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Expansion microscopy, whereby the relative positions of biomolecules are physically increased via hydrogel expansion, can be used to reveal ultrafine structures of cells under a conventional microscope. Despite its utility for achieving super-resolution imaging, expansion microscopy suffers two major drawbacks, namely proteolysis and swelling effects that, respectively, induce protein loss and dilute fluorescence signals. Here, we report two improvements to expansion microscopy that overcome these two challenges, i.e., deploying trypsin digestion to reduce protein loss and tyramide signal amplification to enhance fluorescence signal. We name our new methodology TT-ExM to indicate dual trypsin and tyramide treatments. TT-ExM may be applied for both antibody and lipid staining. Notably, we demonstrate better protein retention for endoplasmic reticulum and mitochondrial markers in COS-7 cell cultures following 2-h trypsin treatment. Subsequent lipid staining revealed the complex 3D membrane structures in entire cells. Through combined lipid and DNA staining, our TT-ExM methodology highlighted mitochondria by revealing their DNA and membrane structures in cytoplasm, as well as the lipid-rich structures formed via phase separation in nuclei at interphase. We also observed lipid-rich chromosome matrices in the mitotic cells. Thus, TT-ExM significantly enhances fluorescent signals and generates high-quality and ultrafine-resolution images under confocal microscopy.

SummaryBehavior requires neural activity across the brain, but most experiments probe neurons in a single area at a time. Here we used multiple Neuropixels probes to record neural activity simultaneously in brain-wide circuits, in mice performing a memory-guided directional licking task. We targeted brain areas that form multi-regional loops with anterior lateral motor cortex (ALM), a key circuit node mediating the behavior. Neurons encoding sensory stimuli, choice, and actions were distributed across the brain. However, in addition to ALM, coding of choice was concentrated in subcortical areas receiving input from ALM, in an ALM-dependent manner. Choice signals were first detected in ALM and the midbrain, followed by the thalamus, and other brain areas. At the time of movement initiation, choice-selective activity collapsed across the brain, followed by new activity patterns driving specific actions. Our experiments provide the foundation for neural circuit models of decision-making and movement initiation.

Interposition microvascular grafting may be required during digital replantation or revascularisation. Although traditionally performed using venous autograft, the use of arterial segments for microvascular grafting confers a number of benefits. Here, we discuss the harvesting of such a graft from the interosseous arterial system and its use in the clinical setting. Level of Evidence: Level V (Therapeutic)

PURPOSE Genomic tests improve accuracy of risk prediction for early breast cancers but these are expensive. This study evaluated the clinical utility of EndoPredict®, in terms of impact on adjuvant therapy recommendations and identification of parameters to guide selective application. METHODS Patients with ER-positive, HER2-negative, and early-stage invasive breast cancer were tested with EndoPredict®. Two cohorts were recruited: one consecutively and another at clinical team discretion. Systemic treatment recommendations were recorded before and after EndoPredict® results were revealed to the multidisciplinary team. RESULTS 233 patients were recruited across five sites: 123 consecutive and 110 at clinical team discretion. In the consecutive cohort 50.6% (62/123) cases were classified high risk of recurrence by EndoPredict®, compared with 62.7% (69/110) in the selective cohort. A change in treatment recommendation was significantly more likely (p

Contact sports players frequently sustain head impacts, most of which are mild impacts exhibiting 10-30 g peak head center-of-gravity (CG) linear acceleration. Wearable head impact sensors are commonly used to measure exposure and typically detect impacts using a linear acceleration threshold. However, linear acceleration across the head can substantially vary during 6-degree-of-freedom motion, leading to triggering biases that depend on sensor location and impact condition. We conducted an analytical investigation with impact characteristics extracted from on-field American football and soccer data. We assumed typical mouthguard sensor locations and evaluated whether simulated multi-directional impacts would trigger recording based on per-axis or resultant acceleration thresholding. Across 1387 impact directions, a 10g peak CG linear acceleration impact would trigger at only 24.7% and 31.8% of directions based on a 10 g per-axis and resultant acceleration threshold, respectively. Anterior impact locations had lower trigger rates and even a 30 g impact would not trigger recording in some directions. Such triggering biases also varied by sensor location and linear-rotational head kinematics coupling. Our results show that linear acceleration-based impact triggering could lead to considerable bias in head impact exposure measurements. We propose a set of recommendations to consider for sensor manufacturers and researchers to mitigate this potential exposure measurement bias.

