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Suprathermal electrons are routinely generated in high-intensity laser produced plasmas via instabilities driven by non-linear laser-plasma interaction. Their accurate characterization is crucial for the performance of inertial confinement fusion as well as for performing experiments in laboratory astrophysics and in general high-energy-density physics. Here, we present studies of non-thermal atomic states excited by suprathermal electrons in kJ-ns-laser produced plasmas. Highly spatially and spectrally resolved X-ray emission from the laser-deflected part of the warm dense Cu foil visualized the hot electrons. A multi-scale two-dimensional hydrodynamic simulation including non-linear laser-plasma interactions and hot electron propagation has provided an input for ab initio non-thermal atomic simulations. The analysis revealed a significant delay between the maximum of laser pulse and presence of suprathermal electrons. Agreement between spectroscopic signatures and simulations demonstrates that combination of advanced high-resolution X-ray spectroscopy and non-thermal atomic physics offers a promising method to characterize suprathermal electrons inside the solid density matter. Suprathermal electrons in laser-generated plasmas are potentially useful in many plasma environments. Here the authors show the characterization of suprathermal electrons in laser-generated Cu plasma using a high-resolution X-ray spectroscopy combined with hydrodynamic and atomic modeling. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment. Methods Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance. Results Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]). Conclusions Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.

Abstract Background Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD) and left ventricular hypertrophy (LVH) and low positive predictive value (PPV) for prediction of left ventricular systolic dysfunction (LVSD). We hypothesized that a ~5-min resting 12-lead advanced ECG test ("A-ECG") that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG. Methods Results from nearly every conventional and advanced resting ECG parameter known from the literature to have diagnostic or predictive value were first retrospectively evaluated in 418 healthy controls and 290 patients with imaging-proven CAD, LVH and/or LVSD. Each ECG parameter was examined for potential inclusion within multi-parameter A-ECG scores derived from multivariate regression models that were designed to optimally screen for disease in general or LVSD in particular. The performance of the best retrospectively-validated A-ECG scores was then compared against that of optimized pooled criteria from the strictly conventional ECG in a test set of 315 additional individuals. Results Compared to optimized pooled criteria from the strictly conventional ECG, a 7-parameter A-ECG score validated in the training set increased the sensitivity of resting ECG for identifying disease in the test set from 78% (72-84%) to 92% (88-96%) (P < 0.0001) while also increasing specificity from 85% (77-91%) to 94% (88-98%) (P < 0.05). In diseased patients, another 5-parameter A-ECG score increased the PPV of ECG for LVSD from 53% (41-65%) to 92% (78-98%) (P < 0.0001) without compromising related negative predictive value. Conclusion Resting 12-lead A-ECG scoring is more accurate than strictly conventional ECG in screening for CAD, LVH and LVSD.

Abstract Background Humans demonstrate a number of unique adaptations that allow for the maintenance of blood pressure and brain blood flow when upright. While several physiological systems, including cerebral autoregulation, are involved in this adaptation the unique role the vestibular system plays in helping to maintain brain blood flow is just beginning to be elucidated. In this study, we tested the hypothesis that stimulation of the vestibular system, specifically the otoliths organs, would result in changes in cerebral blood flow. Results To test our hypothesis, we stimulated the vestibular organs of 25 healthy subjects by pitch tilt (stimulates both canals and otoliths) and by translation on a centrifuge (stimulates otoliths and not the canals) at five frequencies: 0.5, 0.25, 0.125 and 0.0625 Hz for 80 sec and 0.03125 Hz for 160 sec. Changes in cerebral flow velocity (by transcranial Doppler) and blood pressure (by Finapres) were similar during both stimuli and dependent on frequency of stimulation (P < 0.01). However, changes in cerebral blood flow were in opposition to changes in blood pressure and not fully dependent on changes in end tidal CO2. Conclusion The experimental results support our hypothesis and provide evidence that activation of the vestibular apparatus, specifically the otolith organs, directly affects cerebral blood flow regulation, independent of blood pressure and end tidal CO2 changes.

Genetic drift, gene flow, and natural selection commonly influence population genetic diversity. In populations of self-compatible hermaphrodites, the mating system (e.g., self-fertilization) further reduces individual heterozygosity. Furthermore, selfing, as a form of inbreeding, significantly impacts genetic drift by reducing effective population size ( N e ). This can potentially accelerate genetic drift, particularly in small populations where self-fertilization is likely during founder events. To investigate the roles of genetic drift and contemporary mating system in populations of the freshwater snail Lymnaea stagnalis , we examined their effective population sizes ( N e ) and Tajima's D values, which reflect genetic drift over extended time periods, as well as estimates of within-population selfing rates and pairwise relatedness reflecting contemporary mating system. We used 4054 SNP markers obtained using restriction site associated DNA (RAD) sequencing from individuals in five snail populations originating from geographically closely located ponds. We found strong population genetic structure and differences in genetic diversity among populations. Covariation between genetic diversity and N e estimates and Tajima's D values suggested drift being an important determinant of genetic diversity and structure in these populations. However, this effect was independent of the contemporary mating system, as indicated by the similarity of selfing rates and relatedness estimates among populations. Thus, founder events (possibly including historical inbreeding) and/or drift due to small sizes of L. stagnalis populations are likely to explain their genetic structure and limit within-population genetic diversity., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Transporting and translating mRNAs in axons is crucial for neuronal viability. Local synthesis of nuclear-encoded mitochondrial proteins protects long-lived axonal mitochondria from damage; however, the regulatory factors involved are largely unknown. We show that CLUH, which binds mRNAs encoding mitochondrial proteins, prevents peripheral neuropathy and motor deficits in the mouse. CLUH is enriched in the growth cone of developing spinal motoneurons and is required for their growth. The lack of CLUH affects the abundance of target mRNAs and the corresponding mitochondrial proteins more prominently in axons, leading to ATP deficits in the growth cone. CLUH interacts with ribosomal subunits, translation initiation, and ribosome recycling components and preserves axonal translation. Overexpression of the ribosome recycling factor ABCE1 rescues the mRNA and translation defects, as well as the growth cone size, in CLUH-deficient motoneurons. Thus, we demonstrate a role for CLUH in mitochondrial quality control and translational regulation in axons, which is essential for their development and long-term integrity and function.

