protein interaction network analysis identified specific changes in BAG3C151Rprotein interaction partners in cardiomyocytes but not in iPSCs or an immortalized cell line. Knockdown of BAG3 interacting factors in cardiomyocytes followed by myofibrillar analysis revealed that BAG3C151Rassociates more strongly with proteins involved in the maintenance of myofibrillar integrity. Finally, we demonstrate that cardiomyocytes expressing the BAG3C151Rvariant have improved response to proteotoxic stress in an allele dose-dependent manner. This study suggests that the BAG3C151Rvariant increases cardiomyocyte protection from stress by enhancing the recruitment of factors critical to the maintenance of myofibril integrity, hinting that this variant could be responsible for the cardioprotective effect of the haplotype block. By revealing specific changes in preferential binding partners of the BAG3C151Rprotein variant, we also identify potential targets for the development of novel cardioprotective therapies.

UKA has higher revision risk, particularly for lower volume surgeons. While robotic-arm assisted systems allow for increased accuracy, introduction of new systems has been associated with learning curves. The aim of this study was to determine the learning curve of a UKA robotic-arm assisted system. The hypothesis was that this may affect operative times, patient outcomes, limb alignment, and component placement.Between 2017 and 2021, five surgeons performed 152 consecutive robotic-arm assisted primary medial UKA, and measurements of interest were recorded. Patient outcomes were measured with Oxford Knee Score, EuroQol-5D, and Forgotten Joint Score at 6 weeks, 1 year, and 2 years. Surgeons were grouped into 'low' and 'high' usage groups based on total UKA (manual and robotic) performed per year.A learning curve of 11 cases was found with operative time (p 0.01), femoral rotation (p = 0.02), and insert sizing (p = 0.03), which highlighted areas that require care during the learning phase. Despite decreased 6-week EQ-5D-5L VAS in the proficiency group (77 cf. 85, p 0.01), no difference was found with implant survival (98.2%) between phases (p = 0.15), or between 'high' and 'low' usage surgeons (p = 0.23) at 36 months. This suggested that the learning curve did not lead to early adverse effects in this patient cohort.Introduction of a UKA robotic-arm assisted system showed learning curves for operative times and insert sizing but not for implant survival at early follow-up. The short learning curve regardless of UKA usage indicated that robotic-arm assisted UKA may be particularly useful for low-usage surgeons.Level III, Retrospective cohort study.

Exchange of groundwater is an important transfer mechanism for nutrients and pollutants between coastal aquifers and surface waters. Constraining such exchange in salt marshes - where biological productivity and biogeochemical cycling rates are among the highest of all coastal ecosystems – is vital for understanding ecosystem function and vulnerability. Here, we quantify groundwater discharge into the tidal Duplin River from the adjoining salt marsh near Sapelo Island, Georgia using high spatial and temporal resolution field measurements of radon-222. Field campaigns occurred for several weeks each summer during 2013, 2015, and 2016. Spatial surveys reveal a general increase in radon activity upstream through the Duplin River, which may result from either higher groundwater discharge or lower mixing rates in the headwaters. To distinguish between these possibilities, we use a radon mass balance model to determine groundwater input. We find that groundwater discharge (normalized to inundated marsh surface area) to the headwaters average 5.1–5.8 cm3/cm2 marsh/day across all three field campaigns, which are comparable to those to the main channel (averaging 6.0–6.5 cm3/cm2 marsh/day across all three field campaigns). Our work reveals a positive relationship between aerial extent of marsh inundation and groundwater discharge into the Duplin River. Discharge is generally maximal during falling tide, reflecting a hydraulic gradient driver, but also is significant prior to high tide, indicative of sediment compression as a driver of groundwater inputs. Constraining the relationship between marsh inundation and resulting groundwater dynamics is an integral aspect to assessing how salt marsh circulation processes may respond to intensifying inundation (from reduced sediment supply, subsidence, and/or rising sea levels).

Treatment with glucocorticoids is the leading cause of drug-induced osteoporosis. National Osteoporosis Guideline Group (NOGG) 2017 guidelines advise a case-finding strategy for patients at risk. The aims of the audit were to evaluate the implementation of the NOGG 2017 guidelines for patients receiving long-term glucocorticoid therapy in a suburban general practice, to instigate changes to ensure 90% of patients are investigated and treated appropriately, and to evaluate impact at a 6-mo re-audit. Reporting Analysis and Intelligence Delivering Results (RAIDR) is a health-care intelligence tool accessing primary care clinical data. Using RAIDR, data on relevant osteoporotic risk factors were combined to produce FRAX scores for patients who had been prescribed glucocorticoids 3 or more times in the past 12 months. FRAX data were displayed in a NOGG guidance graph for major osteoporotic fracture probability. Patients were assessed as high, intermediate, or low risk. High- and intermediate-risk patients above the NOGG threshold were recommended to start bisphosphonates; these patients were sent a prescription for alendronate and a letter of explanation. There were no intermediate patients below the NOGG threshold. Low-risk patients were recommended to have lifestyle advice; a leaflet was produced and sent to these patients. Initial results showed that only 25% of patients recommended to be on bisphosphonates were taking them. Steps were taken to educate the general practitioners in the FRAX tool and NOGG guidelines; the chronic obstructive pulmonary disease annual template was amended to aid adherence by alerting the nurse to the number of glucocorticoid courses prescribed, with additional boxes for prescribing alendronate and printing the lifestyle leaflet; and 2-monthly RAIDR searches by the practice pharmacist were started. A re-audit 6 mo later showed improvement to 92%. This audit showed that education, reminders, and simple computer prompts can greatly improve the implementation of NOGG guidelines for glucocorticoid-induced osteoporosis.