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Abstract Genomes computationally inferred from large metagenomic data sets are often incomplete and may be missing functionally important content and strain variation. We introduce an information retrieval system for large metagenomic data sets that exploits the sparsity of DNA assembly graphs to efficiently extract subgraphs surrounding an inferred genome. We apply this system to recover missing content from genome bins and show that substantial genomic sequence variation is present in a real metagenome. Our software implementation is available at https://github.com/spacegraphcats/spacegraphcats under the 3-Clause BSD License.

This study explores the viewing patterns of 17 instructional videos in both a traditional and flipped classroom environment by 732 business students taking an IT-related module. While previous work has concentrated mainly on outputs(e.g. student satisfaction/results), this study focuses on how the nature of students’ interactions with videos can be determined through a deep analysis of analytics data. The main findings show that there were less interactions with the instructional videos in the flipped classroom environment compared to the traditional environment, and that videos were used more as a revision aid prior to exams (in both environments) than as an ongoing support to develop skills during term. Implications of this study include the need for regular monitoring of how instructional videos are being used during termand the importance of undertaking a deeper analysis of analytics data as the initial summary data may be misleading.

Abstract Global change research has largely focused on the effects of drought on forest dynamics while the importance of excessive rainfall that can cause waterlogged soils has largely been assessed in riparian zones or seasonally flooded sites. However, increased rainfall may also cause decreased growth and survival of tree species in lowland aseasonal tropical forests due to increased risk from potentially more extensive and frequent waterlogged soils. We used a Bayesian modelling approach on a tree dynamics dataset from 2004 to 2017 to test the concomitant effects of rainfall excess and deficit and dry period length on tree growth and survival across a network of experimentally planted trees in a primary aseasonal forest in Malaysia. Growth declined in 48% of the species and survival decreased in 92% of the species during periods of high rainfall while as little as 4% of species had decreased growth or survival with drought and long dry periods. Climate change is projected to cause more frequent and severe rainfall deficit and excess, and our results suggest increased rainfall may have stronger negative effects on aseasonal tropical forests than that of severe drought.

Abstract One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure.

ABSTRACTDuring the Middle and Late Woodland periods in the American Midwest some small-scale societies transitioned from grit to limestone as the primary clay temper. Limestone offers experimentally demonstrated benefits to vessel manufacture, including decreased wall thickness, but given the society-wide changes in mobility and exchange that also occurred, we investigated whether the use of limestone temper resulted in a different vessel weight relative to an analogous grit-tempered vessel. Our analyses demonstrated a significant difference: post-firing, limestone-tempered vessels were 4.5% lighter than grit-tempered ones. The combination of reduced weight and other benefits could help explain why limestone became the predominant temper type throughout much of the Midwest. These issues have direct analogs in the biological realm, and we use three concepts from evolutionary biology – modularity, mosaic evolution, and constraint – to investigate the role limestone temper played not only in vessel weight but also in other aspects of vessel production and use.

Background: Hepatitis C virus (HCV) is associated with increased complications of risk after arthroplasty. The purpose of this study was to examine the impact of HCV and a pre-arthroplasty antiviral treatment on complications following total shoulder arthroplasty (TSA). Methods: A retrospective matched cohort study was conducted using an administrative claims database. Patients who underwent TSA were identified with Current Procedural Terminology -23472 and International Classification of Diseases procedural codes. A total of 1244 HCV patients were matched 1:3 with 3732 noninfected controls across age, sex, diabetes mellitus, tobacco use, and obesity. The HCV patients with treatment before TSA were identified by claims containing antiviral drug codes. Multivariable logistic regression was used to compare rates of 90-day medical complications and prosthesis-related complications within 2 years postoperatively for (1) HCV patients vs. controls, (2) antiviral-treated HCV patients vs. controls, and (3) antiviral-treated HCV patients vs. untreated HCV patients. Results: Patients with HCV exhibited significantly higher rates of blood transfusion (OR 2.12), acute kidney injuries (OR 1.86), inpatient readmission (OR 2.06), revision TSA (OR 1.48), dislocation (OR 1.92), mechanical complications (OR 1.39), and prosthetic joint infection (OR 1.53) compared to controls. Antiviral-treated HCV patients exhibited a significantly lower rate of myocardial infarction (OR 0.27) and comparable rates of all other complications relative to controls (all P > .05). Compared to untreated HCV patients, antiviral-treated HCV patients exhibited significantly lower rates of 90-day medical complications (OR 0.57) and prosthetic joint infection (OR 0.36). Conclusions: HCV is associated with significantly increased complication rates after TSA. Antiviral treatment before TSA may reduce the risk of postoperative complications.

Functional variations in tropical forests can be determined from remotely sensed forest trait and structural attributes at spatial resolutions relevant to satellite-based observations, according to a coarse resolution analysis of airborne remotely sensed data in Malaysian Borneo.

Abstract Diversity drives both biological and artificial evolution. A prevalent assumption in cultural evolution is that the generation of novel features is an inherent property of a subset of the population (e.g., experts). In contrast, diversity—the fraction of objects in the corpus that are unique—exhibits complex collective dynamics such as oscillations that cannot be simply reduced to individual attributes. Here, we explore how a popular cultural domain can rapidly expand to the point where it exceeds the supply of subject-specific experts and the balance favours imitation over invention. At this point, we expect diversity to decrease and information redundancy to increase as ideas are increasingly copied rather than invented. We test our model predictions on three case studies: early personal computers and home consoles, social media posts, and cryptocurrencies. Each example exhibits a relatively abrupt departure from standard diffusion models during the exponential increase in the number of imitators. We attribute this transition to the “dilution of expertise.” Our model recreates observed patterns of diversity, complexity and artifact trait distributions, as well as the collective boom-and-bust dynamics of innovation.