The high failure rate of rotator cuff repair surgeries is positively correlated with age, yet the biomechanical changes to the tendons of the rotator cuff with age have not been described. As such, we sought to benchmark and characterize the biomechanical and histopathological properties with the accompanying gene expression of human rotator cuff tendons as a function of age and histopathological degeneration. All four rotator cuff tendons from fresh human cadaver shoulders underwent biomechanical, histopathological, and gene expression analyses. Following cadaver availability, samples were grouped into Younger (i.e., less than 36 years of age, n = 2 donors) and Aged (i.e., greater than 55 years of age, n = 3 donors) as a means of characterizing and quantifying the age-related changes exhibited by the tendons. Biomechanical testing and subsequent computational modeling techniques revealed both differences in properties between tendons and greater Young's moduli in the Younger tendons (supraspinatus 3.06x, infraspinatus 1.76x, subscapularis 1.25x, and teres minor 1.32x). Histopathological scoring using the semi-quantitative Bonar scoring scheme revealed a positive correlation with age across all tendons (r = 0.508, p < 0.001). These data contextualize the biomechanical and histopathological changes to tendons that occurs naturally with aging, highlighting the innate differences in biomechanical properties of all four rotator cuff tendons, as well as the difference in their degenerative trajectories. Additionally, the histopathological scoring revealed moderate signs of degeneration within the Younger supraspinatus tendons, suggesting tissue quality may decrease in this specific tendon in patients less than 40 years old, before clinical symptoms or tears., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Centromeres are critical for cell division, loading CENH3 or CENPA histone variant nucleosomes, directing kinetochore formation and allowing chromosome segregation 1,2 . Despite their conserved function, centromere size and structure are diverse across species. To understand this centromere paradox 3,4 , it is necessary to know how centromeric diversity is generated and whether it reflects ancient trans-species variation or, instead, rapid post-speciation divergence. To address these questions, we assembled 346 centromeres from 66 Arabidopsis thaliana and 2 Arabidopsis lyrata accessions, which exhibited a remarkable degree of intra- and inter-species diversity. A. thaliana centromere repeat arrays are embedded in linkage blocks, despite ongoing internal satellite turnover, consistent with roles for unidirectional gene conversion or unequal crossover between sister chromatids in sequence diversification. Additionally, centrophilic ATHILA transposons have recently invaded the satellite arrays. To counter ATHILA invasion, chromosome-specific bursts of satellite homogenization generate higher-order repeats and purge transposons, in line with cycles of repeat evolution. Centromeric sequence changes are even more extreme in comparison between A. thaliana and A. lyrata. Together, our findings identify rapid cycles of transposon invasion and purging through satellite homogenization, which drive centromere evolution and ultimately contribute to speciation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

8-Nitro-4H-benzo[e][1,3]thiazinones (BTZs) are potent in vitro antimycobacterial agents. New chemical transformations, viz. dearomatization and decarbonylation, of two BTZs and their influence on the compounds' antimycobacterial properties are described. Reactions of 8-nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-4-one and the clinical drug candidate BTZ043 with the Grignard reagent CH 3 MgBr afford the corresponding dearomatized stable 4,5-dimethyl-5H- and 4,7-dimethyl-7H-benzo[e][1,3]thiazines. These methine compounds are structurally characterized by X-ray crystallography for the first time. Reduction of the BTZ carbonyl group, leading to the corresponding markedly non-planar 4H-benzo[e][1,3]thiazine systems, is achieved using the reducing agent (CH 3 ) 2 S ⋅ BH 3 . Double methylation with dearomatization and decarbonylation renders the two BTZs studied inactive against Mycobacterium tuberculosis and Mycobacterium smegmatis, as proven by in vitro growth inhibition assays., (© 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Background: Pompe disease is a lysosomal multisystem disorder with predominant proximal myopathy. Treatment with enzyme replacement therapy (ERT) is available requiring life-long biweekly infusions of recombinant α-glucosidase. To minimize the burden of ERT patients ask for home infusion therapy., Aims and Methods: Pompe disease experts from Germany, Austria, and Switzerland discussed in two consensus meetings in 2019 and 2020 requirements for home infusion therapy, adequate execution of treatment, and the legal situation for delegating physicians., Results and Discussion: Home infusion therapy is principally feasible for patients with Pompe disease if certain preconditions are fulfilled, but the decision to implement has to be made on an individual basis. The treating physician delegates the execution of ERT ad personam to nursing staff but retains full legal responsibility. Home infusion therapy has to be carried out by specially trained and qualified staff. Infusion-related risks comprise mainly allergic reactions, and adequate medical treatment must be warranted. In German-speaking countries, clear rules for conducting home infusion therapy are needed to reduce psychosocial stress for patients with Pompe disease, and providing legal certainty for delegating physicians., Competing Interests: Der Inhalt und Konsensus dieses Manuskripts ist unabhängig von jeglichen Industrieinteressen entstanden. Dafür garantieren alle Autoren. Die beiden Konsensus-Treffen aller Autoren (in personam) im Jahr 2019 und 2020 wurden durch die Firma Sanofi-Genzyme finanziell unterstützt. Zusätzlich fanden mehrere nicht unterstützte Telefonkonferenzen statt. Die Firma hatte keinerlei Einfluss auf den Inhalt und war weder in der Erstellung noch der Ausarbeitung des hier vorgelegten Manuskripts involviert.A. Hahn: Honorare für Teilnahme an Advisory Boards und Vorträge auf Symposien/Kongressen der Firmen Sanofi-Genzyme, Amicus, Audentes. Forschungsunterstützung durch die Firmen Sanofi-Genzyme, Shire/Takeda und AvexisC. Lampe: Honorare für Teilnahme an Advisory Boards und Vorträge auf Symposien/Kongressen der Firmen Sanofi-Genzyme, Amicus und Shire/TakedaM. Boentert: Forschungsförderung durch Sanofi-Genzyme, Löwenstein Medical, Deutsche Gesellschaft für Muskelkranke. Honorare und Kostenerstattung von Sanofi-Genzyme, Löwenstein Medical, UCB PharmaT. Hundsberger: Honorare für die Teilnahme an Advisory Boards und/oder Vorträge auf Symposien/Kongressen der Firma Sanofi-Genzyme und KedrionW. Löscher: Honorare für die Teilnahme an Advisory Boards der Firma Sanofi-GenzymeS. Wenninger: Honorare für die Teilnahme an Advisory Boards der Firma Sanofi-Genzyme und KedrionT. Schlegel: Honorar und Kostenerstattung für die Teilnahme an Advisory Boards der Firma Sanofi-GenzymeD. Ballhausen: Unrestricted research grant von Sanofi-GenzymeA. Ziegler und F. Lagler geben an, dass keine Interessenkonflikte bestehen.B. Schoser: Forschungsförderung BMBF (Bundesministerium für Bildung und Forschung), DFG (Deutsche Forschungsgemeinschaft), DGM, Sanofi-Genzyme, Amicus therapeutics, Greenovation. Honorare bzw. Kostenerstattung: Kedrion Beratertätigkeit: Amicus therapeutics, Audentes therapeutics, Lupin, Nexien, Sanofi-Genzyme, (Thieme. All rights reserved.)