Stereotactic body radiation therapy (SBRT) is an emerging treatment for liver cancers whereby large doses of radiation can be delivered precisely to target lesions in 3–5 fractions. The target dose is limited by the dose that can be safely delivered to the non-tumour liver, which depends on the baseline liver functional reserve. Current liver SBRT guidelines assume uniform liver function in the non-tumour liver. However, the assumption of uniform liver function is false in liver disease due to the presence of cirrhosis, damage due to previous chemo- or ablative therapies or irradiation, and fatty liver disease. Anatomical information from magnetic resonance imaging (MRI) is increasingly being used for SBRT planning. While its current use is limited to the identification of target location and size, functional MRI techniques also offer the ability to quantify and spatially map liver tissue microstructure and function. This review summarises and discusses the advantages offered by functional MRI methods for SBRT treatment planning and the potential for adaptive SBRT workflows.

In this retrospective study, we have explored the anatomical factors that lead to the development of radiation necrosis (RN) in the setting of stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM). Between 2014 and 2018, 137 patients underwent SRS for 311 MBM. Lesions were assessed according to anatomical zones: zone 1—peripheral grey-white matter junction and cortical mantle, zone 2—deep white matter, including tumours located at base of sulci, zone 3—tumours adjacent to ependymal lining or in deep locations such as brainstem, basal ganglia and thalamus. Other anatomical factors including lobes, medial-peripheral, supra or infratentorial locations were also recorded. In all, 12.4% (n = 17) of patients and 6.1% (n = 20) of lesions developed RN, actuarial incidence of RN at 12 and 24 months was 10% and 14.2% respectively. Zone 2 lesions recorded the highest rate of development of RN (n = 7/19; 36%), zone 3 (N = 4/24; 16%) and zone 1 (n = 9/268; 3%). Five of 17 patients developed symptomatic RN and 7/17 patients underwent surgery for RN. This study raises awareness of the increased likelihood of deep lesions particularly in white matter structures to develop RN after SRS. Further studies including larger cohorts would be useful in identifying statistical differences in the rate of development of RN in different anatomical zones.

Background Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. Methods Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. Discussion Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. Trial registration This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566.

A prominent trend in single-cell transcriptomics is providing spatial context alongside a characterization of each cell’s molecular state. This typically requires targeting ana prioriselection of genes, often covering less than 1% of the genome, and a key question is how to optimally determine the small gene panel. Reference data from these methods covering the whole genome is unavailable, and using single-cell RNA sequencing (scRNA-seq) datasets as a surrogate can result in suboptimal gene panels due to the fundamentally different data distributions across technologies. We address these challenges by introducing a flexible deep learning framework, PERSIST, to identify informative gene targets for spatial transcriptomics studies by leveraging existing scRNA-seq data. Using datasets spanning different brain regions, species, and scRNA-seq technologies, we show that PERSIST reliably identifies gene panels that provide more accurate prediction of the genome-wide expression profile, thereby capturing more information with fewer genes. Furthermore, PERSIST can be adapted to meet specific biological goals, such as classifying cell types or discerning neuronal electrical properties. Finally, via a simulation study based on a recentin situhybridization-based dataset, we demonstrate that PERSIST’s binarization of gene expression levels enables models trained on scRNA-seq data to generalize with input data obtained using spatial transcriptomics, despite the complex domain shift between these technologies.

INTRODUCTION: Though musculoskeletal complaints account for roughly one-quarter of primary care and emergency department visits, only 2% of US medical school curriculum is devoted to musculoskeletal disease. Many graduating students demonstrate poor knowledge and report low confidence in treating musculoskeletal disorders. This study defines the current state of musculoskeletal curriculum of medical schools in detail to identify variations and potential shortcomings. METHODS: All eleven medical schools in California were invited to participate in an in-depth survey detailing the design and content of their musculoskeletal curriculum. RESULTS: A response rate of 100% was achieved. Overall, schools devoted an average of 58.7 h to musculoskeletal medicine, of which more than half was spent covering anatomy. The primary instructor for musculoskeletal medicine was a clinician in four schools (36.4%). Six schools offered a dedicated musculoskeletal physical exam course. No schools required students to complete a clinical rotation in musculoskeletal medicine. There was high variability among institutions when evaluating core subject coverage. DISCUSSION: There is large variation in the content and structure of musculoskeletal instruction among California medical schools. Increased curricular time, integration of preclinical and clinical experiences, greater specialist participation, and standardized objectives may provide more consistent and comprehensive musculoskeletal education. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-020-01144-3.

