Establishment of clinical exercise physiology as a regulated healthcare profession in the UK: a progress report.

In 2021, a 'call to action' was published to highlight the need for professional regulation of clinical exercise physiologists to be established within UK healthcare systems to ensure patient safety and align training and regulation with other health professions. This manuscript provides a progress report on the actions that Clinical Exercise Physiology UK (CEP-UK) has undertaken over the past 4 years, during which time clinical exercise physiologists have implemented regulation and gained formal recognition as healthcare professionals in the UK. An overview of the consultation process involved in creating a regulated health profession, notably the development of policies and procedures for both individual registration and institutional master's degree (MSc) accreditation is outlined. Additionally, the process for developing an industry-recognised scope of practice, a university MSc-level curriculum framework, the Academy for Healthcare Science Practitioner standards of proficiency and Continuing Professional Development opportunities is included. We outline the significant activities and milestones undertaken by CEP-UK and provide insight and clarity for other health professionals to understand the training and registration process for a clinical exercise physiologist in the UK. Finally, we include short, medium and long-term objectives for the future advocacy development of this workforce in the UK.

[Ultrasound supported identification of the ligamentum conicum in teaching head and neck sonography]. / Sonographisch gestützte Identifikation des Ligamentum conicum in der Kopf-Hals-Ultraschalllehre.

OBJECTIVE: Upper airway obstructions are usually acute emergencies. Coniotomy is the last option to secure the airway and can be supported by sonography. The aim of this study was to establish a training program to teach these skills. MATERIAL AND METHODS: The training consisted of theoretical training with an additional video presentation (10 minutes each) and practical training (45 minutes). Evaluations were completed before (T1) and after (T2) the training to measure prior experience and satisfaction with the training as well as subjective and objective competence levels. At T2, a practical test was also completed by n=113 participants. A standardized evaluation form was used to document the results of the practical test. RESULTS: A large proportion of the participants had neither seen a coniotomy (64.6%) nor performed one independently (79.6%). Significant improvement (T1 to T2) was measured with regard to the subjective assessment of competence (p<0.001). The training received positive ratings for all items tested (scale ranges 1-2). During practical tests, the participants achieved an average of 89.2% of the possible points and needed a mean of 101 ±23 seconds to identify the conic ligament. CONCLUSION: Structured training for sonographic identification of the conic ligament leads to significant improvement in the subjective assessment of competence and a high objective competence level in a short period of time. This type of training should be standardized in head and neck ultrasound training in the future.

Characterizing Adaptive Changes and Patient Survival After 2018 Donor Allocation Restructuring: A UNOS Database Analysis.

PURPOSE: We sought to characterize adaptive changes to the revised United Network for Organ Sharing donor heart allocation policy and estimate long-term survival trends for heart transplant (HTx) recipients. METHODS: Patients listed for HTx between October 17, 2013 and September 30, 2021 were identified from the United Network for Organ Sharing database, and stratified into pre- and postpolicy revision groups. Subanalyses were performed to examine trends in device utilization for extracorporeal membranous oxygenation (ECMO), durable left ventricular assist device (LVAD), intra-aortic balloon pump (IABP), microaxial support (Impella), and no mechanical circulatory support (non-MCS). Survival data post-HTx were fitted to parametric distributions and extrapolated to 5 years. RESULTS: We identified 27,523 HTx waitlist candidates during the study period, most of whom (n = 16,376) were waitlisted in the prepolicy change period. Overall, 19,554 patients underwent HTx during the study period (pre: 12,037 and post: 7517). Listings increased after the policy change for ECMO ( P < 0.01), Impella ( P < 0.01), and IABP ( P < 0.01) patients. Listings for LVAD ( P < 0.01) and non-MCS ( P < 0.01) patients decreased. HTx increased for ECMO ( P < 0.01), Impella ( P < 0.01), and IABP ( P < 0.01) patients after the policy change and decreased for LVAD ( P < 0.01) and non-MCS ( P < 0.01) patients. Waitlist survival increased for the overall ( P < 0.01), ECMO ( P < 0.01), IABP ( P < 0.01), and non-MCS ( P < 0.01) groups. Waitlist survival did not differ for the LVAD ( P = 0.8) and Impella ( P = 0.1) groups. Post-transplant survival decreased for the overall ( P < 0.01), LVAD ( P < 0.01), and non-MCS ( P < 0.01) populations. CONCLUSIONS: Allocation policy revisions have contributed to greater utilization of ECMO, Impella, and IABP, decreased utilization of LVADs and non-MCS, increased waitlist survival, and decreased post-HTx survival.