Background: Chronic degeneration of rotator cuff tendons is a major contributing factor to the unacceptably high prevalence of rotator cuff repair surgery failures. The etiology of chronic rotator cuff degeneration is not well understood, and current therapies are not effective, necessitating preclinical research to fill this knowledge gap. Unfortunately, current large animal models rely on enthesis disruption as a means of model generation, which is not representative of human patients with chronic rotator cuff degeneration prior to full-thickness tears. Following, the goal of this study was to develop and characterize a translational large-animal model of chronic rotator cuff degeneration without enthesis release., Methods: A midsubstance damage model [i.e., "combed fenestration" (CF)] in adult sheep was generated by creating 16 longitudinal cuts within the top third of the infraspinatus tendon thickness. Tendon integrity was characterized through exhaustive non-destructive biomechanical stress relaxation testing [peak stress, peak load, percent relaxation, and cross-sectional area (CSA)], followed by histopathological degeneration scoring and analysis (Bonar score), histomorphological analysis of collagen organization and fatty atrophy (percent adipose area), and gene expression analyses., Results: The CF model tendons exhibited significantly decreased mechanical properties as evidenced by decreased peak stress (P<0.025) and increased percent relaxation (18-week vs. Control, P<0.035) at multiple strain magnitudes and across all timepoints. At all timepoints, the CF tendons exhibited pathological changes aligned with tendon degeneration, as evidenced by increased Bonar scoring (P<0.001) and decreased collagen organization (6-week vs. Control, P=0.013). Increases in intramuscular adipose content were also documented through histomorphology analysis (6- and 18-week vs. Control, P<0.077). Significant changes in gene expression were noted at all timepoints., Conclusions: These data reveal that this new ovine CF model of chronic rotator cuff degeneration results in tendons with decreased mechanical properties, degenerative pathology characteristics, and gene expression profiles that aligned with the degenerative changes that have been noted in humans with tendinopathy. For these reasons, we believe this novel large animal model of chronic rotator cuff degeneration is a translational platform in which to test devices, therapies, and/or technologies aimed at repairing damage to the shoulder., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-2749). Dr. TR receives royalties from devices/products from Arthrex, Inc. and Atreon Orthopaedics. He also has been paid to present in the last 12 months by Arthrex, Inc. He is a paid consultant for Arthrex, Inc. and Atreon Orthopaedics. He has stock/stock options in Paragen. Dr. TS reports grants from Arthrex Education Grant, grants from Gemini Mountain Education Grant, outside the submitted work; and Stock/stock options in the following companies: Kaleo, PRIVIT, Avenu and NASH. The other authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Untreated rotator cuff tears lead to irreversible tendon degeneration, resulting in unacceptable repair prognosis. The inability of current animal models of degenerated rotator cuff tendons to more fully emulate the manifestation and degree of pathology seen in humans with a previously torn rotator cuff tendon (s) significantly impairs the development of novel therapeutics. Therefore, the objective of this study was to develop a large-animal translational model of enthesis damage to the rotator cuff tendons to mimic the chronic degenerative changes that occur in patients that demonstrate clinical manifestations of tendinopathy., Methods: A partial enthesis tear model (i.e., sharp transection) in adult sheep was created by cutting the tendon fibers perpendicularly through the enthesis midpoint, while leaving the other portion of the tendon in-tact. To assess tendon integrity, non-destructive biomechanical tests were performed, followed by histopathological, histomorphological, and gene expression analysis. Samples of degenerated human rotator cuff tendons obtained from patients undergoing reverse total shoulder arthroplasty to use for comparative pathological analysis., Results: In the sheep model, transected tendons at all timepoints had significantly decreased mechanical properties. Histopathologic evaluation and Bonar scoring revealed that the tendons in sheep underwent degenerative changes similar in magnitude and manifestation as the degenerated human tendon samples. Furthermore, similar levels of collagen disorganization were noted between the 6 and 12-week ovine samples and the degenerated human samples., Conclusions: These findings indicate that the new sheep model of rotator cuff injury reliably recapitulates the structural and cellular changes that occur clinically in humans with chronic rotator cuff tendon injuries and suggest that this new model is well suited to evaluation of new therapeutic interventions., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-354). Dr. TR reports personal fees from Arthrex, Inc., personal fees from Atreon Orthopaedics, personal fees from Paragen, outside the submitted work. Dr. TS reports grants from Arthrex Education Grant, grants from Gemini Mountain Education Grant, outside the submitted work; and Stock/stock options in the following companies: Kaleo, PRIVIT, Avenu and NASH. The other authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