Background: Proximal humerus fractures are the third most common fracture in older adults. Because of the aging population, the incidence of these fractures and their impact will continue to grow. With advancement in treatment options for proximal humeral fractures, the aim of this study was to evaluate the trends in acute management of proximal humerus fractures to determine how definitive treatment has changed over the past decade in patients older than 65 years. Methods: Using a commercially available database, patient records were queried from 2010 to 2019 for the incidence of proximal humerus fractures. For each individual year, data were queried to identify the incidence of closed reduction percutaneous pinning (CRPP), hemiarthroplasty (HA), intramedullary nailing (IMN), open reduction internal fixation (ORIF), total shoulder arthroplasty (TSA), reverse total shoulder arthroplasty (RSA), or nonoperative treatment for acute proximal humeral fractures. A Cochran-Armitage trend test was used to determine significant changes in the trends of proximal humerus fracture management. Logistic regression analyses were performed to generate odds ratios (OR) with associated 95% confidence intervals comparing each individual procedure performed in 2019 to 2010. Results: A total of 160,836 patients at least 65 years of age and older were diagnosed with a proximal humerus fracture. Of this total, 28,503 (17.72%) patients received operative treatment and 132,333 (82.28%) received nonoperative treatment. From 2010 to 2019, operative treatment trends of proximal humerus fractures changed such that CRPP decreased by 60.0%, HA decreased by 81.4%, IMN decreased by 81.9%, ORIF decreased by 25.7%, TSA decreased by 80.5%, and RSA increased by 1841.4% (all P

Abstract Purpose Over the past 40 years, advances in the development of anchors and sutures have contributed to the improvement in surgical outcomes for treatment of shoulder instability. Important choices in surgery when treating instability include the use of knotless versus knotted suture anchors, and bony versus soft tissue reconstruction techniques. Methods A literature review was conducted to evaluate the history of instability of the shoulder and the results of specific fixation techniques including bony and soft tissue reconstructions as well as knotted and knotless suture anchors. Results As knotless suture anchors have continued to grow in popularity since their development in 2001, many studies have compared this newer technique to that of the standard knotted suture anchors. In general, these studies have demonstrated no difference in patient‐reported outcome measures between the two options. Additionally, the choice of bony versus soft tissue reconstructions is patient specific as it depends on the specific pathology or combination of injuries. Conclusion In each surgery performed for shoulder instability, it is vitally important that we try to restore normal anatomy. The normal anatomy is best established by knotted mattress sutures. However, loop laxity and tear through by the sutures in the capsule can eliminate this restoration, increasing risk of failure. Knotless anchors may allow better soft tissue fixation of the labrum and capsule to the glenoid, but without complete restoration of normal anatomy.

Objectives: Demonstrate the benefits of using 3D printed skull models when counseling families regarding disorders of the cranial vault (namely plagiocephaly and craniosynostosis), as traditional imaging review and discussion is often insufficient. Methods: 3D printed skull models of a patient with plagiocephaly were used during clinic appointments to aid in the counseling of parents. Surveys were distributed following the appointment to evaluate the utility of these models during the discussion. Results: Fifty surveys were distributed (with a 98% response rate). 3D models were both empirically and anecdotally helpful for parents in understanding their child's diagnosis. Conclusion: Advances in 3D printing technology and software have made producing models more accessible. Incorporating physical, disorder-specific models into our discussions has led to improvements in our ability to communicate with our patients and their families. Innovation: Disorders of the cranial can be challenging to describe to the parents and guardians of affected children; using 3D printed models is a useful adjunct in patient-centered discussions. The subject response to the use of these emerging technologies in this setting suggests a major role for 3D models in patient education and counseling for cranial vault disorders.

Abstract Localized cartilage lesions in early osteoarthritis and acute joint injuries are usually treated surgically to restore function and relieve pain. However, a persistent clinical challenge remains in how to repair the cartilage lesions. We expressed doublecortin (DCX) in human adipose-derived stromal/stem cells (hASCs) and engineered hASCs into cartilage tissues using an in vitro 96-well pellet culture system. The cartilage tissue constructs with and without DCX expression were implanted in the knee cartilage defects of rabbits (n = 42) and monkeys (n = 12). Cohorts of animals were euthanized at 6, 12, and 24 months after surgery to evaluate the cartilage repair outcomes. We found that DCX expression in hASCs increased expression of growth differentiation factor 5 (GDF5) and matrilin 2 in the engineered cartilage tissues. The cartilage tissues with DCX expression significantly enhanced cartilage repair as assessed macroscopically and histologically at 6, 12, and 24 months after implantation in the rabbits and 24 months after implantation in the monkeys, compared to the cartilage tissues without DCX expression. These findings suggest that hASCs expressing DCX may be engineered into cartilage tissues that can be used to treat localized cartilage lesions.

Ng, Kobayashi, et al. present the genome assembly for the dipterocarp Shorea leprosula and present transcriptome data for ten more dipterocarp species of seven genera. The Shorea leprosula genome, along with drought stress experiments, demonstrate evidence for a whole-genome duplication (WGD) event dated to the Cretaceous-Paleogene boundary, with WGD duplicates enriched in genes upregulated during the drought response.

Background: The outcomes and complication rates of patients with isolated greater tuberosity fractures are not well documented. The present study aimed to evaluate the reoperation rates, types of reoperations, and complications for patients undergoing open reduction internal fixation and those undergoing initial nonoperative treatment of isolated greater tuberosity fractures. Methods: An administrative claims database was queried from 2010 to 2018 for adult patients treated with open reduction internal fixation or initial nonoperative treatment within 6 weeks of sustaining a closed isolated greater tuberosity fracture. Reoperation rates, types of reoperations, local/surgical complications, and systemic complications for two cohorts were collected, and statistical analysis was performed using R statistical software for patients initially treated operatively and nonoperatively. Complication rates were compared using multivariate logistic regression, while demographic data were compared using chi-square analysis. Results: Of the 8509 patients who were documented to have sustained a closed isolated greater tuberosity fracture, 333 patients underwent operative treatment and 8176 patients received initial nonoperative treatment within the first 6 weeks of diagnosis. The operative cohort had a reoperation rate of 2.7% at 90 days, 5.7% at 6 months, and 7.8% at 1 year, with the majority of reoperations being rotator cuff repair (40.6%). Within the initial nonoperative cohort, 7.3% had an operation within a year, with the majority of operations being open reduction internal fixation (41.3%). The subsequent reoperation rate for those patients was 3.5% at 2 years with the majority of reoperations being rotator cuff repair (32.4%). In the operative cohort, the 90-day infection rate was 3.0%. Nonunion was demonstrated in the operative cohort at a rate of 1.8% at 6 months and 2.7% at 1 year. Conclusion: When surgical care was provided to patients sustaining isolated greater tuberosity fractures in the first 6 weeks, there was a 7.8% rate of reoperation within the first year. Patients initially treated nonoperatively had a future operation rate of 7.3% within the first year and a 3.5% reoperation rate within the second year. The most common reoperation regardless of initial treatment was rotator cuff repair. With an elevated rate of subsequent operations, education is paramount to provide patients with expectations for the sequelae of this injury especially when presenting with concomitant injuries.

