Determination of the standard deviation for proficiency assessment from past participant's performances

The "uncertainty function" introduced by Thompson et al. estimates the reproducibility standard deviation as a function of concentration or mass fraction. This model was successfully applied to data derived from three proficiency testing schemes aiming at the quantification of cadmium, lead and mercury in blood and urine. This model allows the estimation of standard deviation for the performance assessment for proficiency testing rounds

Neurofilament depletion improves microtubule dynamics via modulation of Stat3/stathmin signaling

In neurons, microtubules form a dense array within axons, and the stability and function of this microtubule network is modulated by neurofilaments. Accumulation of neurofilaments has been observed in several forms of neurodegenerative diseases, but the mechanisms how elevated neurofilament levels destabilize axons are unknown so far. Here, we show that increased neurofilament expression in motor nerves of pmn mutant mice, a model of motoneuron disease, causes disturbed microtubule dynamics. The disease is caused by a point mutation in the tubulin-specific chaperone E (Tbce) gene, leading to an exchange of the most C-terminal amino acid tryptophan to glycine. As a consequence, the TBCE protein becomes instable which then results in destabilization of axonal microtubules and defects in axonal transport, in particular in motoneurons. Depletion of neurofilament increases the number and regrowth of microtubules in pmn mutant motoneurons and restores axon elongation. This effect is mediated by interaction of neurofilament with the stathmin complex. Accumulating neurofilaments associate with stathmin in axons of pmn mutant motoneurons. Depletion of neurofilament by Nefl knockout increases Stat3-stathmin interaction and stabilizes the microtubules in pmn mutant motoneurons. Consequently, counteracting enhanced neurofilament expression improves axonal maintenance and prolongs survival of pmn mutant mice. We propose that this mechanism could also be relevant for other neurodegenerative diseases in which neurofilament accumulation and loss of microtubules are prominent features

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Performance Comparison of Mechanical and Chemical Stabilization of Undercut Subgrades

This study evaluated the performance of undercut subgrade stabilization measures during construction traffic loading prior to final paving. Twenty-two simulated undercut sections with different stabilization configurations over a Coastal Plain subgrade typically undercut in North Carolina were built in a large-scale test pit. The subgrade was placed at a California Bearing Ratio (CBR) of approximately 2.0% and stabilized with granular layers, granular layers reinforced with geosynthetics, and lime. Granular layers consisted of either aggregate base course (ABC), sandy select fill, or a multi-layer system with both soil types. The four geosynthetics tested were a woven reinforcement geotextile, a woven separation geotextile, and two biaxial polypropylene geogrids. A circular steel plate loaded the sections statically, as well as with simulated proof-roll inspection and construction traffic equipment pulses. After initial cycles, deformations were refilled to simulate rut repair before final paving. The sections were then re-loaded to simulate paving traffic. Resulting surface displacement and subgrade stress increase were recorded using electronic instrumentation. Cyclic loading showed that, in general, tests with thicker granular layers had less surface displacement. Some differences occurred likely as a result of reusing the same Coastal Plain subgrade throughout testing. Remolding caused a reduction in the measured undrained shear strength, which was reflected in an increasing dry unit weight and DCP Index at a given water content as testing progressed. Typical material prices were used to calculate the unit cost of each stabilization configuration. A performance-cost analysis was performed by coupling these values with the cyclic load displacements to determine the most economical stabilization alternatives. The results showed that tests with lime stabilized subgrade (LSS) test were the most economical over initial and post-rut repair cycles. The LSS had low construction cost and when the LSS had higher tested strength, loading caused less surface displacement. Unreinforced ABC (between 14 and 20 inches) was economical during initial cycles. Geosynthetic-reinforced tests showed that when the ABC layer was approximately as thick as the load plate diameter (12 inches), high displacements caused significant geosynthetic mobilization during initial cycles that proved economical during long-term loading applications. This was particularly true of tests with the reinforcement geotextile, as it was the geosynthetic with the highest tensile strength and also provided layer separation. At these depths, the less stiff separation geotextile and both geogrids were not strong enough to be economically viable. When the ABC layer was thicker (between 18 and 20 inches), these geosynthetics proved moderately economical, but differences in the reinforcement type at these depths were less significant. Tests with thirty-six inch select fill and three inch ABC stabilization had a high unit cost, but were moderately economical during all cycles. Inclusion of separation geotextile in deep select fill tests did not significantly reduce surface deformation because the fabric was far enough from the load plate to have little influence. Tests with less (fourteen to seventeen inches) of select fill and three inches ABC reinforced with separation geotextile experienced more displacement because the load plate punched through the thin ABC layer at low cycles. The displacements likely caused lateral spreading of the select fill without mobilization of the fabric. Thus, the tests were not as economical as the other tested configurations