8-Nitro-1,3-benzo-thia-zin-4-ones are a promising class of new anti-tubercular agents, two candidates of which, namely BTZ043 and PBTZ169 (INN: macozinone), have reached clinical trials. The crystal and mol-ecular structures of two synthetic precursors, 2-chloro-3-nitro-5-(tri-fluoro-meth-yl)benzoic acid, C 8 H 3 ClF 3 NO 4 ( 1 ), and 2-chloro-3-nitro-5-(tri-fluoro-meth-yl)benzamide, C 8 H 4 ClF 3 N 2 O 3 ( 2 ), are reported. In 1 and 2 , the respective carb-oxy, carboxamide and the nitro groups are significantly twisted out of the plane of the benzene ring. In 1 , the nitro group is oriented almost perpendicular to the benzene ring plane. In the crystal, 1 and 2 form O-H⋯O and N-H⋯O hydrogen-bonded dimers, respectively, which in 2 extend into primary amide tapes along the [101] direction. The tri-fluoro-methyl group in 2 exhibits rotational disorder with an occupancy ratio of 0.876 (3):0.124 (3)., (© Richter et al. 2021.)

Objective:  Rotator cuff tendon tears are the most common soft tissue injuries in the shoulder joint. Various animal models have been described for this condition, but all current translational animal models have inherent weaknesses in their ability to generate chronically degenerated rotator cuff tendons. The objective of this study was to evaluate a partial infraspinatus tendon transection model as a means of creating a chronically degenerated rotator cuff tendon in an ovine model and compare the injury characteristics of this model to those observed in human patients with severe chronic rotator cuff tendon injuries., Study Design:  The infraspinatus tendons of six sheep were partially detached followed by capping of the detached medial section of the tendon with Gore-Tex. Human tissue samples of the supraspinatus tendon were harvested from patients undergoing primary reverse shoulder arthroplasty and served as positive controls of chronic rotator cuff tendinopathy., Results:  Transected sheep tendons were characterized predominantly by an acute reactive and reparative pathological process as compared with the chronic degenerative changes observed in the human tendons. In contrast, the non-transected portion of the ovine tendon showed histological changes, which were more chronic and degenerative in nature when compared with the transected tendon., Conclusion:  Overall, histological features of the non-transected portion of ovine tendon were more similar to those observed in the chronic degenerated human tendon., Competing Interests: Dr. Romeo receives royalties from devices/products from Arthrex, Inc. and Atreon Orthopaedics. He also has been paid to present in the last 12 months by Arthrex, Inc. He is a paid consultant for Arthrex, Inc. and Atreon Orthopaedics. He has stock/stock options in Paragen. Dr. Schlegel reports grants from Arthrex Education Grant, grants from Gemini Mountain Education Grant, outside the submitted work; and stock/stock options in the following companies: Kaleo, PRIVIT, Avenu and NASH., (Georg Thieme Verlag KG Stuttgart · New York.)

Compaction simulators are frequently used in the formulation and process development of tablets, bringing about the advantages of flexibility, low material consumption, and high instrumentation to generate the most possible process understanding. However, their capability of resembling general aspects of rotary press compaction and their precision in simulating or mimicking sub-processes such as feeding and filling need to be systematically studied. The effect of material deformation behavior, blend composition, and feeding on tensile strength and simulation precision as compared with rotary presses of different scales is evaluated in this study. Generally, good simulation performance was found for the studied compaction simulator. Compaction profile-sensitivity was demonstrated for highly visco-plastic materials while shear-sensitivity in feeding was demonstrated for lubricated blends of ductile particles. Strategies for the compensation of both in compaction simulator experiments are presented by careful investigation of the compaction stress over time profiles and introduction of a compaction simulator-adapted shear number approach to account for differences in layout and operation mode between compaction simulator and rotary press, respectively. These approaches support the general aim of this study to provide a more straightforward determination of scaling process parameters between rotary press and compaction simulator and facilitate a quicker and more reliable process transfer.

Suprathermal electrons are routinely generated in high-intensity laser produced plasmas via instabilities driven by non-linear laser-plasma interaction. Their accurate characterization is crucial for the performance of inertial confinement fusion as well as for performing experiments in laboratory astrophysics and in general high-energy-density physics. Here, we present studies of non-thermal atomic states excited by suprathermal electrons in kJ-ns-laser produced plasmas. Highly spatially and spectrally resolved X-ray emission from the laser-deflected part of the warm dense Cu foil visualized the hot electrons. A multi-scale two-dimensional hydrodynamic simulation including non-linear laser-plasma interactions and hot electron propagation has provided an input for ab initio non-thermal atomic simulations. The analysis revealed a significant delay between the maximum of laser pulse and presence of suprathermal electrons. Agreement between spectroscopic signatures and simulations demonstrates that combination of advanced high-resolution X-ray spectroscopy and non-thermal atomic physics offers a promising method to characterize suprathermal electrons inside the solid density matter.