The relationship of mycorrhizal associations with latitudinal gradients in tree beta-diversity is unexplored. Using a global dataset approach, this study examines how trees with arbuscular mycorrhizal and ectomycorrhizal associations contribute to latitudinal beta-diversity patterns and the environmental controls of these patterns.

AbstractIntroduction Bupropion overdose can produce seizures, arrhythmias, and shock. The toxicokinetics of massive bupropion ingestions are not well characterized.Case report A 22-year-old female ingested an estimated 40.5 g (644 mg/kg) of extended release bupropion. Subsequently she experienced seizures, required intubation, developed torsades des pointes that progressed to cardiac arrest, and required cannulation with venous-arterial extracorporeal membrane oxygenation (VA-ECMO). Intravenous lipid emulsion was administered without adversely affecting the ECMO circuit. The patient was successfully decannulated after 84 h of ECMO support and discharged neurologically intact. Serial bupropion and hydroxybupropion serum concentrations were drawn every 6-12 h starting on hospital day one and continuing for seven days, for a total of 22 serum concentrations each.Discussion The patient’s first bupropion and hydroxybupropion serum concentrations were 4000 ng/mL and 5300 ng/mL, respectively. Clearance of bupropion followed first order kinetics (t ½ = 20.6 h) while hydroxybupropion had zero order kinetics (t ½ = 118.5 h).Conclusion This bupropion overdose was treated with VA-ECMO with 20% lipid emulsion therapy, without complications. In this patient, the toxicokinetics of bupropion were first-order.

News claims that travel the Internet and online social networks (OSNs) originate from different, sometimes unknown sources, which raises issues related to the credibility of those claims and the drivers behind them. Fact-checking websites such as Snopes, FactCheck, and Emergent use human evaluators to investigate and label news claims, but the process is labor- and time-intensive. Driven by the need to use data analytics and algorithms in assessing the credibility of news claims, we focus on what can be generalized about evaluating human-labeled claims. We developed tools to extract claims from Snopes and Emergent and used public datasets collected by and published on those websites. Claims extracted from those datasets were supervised or labeled with different claim ratings. We focus on claims with definite ratings—false, mostly false, true, and mostly true, with the goal of identifying distinctive features that can be used to distinguish true from false claims. Ultimately, those features can be used to predict future unsupervised or unlabeled claims. We evaluate different methods to extract features as well as different sets of features and their ability to predict the correct claim label. By far, we noticed that OSN websites report high rates of false claims in comparison with most of the other website categories. The rate of reported false claims is higher than the rate of true claims in fact-checking websites in most categories. At the content-analysis level, false claims tend to have more negative tones in sentiments and hence can provide supporting features to predict claim classification.

Physical insult from a mild Traumatic Brain Injury (mTBI) leads to changes in blood flow in the brain and measurable changes in white matter, suggesting a physiological basis for chronic symptom presentation. Post-traumatic headache (PTH) is frequently reported by persons after an mTBI that may persist beyond the acute period (>3 months). It remains unclear whether ongoing inflammation may contribute to the clinical trajectory of PTH. We recruited a cohort of pediatric subjects with PTH who had an acute or a persistent clinical trajectory, each around the 3-month post-injury time point, as well as a group of age and sex-matched healthy controls. We collected salivary markers of mRNA expression as well as brain imaging and psychological testing. The persistent PTH group showed the highest levels of psychological burden and pain symptom reporting. Our data suggest that the acute and persistent PTH cohort had elevated levels of complement factors relative to healthy controls. The greatest change in mRNA expression was found in the acute-PTH cohort wherein the complement cascade and markers of vascular health showed a prominent role for C1Q in PTH pathophysiology. These findings (1) underscore a prolonged engagement of what is normally a healthy response and (2) show that a persistent PTH symptom trajectory may parallel a poorly regulated inflammatory response.

The identification of cannabinoid ligands Cannabidiol and O-1918 as inverse agonists of the orphan receptor GPR52 is reported. Detailed characterisation of GPR52 pharmacology and modelling of the proposed receptor interaction is described. The identification of a novel and further CNS pharmacology for the polypharmacological agent and marketed drug Cannabidiol is noteworthy.

Viral infections and the harm they cause to their host are a perpetual threat to living organisms. Pathogenesis and subsequent spread of infection requires replication of the viral genome and expression of structural and non-structural proteins of the virus. Generally, viruses use transcription and translation machinery of the host cell to achieve this objective. The viral genome encodes transcriptional regulators that alter the expression of viral and host genes by manipulating initiation and termination steps of transcription. The regulation of the initiation step is often through interactions of viral factors with gene specific factors as well as general transcription factors (GTFs). Among the GTFs, TFIIB (Transcription Factor IIB) is a frequent target during viral pathogenesis. TFIIB is utilized by a plethora of viruses including human immunodeficiency virus, herpes simplex virus, vaccinia virus, Thogoto virus, hepatitis virus, Epstein-Barr virus and gammaherpesviruses to alter gene expression. A number of viral transcriptional regulators exhibit a direct interaction with host TFIIB in order to accomplish expression of their genes and to repress host transcription. Some viruses have evolved proteins with a three-dimensional structure very similar to TFIIB, demonstrating the importance of TFIIB for viral persistence. Upon viral infection, host transcription is selectively altered with viral transcription benefitting. The nature of viral utilization of TFIIB for expression of its own genes, along with selective repression of host antiviral genes and downregulation of general host transcription, makes TFIIB a potential candidate for antiviral therapies.

