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•SES was associated with transplant outcomes after diagnosis of aGVHD and cGVHD.•In patients with aGVHD, non-Hispanic Black race was associated with increased TRM and overall mortality.

•Haploidentical HCT has similar survival as MUD-HCT in myelofibrosis.•Strategies to prevent graft failure in haploidentical HCT need to be investigated.

Parkinson’s disease (PD) is characterized by striatal dopamine deficiency. Since dopamine cannot cross the digestive and blood-brain barriers, its precursor, levodopa (L-DOPA), remains the mainstay of treatment. However, the significant pharmacokinetic (Pk) and pharmacodynamic (Pd) limitations of L-DOPA, combined with the severity of PD, may trigger motor and non-motor complications, for which continuous dopaminergic delivery therapies have been developed. The aim of this study was to review the literature on the Pk/Pd limitations of L-DOPA and how current treatments of continuous dopaminergic administration ameliorate these problems, in order to identify the need for new therapeutic avenues. A comprehensive literature search was carried out using PubMed and 75 articles were initially extracted. Following independent screening by two reviewers and consideration of eligibility, 10 articles were chosen for further analysis. Information concerning the Pk/Pd of L-DOPA was classified for each article. Pk/Pd problems notably include: (i) restricted digestive and cerebral absorption; (ii) unnecessary peripheral distribution; (iii) short half-life; (iv) age- and PD-induced decline of central aromatic L-amino acid decarboxylase; (v) misdistribution in many cells; and (vii) pulsatile stimulation of dopaminergic receptors. Current treatments only slightly ameliorate some of these problems. Many Pk/Pd constraints are not resolved by existing continuous dopaminergic delivery therapies. This highlights the significant gap between these treatments and the ideal of continuous dopaminergic stimulation.

This article addresses a critically important topic for the occupational therapy (OT) profession and driver rehabilitation specialists (DRS), related to the introduction and deployment of personal and public automated vehicles (AVs); and discusses the current and corresponding changing roles for these professionals. Within this commentary, we provide an overview of the relevant literature on AV regulations, policy, and legislation in North America, the various levels of AV technology, and inclusive and universal design principles to consider in AV deployment for people with disabilities. The role of the OT practitioner and DRS is described within the context of the person–environment–occupation–performance model, and within the guidelines of the Association for Driver Rehabilitation Specialists and the American Occupational Therapy Association. The article concludes with considerations for an extended clinical agenda, a new research agenda, and a call for action to OT practitioners and DRS, as well as to educators, certification bodies, professional organizations, and collaborators.

Reductive catalytic fractionation (RCF) is a promising method to extract and depolymerize lignin from biomass, and bench-scale studies have enabled considerable progress in the past decade. RCF experiments are typically conducted in pressurized batch reactors with volumes ranging between 50 and 1000 mL, limiting the throughput of these experiments to one to six reactions per day for an individual researcher. Here, we report a high-throughput RCF (HTP-RCF) method in which batch RCF reactions are conducted in 1 mL wells machined directly into Hastelloy reactor plates. The plate reactors can seal high pressures produced by organic solvents by vertically stacking multiple reactor plates, leading to a compact and modular system capable of performing 240 reactions per experiment. Using this setup, we screened solvent mixtures and catalyst loadings for hydrogen-free RCF using 50 mg poplar and 0.5 mL reaction solvent. The system of 1:1 isopropanol/methanol showed optimal monomer yields and selectivity to 4-propyl substituted monomers, and validation reactions using 75 mL batch reactors produced identical monomer yields. To accommodate the low material loadings, we then developed a workup procedure for parallel filtration, washing, and drying of samples and a 1H nuclear magnetic resonance spectroscopy method to measure the RCF oil yield without performing liquid–liquid extraction. As a demonstration of this experimental pipeline, 50 unique switchgrass samples were screened in RCF reactions in the HTP-RCF system, revealing a wide range of monomer yields (21–36%), S/G ratios (0.41–0.93), and oil yields (40–75%). These results were successfully validated by repeating RCF reactions in 75 mL batch reactors for a subset of samples. We anticipate that this approach can be used to rapidly screen substrates, catalysts, and reaction conditions in high-pressure batch reactions with higher throughput than standard batch reactors.