Background: This study assessed the current political standings and active political engagement of American Shoulder and Elbow Surgeons (ASES) members along with the political process as it relates to health care policy., Methods: This survey study involved 552 ASES members. The survey was open for 2 weeks. Responses were received from 254 of the 552 members (46%), and their answers were analyzed., Results: Six (2%) of the responding members were solo practitioners, 100 (39%) belonged to a private practice, 106 (42%) were providers at academic institutions or residency training programs, 25 (10%) were employed by a hospital, and 17 (7%) categorized themselves as other. Email was the preferred method of communication. Of all responding members, 110 (43%) stated they had contributed to the American Academy of Orthopaedic Surgery Political Advocacy Committee in the last 12 months. Four (10%) of the responding members have a relationship with an elected official, and 220 (87%) would be willing to become a key contact and reach out to a legislator., Conclusion: Moving forward, this survey can be used to better shape the political advocacy efforts of the ASES and potentially other subspecialty societies. The response that "a high percentage of members would like to be more involved" suggests the need for a program to help further educate and facilitate the membership on political advocacy., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Postoperative scarring is a known complication after arthroscopic anterior ligament reconstruction of the knee. The anterior interval of the knee has been previously identified as a common location for anterior scar formation. The anterior interval is defined as the space between the infrapatellar fat pad and the anterior border of the tibia. Patients with anterior interval scarring often present with lack of terminal knee extension, anterior knee pain, decreased patellar mobility, and quadriceps atrophy. The goal of this paper is to describe the technique for anterior interval release of the knee.

Animals that live together in groups often face difficult choices, such as which food resource to exploit, or which direction to flee in response to a predator. When there are costs associated with deadlock or group fragmentation, it is essential that the group achieves a consensus decision. Here, we study consensus formation in emigrating ant colonies faced with a binary choice between two identical nest-sites. By individually tagging each ant with a unique radio-frequency identification microchip, and then recording all ant-to-ant 'tandem runs'-stereotyped physical interactions that communicate information about potential nest-sites-we assembled the networks that trace the spread of consensus throughout the colony. Through repeated emigrations, we show that both the order in which these networks are assembled and the position of each individual within them are consistent from emigration to emigration. We demonstrate that the formation of the consensus is delegated to an influential but exclusive minority of highly active individuals-an 'oligarchy'-which is further divided into two subgroups, each specialized upon a different tandem running role. Finally, we show that communication primarily occurs between subgroups not within them, and further, that such between-group communication is more efficient than within-group communication., (© 2018 The Authors.)

Purpose: The aim of the study was to assess the spatial QRS-T angle (QRS-TA) in a group of newly diagnosed and untreated adult patients with obstructive sleep apnea syndrome (OSAS) and to identify potential factors affecting this parameter., Patients and Methods: The study group (PSG-confirmed OSAS) included 62 individuals, aged 51.7±10.3 years. The control group consisted of 25 individuals, aged 46.6±16.6 years with no sleep-disordered breathing. The diagnosis of OSAS and assessment of its severity was based on unattended all-night screening polysomnography. The spatial QRS-TA was reconstructed from 12-lead ECG using Kors' regression method., Results: Significant differences of spatial QRS-TA values were found between patients with severe OSAS (36.9±18.9°) and the controls (20.3±13.4°; p<0.01) and between patients with mild or moderate OSAS (32.3±20.1°) and the controls (p=0.01). Statistically significant correlations were found between spatial QRS-TA and polysomnographic indices (i.e. AHI, AI, RDT and RDTI)., Conlusions: Spatial QRS-TA values are significantly higher in patients with OSAS than in controls, thus indicating increased heterogeneity of myocardial action potential. Further long-term prospective studies evaluating the prognostic value of spatial QRS-TA in OSAS patients are needed., (Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

We apply Fourier-transform spectral interferometry (FTSI) to study the interaction of intense laser pulses with ultrathin targets. Ultrathin submicrometer-thick solid CH targets were shot at the PHELIX laser facility with an intensity in the mid to upper 10^{19}  W/cm^{2} range using an innovative double-pulse structure. The transmitted pulse structure was analyzed by FTSI and shows a transition from a relativistic transparency-dominated regime for targets thinner than 500 nm to a hole-boring-dominated laser-plasma interaction for thicker targets. The results also confirm that the inevitable preplasma expansion happening during the rising slope of the pulse, a few picoseconds before the maximum of the pulse is reached, cannot be neglected and plays a dominant role in laser-plasma interaction with ultrathin solid targets.

The energy deposition of ions in dense plasmas is a key process in inertial confinement fusion that determines the α-particle heating expected to trigger a burn wave in the hydrogen pellet and resulting in high thermonuclear gain. However, measurements of ion stopping in plasmas are scarce and mostly restricted to high ion velocities where theory agrees with the data. Here, we report experimental data at low projectile velocities near the Bragg peak, where the stopping force reaches its maximum. This parameter range features the largest theoretical uncertainties and conclusive data are missing until today. The precision of our measurements, combined with a reliable knowledge of the plasma parameters, allows to disprove several standard models for the stopping power for beam velocities typically encountered in inertial fusion. On the other hand, our data support theories that include a detailed treatment of strong ion-electron collisions.