Purpose: To compare the likelihood of spiral fracture of the humerus using torsional load to failure after intraosseous biceps tenodesis at the position of the arthroscopic suprapectoral tenodesis versus the subpectoral meta-diaphyseal location. Methods: Eight matched pairs of humeri were dissected. Unicortical tenodesis holes were drilled, either at the bottom of the bicipital groove (group 1) or just below the pectoralis major tendon insertion (subpectoral) in the humeral diaphysis (group 2). Tenodesis was performed in a 7-mm bone tunnel, with suture fixation distal to this site using 2 separate 2-mm holes, secured with No. 2 polyester suture. Each humerus was potted in plaster and mounted to a hydraulic torsional load frame, consistent with previously validated models for creating humeral spiral fractures. External rotation torque was applied to each humerus distally until fracture occurred. The paired t test was used to compare the 2 groups. Results: Fracture occurred at the subpectoral cortical drill hole in all 8 specimens in group 2. In group 1, only 2 fractures occurred through the tenodesis hole, with spiral fracture resulting in the diaphysis of the humerus in 6 of 8 specimens. Average torque to failure measured 31.35 Nm in group 1 and 25.08 Nm in group 2; the difference was statistically significant (P < .0001). Conclusions: Subpectoral cortical drill holes for biceps tenodesis were shown to be a stress riser for humeral spiral fracture. Suprapectoral cortical drill holes were shown to be significantly less of a stress riser. The amount of torque required to fracture the humerus through the subpectoral drill holes was less than with the suprapectoral drill holes. Only 2 fractures occurred through the suprapectoral tenodesis holes, and significantly more torque was required to create these fractures. Clinical Relevance: Clinically, the difference between suprapectoral and subpectoral tenodesis fracture potential should be considered when selecting a tenodesis location.

Purpose: To evaluate the volume and yield of morselized cartilage that can be harvested from the shoulder for immediate reimplantation and repair. Methods: A standard arthroscopic approach was used to harvest non–load-bearing cartilage from 5 cadaveric shoulder specimens. Cartilage was separated from the humerus, grasped, added to the cartilage particulator, and morselized to form a cartilage paste. The volume of reclaimed cartilage was measured and compared with average humeral and glenoid defects. Results: The total yield of cartilage paste following tissue processing that was obtained from the 5 glenohumeral joints ranged from 1.0 mL to 2.4 mL with a mean volume of 1.9 ± 0.5 mL, yielding a theoretical 18.6 cm2 ± 5.2 cm2 of coverage with a 1-mm monolayer. Previously reported mean glenoid defect size ranges from 1.12 cm2 to 2.73 cm2, while the mean humeral defect size ranges from 4.22 cm2 to 6.00 cm2. Conclusions: This study validated that through a single-stage surgical and processing technique it is possible to obtain a sufficient volume for re-implantable autologous morselized cartilage graft to address most glenohumeral articular cartilage defects. Clinical Relevance: Chondrocyte grafts have been shown to be effective in cartilage repair. A single-site, single-staged procedure that uses a patient’s autologous shoulder cartilage from the same joint has the potential to reduce morbidity associated with multiple surgical sites, multistaged procedures, or nonautologous tissue in shoulder surgery.

Injuries to the acromioclavicular (AC) joint are common and comprise ∼12% of shoulder injuries. Stability to the AC joint depends on the coracoclavicular (CC) ligaments for vertical stability and AC ligaments and capsular structures for horizontal stability. Injuries to the AC ligaments can lead to horizontal instability of the AC joint. There is no gold standard technique for treating these injuries surgically, and many of the described procedures focus on vertical instability rather than horizontal instability. This article describes an open AC ligament reconstruction with semitendinosus allograft to restore horizontal stability of the AC joint.

Purpose: The purpose of this study was to identify the most commonly used outcome measurements following shoulder surgery and to investigate demographic variables related to their use. Methods: PubMed and Embase were searched to identify studies in which at least 1 shoulder-specific outcome measurement was used. Exclusion criteria included duplicate studies, review articles, lack of surgical arm, written in a language other than English, or not adult-specific. Additionally, surgeries were subcategorized based on the type of pathology leading to surgery. Results: Of the 589 articles identified in the search, 180 met the inclusion criteria. A total of 35 shoulder-specific outcome measurements were reported. The Constant-Murley score (CMS), American Shoulder and Elbow Surgeons Shoulder Score (ASES), Subjective Shoulder Value (SSV), Simple Shoulder Test (SST), and University of California Los Angeles Score (UCLA) were used in more than 10% of the articles. The CMS and SSV were used more commonly together than individually (P = .0074). Additionally, the ASES (P < .00001) and CMS (P = .0109) were associated with the country of origin of the article. The SST was used more frequently in randomized control trials (P = .0287). The ASES and DASH were associated with surgeries categorized under the degenerative indication (P = .001 and P = .0146). Finally, the SSV, ASES and DASH were all found to be significantly paired with surgeries that indicated traumatic pathology (P = .0061, P = .0077 and P = .0069, respectively). Conclusions: There is great variability among the outcome measurements currently being used for assessing function following orthopaedic shoulder surgery; however, 5 scoring systems are used more frequently than others. There remains a large discrepancy between the ideal reporting, as noted in the recent literature review, and the current state of outcomes reported at this time. Clinical Relevance: By identifying and evaluating the heterogeneity of the reporting and the usage of the performance indicators, these results can guide the standardization of outcome measurements in shoulder surgery and allow for better comparability when assessing outcomes between patients and studies.

