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Bone fractures often require internal fixation using plates or screws. Normally, these devices are made of permanent metals like titanium providing necessary strength and biocompatibility. However, they can also cause long-term complications and may require removal. An interesting alternative are biocompatible degradable devices, which provide sufficient initial strength and then degrade gradually. Among other materials, biodegradable magnesium alloys have been developed for craniofacial and orthopaedic applications. Previously, we tested implants made of magnesium hydroxide and RS66, a strong and ductile ZK60-based alloy, with respect to biocompatibility and degradation behaviour. Here, we compare the effects of dissolving magnesium hydroxide and RS66 cylinders on bone regeneration and bone growth in rabbit condyles using microtomographical and histological analysis. Both magnesium hydroxide and RS66 induced a considerable osteoblastic activity leading to distinct but different spatio-temporal patterns of cancellous and periosteal bone growth. Dissolving RS66 implants induced a prominent periosteal bone formation on the medial surface of the original condyle whereas dissolving magnesium hydroxide implants enhance mainly cancellous bone formation. Especially periosteal bone formation was completed after 6 and 8 weeks, respectively. The observed bone promoting functions are in line with previous reports of magnesium stimulating cancellous and periosteal bone growth and possible underlying signalling mechanisms are discussed. Biodegradable magnesium based implants are promising candidates for use in orthopedic and traumatic surgery. Although these implants are in the scientific focus for a long time, comparatively little is known about the interactions between degrading magnesium and the biological environment. In this work, we investigated the effects of two degrading cylindrical magnesium implants (MgOH 2 and RS66) both on bone regeneration and on bone growth. Both MgOH 2 and RS66 induce remarkable osteoblastic activities, however with different spatio-temporal patterns regarding cancellous and periosteal bone growth. We hypothesize that degradation products do not diffuse directionless away, but are transported by the restored blood flow in specific spatial patterns which is also dependent on the used surgical technique. [Display omitted] [ABSTRACT FROM AUTHOR]

Increased gray matter volume (GMV) following electroconvulsive therapy (ECT) has been well-documented, with limited studies reporting a subsequent decrease in GMV afterwards. This study characterized the reversion pattern of GMV after ECT and its association with clinical depression outcome, using multi-site triple time-point data from the Global ECT-MRI Research Collaboration (GEMRIC). 86 subjects from the GEMRIC database were included, and GMV in 84 regions-of-interest (ROI) was obtained from automatic segmentation of T1 MRI images at three timepoints: pre-ECT (T 0), within one-week post-ECT (T 1), and one to six months post-ECT (T 2). RM-ANOVAs were used to assess longitudinal changes and LMM analyses explored associations between GMV changes and demographical and clinical characteristics. 63 of the 84 ROIs showed a significant increase-and-decrease pattern (RM-ANOVA, Bonferroni corrected p < 0.00059). Post hoc tests indicated a consistent pattern in each of these 63 ROIs: significant increase from T 0 to T 1 in GMV , followed by significant decrease from T 1 to T 2 and no difference between T 0 and T 2 , except for both amygdalae, right hippocampus and pars triangularis, which showed the same increase and decrease but GMV at T 2 remained higher compared to T 0. No consistent relationship was found between GMV change pattern and clinical status. The GEMRIC cohort confirmed a rapid increase of GMV after ECT followed by reversion of GMV one to six months thereafter. The lack of association between the GMV change pattern and depression outcome scores implies a transient neurobiological effect of ECT unrelated to clinical improvement. • A mega-analysis of longitudinal T1-weighted MRI data of patients receiving ECT from eight different sites was performed. • A pattern of gray matter volume (GMV) increase during ECT and a subsequent decrease one to six months thereafter was observed. • Four regions – associated with cognition and emotions – showed sustained higher GMV at one to six months after the ECT-course. • The pattern of GMV change did not correspond with clinical improvement after ECT. [ABSTRACT FROM AUTHOR]