Introduction: The conventional ECG is commonly used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of adults and possibly larger percentages of children with HCM have no distinctive abnormalities on the conventional ECG, whereas 5 to 15% of healthy young athletes do. Recently, a 5-min resting advanced 12-lead ECG test ("A-ECG score") showed superiority to pooled criteria from the strictly conventional ECG in correctly identifying adult HCM. The purpose of this study was to evaluate whether in children and young adults, A-ECG scoring could detect echocardiographic HCM associated with the MYBPC3 genetic mutation with greater sensitivity than conventional ECG criteria and distinguish healthy young controls and athletes from persons with MYBPC3 HCM with greater specificity., Methods: Five-minute 12-lead ECGs were obtained from 15 young patients (mean age 13.2years, range 0-30years) with MYBPC3 mutation and phenotypic HCM. The conventional and A-ECG results of these patients were compared to those of 198 healthy children and young adults (mean age 13.2, range 1month-30years) with unremarkable echocardiograms, and to those of 36 young endurance-trained athletes, 20 of whom had athletic (physiologic) left ventricular hypertrophy., Results: Compared with commonly used, age-specific pooled criteria from the conventional ECG, a retrospectively generated A-ECG score incorporating results from just 2 derived vectorcardiographic parameters (spatial QRS-T angle and the change in the vectorcardiographic QRS azimuth angle from the second to the third eighth of the QRS interval) increased the sensitivity of ECG for identifying MYBPC3 HCM from 46% to 87% (p<0.05). Use of the same score also demonstrated superior specificity in a set of 198 healthy controls (94% vs. 87% for conventional ECG criteria; p<0.01) including in a subset of 36 healthy, young endurance-trained athletes (100% vs. 69% for conventional ECG criteria, p<0.001)., Conclusions: In children and young adults, a 2-parameter 12-lead A-ECG score is retrospectively significantly more sensitive and specific than pooled, age-specific conventional ECG criteria for detecting MYBPC3-HCM and in distinguishing such patients from healthy controls, including endurance-trained athletes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Calcific aortic stenosis (AS) is a common valvular disease among the elderly. Often, AS leads to left ventricular hypertrophy (LVH) and symptoms of heart failure. Severe AS can be treated by transcatheter aortic valve replacement (TAVR). Previous studies have shown that electrocardiogram (ECG) criteria for LVH correlate poorly with left ventricular mass (LVM) in echocardiography. However, such correlations have not been studied in TAVR patients., Aims: To evaluate ECG LVH criteria as a method of diagnosing and quantifying LVH in patients with AS undergoing TAVR., Material and Methods: Twenty-four patients, with neither pacemaker nor bundle branch block, who had undergone pre-TAVR ECG and echocardiography were included. The ECGs were evaluated using the Sokolow-Lyon, Romhilt-Estes and Cornell Voltage criteria for LVH as well as spatial maximal QRS-T angle and 3D QRS maximal spatial vector. The LVM was measured by echocardiography., Results: 15 (63%) patients met the echocardiographic threshold for LVH. 7 patients (29%) were positive by the Sokolow-Lyon, 5 (21%) by the Romhilt-Estes and 12 (50%) by the Cornell Voltage criteria for LVH. There was no correlation between LVM and conventional ECG LVH criteria or spatial parameters. QRS duration correlated with LVM (r=0.56, R(2)=0.31, p=0.005). However, there was no correlation between QRS duration and LVM index or relative wall thickness (RWT)., Conclusions: In TAVR patients, none of the ECG LVH criteria should be used for evaluation of LVM. QRS duration is moderately correlated to LVM and is the most useful ECG estimate of LVM., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Organisms should invest more in gathering information when the pay-off from finding a profitable resource is likely to be greater. Here, we ask whether animal societies put more effort in scouting for a new nest when their current one is of low quality. We measured the scouting behaviour of Temnothorax albipennis ant colonies when they inhabit nest-sites with different combinations of desirable attributes. We show that the average probability of an ant scouting decreases significantly with an increase in the quality of the nest in which the colony currently resides. This means that the greater the potential gain from finding a new nest, the more effort a colony puts into gathering information regarding new nest-sites. Our results show, for the first time to our knowledge, the ability of animal societies to respond collectively to the quality of a resource they currently have at their disposal (e.g. current nest-site) and regulate appropriately their information gathering efforts for finding an alternative (e.g. a potentially better nest-site).

We present a dynamical systems analysis of a decision-making mechanism inspired by collective choice in house-hunting honeybee swarms, revealing the crucial role of cross-inhibitory 'stop-signalling' in improving the decision-making capabilities. We show that strength of cross-inhibition is a decision-parameter influencing how decisions depend both on the difference in value and on the mean value of the alternatives; this is in contrast to many previous mechanistic models of decision-making, which are typically sensitive to decision accuracy rather than the value of the option chosen. The strength of cross-inhibition determines when deadlock over similarly valued alternatives is maintained or broken, as a function of the mean value; thus, changes in cross-inhibition strength allow adaptive time-dependent decision-making strategies. Cross-inhibition also tunes the minimum difference between alternatives required for reliable discrimination, in a manner similar to Weber's law of just-noticeable difference. Finally, cross-inhibition tunes the speed-accuracy trade-off realised when differences in the values of the alternatives are sufficiently large to matter. We propose that the model, and the significant role of the values of the alternatives, may describe other decision-making systems, including intracellular regulatory circuits, and simple neural circuits, and may provide guidance in the design of decision-making algorithms for artificial systems, particularly those functioning without centralised control.

To determine if an absorbable collagen scaffold of high porosity would allow rapid tissue in-growth and permit the functional maturation and alignment of tendon-like tissue, scaffolds were sutured to the superficial surface of the infraspinatus tendons of adult sheep. Histology demonstrated complete ingrowth with fibrovascular tissue by 6 weeks and by 12 weeks the scaffold had induced the formation of a layer of dense, regularly-oriented collagenous tissue which significantly increased the thickness of the native tendon. This new tissue was well-integrated into the host tissues at both the bone interface and along the length of the tendon. At 26 weeks the scaffold was completely absorbed leaving a stable layer of mature tendon-like tissue over the surface of the host tendon which was still present at 52 weeks. The use of a reconstituted collagen scaffold consistently increased the thickness of a rotator cuff tendon by inducing the formation of a well-integrated and mature tendon-like tissue.