Alpha-1 antitrypsin (AAT) deficiency (AATD) is characterized by increased risk for emphysema, chronic obstructive pulmonary disease (COPD), vasculitis, and wound-healing impairment. Neutrophils play a central role in the pathogenesis of AATD. Dysregulated complement activation in AATD results in increased plasma levels of C3d. The current study investigated the impact of C3d on circulating neutrophils. Blood was collected from AATD (n = 88) or non-AATD COPD patients (n = 10) and healthy controls (HC) (n = 40). Neutrophils were challenged with C3d, and degranulation was assessed by Western blotting, ELISA, or fluorescence resonance energy transfer (FRET) substrate assays. Ex vivo, C3d levels were increased in plasma (p < 0.0001) and on neutrophil plasma membranes (p = 0.038) in AATD compared to HC. C3d binding to CR3 receptors triggered primary (p = 0.01), secondary (p = 0.004), and tertiary (p = 0.018) granule release and increased CXCL8 secretion (p = 0.02). Ex vivo plasma levels of bactericidal-permeability-increasing-protein (p = 0.02), myeloperoxidase (p < 0.0001), and lactoferrin (p < 0.0001) were significantly increased in AATD patients. In endothelial cell scratch wound assays, C3d significantly decreased cell migration (p < 0.0001), an effect potentiated by neutrophil degranulated proteins (p < 0.0001). In summary, AATD patients had increased C3d in plasma and on neutrophil membranes and, together with neutrophil-released granule enzymes, reduced endothelial cell migration and wound healing, with potential implications for AATD-related vasculitis.

Articular surface partial rotator cuff tendon tears are a common source of shoulder pain and dysfunction, and there is no consensus regarding the optimal arthroscopic treatment. Commonly accepted techniques, such as transtendinous repair or tear takedown with primary repair, may violate healthy tendon tissue and increase the suture anchor density. In this note, we describe an outside-in double row–equivalent technique for repair of partial articular-sided rotator cuff tears. A medial row of inverted horizontal mattress stitches is placed percutaneously using spinal needles to shuttle partially absorbable braided sutures into the joint. The technique may incorporate a soft tissue biceps tenodesis into the rotator cuff with a second, oblique medial row mattress stitch. Suture limbs are retrieved and tied in the subacromial space and then secured to a lateral anchor. The result is a side-to-side double row–equivalent rotator cuff repair, anatomically reproducing the footprint of the rotator cuff without removing healthy tissue. We believe this is an efficient and reproducible technique that preserves intact bursal tissue, limits implant costs, and produces reliable healing in partial articular-sided tears of the rotator cuff.

Lateral epicondylitis, or tennis elbow, involves degeneration of the extensor carpi radialis brevis tendon and is often self-limiting, with surgery reserved for recalcitrant cases. Surgical management of tennis elbow consists primarily of either debridement alone or debridement with repair. Surgical repair is often performed using either a suture or a suture anchor. Good outcomes have been reported using standard repair methods; however, complications exist. Complications include potential loss of grip strength with debridement alone, as well as soft-tissue irritation caused by a prominent suture or knot stack after suture repair and suture anchor techniques. We describe a technique for debridement and repair of the extensor carpi radialis brevis tendon to the lateral epicondyle of the humerus using a knotless suture anchor, allowing for a watertight anatomic repair, maximum preservation of grip strength, and absence of a knot stack and resultant suture prominence.

Shoulder arthroscopy is the second most common orthopaedic procedure. Diagnostic arthroscopy of the shoulder requires an efficient and reproducible technique. In this Technical Note, we describe a step-wise approach to diagnostic arthroscopy of the shoulder. This technique is performed using a posterior viewing portal. It can be performed from the beach chair or the lateral decubitus position. This technique uses a 2-circle approach: the surgeon first evaluates the glenoid aspect of the joint space, followed by the humeral aspect of the joint space. This method ensures a complete and consistent evaluation of the glenohumeral joint.

There is a long and rich tradition in the social sciences of using models of collective behavior in animals as jumping-off points for the study of human behavior, including collective human behavior. Here, we come at the problem in a slightly different fashion. We ask whether models of collective human behavior have anything to offer those who study animal behavior. Our brief example of tipping points, a model first developed in the physical sciences and later used in the social sciences, suggests that the analysis of human collective behavior does indeed have considerable to offer [Current Zoology 58(2): 298-306, 2012].

The purpose of this report is to describe our modification of the Verma-Trenhaile biceps tenodesis technique using a superior viewing portal that allows placement of the tenodesis site at the top of the pectoralis major tendon with interference screw fixation. The advantages of this technique include the following: (1) There is no need to exteriorize the tendon through the skin. (2) Viewing from superiorly allows a panoramic view of the groove all the way to the pectoralis major tendon insertion. (3) This panoramic view allows a more complete view of the biceps down to the muscle-tendon junction beneath the pectoralis major tendon. (4) The improved visualization permits the drill hole to be contained within the constraints of the groove. Short-term follow-up shows favorable results clinically, and no major complications have been associated with this technique.

Efficiently passing spiking messages in a neural model is an important aspect of high-performance simulation. As the scale of networks has increased so has the size of the computing systems required to simulate them. In addition, the information exchange of these resources has become more of an impediment to performance. In this paper we explore spike message passing using different mechanisms provided by the Message Passing Interface (MPI). A specific implementation, MVAPICH, designed for high-performance clusters with Infiniband hardware is employed. The focus is on providing information about these mechanisms for users of commodity high-performance spiking simulators. In addition, a novel hybrid-method for spike exchange was implemented and benchmarked.

Modeling work suggests that population size affects cultural evolution such that larger populations can be expected to have richer and more complex cultural repertoires than smaller populations. Empirical tests of this hypothesis, however, have yielded conflicting results. Here, we report a study in which we investigated whether the subsistence toolkits of small-scale food-producers are influenced by population size in the manner the hypothesis predicts. We applied simple linear and standard multiple regression analysis to data from 40 nonindustrial farming and pastoralist groups to test the hypothesis. Results were consistent with predictions of the hypothesis: both the richness and the complexity of the toolkits of the food-producers were positively and significantly influenced by population size in the simple linear regression analyses. The multiple regression analyses demonstrated that these relationships are independent of the effects of risk of resource failure, which is the other main factor that has been found to influence toolkit richness and complexity in nonindustrial groups. Thus, our study strongly suggests that population size influences cultural evolution in nonindustrial food-producing populations.