Protein disulfide isomerase-9 interacts with the lumenal region of the transmembrane endoplasmic reticulum stress sensor kinase, IRE1, to modulate the unfolded protein response in Arabidopsis.

Environmental stressors disrupt secretory protein folding and proteostasis in the endoplasmic reticulum (ER), leading to ER stress. The unfolded protein response (UPR) senses ER stress and restores proteostasis by increasing the expression of ER-resident protein folding chaperones, such as protein disulfide isomerases (PDIs). In plants, the transmembrane ER stress sensor kinase, IRE1, activates the UPR by unconventionally splicing the mRNA encoding the bZIP60 transcription factor, triggering UPR gene transcription. The induced PDIs catalyze disulfide-based polypeptide folding to restore the folding capacity in the ER; however, the substrates with which PDIs interact are largely unknown. Here, we demonstrate that the Arabidopsis PDI-M subfamily member, PDI9, modulates the UPR through interaction with IRE1. This PDI9-IRE1 interaction was largely dependent on Cys63 in the first dithiol redox active domain of PDI9, and Cys233 and Cys107 in the ER lumenal domain of IRE1A and IRE1B, respectively. In vitro and in vivo, PDI9 coimmunoprecipitated with IRE1A and IRE1B. Moreover, the PDI9:RFP and Green Fluorescence Protein (GFP):IRE1 fusions exhibited strong interactions as measured by fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) when coexpressed in mesophyll protoplasts. The UPR-responsive PDI9 promoter:mCherry reporter and the UPR-dependent splicing of the bZIP60 intron from the mRNA of the 35S::bZIP60-intron:GFP reporter were both significantly induced in the pdi9 mutants, indicating a derepression and hyperactivation of UPR. The inductions of both reporters were substantially attenuated in the ire1a-ire1b mutant. We propose a model in which PDI9 modulates the UPR through two competing activities: secretory protein folding and via interaction with IRE1 to maintain proteostasis in plants.

Effect of an Electric Field on the Structure and Stability of Atmospheric Clusters.

We study the influence of an applied electric field on the structure and stability of some common bimolecular clusters that are found in the atmosphere. These clusters play an important role in new particle formation (NPF). For low values of the electric field (i.e., |E| ≤ 0.01 V Å-1), we demonstrate that the field response of the clusters can be predicted from simply calculating the dipole moment of the cluster and the dipole moments of the constituent molecules and that the influence on the association energy of the cluster is minimal (i.e., <0.5 kcal mol-1). For higher field strengths |E| > 0.2 V Å-1, there can be more dramatic effects on both structure and energetics, as the induced dipole, charge transfer, and geometric distortion play a larger role. Although such large fields are not very relevant in the atmosphere, they do exist in some situations of experimental interest, such as near interfaces and in intense laser fields.

Scalable Non-Volatile Tuning of Photonic Computational Memories by Automated Silicon Ion Implantation.

Photonic integrated circuits (PICs) are revolutionizing the realm of information technology, promising unprecedented speeds and efficiency in data processing and optical communication. However, the nanoscale precision required to fabricate these circuits at scale presents significant challenges, due to the need to maintain consistency across wavelength-selective components, which necessitates individualized adjustments after fabrication. Harnessing spectral alignment by automated silicon ion implantation, in this work scalable and non-volatile photonic computational memories are demonstrated in high-quality resonant devices. Precise spectral trimming of large-scale photonic ensembles from a few picometers to several nanometres is achieved with long-term stability and marginal loss penalty. Based on this approach, spectrally aligned photonic memory and computing systems for general matrix multiplication are demonstrated, enabling wavelength multiplexed integrated architectures at large scales.

Evaluation of a novel eating disorder prevention program for young women with type 1 diabetes: A preliminary randomized trial.