The expansion of a semi-infinite plasma slab into vacuum is analyzed with a hydrodynamic model implying a steplike electron energy distribution function. Analytic expressions for the maximum ion energy and the related ion distribution function are derived and compared with one-dimensional numerical simulations. The choice of the specific non-Maxwellian initial electron energy distribution automatically ensures the conservation of the total energy of the system. The estimated ion energies may differ by an order of magnitude from the values obtained with an adiabatic expansion model supposing a Maxwellian electron distribution. Furthermore, good agreement with data from experiments using laser pulses of ultrashort durations τ(L)

Of the many signals used by honey bees during the process of swarming, two of them--the stop signal and the worker piping signal--are not easily distinguished for both are mechano-acoustic signals produced by scout bees who press their bodies against other bees while vibrating their wing muscles. To clarify the acoustic differences between these two signals, we recorded both signals from the same swarm and at the same time, and compared them in terms of signal duration, fundamental frequency, and frequency modulation. Stop signals and worker piping signals differ in all three variables: duration, 174 ± 64 vs. 602 ± 377 ms; fundamental frequency, 407 vs. 451 Hz; and frequency modulation, absent vs. present. While it remains unclear which differences the bees use to distinguish the two signals, it is clear that they do so for the signals have opposite effects. Stop signals cause inhibition of actively dancing scout bees whereas piping signals cause excitation of quietly resting non-scout bees.

Ketorolac tromethamine (Toradol(®)) is a non-steroidal anti-inflammatory drug that has potent analgesic and anti-inflammatory properties. It can be administered orally, intravenously, intramuscularly, or via a nasal route. Ketorolac injections have been used for several years in the National Football League (NFL), in both the oral and injectable forms, to treat musculoskeletal injuries and to prevent post-game soreness. In an attempt to determine the appropriate use of this medication in NFL players, the NFL Team Physician Society appointed a Task Force to consider the best available evidence as to how ketorolac should be used for pain management in professional football players. These treatment recommendations were established based on the available medical literature taking into consideration the pharmacokinetic properties of ketorolac, its accepted indications and contraindications, and the unique clinical challenges of the NFL. The Task Force recommended that 1) ketorolac should only be administered under the direct supervision and order of a team physician; 2) ketorolac should not be used prophylactically as a means of reducing anticipated pain either during or after participation in NFL games or practices and should be limited to those players diagnosed with an injury or condition and listed on the teams' injury report; 3) ketorolac should be given in the lowest effective therapeutic dose and should not be used in any form for more than 5 days; 4) ketorolac should be given in its oral preparation under typical circumstances; 5) ketorolac should not be taken concurrently with other NSAIDs or by those players with a history of allergic reaction to ketorolac, other NSAIDs or aspirin; and 6) ketorolac should not be used by a player with a history of significant gastrointestinal bleeding, renal compromise, or a past history of complications related to NSAIDs.

Background: Interest in double-row techniques for arthroscopic rotator cuff repair has increased over the last several years, presumably because of a combination of literature demonstrating superior biomechanical characteristics and recent improvements in instrumentation and technique. As a result of the increasing focus on value-based health-care delivery, orthopaedic surgeons must understand the cost implications of this practice. The purpose of this study was to examine the cost-effectiveness of double-row arthroscopic rotator cuff repair compared with traditional single-row repair., Methods: A decision-analytic model was constructed to assess the cost-effectiveness of double-row arthroscopic rotator cuff repair compared with single-row repair on the basis of the cost per quality-adjusted life year gained. Two cohorts of patients (one with a tear of <3 cm and the other with a tear of ≥3 cm) were evaluated. Probabilities for retear and persistent symptoms, health utilities for the particular health states, and the direct costs for rotator cuff repair were derived from the orthopaedic literature and institutional data., Results: The incremental cost-effectiveness ratio for double-row compared with single-row arthroscopic rotator cuff repair was $571,500 for rotator cuff tears of <3 cm and $460,200 for rotator cuff tears of ≥3 cm. The rate of radiographic or symptomatic retear alone did not influence cost-effectiveness results. If the increase in the cost of double-row repair was less than $287 for small or moderate tears and less than $352 for large or massive tears compared with the cost of single-row repair, then double-row repair would represent a cost-effective surgical alternative., Conclusions: On the basis of currently available data, double-row rotator cuff repair is not cost-effective for any size rotator cuff tears. However, variability in the values for costs and probability of retear can have a profound effect on the results of the model and may create an environment in which double-row repair becomes the more cost-effective surgical option. The identification of the threshold values in this study may help surgeons to determine the most cost-effective treatment.

In the identification of subjects with lung cancer, increased DNA methylation of the SHOX2 gene locus in bronchial aspirates has previously been proven to be a clinically valuable biomarker. This is particularly true in cases where the cytological and histological results following bronchoscopy are undetermined. This previous case control study was conducted using research assay components and a complex work flow. To facilitate the use in a diagnostic setting, a CE marked in vitro diagnostic test kit to quantify SHOX2 DNA methylation in bronchial aspirates was developed and characterized. The presented assay for measuring SHOX2 DNA methylation in bronchial aspirates is based on two major steps: generation of bisulfite converted template DNA from patient samples followed by subsequent determination of SHOX2 biomarker methylation by real-time PCR. Individual kits for DNA preparation, real-time PCR analysis and work flow control were developed. This study describes the analytical performance (reproducibility, accuracy, interfering substances, cross-reactivity) of the in vitro diagnostic (IVD) test kit 'Epi proLung BL Reflex Assay'. In addition, the intended use of the test was validated in a clinical performance evaluation (case control) study comprised of 250 patients (125 cases, 125 controls). The results describe the test as a robust and reliable diagnostic tool for identifying patients with lung cancer using Saccomanno-fixed bronchial lavage specimens (AUC [95% confidence intervals] = 0.94 [0.91-0.98], sensitivity 78% [69-86]/specificity 96% [90-99]). This test may be used as a diagnostic adjunct to existing clinical and pathological investigations in lung cancer.