As public and political debates often demonstrate, a substantial disjoint can exist between the findings of science and the impact it has on the public. Using climate-change science as a case example, we reconsider the role of scientists in the information-dissemination process, our hypothesis being that important keywords used in climate science follow "boom and bust" fashion cycles in public usage. Representing this public usage through extraordinary new data on word frequencies in books published up to the year 2008, we show that a classic two-parameter social-diffusion model closely fits the comings and goings of many keywords over generational or longer time scales. We suggest that the fashions of word usage contributes an empirical, possibly regular, correlate to the impact of climate science on society.

It has long been argued that the form of North American Paleoindian points was affected by hafting. According to this hypothesis, hafting constrained point bases such that they are less variable than point blades. The results of several studies have been claimed to be consistent with this hypothesis. However, there are reasons to be skeptical of these results. None of the studies employed statistical tests, and all of them focused on points recovered from kill and camp sites, which makes it difficult to be certain that the differences in variability are the result of hafting rather than a consequence of resharpening. Here, we report a study in which we tested the predictions of the hafting hypothesis by statistically comparing the variability of different parts of Clovis points. We controlled for the potentially confounding effects of resharpening by analyzing largely unused points from caches as well as points from kill and camp sites. The results of our analyses were not consistent with the predictions of the hypothesis. We found that several blade characters and point thickness were no more variable than the base characters. Our results indicate that the hafting hypothesis does not hold for Clovis points and indicate that there is a need to test its applicability in relation to post-Clovis Paleoindian points.

Recent work suggests that global variation in toolkit structure among hunter-gatherers is driven by risk of resource failure such that as risk of resource failure increases, toolkits become more diverse and complex. Here we report a study in which we investigated whether the toolkits of small-scale farmers and herders are influenced by risk of resource failure in the same way. In the study, we applied simple linear and multiple regression analysis to data from 45 small-scale food-producing groups to test the risk hypothesis. Our results were not consistent with the hypothesis; none of the risk variables we examined had a significant impact on toolkit diversity or on toolkit complexity. It appears, therefore, that the drivers of toolkit structure differ between hunter-gatherers and small-scale food-producers.

Objectives. The objective of this study was to compare the damage to the rotator cuff tendons caused by four different anchor systems. Methods. 20 cadaveric human shoulder joints were used for transtendon insertion of four anchor systems. The Healix Peek, Fastin RC, Bio-Corkscrew Suture, and Healix Transtend anchors were inserted through the tendons using standard transtendon procedures. The areas of tendon damage were measured. Results. The areas of tendon damage (mean ± standard deviation, n=7) were 29.1 ± 4.3 mm2 for the Healix Peek anchor, 20.4 ± 2.3 mm2 for the Fastin RC anchor, 23.4 ± 1.2 mm2 for the Bio-Corkscrew Suture anchor, 13.7 ± 3.2 mm2 for the Healix Transtend anchor inserted directly, and 9.1 ± 2.1 mm2 for the Healix Transtend anchor inserted through the Percannula system (P

Despite a growing number of social scientists who view the evolution of culture as a Darwinian process, research in the field at large is still rooted in the orthogenetic, progressive models of cultural evolution that were popularized in the nineteenth century and brought back in a new form in the mid-twentieth century. This is unfortunate because it shifts the focus away from the fact that cultural evolution is driven by some exceedingly complicated and highly interesting mechanisms that await further analytical attention. A better understanding of human behaviour, which is at the heart of cultural evolution, depends on a general recognition that genes and culture are not separately evolving entities but rather co-evolving components of the human enterprise.

The paper describes our approach to early process development in the context of the new Wyeth productivity model to deliver two New molecular entities every year. As a consequence, the number of compounds in Predevelopment and Phase 0 increased fourfold, the cycle time from Discovery to the IND was shortened by 6 months, and the quantities for the Phase-0 batch increased to include Phase I supply. our new way of working to meet this paradigm without a major increase in headcount is delineated in this article.

Abstract Background Elastin breakdown and the resultant loss of lung elastic recoil is a hallmark of pulmonary emphysema in susceptible individuals as a consequence of tobacco smoke exposure. Systemic alterations to the synthesis and degradation of elastin may be important to our understanding of disease phenotypes in chronic obstructive pulmonary disease. We investigated the association of skin elasticity with pulmonary emphysema, obstructive lung disease, and blood biomarkers of inflammation and tissue protease activity in tobacco-exposed individuals. Methods Two hundred and thirty-six Caucasian individuals were recruited into a sub-study of the University of Pittsburgh Specialized Center for Clinically Orientated Research in chronic obstructive pulmonary disease, a prospective cohort study of current and former smokers. The skin viscoelastic modulus (VE), a determinant of skin elasticity, was recorded from the volar forearm and facial wrinkling severity was determined using the Daniell scoring system. Results In a multiple regression analysis, reduced VE was significantly associated with cross-sectional measurement of airflow obstruction (FEV1/FVC) and emphysema quantified from computed tomography (CT) images, β = 0.26, p = 0.001 and β = 0.24, p = 0.001 respectively. In emphysema-susceptible individuals, elasticity-determined skin age was increased (median 4.6 years) compared to the chronological age of subjects without emphysema. Plasma biomarkers of inflammation (TNFR1, TNFR2, CRP, PTX3, and SAA) and matrix metalloproteinase activity (MMP1, TIMP1, TIMP2, and TIMP4) were inversely associated with skin elasticity. Conclusions We report that an objective non-invasive determinant of skin elasticity is independently associated with measures of lung function, pulmonary emphysema, and biomarkers of inflammation and tissue proteolysis in tobacco-exposed individuals. Loss of skin elasticity is a novel observation that may link the common pathological processes that drive tissue elastolysis in the extracellular matrix of the skin and lung in emphysema-susceptible individuals.