Data-independent acquisition (DIA) has become a well-established method for MS-based proteomics. However, the list of options to analyze this type of data is quite extensive, and the use of spectral libraries has become an important factor in DIA data analysis. More specifically the use of in silico predicted libraries is gaining more interest. By working with a differential spike-in of human standard proteins (UPS2) in a constant yeast tryptic digest background, we evaluated the sensitivity, precision, and accuracy of the use of in silico predicted libraries in data DIA data analysis workflows compared to more established workflows. Three commonly used DIA software tools, DIA-NN, EncyclopeDIA, and Spectronaut, were each tested in spectral library mode and spectral library-free mode. In spectral library mode, we used independent spectral library prediction tools PROSIT and MS2PIP together with DeepLC, next to classical data-dependent acquisition (DDA)-based spectral libraries. In total, we benchmarked 12 computational workflows for DIA. Our comparison showed that DIA-NN reached the highest sensitivity while maintaining a good compromise on the reproducibility and accuracy levels in either library-free mode or using in silico predicted libraries pointing to a general benefit in using in silico predicted libraries.

In 2011, the UK medical research charity Cure Parkinson’s set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson’s disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD experts has subsequently met annually to assess and prioritize agents that may slow the progression of this neurodegenerative condition, using a systematic approach based on preclinical, epidemiological and, where possible, clinical data. Over the last 12 years, 171 unique agents have been evaluated by the iLCT committee, and there have been 21 completed clinical studies and 20 ongoing trials associated with the initiative. In this review, we briefly outline the iLCT process as well as the clinical development and outcomes of some of the top prioritized agents. We also discuss a few of the lessons that have been learnt, and we conclude with a perspective on what the next decade may bring, including the introduction of multi-arm, multi-stage clinical trial platforms and the possibility of combination therapies for PD.

While tubular microcrystallizers offer distinct advantages over conventional crystallization setups for manipulating crystallization conditions, precisely controlling mixing, fluid shear, and therefore also the nucleation step remains a challenge. In this study, the potential of acoustic streaming as a tool to manipulate nucleation was investigated. Acoustic streaming is fluid flow as a result of the attenuation of an ultrasonic wave propagating through a viscous medium, which in the developed setup leads to the formation of reproducible and controllable rotating and counterrotating vortices (known as Rayleigh streaming). By increasing the ultrasound wave amplitude, the fluid shear within the microcrystallizer also increases. This method to precisely control the shear rate was exploited for manipulating the primary nucleation kinetics of paracetamol from an aqueous solution. Additionally, the acoustic streaming microcrystallizer was utilized as an in-line nuclei generator for continuous crystallization. By narrowing the residence time distribution in the microcrystallizer with the acoustic streaming, the variability in the number of produced crystals can be substantially decreased, thus improving the reliability and controllability of continuous microscale crystallization processes. By demonstrating nucleation control and outlooks for continuous applications, this research highlights the potential of acoustic streaming as a powerful tool to manipulate nucleation events in small scale setups.