Background and Purpose: Aerobic exercise can elicit positive effects on neuroplasticity and cognitive executive function but is poorly understood after stroke. We tested the effect of 4 weeks of aerobic exercise training on inhibitory and facilitatory elements of cognitive executive function and electroencephalography markers of cortical inhibition and facilitation. We investigated relationships between stimulus-evoked cortical responses, blood lactate levels during training, and aerobic fitness postintervention. Methods: Twelve individuals with chronic (>6 months) stroke completed an aerobic exercise intervention (40 minutes, 3×/wk). Electroencephalography and motor response times were assessed during congruent (response facilitation) and incongruent (response inhibition) stimuli of a Flanker task. Aerobic fitness capacity was assessed as V ˙ o 2peak during a treadmill test pre- and postintervention. Blood lactate was assessed acutely (<1 minute) after exercise each week. Cortical inhibition (N2) and facilitation (frontal P3) were quantified as peak amplitudes and latencies of stimulus-evoked electroencephalographic activity over the frontal cortical region. Results: Following exercise training, the response inhibition speed increased while response facilitation remained unchanged. A relationship between earlier cortical N2 response and faster response inhibition emerged postintervention. Individuals who produced higher lactate during exercise training achieved faster response inhibition and tended to show earlier cortical N2 responses postintervention. There were no associations between V ˙ o 2peak and metrics of behavioral or neurophysiologic function. Discussion and Conclusions: These preliminary findings provide novel evidence for selective benefits of aerobic exercise on inhibitory control during the initial 4-week period after initiation of exercise training and implicate a potential therapeutic effect of lactate on poststroke inhibitory control. Video Abstract available for more insights from the authors (see the video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A450). [ABSTRACT FROM AUTHOR]

Background: Hospitals use triage systems to prioritize the needs of patients within available resources. Misclassification of a patient can lead to either adverse outcomes in a patient who did not receive appropriate care in the case of undertriage or a waste of hospital resources in the case of overtriage. Recent advances in machine learning algorithms allow for the quantification of variables important to under- and overtriage. Objective: This study aimed to identify clinical features most strongly associated with triage misclassification using a machine learning classification model to capture nonlinear relationships. Methods: Multicenter retrospective cohort data from 2 big regional hospitals in Norway were extracted. The South African Triage System is used at Bergen University Hospital, and the Rapid Emergency Triage and Treatment System is used at Trondheim University Hospital. Variables included triage score, age, sex, arrival time, subject area affiliation, reason for emergency department contact, discharge location, level of care, and time of death were retrieved. Random forest classification models were used to identify features with the strongest association with overtriage and undertriage in clinical practice in Bergen and Trondheim. We reported variable importance as SHAP (SHapley Additive exPlanations)-values. Results: We collected data on 205,488 patient records from Bergen University Hospital and 304,997 patient records from Trondheim University Hospital. Overall, overtriage was very uncommon at both hospitals (all <0.1%), with undertriage differing between both locations, with 0.8% at Bergen and 0.2% at Trondheim University Hospital. Demographics were similar for both hospitals. However, the percentage given a high-priority triage score (red or orange) was higher in Bergen (24%) compared with 9% in Trondheim. The clinical referral department was found to be the variable with the strongest association with undertriage (mean SHAP +0.62 and +0.37 for Bergen and Trondheim, respectively). Conclusions: We identified subgroups of patients consistently undertriaged using 2 common triage systems. While the importance of clinical patient characteristics to triage misclassification varies by triage system and location, we found consistent evidence between the two locations that the clinical referral department is the most important variable associated with triage misclassification. Replication of this approach at other centers could help to further improve triage scoring systems and improve patient care worldwide. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy (ECT) is effective for major depressive episodes. Understanding of underlying mechanisms has been increased by examining changes of brain connectivity but studies often do not correct for test-retest variability in healthy controls (HC). In this study, we investigated changes in resting-state networks after ECT in a multicenter study. Functional resting-state magnetic resonance imaging data, acquired before start and within one week after ECT, from 90 depressed patients were analyzed, as well as longitudinal data of 24 HC. Group-information guided independent component analysis (GIG-ICA) was used to spatially restrict decomposition to twelve canonical resting-state networks. Selected networks of interest were the default mode network (DMN), salience network (SN), and left and right frontoparietal network (LFPN, and RFPN). Whole-brain voxel-wise analyses were used to assess group differences at baseline, group by time interactions, and correlations with treatment effectiveness. In addition, between-network connectivity and within-network strengths were computed. Within-network strength of the DMN was lower at baseline in ECT patients which increased after ECT compared to HC, after which no differences were detected. At baseline, ECT patients showed lower whole-brain voxel-wise DMN connectivity in the precuneus. Increase of within-network strength of the LFPN was correlated with treatment effectiveness. We did not find whole-brain voxel-wise or between-network changes. DMN within-network connectivity normalized after ECT. Within-network increase of the LFPN in ECT patients was correlated with higher treatment effectiveness. In contrast to earlier studies, we found no whole-brain voxel-wise changes, which highlights the necessity to account for test-retest effects. • The default mode network normalizes after electroconvulsive therapy. • The left frontoparietal network is associated with treatment effectiveness. • Absence of voxel-wise changes shows necessity to account for test-retest effects. [ABSTRACT FROM AUTHOR]