Abstract Background The ubiquitin-proteasome pathway, mediated in part, by ubiquitin E3 ligases, is critical in regulating cellular processes such as cell proliferation, apoptosis, and migration. FBXO17 was recently identified as an F-box protein that targets glycogen synthase kinase-3β to the E3 ubiquitin ligase protein complex for polyubiquitination and proteasomal degradation. Here, we identified that in several lung adenocarcinoma cell lines, FBXO17 cellular protein was detected at relatively high levels, as was expression in a subset of lung cancers. Hence, we investigated the effects of FBXO17 on cell proliferation. Methods Single cell RNA sequencing analysis was performed on a resection of a non-small cell lung carcinoma tumor to examine FBXO17 expression. Multiple lung cancer cell lines were immunoblotted, and The Cancer Genome Atlas was analyzed to determine if FBXO17 expression was amplified in a subset of lung cancers. A549 cells were transfected with empty vector or FBXO17-V5 plasmid and immunoblotted for Akt pathway mediators including PDK1, ERK1/2, ribosomal protein S6, and CREB. Cell proliferation and viability were analyzed by trypan blue exclusion, BrdU incorporation and an MTS-based fluorometric assay. Studies were also performed after transfecting with sifbxo17. Samples were used in an RNA microarray analysis to evaluate pathways affected by reduced FBXO17 gene expression. Results We observed that overexpression of FBXO17 increased A549 cell proliferation coupled with Akt activation. Ectopically expressed FBXO17 also increased ERK1/2 kinase activation and increased phosphorylation of RPS6, a downstream target of mTOR. We also observed an increased number of cells in S-phase and increased metabolic activity of lung epithelial cells expressing FBXO17. FBXO17 knockdown reduced Akt Ser 473 phosphorylation approaching statistical significance with no effect on Thr 308. However, ERK1/2 phosphorylation, cellular metabolic activity, and overall cell numbers were reduced. When we analyzed RNA profiles of A549 cells with reduced FBXO17 expression, we observed downregulation of several genes associated with cell proliferation and metabolism. Conclusions These data support a role for FBXO17 abundance, when left unchecked, in regulating cell proliferation and survival through modulation of Akt and ERK kinase activation. The data raise a potential role for the F-box subunit in modulating tumorigenesis.

Transcranial Doppler (TCD) ultrasound has been demonstrated to be a valuable tool for assessing cerebral hemodynamics via measurement of cerebral blood flow velocity (CBFV), with a number of established clinical indications. However, CBFV waveform analysis depends on reliable pulse onset detection, an inherently difficult task for CBFV signals acquired via TCD. We study the application of a new algorithm for CBFV pulse segmentation, which locates pulse onsets in a sequential manner using a moving difference filter and adaptive thresholding. The test data set used in this study consists of 92,012 annotated CBFV pulses, whose quality is representative of real world data. On this test set, the algorithm achieves a true positive rate of 99.998% (2 false negatives), positive predictive value of 99.998% (2 false positives), and mean temporal offset error of 6.10 ± 4.75 ms. We do note that in this context, the way in which true positives, false positives, and false negatives are defined caries some nuance, so care should be taken when drawing comparisons to other algorithms. Additionally, we find that 97.8% and 99.5% of onsets are detected within 10 and 30 ms, respectively, of the true onsets. The algorithm's performance in spite of the large degree of variation in signal quality and waveform morphology present in the test data suggests that it may serve as a valuable tool for the accurate and reliable identification of CBFV pulse onsets in neurocritical care settings.

Over the past several decades, archaeologists, anthropologists, linguists, and others who study cultural phenomena have begun to appreciate that methods developed to reconstruct the evolutionary, or phylogenetic, relationships among biological taxa can be used to create cultural sequences based on heritable continuity. One method in particular is cladistics, which creates hypothetical statements of relatedness—rendered as trees—based on the model and parameters used. To date, cladistics has been used to create phylogenetic orderings of a wide variety of cultural phenomena, including basketry and other textiles, ceramic vessels, stone projectile points, languages, folk tales, manuscripts, residence patterns, and political organization. Here we lay out the basic method of cladistics and show how it has formed the basis for long-term studies of the colonization of eastern North America during the Early Paleoindian period (ca. 13,300–11,900 calendar years before the present). Statement of Significance Archaeologists have long used changes in artifact form to measure the passage of time, the supposition being that if the changes are ordered correctly, a historical sequence of forms is created. This is correct, but oftentimes what archaeologists really want to know is which thing produced another thing as opposed to simply preceding it. This is an evolutionary sequence. Over the past several decades, not only archaeologists but also anthropologists, linguists, and others who study cultural phenomena have begun to use a suite of methods that were developed to reconstruct the evolutionary, or phylogenetic, relationships among biological taxa, one of which is cladistics. This marks a return to the questions on which the founding of much of anthropology rests: the writing of cultural lineages. This return is important to the growth and continued health of archaeology and anthropology because a reconstructed phylogeny helps guide interpretation of the evolution of traits in that it generates hypotheses about the lineages in which those traits arose and under what circumstances. Data availability The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are contained within the paper.

The microvasculature is prominently affected by traumatic brain injury (TBI), including mild TBI (concussion). Assessment of cerebral hemodynamics shows promise as biomarkers of TBI, and may help inform development of therapies aimed at promoting neurologic recovery. The objective of this study was to assess the evolution in cerebral hemodynamics observable with transcranial Doppler (TCD) ultrasound in subjects suffering from a concussion at different intervals during recovery. Pediatric subjects between the ages of 14 and 19 years clinically diagnosed with a concussion were observed at different points post-injury. Blood flow velocity in the middle cerebral artery was measured with TCD. After a baseline period, subjects participated in four breath holding challenges. Pulsatility index (PI), resistivity index (RI), the ratio of the first two pulse peaks (P2R), and the mean velocity (MV) were computed from the baseline section. The breath hold index (BHI) was computed from the challenge sections. TCD detected two phases of hemodynamic changes after concussion. Within the first 48 h, PI, RI, and P2R show a significant difference from the controls (U = −3.10; P

Música popular in Spanish comprises an overlapping but distinct category from its English language cognate popular music. Latin American scholars and musicians alike recognize the category as fundamentally linked to subaltern or counterhegemonic subjectivities, and música popular occupies a complex relationship to hegemonic institutions (the state, educational institutions, and the culture industry) in populist democracies like that of contemporary Argentina. Perhaps nowhere are these tensions between populism and hegemony more apparent than in state-sponsored schools of popular music that began to emerge in the 1980s. Based on an ethnographic study of the oldest and one of the best known of these schools in Latin America, this article explores the conceptual tensions inherent in the notion of a populist and counterhegemonic school of music, and provides evidence of the ways those tensions are expressed and partially resolved through discourse and musical performance in and outside of the classroom.