OBJECTIVE: Evaluate whether the Body Project prevention program adapted for young women with type 1 diabetes (Diabetes Body Project) reduces eating disorder (ED) risk factors and symptoms. METHODS: Young women (aged 15-30) at high-risk for EDs due to having type 1 diabetes and body image concerns (N = 55) were randomized to virtually delivered Diabetes Body Project groups or an educational control condition, completing measures at pretest, posttest, and 3-month follow-up. RESULTS: Diabetes Body Project versus the control participants showed significantly greater reductions in thin-ideal internalization, body dissatisfaction, diabetes distress, diabetes eating pathology, and ED symptoms by posttest, and greater reductions in diabetes eating pathology and ED symptoms, and greater improvements in quality of life by 3-month follow-up, which were medium to large effects (d's ranged from -0.43 to -0.90). Although control participants showed a worsening of glycemic control (time in range) verses Diabetes Body Project participants, this difference was non-significant (d = 0.26). CONCLUSIONS: Virtually delivered Diabetes Body Project decreased ED risk factors and symptoms in young women with type 1 diabetes. A well powered randomized controlled trial is warranted to evaluate this intervention over longer follow-up.

Sequencing of symptom emergence in anorexia nervosa, bulimia nervosa, binge eating disorder, and purging disorder in adolescent girls and relations of prodromal symptoms to future onset of these eating disorders.

BACKGROUND: To advance knowledge regarding the etiology of eating disorders, we characterized the sequencing of eating disorder symptom emergence for adolescent girls who subsequently developed anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD) for community-recruited adolescents and tested whether prodromal symptoms increased risk for future onset of each eating disorder. METHODS: Data collected from adolescent girls (N = 496; M age = 13.02, s.d.= 0.73) who completed a diagnostic interview annually over an 8-year period were used to address these aims. RESULTS: For all four eating disorders, compensatory weight-control behaviors were the first behavioral symptom to emerge and weight/shape overvaluation was the first cognitive symptom to emerge. Moreover, lower-than-expected BMI predicted future AN onset, binge eating and all cognitive symptoms predicted future BN onset, weight/shape overvaluation predicted future BED onset, and compensatory behavior and all cognitive symptoms predicted future PD onset. These predictive effects were small-to-large in magnitude. Collectively, prodromal symptoms predicted an eating disorder onset with 83-87% accuracy. CONCLUSIONS: Results suggest that compensatory weight-control behaviors and weight/shape overvaluation typically emerge before other prodromal symptoms in all eating disorders during adolescence. Moreover, different prodromal symptoms seem to predict future onset of different eating disorders. Screening adolescent girls for these prodromal symptoms and implementing indicated prevention programs designed to reduce these symptoms may prove effective in preventing future onset of eating disorders.

Large Gas-Phase Source of Esters and Other Accretion Products in the Atmosphere.

Dimeric accretion products have been observed both in atmospheric aerosol particles and in the gas phase. With their low volatilities, they are key contributors to the formation of new aerosol particles, acting as seeds for more volatile organic vapors to partition onto. Many particle-phase accretion products have been identified as esters. Various gas- and particle-phase formation pathways have been suggested for them, yet evidence remains inconclusive. In contrast, peroxide accretion products have been shown to form via gas-phase peroxy radical (RO2) cross reactions. Here, we show that these reactions can also be a major source of esters and other types of accretion products. We studied α-pinene ozonolysis using state-of-the-art chemical ionization mass spectrometry together with different isotopic labeling approaches and quantum chemical calculations, finding strong evidence for fast radical isomerization before accretion. Specifically, this isomerization seems to happen within the intermediate complex of two alkoxy (RO) radicals, which generally determines the branching of all RO2-RO2 reactions. Accretion products are formed when the radicals in the complex recombine. We found that RO with suitable structures can undergo extremely rapid C-C ß scissions before recombination, often resulting in ester products. We also found evidence of this previously overlooked RO2-RO2 reaction pathway forming alkyl accretion products and speculate that some earlier peroxide identifications may in fact be hemiacetals or ethers. Our findings help answer several outstanding questions on the sources of accretion products in organic aerosol and bridge our knowledge of the gas phase formation and particle phase detection of accretion products. As esters are inherently more stable than peroxides, this also impacts their further reactivity in the aerosol.

Efficacy of virtual delivery of a dissonance-based eating disorder prevention program and evaluation of a donation model to support sustained implementation.