Purpose The purpose of this study was to determine the (1) reoperation rate and (2) 30-day complication rate in a large insurance database. Methods The Truven Database was queried for subjects that underwent meniscus allograft transplantation (Current Procedural Terminology code 29868) in the outpatient setting with minimal 2-year follow-up. Patients without confirmed laterality and patients that underwent concomitant ligament reconstruction were excluded. Reoperation was defined by ipsilateral knee procedure after the index surgery. The 30-day postoperative complication rates were assessed using International Classification of Diseases, 9th Revision, Clinical Modification codes. Results A total of 284 patients (mean age of 26.2 ± 10.4 years; 49.6% females) were included in this study with mean follow up of 43.2 ± 19.2 months. One hundred and sixty-seven subjects (58.8%) undergoing meniscus allograft transplantation underwent reoperation at an average of 11.9 ± 12.2 months postoperatively. There was a low number of subjects that required ipsilateral unicompartmental knee arthroplasty and total knee arthroplasty postoperatively (0.7% and 1.1%, respectively). The overall 30-day complication rate following meniscus allograft transplantation was 1.4%. Conclusions Patients undergoing meniscus allograft transplantation have a 58.8% reoperation rate at final follow up with low (1.4%) 30-day complication rates in a large insurance database. Level of Evidence Level IV, case series.

PurposeThe aim of this study was to evaluate the efficacy and safety of adjuvant multifractionated stereotactic radiotherapy (SRS) for patients with resected brain metastases (BM). Methods and MaterialsWe retrospectively assessed 54 patients with brain metastases who underwent surgery and postoperative SRS in a single institution between January 2016 and June 2021. All but one patient were treated with hypo fractionated stereotactic radiotherapy (HF-SRT) with doses ranging from 30 Gy in 5 fractions, 25 Gy in 5 fractions, or 27 Gy in 3 fractions. The primary outcome for this study was local control (LC) within the resection cavity. The secondary endpoints were overall survival (OS), distant brain failure (DBF), leptomeningeal disease (LMD), and brain radionecrosis (RN). ResultsThe median follow-up was 14.9 months. Local control was 90.6% at 6 months and 82.1% at 12 months. The six and twelve-month estimates of DBF were 19.2% and 25.9%, respectively. Seven patients (12.9%) experienced both local and distant failures, including 2 cases with leptomeningeal disease. At the time of final analysis, median times to local failure, DBF and LMD were not reached. OS rates at 6 months and 12 months were 80.8% and 56.6%, respectively. RN was present in 4 cases (7.4%). ConclusionsThis single-institution retrospective study shows that postoperative HF-SRT in patients with BM seems to be associated with favourable outcomes for LC and relatively low-risk of RN.

Genomic tests improve accuracy of risk prediction for early breast cancers but these are expensive. This study evaluated the clinical utility of EndoPredict®, in terms of impact on adjuvant therapy recommendations and identification of parameters to guide selective application.Patients with ER-positive, HER2-negative, and early-stage invasive breast cancer were tested with EndoPredict®. Two cohorts were recruited: one consecutively and another at clinical team discretion. Systemic treatment recommendations were recorded before and after EndoPredict® results were revealed to the multidisciplinary team.233 patients were recruited across five sites: 123 consecutive and 110 at clinical team discretion. In the consecutive cohort 50.6% (62/123) cases were classified high risk of recurrence by EndoPredict®, compared with 62.7% (69/110) in the selective cohort. A change in treatment recommendation was significantly more likely (p 0.0001) in the selective cohort (43/110, 39.1%) compared to the consecutive group (11/123, 8.9%). The strongest driver of selective recruitment was intermediate grade histology, whilst logistic regression modelling demonstrated that nodal status (p 0.001), proliferative rate (p = 0.001), and progesterone receptor positivity (p 0.001) were the strongest discriminators of risk.Whilst molecular risk can be predicted by traditional variables in a high proportion of cases, EndoPredict® had a greater impact on treatment decisions in those cases selected for testing at team discretion. This is indicative of the robust ability of the clinical team to identify cases most likely to benefit from testing, underscoring the value of genomic tests in the oncologists' tool kit.