With current trends in proteomics, especially regarding clinical and low input (to single cell) samples, it is increasingly important to both maximize the throughput of the analysis and maintain as much sensitivity as possible. The new generation of mass spectrometers (MS) are taking a huge leap in sensitivity, allowing analysis of samples with shorter liquid chromatography (LC) methods while digging as deep in the proteome. However, the throughput can be doubled by implementing a dual column nano-LC-MS configuration. For this purpose, we used a dual-column setup with a two-outlet electrospray source and compared it to a classic dual-column setup with a single-outlet source.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a preferred treatment for parkinsonian patients with severe motor fluctuations. Proper targeting of the STN sensorimotor segment appears to be a crucial factor for success of the procedure. The recent introduction of directional leads theoretically increases stimulation specificity in this challenging area but also requires more precise stimulation parameters.Objective: We investigated whether commercially available software for image guided programming (IGP) could maximize the benefits of DBS by informing the clinical standard care (CSC) and improving programming workflows.Methods: We prospectively analyzed 32 consecutive parkinsonian patients implanted with bilateral directional leads in the STN. Double blind stimulation parameters determined by CSC and IGP were assessed and compared at three months post-surgery. IGP was used to adjust stimulation parameters if further clinical refinement was required. Overall clinical efficacy was evaluated one-year post-surgery.Results: We observed 78% concordance between the two electrode levels selected by the blinded IGP prediction and CSC assessments. In 64% of cases requiring refinement, IGP improved clinical efficacy or reduced mild side effects, predominantly by facilitating the use of directional stimulation (93% of refinements).Conclusions: The use of image guided programming saves time and assists clinical refinement, which may be beneficial to the clinical standard care for STN-DBS and further improve the outcomes of DBS for PD patients.

Although dye plants were a key element in the medieval cloth industry, their use has rarely been documented through archaeobotanical studies. This paper describes and discusses new archaeobotanical finds related to textile dyeing in the southern Low Countries, which was among the most important areas of cloth production and export in Europe during the late medieval period. Remains of weld, madder and woad, the three main medieval dye plant species, were identified via archaeobotanical analysis and high-performance liquid chromatography with photodiode array detection (HPLC-PDA). The remains were found in river deposits, dating between the 10th/12th and 15th century, from two medieval cloth-producing towns, Brussels and Mechelen. Most likely, the finds must be interpreted as waste discarded by textile dyers, which were often concentrated along the urban riverbanks. This study not only documents the use of dye plants in both cities, but also demonstrates the importance of archaeobotanical analyses of fluvial deposits for the reconstruction of artisanal activities within ancient towns. The assemblages are confronted with historic sources and mapped with other medieval remains of dye plants in the region.

AbstractSelf-organised initiatives are increasingly recognised as an alternative to the structural deficit of participatory planning approaches, both in theory and in practice. Nevertheless, public governance is struggling to find ways to deal with such initiatives. This article identifies four prominent categories of self-organised practice, analysing the main motivation to engage in and with these practices, from the perspective of government as well as the self-organised actors. This is in turn linked to three prominent theoretical answers on how governments might deal with self-organisation. Lastly, we reflect on the complexities of a possible double connection between policymakers and self-organisations.

In 2011, the UK medical research charity Cure Parkinson’s set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson’s disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD experts has subsequently met annually to assess and prioritize agents that may slow the progression of this neurodegenerative condition, using a systematic approach based on preclinical, epidemiological and, where possible, clinical data. Over the last 12 years, 171 unique agents have been evaluated by the iLCT committee, and there have been 21 completed clinical studies and 20 ongoing trials associated with the initiative. In this review, we briefly outline the iLCT process as well as the clinical development and outcomes of some of the top prioritized agents. We also discuss a few of the lessons that have been learnt, and we conclude with a perspective on what the next decade may bring, including the introduction of multi-arm, multi-stage clinical trial platforms and the possibility of combination therapies for PD.

BackgroundNMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson’s disease (PD).MethodsPatients with PD were included in presurgical situation for deep brain stimulation of subthalamic nuclei. They participated in the PREDISTIM cohort (a study evaluating the predictive factors for therapeutic response of subthalamic stimulation in PD) in 17 centres in France. Our questionnaire, resulting from previous phases of development, included 11 non-motor symptoms (NMS). Their severity ranged from 0 to 10 and was assessed in OFF and then ON-Dopa to study their fluctuations.Results310 patients were included, of whom 98.8% had NMS and 98.0% had NMF. Each NMS was significantly improved by L-Dopa (decrease in severity score ranging from 43.1% to 69.9%). Fatigue was the most frequent and most severe NMS. NMS were considered more bothersome than motor symptoms by 37.5% of patients in OFF-Dopa and 34.9% in ON-Dopa.ConclusionsThis is the first questionnaire allowing a real-time quantification of the severity of NMS and their fluctuation with levodopa. It was able to confirm and measure the effect of L-dopa and show differences according to the patients and the NMS. It differs from other questionnaires by its measurement at a precise moment of the severity of the NMS, allowing its use during pretherapeutic assessments.Our questionnaire has been validated to measure the severity of NMF. It will be able to quantify the non-motor effect of anti-parkinsonian treatments and could facilitate the integration of NMF in therapeutic decisions.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a preferred treatment for parkinsonian patients with severe motor fluctuations. Proper targeting of the STN sensorimotor segment appears to be a crucial factor for success of the procedure. The recent introduction of directional leads theoretically increases stimulation specificity in this challenging area but also requires more precise stimulation parameters. We investigated whether commercially available software for image guided programming (IGP) could maximize the benefits of DBS by informing the clinical standard care (CSC) and improving programming workflows. We prospectively analyzed 32 consecutive parkinsonian patients implanted with bilateral directional leads in the STN. Double blind stimulation parameters determined by CSC and IGP were assessed and compared at three months post-surgery. IGP was used to adjust stimulation parameters if further clinical refinement was required. Overall clinical efficacy was evaluated one-year post-surgery. We observed 78% concordance between the two electrode levels selected by the blinded IGP prediction and CSC assessments. In 64% of cases requiring refinement, IGP improved clinical efficacy or reduced mild side effects, predominantly by facilitating the use of directional stimulation (93% of refinements). The use of image guided programming saves time and assists clinical refinement, which may be beneficial to the clinical standard care for STN-DBS and further improve the outcomes of DBS for PD patients.

Il existe dans la littérature relative à la chirurgie orthopédique et traumatologique un manque de données concernant les articles négatifs. Il est important de connaître les prises en charge ou les techniques apportant un effet bénéfique tout autant que celles ayant un effet nul ou péjoratif, aussi nous avons mené une étude sur les articles négatifs afin de : (1) déterminer leur proportion dans les dix principales revues de chirurgie orthopédique et traumatologique ; (2) rechercher une variabilité de leur taux de publication selon les revues et les années et comparer leur taux de citation à celui des articles positifs ; (3) préciser si un article positif avait plus de probabilité d’être cité par rapport à un article négatif ; (4) mener avec Orthopaedics & Traumatology: Surgery & Research (OTSR)la même analyse bibliométrique et détecter un éventuel biais de sélection des articles négatifs lors du reviewing.

The article explains reasons for shutting down the U.S. Department of Education and considers ways to help students. It shows the department's failure in funding K-12 education. It outlines policy ideas to empower students and improve the teaching profession, including educational freedom, blocking grant funds to the states, making the Federal Student Aid Office an autonomous government corporation, and combining forces to protect students against discrimination and uphold their civil rights.

Le financement de la recherche au sein des établissements de santé a longtemps été forfaitaire (13 %) et réservée à certaines catégories d’établissements. En 2008, le ministère de la Santé a mis en place une réforme du financement en instaurant un nouveau modèle, le modèle MERRI : missions d’enseignement, de recherche, de référence et d’innovation. Ce modèle comporte différents volets de financement dont la dotation socle d’un montant de près de 2 milliards d’euros et basé sur des indicateurs d’activité. 75 % de la dotation socle sont attribués à partir des données SIGAPS (publications scientifiques) et SIGREC (essais cliniques). Mise à disposition d’environ 70 établissements en 2008, la plateforme SIGAPS/SIGREC est maintenant installée dans 650 établissements, comprenant près de 200 000 chercheurs qui ont produit entre 2000 et 2021 plus de 400 000 publications (Articles, Reviews et Editorials). Le nombre de publications a fortement augmenté, passant de 12 375 en 2000 à 28 430 en 2021 (+ 130 %). Le montant de la dotation socle est lui passé de 1,5 milliards d’euros en 2015 à 1,87 milliards d’euros en 2022. Les modalités de calcul de ces indicateurs sont relativement complexes et l’objectif de cette mise au point est de vous aider à les décrypter. Enfin, l’évaluation de la recherche a évolué depuis 15 ans et une réflexion est à mener sur les évolutions possibles, en distinguant bien les évaluations des établissements des évaluations individuelles.