Honeybee swarms and complex brains show many parallels in how they make decisions. In both, separate populations of units (bees or neurons) integrate noisy evidence for alternatives, and, when one population exceeds a threshold, the alternative it represents is chosen. We show that a key feature of a brain--cross inhibition between the evidence-accumulating populations--also exists in a swarm as it chooses its nesting site. Nest-site scouts send inhibitory stop signals to other scouts producing waggle dances, causing them to cease dancing, and each scout targets scouts' reporting sites other than her own. An analytic model shows that cross inhibition between populations of scout bees increases the reliability of swarm decision-making by solving the problem of deadlock over equal sites.

Background: Multiple advanced resting ECG (A-ECG) techniques have improved the diagnostic or prognostic value of ECG in detecting human cardiac diseases even before onset of clinical signs or changes in conventional ECG., Objective: To determine which A-ECG parameters, derived from 12-lead A-ECG recordings, change with severity of mitral regurgitation (MR) caused by myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCSs) in sinus rhythm., Animals: Seventy-six privately owned CKCSs., Methods: Dogs were prospectively divided into 5 groups according to the degree of MR (estimated by color Doppler mapping as the percentage of the left atrial area affected by the MR jet) and presence of clinical signs. High fidelity approximately 5-minute 12-lead ECG recordings were evaluated using custom software to calculate multiple conventional and A-ECG parameters., Results: Nineteen of 76 ECG parameters were significantly different (P < .05) across the 5 dog groups. A 4-parameter model that incorporated results from 1 parameter of heart rate variability, 2 parameters of QT variability, and 1 parameter of QRS amplitude was identified that explained 82.4% of the variance with a correlation coefficient (R) of 0.60 (P < .01). When age or murmur grade was included in the statistical model the prediction value further increased the R to 0.74 and 0.85 (P < .01), respectively., Conclusion: In CKCSs with sinus rhythm, 4 selected A-ECG parameters further improve prediction of MR jet severity beyond age and murmur grade, although the predictive increment in this study probably is not sufficient to warrant utilization in clinical veterinary practice., (Copyright © 2011 by the American College of Veterinary Internal Medicine.)

Background: Although knee injuries are common among professional football players, ruptures of the patellar tendon are relatively rare. Predisposing factors, mechanisms of injury, treatment guidelines, and recovery expectations are not well established in high-level athletes., Hypothesis: Professional football players with isolated rupture of the patellar tendon treated with timely surgical repair will return to their sport., Study Design: Case series; Level of evidence, 4., Methods: Twenty-four ruptures of the patellar tendon in 22 National Football League (NFL) players were identified from 1994 through 2004. Team physicians retrospectively reviewed training room and clinic records, operative notes, and imaging studies for each of these players. Player game statistics and draft status were analyzed to identify return to play predictors. A successful outcome was defined as participating in 1 regular-season NFL game., Results: Eleven of the 24 injuries had antecedent symptoms. The most common mechanism of injury was an eccentric overload to a contracting extensor mechanism. Physical examination demonstrated a palpable defect in all players. Twenty-two were complete ruptures, and 2 were partial injuries. Three of the 24 cases had a concomitant anterior cruciate ligament (ACL) injury. In 19 of the 24 injuries, the player returned to participate in at least 1 game in the NFL. Players who returned were drafted, on average, in the fourth round, while those who failed to return to play were drafted, on average, in the sixth round. Of those players who returned to play, the average number of games played was 45.4, with a range of 1 to 142 games., Conclusion: Patellar tendon ruptures can occur in otherwise healthy professional football players without antecedent symptoms or predisposing factors. The most common mechanism of injury is eccentric overload. Close attention should be paid to stability examination of the knee given the not uncommon occurrence of concomitant ACL injury. Although this is usually a season-ending injury when it occurs in isolation, acute surgical repair generally produces good functional results and allows for return to play the following season. Players chosen earlier in the draft are more likely to return to play.

Background: This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment., Methods: Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance., Results: Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%])., Conclusions: Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.

RASSF2 is a novel proapoptotic effector of K-Ras. Inhibition of RASSF2 expression enhances the transforming effects of K-Ras, and epigenetic inactivation of RASSF2 is frequently detected in mutant Ras-containing primary tumors. Thus, RASSF2 is implicated as a tumor suppressor whose inactivation facilitates transformation by disconnecting apoptotic responses from Ras. The mechanism of action of RASSF2 is not known. Here we show that RASSF2 forms a direct and endogenous complex with the prostate apoptosis response protein 4 (PAR-4) tumor suppressor. This interaction is regulated by K-Ras and is essential for the full apoptotic effects of PAR-4. RASSF2 is primarily a nuclear protein, and shuttling of PAR-4 from the cytoplasm to the nucleus is essential for its function. We show that RASSF2 modulates the nuclear translocation of PAR-4 in prostate tumor cells, providing a mechanism for its biological effects. Thus, we identify the first tumor suppressor signaling pathway emanating from RASSF2, we identify a novel mode of action of a RASSF protein, and we provide an explanation for the extraordinarily high frequency of RASSF2 inactivation we have observed in primary prostate tumors.

DNA methylation is an important epigenetic mechanism involved in fundamental biological processes such as development, imprinting, and carcino-genesis. For these reasons, DNA methylation represents a valuable source for cancer biomarkers. Methods for the sensitive and specific detection of methylated DNA are a prerequisite for the implementation of DNA biomarkers into clinical routine when early detection based on the analysis of body fluids is desired. Here, a novel technique is presented for the detection of DNA methylation biomarkers, based on real-time PCR of bisulfite-treated template with enzymatic digestion of background DNA during amplification using the heat-stable enzyme Tsp509I. An assay for the lung cancer methylation biomarker BARHL2 was used to show clinical and analytical performance of the method in comparison with methylation-specific PCR technology. Both technologies showed comparable performance when analyzing technical DNA mixtures and bronchial lavage samples from 75 patients suspected of having lung cancer. The results demonstrate that the approach is useful for sensitive and specific detection of a few copies of methylated DNA in samples with a high background of unmethylated DNA, such as in clinical samples from body fluids.