When planning an adolescent's primary surgery for recurrent patella instability, the surgeon must weigh the failure risk of performing medial patellofemoral reconstruction (MPFLR) versus the potential morbidity of adding a concomitant bony procedure, such as tibial tubercle osteotomy. In this age group, isolated MPFLR is an excellent operation with high clinical success, low failure rates, and favorable complication profile. Patients with high grade J-sign and severe trochlea dysplasia, apprehension into deep flexion, and extremes of bony malalignment, including elevated tibial tubercle-trochlear groove distance, may benefit from "doing more" than MPFLR alone. Other factors to be considered include patella alta, generalized ligament laxity, femoral rotation, tibial torsion, and valgus malalignment. In challenging situations, such as syndromic patients (e.g., neuromuscular disorders), congenital (habitual) patella dislocation, fixed dislocations, and failed prior to MPFLR, a combined surgical approach is likely needed. Patients who require "unloading" for symptomatic chondrosis also benefit from combined bony and soft tissue surgery. However, for the majority of patients with recurrent instability and no prior surgery, an isolated soft tissue reconstruction is a rational, safe, efficient, and evidence-based selection. [ABSTRACT FROM AUTHOR]

Objective: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. Background: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. Methods: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016--2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. Results: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly betweenmalignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. Conclusion: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Environmental challenges associated with stormwater management, including flooding, droughts and depleting water quality, are exacerbated in urban areas. Despite growing expertise and policy advocacy for alternatives to conventional stormwater management approaches, Ghanaian cities, like many cities in developing countries, have not adopted governance principles to mainstream green stormwater infrastructure (GSI). There is very limited research which examines the governance barriers to mainstreaming GSI and their nuances within the Ghanaian context. Based on document analysis and interviews, this article explores the governance factors influencing GSI implementation and their associated barriers in Ghana's most populated water catchment. It analyses the governance dimensions comprising actors, rules of the game, discourse, and resources and power that could influence stormwater management. The article highlights that governance dimensions are currently not framed to facilitate GSI implementation. This shortfall reflects 11 specific barriers, including poverty, unresponsive culture, lack of knowledge, and lack of collaboration. The barriers transcend multiple governance components, particularly the actors. Yet, several governance components, including the specific actors and existing policies, are not currently integrated into stormwater management despite having strong potential to overcome the barriers and facilitate GSI implementation. The article proposes a good green governance framework, which accounts for the holistic nature of the identified barriers and envisages active inclusion and collaboration between diverse actors, including a basin authority as an intermediary, communities, local governments and national-level agencies. • Governance dimensions involve actors, rules of the game, discourse and resources. • Barriers to mainstream green stormwater infrastructure transcend multiple dimensions. • Governance potentials for addressing barriers are often overlooked. • Good green governance in policy, strategic and operational domains is required. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depressive disorders. A recent multi-center study found no consistent changes in correlation-based (undirected) resting-state connectivity after ECT. Effective (directed) connectivity may provide more insight into the working mechanism of ECT. We investigated whether there are consistent changes in effective resting-state connectivity. This multi-center study included data from 189 patients suffering from severe unipolar depression and 59 healthy control participants. Longitudinal data were available for 81 patients and 24 healthy controls. We used dynamic causal modeling for resting-state functional magnetic resonance imaging to determine effective connectivity in the default mode, salience and central executive networks before and after a course of ECT. Bayesian general linear models were used to examine differences in baseline and longitudinal effective connectivity effects associated with ECT and its effectiveness. Compared to controls, depressed patients showed many differences in effective connectivity at baseline, which varied according to the presence of psychotic features and later treatment outcome. Additionally, effective connectivity changed after ECT, which was related to ECT effectiveness. Notably, treatment effectiveness was associated with decreasing and increasing effective connectivity from the posterior default mode network to the left and right insula, respectively. No effects were found using correlation-based (undirected) connectivity. A beneficial response to ECT may depend on how brain regions influence each other in networks important for emotion and cognition. These findings further elucidate the working mechanisms of ECT and may provide directions for future non-invasive brain stimulation research. • Previous mega-analyses did not show any associations between changes in brain structure or function and ECT outcome. • We used Dynamic causal modeling on multi-center resting-state fMRI data to infer effective connectivity before and after ECT. • The outcome of ECT was associated with effective connectivity from the posterior cingulate cortex to the bilateral insula. • This is the first study to show consistent changes in brain function related to ECT outcome. [ABSTRACT FROM AUTHOR]