Hepatitis B virus (HBV) infection disproportionately affects the Hmong ethnic group, with reported US prevalence rates up to 20%, but data for Wisconsin's large Hmong community is lacking. We assessed the prevalence of HBV at Hmong screening events and whether small-group counseling affects HBV knowledge.Free HBV screening events were held in Milwaukee, Wisconsin at a Hmong market, a local church, and annual Hmong New Year festival. Eligible Hmong subjects age 18 years and older also were invited to complete a 15-point survey on HBV knowledge at baseline and after education sessions. Hmong interpreters were available, and free HBV screening was offered.A total of 187 participants were tested for HBV, and 161 completed surveys. After education sessions, the mean knowledge score rose to 10.6 (71%) vs the pre-education score of 6.7 (45%) (Despite evidence that small-group education with visual aids is effective in enhancing HBV knowledge in the Hmong population, a significant knowledge gap remained on post-education scores, suggesting that better tools or repeated interventions may be warranted. While we acknowledge that this convenience sampling may have introduced biases, the rate of active HBV infection in Wisconsin is much higher than general US population reports, and a quarter of those tested were found to be susceptible to HBV.

The International Integrated Reporting Council (IIRC) and the South African King III Report on Governance emphasize the role of corporate governance in preparing a high-quality integrated report an...

This study utilizes an advanced machine learning method known as TreeNet® (Salford Systems, 2017) to predict a variety of private company failure states, ranging from binary settings (i.e. failed vs non-failed) to more complex multi-class settings with up to five states of failure. Based on a large global sample, TreeNet® proved to be a significantly better predictor of private company failure than conventional models such as logistic regression. While the out-of-sample predictive performance of TreeNet® is best in binary settings, the model also produces strong area under the ROC curve (AUC) results for the multi-class models. We also find that the predictive performance of financial variables is significantly enhanced when combined with external risk factors such as macro-economic variables and other non-financial measures. The results of this study have several implications for the private company failure literature and the usefulness of machine learning methods in accounting and finance more generally.

This paper introduces a non-destructive measurement technique that extracts the as-fabricated substrate height of printed circuit boards. The as-fabricated substrate height is a crucial parameter for dielectric constant extraction and impedance prediction of any fabricated printed circuit board. Multi-measurement and line fitting techniques were introduced to convert measured S-parameters of shorted transmission lines to frequency-dependent per-unit-length inductance. A computation routine used analytical PUL inductance equations to generate frequency-dependent PUL inductance curve with given substrate height. By changing the input substrate height and minimizing the difference between the calculated and measured PUL inductance results, the as-fabricated height was extracted. The obtained height value with associated uncertainty was shown to be consistent with substrate height measured with direct cross-section inspection.

The paper investigates how much the crosstalk within the fixtures for multi-port device measurements affect the de-embedded results. Usually such type of fixtures are designed to minimize the crosstalk among the lines or the differential pairs, thus the de-embedded can be performed by applying iteratively the well-known 4-port de-embedding process based on the S-to-T and T-to-S parameter conversion. However such process ignores the crosstalk among the lines within the fixtures; in the case that the coupling is not negligible or it is ignored, especially for devices working at very high frequency (tens of GHz), the simple 4-port de-embedding leads to errors in the extraction DUT S-parameters. The multiport de-embedding algorithm reviewed in this paper, instead, is able to take this coupling into account, independently on the amount of crosstalk within the fixtures. The de-embedding based on multiport S-to-T parameters conversion (and vice-versa) always provides perfectly de-embedded DUT parameters, as highlighted by a realistic exampled based on a multipin connector for PAM4-based 112 Gbps applications.