Deltotrapezial Stabilization of Acromioclavicular Joint Rotational Stability: A Biomechanical Evaluation

Background: Despite advances in surgical management of acromioclavicular (AC) joint reconstruction, many patients fail to maintain sustained anatomic reduction postoperatively. Purpose: To determine the biomechanical support of the deltoid and trapezius on AC joint stability, focusing on the rotational stability provided by the muscles to posterior and anterior clavicular rotation. A novel technique was attempted to repair the deltoid and trapezius anatomically. Study Design: Controlled laboratory study. Methods: Twelve human cadaveric shoulders (mean ± SD age, 60.25 ± 10.25 years) underwent servohydraulic testing. Shoulders were randomly assigned to undergo serial defects to either the deltoid or trapezius surrounding the AC joint capsule, followed by a combined deltotrapezial muscle defect. Deltotrapezial defects were repaired with an all-suture anchor using an anatomic technique. The torque (N·m) required to rotate the clavicle 20° anterior and 20° posterior was recorded for the following conditions: intact (native), deltoid defect, trapezius defect, combined deltotrapezial defect, and repair. Results: When compared with the native condition, the deltoid defect decreased the torque required to rotate the clavicle 20° posteriorly by 7.1% ( P = .206) and 20° anteriorly by 6.1% ( P = .002); the trapezial defect decreased the amount of rotational torque posteriorly by 5.3% ( P = .079) and anteriorly by 4.9% ( P = .032); and the combined deltotrapezial defect decreased the amount of rotational torque posteriorly by 9.9% ( P = .002) and anteriorly by 9.4% ( P &lt; .001). Anatomic deltotrapezial repair increased posterior rotational torque by 5.3% posteriorly as compared with the combined deltotrapezial defect ( P = .001) but failed to increase anterior rotational torque ( P &gt; .999). The rotational torque of the repair was significantly lower than the native joint in the posterior ( P = .017) and anterior ( P &lt; .001) directions. Conclusion: This study demonstrated that the deltoid and trapezius play a role in clavicular rotational stabilization. The proposed anatomic repair improved posterior rotational stability but did not improve anterior rotational stability as compared with the combined deltotrapezial defect; however, neither was restored to native stability. Clinical Relevance: Traumatic or iatrogenic damage to the deltotrapezial fascia and the inability to restore anatomic deltotrapezial attachments to the acromioclavicular joint may contribute to rotational instability. Limiting damage and improving the repair of these muscles should be a consideration during AC reconstruction. </jats:sec

DSAI-07 DATA-DRIVEN MODELING OF EMERGING TRENDS AND COLLABORATIVE NETWORKS ACROSS BRAIN METASTASES RESEARCH: THE PAST DECADE OF INNOVATION

With recent significant growth in brain metastases literature output, more comprehensive research is necessary to understand emerging trends and novel methods of diagnosis and treatment. We aimed to address this by providing a contemporary systematic global analysis of emerging brain metastases research in the last decade while visually depicting the international collaborative environment among its researchers. Data mining was performed on all brain metastases publications across the last decade indexed in Elsevier’s Scopus database. Our Scopus search revealed 6,362 publications from 1,184 sources from 2013-2022. Of those, 252 were identified as high-impact articles with an annual citation rate (CR) > 10. The compounded annual growth rate (CAGR) of brain metastases publications was 7.2% per year since 2013. There was an acceleration of scientific production, from 5.9% CAGR across 2013-2018 to 9.6% across 2019-2022. Authors per document increased from 7.2% to 8.5% while international co-authorships increased from 16.6% to 18.3% in the same periods, respectively. Recent trending topics were noted to be artificial intelligence, understanding the brain microenvironment, exosomes, novel mechanisms of diagnosis (such as circulating tumor cells), and targeted treatments. High-impact articles tended to revolve around specific therapies or biomarkers as opposed to general synopses. Clustering analysis revealed three separate pivotal collaborative communities centered around Brown PD/Sahgal A, Ahluwalia MS, and Wang Y, with Brown PD as most notable for high impact research. While the top institutional collaborative group centered around Mayo Clinic, the highest impact research centered around the Dana-Farber Cancer Institute. Sub-analyses revealed that studies involving multiple countries tended to have a higher impact. The median overall survival of brain metastases, by primary source, was illustrated across the last five decades. Overall, significant growth in scientific production is driven by the integration of novel technologies (such as artificial intelligence), interdisciplinary approaches, and collaboration across global communities