In a proclaimed age of 'post-truth,' scholars have raised concerns about the spread of false information and the questioning of epistemic authorities. In this paper, we develop an analytical model to capture the digital transformation of knowledge order. Drawing on insights from social epistemology, sociology and history of knowledge, and media history, we identify epistemic practices as basic elements of knowledge order. We then analyze how epistemic practices are organized into an overarching structure of knowledge phases, contexts, roles, and hierarchies. Digital media tend to destabilize the traditional knowledge order. This destabilization is characterized by a more flexible order of phases, a dissolution of boundaries between contexts, an opening of professional roles to new actors, and a flattening of hierarchies. [ABSTRACT FROM AUTHOR]

Sowohl im Tier- als auch Menschenversuch wurde gezeigt, wie emotionaler Stress sich auf myofasziale Eigenschaften auswirkt. Erst in den letzten Jahren wendet sich die Forschung hierbei gezielt den zahlreichen sympathischen Nervenendigungen in den Faszien zu. Es wird vermutet, dass diese Nervenendigungen nicht nur die Mikrozirkulation regulieren, sondern auch mit dem Immunsystem interagieren. Fasziale Fibroblasten wirken als notwendige Teamplayer im Zusammenspiel zwischen Emotionen, Vegetativum, Immunsystem, Entzündungsreaktion und dem enterischen sowie faszialen Mikrobiom. Erste manualtherapeutische Tierversuche deuten an, über welche pro- und antientzündlichen Botenstoffe eine positive Wirkung auf dieses dynamische Wechselspiel bewirkt werden kann. Both animal and human experiments have shown how emotional stress affects myofascial properties. Only in recent years has research turned to the numerous sympathetic nerve endings in the fascia. It is believed that these not only regulate microcirculation, but also interact with the immune system. Fascial fibroblasts act as necessary team players in the interplay between emotions, the autonomic nervous system, immune regulation, the inflammatory response, and the enteric as well as fascial microbiome. First manualtherapeutic animal experiments indicate which pro- and anti-inflammatory messenger substances tend to express positive effects on this dynamic interplay. [ABSTRACT FROM AUTHOR]

Production control is an essential component of a production system used to monitor and manage production orders. Centrally controlled production systems rely on basic data management, such as storing the bill of materials and required work schedules. Components of customer orders are added to generate the corresponding production orders. However, this type of production control can pose serious problems in case of unforeseen events such as machine failure or changing customer requirements during production. In such scenarios, costly and time-consuming re-scheduling becomes necessary, which endangers the company's competitive position and leads to data retention issues. This paper introduces a new method of production control based on the concept of smart orders. Smart orders use smart contracts for autonomous routing based on programmed information in the source code, enabling self-control through the production system. Smart contracts are transaction programs that work with 'if-then logic", allowing for partially flexible process schedules and reducing the need for human intervention. The smart order uses the functionalities of blockchain technology, such as security, transparency, and immutability, to ensure the integrity of production data. The paper concludes by presenting the expected value propositions of smart order-based production control on the production system. Depending on the production control system used, companies can integrate the results presented in this paper into their own blockchain implementation strategy. [ABSTRACT FROM AUTHOR]