Head Post and Cranial Window Outline Janelia Research Campus Svoboda Lab Developed by Karel Svoboda for Trachtenberg et al 2002 Improved by Anthony Holtmaat for Holtmaat et al 2006 and Holtmaat et al 2009 Improved by Daniel Huber for Huber et al 2012 Compiled by Bryan Maclennan (2013), Abridged version by Courtney Davis (2015) Compiled to protocols.io by JJ Kim (2019) Note: This outline only provides practical step-by-step advice. All surgeons should be familiar with and carefully adhere to the official animal protocol and current procedures posted on the Svoboda lab wiki. Trachtenberg, J. T., Chen, B. E., Knott, G. W., Feng, G., Sanes, J. R., Welker, E., & Svoboda, K. (2002). Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature, 420(6917), 788–794. https://doi.org/10.1038/nature01273 Holtmaat, A., Wilbrecht, L., Knott, G. W., Welker, E., & Svoboda, K. (2006). Experience-dependent and cell-type-specific spine growth in the neocortex. Nature, 441(7096), 979–983. https://doi.org/10.1038/nature04783 Holtmaat, A., Bonhoeffer, T., Chow, D. K., Chuckowree, J., De Paola, V., Hofer, S. B., Hübener, M., Keck, T., Knott, G., Lee, W. C. A., Mostany, R., Mrsic-Flogel, T. D., Nedivi, E., Portera-Cailliau, C., Svoboda, K., Trachtenberg, J. T., & Wilbrecht, L. (2009). Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nature Protocols, 4(8), 1128–1144. https://doi.org/10.1038/nprot.2009.89 Huber, D., Gutnisky, D. A., Peron, S., O’Connor, D. H., Wiegert, J. S., Tian, L., Oertner, T. G., Looger, L. L., & Svoboda, K. (2012). Multiple dynamic representations in the motor cortex during sensorimotor learning. Nature, 484(7395), 473–478. https://doi.org/10.1038/nature11039

In this retrospective study, we have explored the anatomical factors that lead to the development of radiation necrosis (RN) in the setting of stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM).Between 2014 and 2018, 137 patients underwent SRS for 311 MBM. Lesions were assessed according to anatomical zones: zone 1-peripheral grey-white matter junction and cortical mantle, zone 2-deep white matter, including tumours located at base of sulci, zone 3-tumours adjacent to ependymal lining or in deep locations such as brainstem, basal ganglia and thalamus. Other anatomical factors including lobes, medial-peripheral, supra or infratentorial locations were also recorded.In all, 12.4% (n = 17) of patients and 6.1% (n = 20) of lesions developed RN, actuarial incidence of RN at 12 and 24 months was 10% and 14.2% respectively. Zone 2 lesions recorded the highest rate of development of RN (n = 7/19; 36%), zone 3 (N = 4/24; 16%) and zone 1 (n = 9/268; 3%). Five of 17 patients developed symptomatic RN and 7/17 patients underwent surgery for RN.This study raises awareness of the increased likelihood of deep lesions particularly in white matter structures to develop RN after SRS. Further studies including larger cohorts would be useful in identifying statistical differences in the rate of development of RN in different anatomical zones.

The advent of Hyperscale Networks with the internet infrastructure has pushed digital data rates to the highest levels of performance. Emerging applications using 56Gbps and above are requiring new methods of validation, compared to the traditional metrics of BER and eye diagrams, to avoid throwing channel margin away unnecessarily. The Channel Operating Margin (COM) figure-of-merit along with measurement/simulation correlation is becoming a critical part of the design cycle. The analysis of the test cases proposed herein will present an extensive validation of a high speed connector for differential interconnects working up to 112 Gbps, by providing an in-depth analysis of such component, as a critical portion of the channel. A comprehensive correlation of the connector model to experimental results in terms of thru and crosstalk responses in both time and frequency domains provides a reliable connector model for the subsequent channel design. Comparison of new test methodologies will be shown to accurately predict how to optimize channel performance at today’s ultra-fast data rates.

High speed digital design is constantly attracting the attention of the electronic industry due to the constant development of telecommunication standards, with the consequence of ever growing data rate and new modulation schemes. The Channel Operating Margin (COM) comes up as a powerful tool for channel and physical layer designers to explore the design space at an early stage, as well as to optimize the channel physical parameters, thus overcoming the classic channel performance metrics such as eye diagram and BER. The analysis of the test cases proposed herein will guide through the use of COM and the channel analysis by investigating a 112 Gbps PAM4 chip-to-chip communication over a complex channel composed of a host board, a mezzanine connector, and a daughter card. Accurate analysis of these elements is carried out based on the connector characterization by measurements and full wave models; the PCBs, instead, are modeled as multiconductor transmission lines to resemble the typical configuration of coupled differential striplines. A comprehensive discussion of the COM results set relevant guidelines for a pre-layout analysis of such high speed communication channels.