Background: The tibiotalar arthrodesis for end-stage ankle osteoarthritis is a surgical procedure that leads to a modification of the kinematics of the adjacent joints and may result in the development of secondary osteoarthritic degeneration of the subtalar joint. It has previously been observed that subtalar arthrodesis in this context shows a lower fusion rate than isolated subtalar arthrodesis. This retrospective study reports the results of subtalar joint arthrodesis with previous ipsilateral tibiotalar arthrodesis and suggests some factors that may compromise the fusion of the joint.Methods: Between September 2010 and October 2021, 15 arthrodeses of the subtalar joint with screw fixation were performed in 14 patients, with a fusion of the ipsilateral tibiotalar joint. Fourteen of 15 cases used an open sinus tarsi approach, 13 were augmented with iliac crest bone graft, and 11 had supplemental demineralized bone matrix (DBM). The outcome variables were fusion rate, time to fusion, and revision rate. Fusion was assessed by radiographs and computed tomography scan.Results: Twelve of the 15 subtalar arthrodeses (80%) fused at the first attempt with an average fusion time of 4.7 months.Conclusion: In this limited retrospective case series, compared to the fusion rate of isolated subtalar arthrodesis reported in the literature, the rate of subtalar fusion in the presence of an ipsilateral tibiotalar arthrodesis was found to be lower.Level of Evidence: Level IV, retrospective case series.

Background: Previous studies have examined the effect of concomitant triceps surae lengthening on ankle dorsiflexion motion at the time of total ankle arthroplasty (TAA). As plantarflexor muscle-tendon structures are important for producing positive ankle work during the propulsive phase of gait, caution should be exercised when lengthening triceps surae, as it may decrease plantarflexion strength. In order to develop an understanding of the work of the anatomical structures crossing the ankle during propulsion, joint work must be measured. The aim of this explorative study was to assess the effect of concomitant triceps surae lengthening with TAA on the resultant ankle joint work.Methods: Thirty-three patients were recruited to the study and divided into 3 groups of 11. The first group underwent both triceps surae lengthening (Strayer and TendoAchilles) and TAA (Achilles group), the second group underwent only TAA (Non-Achilles group), and the third group underwent only TAA, but had a greater radiographic prosthesis range of motion (Control group) compared to the first 2 groups. The 3 groups were matched in terms of demographic variables and walking speed. All patients underwent a 3D gait analysis 1 year after surgery to measure intersegmental joint work using a 4-segmented kinetic foot model. An analysis of variance (ANOVA) or Kruskal-Wallis test was used to compare the 3 groups.Results: The ANOVA showed significant differences between the 3 groups. Post hoc analyses suggested that (1) the Achilles group had less positive work at the ankle joint than the Non-Achilles and Control groups; (2) the Achilles group produced less positive work performed by all foot and ankle joints than the Control group; and (3) the Achilles and Non-Achilles groups absorbed less energy across all foot and ankle joints during the stance phase than the Control group.Conclusion: Concomitant triceps surae lengthening in TAA may reduce the positive work at the ankle joint.Level of Evidence: Level III, retrospective comparative study.

AbstractWe investigate the relation between commercial real estate (CRE) returns and regional innovativeness and find that regions with more innovation exhibit higher total returns on commercial property. And, when we investigate the extent to which income return and capital return on commercial properties are related to local innovativeness, we report a positive relation between innovativeness and income return but little to no association between innovativeness and capital return. Our paper also provides some initial evidence suggesting that local innovativeness is related to better future CRE performance. Overall, this paper suggests that the innovativeness of a region is economically and statistically positively related to CRE returns, adding to a budding literature investigating CRE returns and extensive literature researching innovation.