Short-term plasticity (STP) is a phenomenon that widely occurs in the neocortex with implications for learning and memory. Based on a widely used STP model, we develop an analytical characterization of the STP parameter space to determine the nature of each synapse (facilitating, depressing or both) in a spiking neural network based on presynaptic firing rate and the corresponding STP parameters. We demonstrate consistency with previous work by leveraging the power of our characterization to replicate the functional volumes that are integral for the previous network stabilization results. We then use our characterization to predict the precise transitional point from the facilitating regime to the depressing regime in a simulated synapse, suggesting 'in vitro' experiments to verify the underlying STP model. We conclude the work by integrating our characterization into a framework for finding suitable STP parameters for self-sustaining random, asynchronous activity in a prescribed recurrent spiking neural network. The systematic process resulting from our analytical characterization improves the success rate of finding the requisite parameters for such networks by three orders of magnitude over a random search.

The additional capabilities provided by high-performance neural simulation environments and modern computing hardware has allowed for the modeling of increasingly larger spiking neural networks. This is important for exploring more anatomically detailed networks but the corresponding accumulation in data can make analyzing the results of these simulations difficult. This is further compounded by the fact that many existing analysis packages were not developed with large spiking data sets in mind. Presented here is a software suite developed to not only process the increased amount of spike-train data in a reasonable amount of time, but also provide a user friendly Python interface. We describe the design considerations, implementation and features of the HRLAnalysis suite. In addition, performance benchmarks demonstrating the speedup of this design compared to a published Python implementation are also presented. The result is a high-performance analysis toolkit that is not only usable and readily extensible, but also straightforward to interface with existing Python modules.

Prehistoric material culture proposed to be symbolic in nature has been the object of considerable archaeological work from diverse theoretical perspectives, yet rarely are methodological tools used to test the interpretations. The lack of testing is often justified by invoking the opinion that the slippery nature of past human symbolism cannot easily be tackled by the scientific method. One such case, from the southwestern Iberian Peninsula, involves engraved stone plaques from megalithic funerary monuments dating ca. 3,500-2,750 B.C. (calibrated age). One widely accepted proposal is that the plaques are ancient mnemonic devices that record genealogies. The analysis reported here demonstrates that this is not the case, even when the most supportive data and techniques are used. Rather, we suspect there was a common ideological background to the use of plaques that overlay the southwestern Iberian Peninsula, with little or no geographic patterning. This would entail a cultural system in which plaque design was based on a fundamental core idea, with a number of mutable and variable elements surrounding it.

Studies of the evolution of collective behavior consider the payoffs of individual versus social learning. We have previously proposed that the relative magnitude of social versus individual learning could be compared against the transparency of payoff, also known as the "transparency" of the decision, through a heuristic, two-dimensional map. Moving from west to east, the estimated strength of social influence increases. As the decision maker proceeds from south to north, transparency of choice increases, and it becomes easier to identify the best choice itself and/or the best social role model from whom to learn (depending on position on east-west axis). Here we show how to parameterize the functions that underlie the map, how to estimate these functions, and thus how to describe estimated paths through the map. We develop estimation methods on artificial data sets and discuss real-world applications such as modeling changes in health decisions.

Climate change induced alterations to rainfall patterns have the potential to affect the regeneration dynamics of plant species, especially in historically everwet tropical rainforest. Differential species response to infrequent rainfall may influence seed germination and seedling establishment in turn affecting species distributions. We tested the role of watering frequency intervals (from daily to six-day watering) on the germination and the early growth of Dipterocarpaceae seedlings in Borneo. We used seeds that ranged in size from 500 to 20,000 mg in order to test the role of seed mass in mediating the effects of infrequent watering. With frequent rainfall, germination and seedling development traits bore no relationship to seed mass, but all metrics of seedling growth increased with increasing seed mass. Cumulative germination declined by 39.4% on average for all species when plants were watered at six-day intervals, and days to germination increased by 76.5% on average for all species from daily to six-day intervals. Final height and biomass declined on average in the six-day interval by 16% and 30%, respectively, but the percentage decrease in final size was greater for large-seeded species. Rooting depth per leaf area also significantly declined with seed mass indicating large-seeded species allocate relatively more biomass for leaf production. This difference in allocation provided an establishment advantage to large-seeded species when water was non-limiting but inhibited their growth under infrequent rainfall. The observed reduction in the growth of large-seeded species under infrequent rainfall would likely restrict their establishment in drier microsites associated with coarse sandy soils and ridge tops. In total, these species differences in germination and initial seedling growth indicates a possible niche axis that may help explain both current species distributions and future responses to climate change.

Human culture has evolved through a series of major tipping points in information storage and communication. The first was the appearance of language, which enabled communication between brains and allowed humans to specialize in what they do and to participate in complex mating games. The second was information storage outside the brain, most obviously expressed in the Upper Paleolithic Revolution—the sudden proliferation of cave art, personal adornment, and ritual in Europe some 35,000–45,000 years ago. More recently, this storage has taken the form of writing, mass media, and now the Internet, which is arguably overwhelming humans’ ability to discern relevant information. The third tipping point was the appearance of technology capable of accumulating and manipulating vast amounts of information outside humans, thus removing them as bottlenecks to a seemingly self-perpetuating process of knowledge explosion. Important components of any discussion of cultural evolutionary tipping points are tempo and mode, given that the rate of change, as well as the kind of change, in information storage and transmission has not been constant over the previous million years.