Revision hip arthroplasty in the setting of periacetabular bone loss presents a significant challenge, as options for restoring bone loss are limited. Recombinant human bone morphogenetic protein-2 may offer a solution by promoting bone growth to restore bone stock before implant reimplantation. Here we present a case of a patient with a periprosthetic acetabulum fracture, resulting in pelvic discontinuity as the result of significant periacetabular bone loss. Using a staged approach, periacetabular bone stock was nearly entirely reconstituted using recombinant BMPs and allograft, which resulted in stable fixation, but with abundant heterotopic bone formation. Recombinant BMP-2 offers a useful tool for restoring bone stock in complex hip arthroplasty revision cases with periacetabular bone loss; however, caution must be used as overabundant bone growth as heterotopic ossification may result.

The study assesses the use of non‐financial information in predicting financial distress in private companies by developing credit risk models tailored to Italian private companies. The in‐sample and out‐of‐sample prediction test results are indicative of the incremental predictive ability of the two new non‐financial variables, that is, number of shareholders and number of subsidiaries, over accounting ratios and other widely used non‐financial information, including firm age and industry dummies. To be more specific, number of shareholders and number of subsidiaries are negatively associated with private company failures, and the models augmented by the two non‐financial variables improve forecasting performance from acceptable discrimination to excellent discrimination over one‐ to three‐year time horizons.

To investigate return to play (RTP) and functional performance after anterior cruciate ligament reconstruction (ACLR) in National Basketball Association (NBA) players and to perform a systematic review of the literature to understand RTP after ACLR in professional basketball.NBA players undergoing ACLR between 2008 and 2014 by two surgeons were identified. RTP and performance were assessed based on a review of publically available statistics. A systematic review of the literature was performed using the MEDLINE database. Inclusion criteria were: English language, ACL surgery outcome, professional basketball and RTP outcome. We reviewed studies for RTP rates and RTP performance.Our study included 12 professional basketball players with NBA level experience. Eleven of the 12 players returned to their prior level of play. Eight of the 9 (88.9%) players actively playing in the NBA returned to play in the NBA at a mean 9.8 months. Among players returning to NBA play, during RTP season 1, mean per game statistics decreased for the following: minutes, points, rebounds, assists, steals, blocks, turnovers and personal fouls - none of these changes reached statistical significance. Player efficiency ratings significantly declined from pre-injury (12.5) to the first RTP season (7.6) (p = 0.05). By RTP season 2, player performance metrics approximated pre-injury levels and were not significantly different. Six studies met inclusion criteria; reported RTP rates ranged from 78-86%. Identified studies similarly found a decline in functional performance after RTP.There is a high rate (89%) of return to NBA play for NBA players undergoing ACLR. After RTP, however, there is a quantitative decline in initial season 1 RTP statistics with a significant decrease in player efficiency rating. By RTP season 2, performance metrics demonstrated an improvement compared to RTP season 1 but did not reach pre-injury functional performance, though performance metrics are not significantly different between pre-injury and RTP season 2.

Focal white matter lesions are the defining pathological and imaging hallmark of the multiple sclerosis. Until recently, elucidation of the pathophysiology of lesion formation, progression and repair has relied on point neuropathological observations. Here, we review current and emerging concepts of the MRI-defined multiple sclerosis lesion phenotype, advanced longitudinal imaging techniques that permit in-vivo exploration of dynamic microstructural change within lesions and emerging MRI measures of lesion repair.Novel MRI techniques have elucidated dynamic features of the active multiple sclerosis lesion, defined imaging surrogates for chronic active lesions and revealed progressive microstructural change within chronic inactive lesions. Lesion-related anterograde, retrograde and trans-synaptic neurodegenerative mechanisms are being unravelled in vivo through MRI. An array of myelin-imaging techniques have emerged and in some cases have already been integrated into Phase 2 remyelination trials.MRI has shed new light on dynamic processes that occur over the lifespan of the multiple sclerosis lesion, and reaffirms the critical role of focal pathology as a determinant of disease progression. The development of robust, longitudinal biomarkers of lesion microstructure, such as advanced diffusion imaging, will be especially important as the era of neurorepair trials in multiple sclerosis dawns.

The study assesses the use of non-financial information in predicting financial distress in private companies by developing credit risk models tailored to Italian private companies. The in-sample and out-of-sample prediction test results are indicative of the incremental predictive ability of the two new non-financial variables, that is, number of shareholders and number of subsidiaries, over accounting ratios and other widely used non-financial information, including firm age and industry dummies. To be more specific, number of shareholders and number of subsidiaries are negatively associated with private company failures, and the models augmented by the two non-financial variables improve forecasting performance from acceptable discrimination to excellent discrimination over one- to-three year time horizons.