OBJECTIVE: Evaluate whether the Body Project prevention program reduces eating disorder risk factors and symptoms when implemented via synchronous video telepsychiatry, which could markedly increase the reach of this intervention and test whether a pay-it-forward donation model could support sustained implementation of this intervention. METHOD: Young women at high risk for eating disorders because of body image concerns (N = 75; age range 16-27) were randomized to Body Project groups delivered virtually by peer educators or a waitlist control condition; participants who completed the Body Project for free because of past donations were encouraged to donate money so that this intervention could be provided for free to others. RESULTS: Participants randomized to virtually delivered Body Project groups showed significantly or marginally greater pretest-to-posttest reductions in pursuit of the thin ideal, body dissatisfaction, dieting, negative affect, and eating disorder symptoms than controls. The average effect was large (d = .79), which was 49% larger than the average effect observed previously for in-person peer-educator-delivered Body Project groups (d = .53; [.76-.53 = .23/.53 = 49%]). However, only 3.6% of participants donated money to support future implementation of this intervention. CONCLUSIONS: The evidence that the Body Project produced large reductions in eating disorder risk factors and symptoms when implemented virtually and that the effects were larger than for in-person Body Project groups suggests it would be useful to implement this prevention program virtually, which could expand the reach of this intervention. Future studies should evaluate alternative methods for supporting sustained implementation of this prevention program. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Impact of implementing structured note templates on data capture for hernia surgery.

BACKGROUND: Electronic medical record notes have been determined to be lacking in quality, accessibility and content. Structured note templates could provide a way to improve these aspects, particularly with regard to data availability for research and quality improvement. OBJECTIVE: To determine whether the implementation of a standardised template for hernia documentation can improve data completeness and timeliness. METHOD: Retrospective review of clinic notes of 30 patients, 15 prior to implementation of a standardised note template and 15 after implementation of the template. The number of the 21 Americas Hernia Society Quality Collaborative (AHSQC) variables which were present in the notes was recorded, as was the time that the consultation ended and the time that the note was submitted. RESULTS: Mean number of variables collected prior to implementation of the template was 5.9 ± 1.6 vs. 20 ± 0.4 after implementation (p < 0.001). In the pre-implementation group, 20% of the notes were completed after the day of the visit, while all of the notes in the post-implementation group were completed on the same day as the visit (p = 0.367). CONCLUSION: Implementation of a structured note template resulted in significantly improved capture of specific database variables within clinical notes. Structured note templates are an effective tool to improve data capture from the clinical setting for research and quality improvement.

Augmented Reality-Assisted Design of Local Flaps: A New Practical and Educational Tool in the Field of Plastic Surgery.

ABSTRACT: Augmented reality (AR) is a new and promising technology that has been incorporated into several aspects of our everyday life, including surgery. Examples of its application throughout various fields of surgery, although most of them are in experimental stage, have already been demonstrated and published. In this article, we describe the utilization of AR to design effectively and accurately surgical flap markings just with the help of an AR-compatible mobile phone and a low-cost application. We believe that, due to its ease of use, AR will play a pivotal role to the education and the training in the field of plastic surgery and burns, and other surgical specialties alike.

Maxillofacial Horse Trauma: A 10-Year Retrospective Study at a UK Major Trauma Center.

Introduction/Objecive: There are very few studies that have investigated equestrian-related maxillofacial injuries. A retrospective review was performed to investigate maxillofacial horse trauma at a Level 1 Trauma Centre at the Royal Stoke Hospital over the last 10 years between 2010 and 2020. Study Design/Methods: Search of the hospital's major trauma database as well as ED records showed 51 patients who sustained maxillofacial injuries related to horses. Statistical analysis was performed using Chi Squared tests. Results: 41 patients were female and the remaining 10 were male. 43% of patients were female and aged 30 and under. Kicks from horses accounted for 64.4% of equine-related maxillofacial injuries. A total of 90 injuries were recorded. Hard tissue injuries which include all fractures accounted for 66.3% of injuries sustained. 70.5% patients sustained isolated maxillofacial trauma. There was an association between patients sustaining non-isolated maxillofacial trauma and hard tissue maxillofacial injuries (P = 0.04). 65.6% of injuries were managed operatively. Patients aged 30 and under were more likely to be managed operatively (P = 0.03). Conclusion: Equestrian related maxillofacial trauma represents a proportion of trauma workload. The safety aspect of horse riding should be considered and education in safe riding and the use of appropriate safety equipment is vital.

Development of a GFP biosensor reporter for the unfolded protein response-signaling pathway in plants: incorporation of the bZIP60 intron into the GFP gene.