Das menschliche Fasziennetzwerk versorgt uns mit nozizeptiven, propriozeptiven sowie interozeptiven Stimulationen für die eigene Körperwahrnehmung. Mit ca. 250 Millionen sensorischen Nerven stellt es unser reichhaltigstes Sinnesorgan dar. Über Wide-Dynamic-Range-Neurone im Rückenmark besteht eine sich gegenseitig hemmende Rückkopplung zwischen regionaler Propriozeption und Weichteilschmerzen. Eine auf interozeptive Körperempfindungen ausgerichtete therapeutische Stimulation empfiehlt sich bei Patient*innen mit posttraumatischen Belastungsstörung sowie anderen Dysregulationen rund um das Insula-Areal im Gehirn. Lokale Versteifungen des Fasziennetzes können durch chronisch sympathische Einflüsse des autonomen Nervensystems ausgelöst werden und auf diese Weise sowohl die Beweglichkeit als auch die sensorische Empfindsamkeit beeinträchtigen. Propriozeption, Weichteilschmerz, Interozeption, Insula, Fibrotisierung The human fascial network provides us with nociceptive, proprioceptive as well as interoceptive stimulation for perceiving our own bodies. With approximately 250 million sensory nerves, it represents our richest sensory organ. Via wide dynamics range neurons in the spinal cord, there is a mutually inhibitory feedback loop between regional proprioception and soft tissue pain. Therapeutic stimulation focused on interoceptive body sensations is recommended for patients with post traumatic stress disorder as well as other dysregulations around the insular cortext. Local stiffening of the fascial network can be triggered by chronic sympathetic influences of the autonomic nervous system, thereby impairing both mobility and sensory sensitivity. [ABSTRACT FROM AUTHOR]

• Patients with HER2-positive MBC have a significant risk developing BrM. • Experts created statements regarding BrM prevention in HER2-positive MBC. • Using a modified Delphi process, experts reached consensus on 34 statements. • Statements covered definitions, screening, treatment efficacy and prevention of BrM. • These statements can provide guidance in daily practice and clinical trial design. Patients with HER2-positive breast cancer have a significant risk of developing brain metastases (BrM), which have detrimental effects on survival outcomes and quality of life. Although there are several systemic treatment options available that may delay the appearance of BrM and secondary progression of previously treated BrM, there are still substantial unmet needs for this patient population and primary prevention remains elusive. A group of experts created consensus statements, through a modified Delphi process, to bridge the gap between current unmet needs, available evidence, and international guidelines. The steering committee reviewed all relevant literature and formed research questions to be answered by the subsequent consensus statements. In total, 61 contributors provided feedback on the consensus statements, with 34 statements reaching agreement out of the 55 statements that were voted on altogether. Statements with consensus aimed to define BrM primary and secondary prevention, screening procedures, assessment of symptoms, treatment efficacy, and preventing the occurrence and progression of BrM, while acknowledging the possibilities and limitations in daily clinical practice. Some statements did not reach agreement for a variety of reasons, mostly due to lack of evidence. The consensus statements outlined in this publication provide a point of reference for daily clinical practice and can act as recommendations for clinical trial procedures and future guidelines. [ABSTRACT FROM AUTHOR]

• Recommendations exist for sequencing treatments in HER2+ metastatic breast cancer. • There is a lack of clarity of preferred agent choice in the 3L+ treatment setting. • Clinicians may face scenarios where the optimal therapeutic approach is unknown. • We provide practical guidance on approaching real-world challenging scenarios. • Clinical trials investigating optimal management strategies are required. Human epidermal growth factor receptor 2 (HER2) overexpression and/or ERBB2 gene amplification occurs in approximately 15–20% of breast cancers and is associated with poor prognosis. While the introduction of HER2-targeted therapies has significantly improved survival in patients with HER2-positive metastatic breast cancer, the incidence of brain metastases has increased due to patients living longer. Current recommendations sequence treatments by line of therapy, as well as by the status of brain metastases in patients with HER2-positive breast cancer. However, in the third-line treatment setting and beyond, there is a lack of clarity of the preferred choice of therapy. In clinical practice, clinicians may also encounter challenging scenarios where the optimal therapeutic approach has not been defined by clinical studies, so there is a need for clarity in such situations. Two consensus meetings of expert oncologists (12 from Europe and one from Canada) were convened to discuss these scenarios. We subsequently developed this article to present an overview of current treatment recommendations for HER2-positive metastatic breast cancer and give practical guidance on addressing challenging scenarios in a real-world setting. Based on our clinical experience, we provide a unanimous consensus concerning the treatment of elderly patients as well as those with brain-only metastases, leptomeningeal disease, oligometastatic disease, central nervous system oligo-progressive disease or ERBB2 -mutant disease. We also discuss how to combine HER2-targeted therapy with endocrine therapy in patients with HER2-positive/hormone-receptor-positive disease, considerations for potential discontinuation of HER2-targeted therapy in patients with long-term remission and how to treat patients whose metastatic biopsy no longer confirms their HER2-positive status. [ABSTRACT FROM AUTHOR]