The ability to measure the activation of the unfolded protein response (UPR) in plants is important when they are exposed to stressful environments. To this end, we developed a unique and versatile biosensor-reporter system to indicate the activation of UPR in living plant cells. The small cytoplasmically spliced intron from the bZIP60 locus was incorporated into the 5' end of the GFP gene, creating the 35S::bZIP60 intron:GFP construct. When this construct is transiently expressed in Arabidopsis protoplasts, the presence of the bZIP60 intron prevents GFP mRNA from being translated under non-UPR conditions. However, when UPR is activated, the IRE1 kinase/ribonuclease splices this intron from the GFP mRNA and its translation proceeds, generating GFP fluorescence. We demonstrated the utility of the system in Arabidopsis leaf protoplasts treated with DTT, which is a chemical inducer of UPR, followed by visualization and quantification using confocal microscopy. The 35S::bZIP60 intron:GFP construct was also expressed in protoplasts from an overexpressor line containing the coding sequence for the UPR-induced, protein folding chaperone, protein disulfide isomerase-9 (PDI9). PDI9 also influences the strength of the UPR signaling pathway. Protoplasts from WT and PDI9 overexpressor plants treated with DTT exhibited significantly higher GFP fluorescence relative to untreated protoplasts, indicating that the bZIP60 intron was spliced from the GFP mRNA in response to activation of UPR. RT-PCR further confirmed the higher induction of PDI9 and bZIP60 (total and spliced) mRNA levels in DTT-treated protoplasts relative to controls. This system can be adapted for monitoring crop stress and for basic studies dissecting the UPR signaling pathway.

Young women who develop anorexia nervosa exhibit a persistently low premorbid body weight on average: A longitudinal investigation of an important etiologic clue.

OBJECTIVE: test whether (1) young women who subsequently show onset of anorexia nervosa (AN) exhibit persistently lower average premorbid BMI than those who subsequently show onset of bulimia nervosa (BN), binge eating disorder (BED), purging disorder (PD), or no eating disorder; (2) a proximal spike in other risk factors occurs immediately before AN emergence; and (3) psychological and behavioral factors differentiate youth who show persistently low BMI from those who do not. METHOD: Data from a sample (N = 1952) of young women at high-risk for eating disorders followed for 3 years and a socioethno-racially representative sample (N = 496) of adolescent girls followed for 8 years were used to address these aims. RESULTS: Participants who developed AN exhibited significantly lower average measured premorbid BMI over repeated assessments than those who showed onset of other or no eating disorders. Dietary restraint, negative affect, and eating affect regulation expectancies significantly increased immediately before AN onset. Youth who showed persistently low BMI reported lower pressure for thinness, body dissatisfaction, and dieting at baseline, implying that elevations in these factors did not drive the low BMI. CONCLUSIONS: The evidence that young women who subsequently show AN onset exhibit a low premorbid BMI on average is novel and suggests that etiologic models should incorporate this finding and selective prevention programs should target low-BMI adolescent girls. The finding that dieting, negative affect, affect-regulation eating expectances spiked immediately before emergence of AN is also novel and suggests that it might be useful for selective prevention programs to target these factors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Investigation of electron-induced cross-linking of self-assembled monolayers by scanning tunneling microscopy.

Ultrathin membranes with subnanometer pores enabling molecular size-selective separation were generated on surfaces via electron-induced cross-linking of self-assembled monolayers (SAMs). The evolution of p-terphenylthiol (TPT) SAMs on Au(111) surfaces into cross-linked monolayers was observed with a scanning tunneling microscope. As the irradiation dose was increased, the cross-linked regions continued to grow and a large number of subnanometer voids appeared. Their equivalent diameter is 0.5 ± 0.2 nm and the areal density is ≈1.7 × 1017 m-2. Supported by classical molecular dynamics simulations, we propose that these voids may correspond to free volumes inside a cross-linked monolayer.

Halicin Is Effective Against Staphylococcus aureus Biofilms In Vitro.

BACKGROUND: Biofilms protect bacteria from the host immune system and many antibiotics, making the treatment of orthopaedic infections difficult. Halicin, a recently discovered antibiotic, has potent activity against nonorthopaedic infections in mice and the planktonic, free-living forms of many bacterial species, including Staphylococcus aureus , a common cause of orthopaedic infections. Importantly, halicin did not induce resistance in vitro and was effective against drug-resistant bacteria and proliferating and quiescent bacteria. Quiescence is an important cause of antibiotic tolerance in biofilms. However, whether halicin acts on biofilms has not been tested. QUESTIONS/PURPOSES: (1) Does halicin reduce the viability of S. aureus in less mature and more mature biofilms as it does in planktonic cultures? (2) How do the relative effects of halicin on S. aureus biofilms and planktonic cultures compare with those of conventional antibiotics (tobramycin, cefazolin, vancomycin, or rifampicin) that are commonly used in clinical orthopaedic infections? METHODS: To measure minimal biofilm eradication concentrations (MBECs) with less mature 3-day and more mature 7-day biofilms, we used 96-well peg plates that provided high throughput and excellent reproducibility. After S. aureus -Xen36 biofilm formation, planktonic bacteria were removed from the cultures, and the biofilms were exposed to various concentrations of halicin, tobramycin, cefazolin, vancomycin, or rifampicin for 20 hours. Biofilm viability was determined by measuring resazurin reduction or by counting colony-forming units after sonication. To determine effects of halicin and the conventional antibiotics on biofilm viability, we defined MBEC 75 as the lowest concentration that decreased viability by 75% or more. To determine effects on bacterial viability in planktonic cultures, minimum inhibitory concentrations (MICs) were determined with the broth dilution method. Each result was measured in four to 10 independent experiments. RESULTS: We found no differences between halicin's effectiveness against planktonic S. aureus and 3-day biofilms (MIC and MBEC 75 for 3-day biofilms was 25 µM [interquartile range 25 to 25 and 25 to 25, respectively]; p > 0.99). Halicin was eightfold less effective against more mature 7-day biofilms (MBEC 75 = 200 µM [100 to 200]; p < 0.001). Similarly, tobramycin was equally effective against planktonic culture and 3-day biofilms (MIC and MBEC 75 for 3-day biofilms was 20 µM [20 to 20 and 10 to 20, respectively]; p > 0.99). Tobramycin's MBEC 75 against more mature 7-day biofilms was 320 µM (320 to 480), which is 16-fold greater than its planktonic MIC (p = 0.03). In contrast, the MBEC 75 for cefazolin, vancomycin, and rifampicin against more mature 7-day biofilms were more than 1000-fold (> 1000; p < 0.001), 500-fold (500 to 875; p < 0.001), and 3125-fold (3125 to 5469; p = 0.004) greater than their planktonic MICs, respectively, consistent with those antibiotics' relative inactivity against biofilms. CONCLUSION: Halicin was as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but eightfold higher concentrations were needed for more mature 7-day biofilms. Tobramycin, an antibiotic whose effectiveness depends on biofilm maturity, was also as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but 16-fold higher concentrations were needed for more mature 7-day biofilms. In contrast, cefazolin, vancomycin, and rifampicin were substantially less active against both less and more mature biofilms than against planktonic cultures. CLINICAL RELEVANCE: Halicin is a promising antibiotic that may be effective against S. aureus osteomyelitis and infections on orthopaedic implants. Future studies should assess the translational value of halicin by testing its effects in animal models of orthopaedic infections; on the biofilms of other bacterial species, including multidrug-resistant bacteria; and in combination therapy with conventional antibiotics.

Energy transfer, pre-reactive complex formation and recombination reactions during the collision of peroxy radicals.

In this paper we study collisions between polyatomic radicals - an important process in fields ranging from biology to combustion. Energy transfer, formation of intermediate complexes and recombination reactions are treated, with applications to peroxy radicals in atmospheric chemistry. Multi-reference perturbation theory, supplemented by coupled-cluster calculations, describes the potential energy surfaces with high accuracy, including the interaction of singlet and triplet spin states during radical recombination. Our multi-reference molecular dynamics (MD) trajectories on methyl peroxy radicals confirm the reaction mechanism postulated in earlier studies. Specifically, they show that if suitable pre-reactive complexes are formed, they will rapidly lead to the formation and subsequent decomposition of tetroxide intermediates. However, generating multi-reference MD trajectories is exceedingly computationally demanding, and we cannot adequately sample the whole conformational space. To answer this challenge, we promote the use of a novel simplified semi-empirical MD methodology. It assumes the collision is governed by two states, a singlet (S0) and a triplet (T1) state. The method predicts differences between collisions on S0 and T1 surfaces, and qualitatively includes not only pre-reactive complex formation, but also recombination processes such as tetroxide formation. Finally, classical MD simulations using force-fields for non-reactive collisions are employed to generate thousands of collision trajectories, to verify that the semi-empirical method is sampling collisions adequately, and to carry out preliminary investigations of larger systems. For systems with low activation energies, the experimental rate coefficient is surprisingly well reproduced by simply multiplying the gas-kinetic collision rate by the simulated probability for long-lived complex formation.

The Impact of High Dose Glucocorticoids on Bone Health and Fracture Risk in Systemic Vasculitides.

Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field.