Radiation Oncology Opinions and Practice on Cardiotoxicity in Lung Cancer: A Cross-sectional Study by the International Cardio-oncology Society.

AIMS: Symptomatic radiation cardiotoxicity affects up to 30% patients with lung cancer and several heart substructure doses are associated with reduced overall survival. A greater focus on minimising cardiotoxicity is now possible due to advancements in radiotherapy technology and the new discipline of cardio-oncology, but uptake of emerging data has not been ascertained. A global cross-sectional analysis of Radiation Oncologists who treat lung cancer was therefore conducted by the International Cardio-Oncology Society in order to establish the impact of recently published literature and guidelines on practice. MATERIALS AND METHODS: A bespoke questionnaire was designed following an extensive review of the literature and from recurring relevant themes presented at Radiation Oncology and Cardio-Oncology research meetings. Six question domains were retained following consensus discussions among the investigators, comprising 55 multiple choice stems: guidelines, cardiovascular assessment, cardiology investigations, radiotherapy planning strategies, primary prevention prescribing and local cardio-oncology service access. An invitation was sent to all Radiation Oncologists registered with ICOS and to Radiation Oncology colleagues of the investigators. RESULTS: In total 118 participants were recruited and 92% were consultant physicians. The ICOS 2021 expert consensus statement was rated as the most useful position paper, followed by the joint ESC-ESTRO 2022 guideline. The majority (80%) of participants indicated that a detailed cardiovascular history was advisable. Although 69% of respondents deemed the availability of cardiac substructure auto-segmentation to be very/quite important, it was implemented by only a few, with the most common being the left anterior descending coronary artery V15. A distinct cardio-oncology service was available to 39% participants, while the remainder utilised general cardiology services. CONCLUSION: The uptake of recent guidelines on cardiovascular optimisation is good, but access to cardiology investigations and consultations, and auto-segmentation, represent barriers to modifying radiotherapy practices in lung cancer to reduce the risk of radiation cardiotoxicity.

LAIR-1 and PECAM-1 function via the same signaling pathway to inhibit GPVI-mediated platelet activation.

Background: Inhibition of platelet responsiveness is important for controlling thrombosis. It is well established that platelet endothelial cell adhesion molecule-1 (PECAM-1) serves as a physiological negative regulator of platelet-collagen interactions. We recently demonstrated that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a negative regulator of platelet production and reactivity. It is however not known if LAIR-1 and PECAM-1 function in the same or different inhibitory pathways. Objectives: In this study, we investigated the role of LAIR-1 alongside PECAM-1 in megakaryocyte development and platelet production and determined the functional redundancy through characterization of a LAIR-1/PECAM-1 double knockout (DKO) mouse model. Methods: LAIR-1 and PECAM-1 expression in megakaryocytes were evaluated by western blotting. Megakaryocyte ploidy and proplatelet formation were evaluated by flow cytometry and fluorescent microscopy. Platelet function and signalling were compared in wild-type, LAIR-1 -/- , PECAM-1 -/-  and DKO mice using aggregometry, flow cytometry and western blotting. Thrombosis was evaluated using the FeCl 3  carotid artery model. Results: We show that LAIR-1/PECAM-1 DKO mice exhibit a 17% increase in platelet count. Bone marrow-derived megakaryocytes from all 3 mouse models had normal ploidy in vitro, suggesting that neither LAIR-1 nor PECAM-1 regulates megakaryocyte development. Furthermore, relative to wild-type platelets, platelets derived from LAIR-1, PECAM-1, and DKO mice were equally hyperresponsive to collagen in vitro, indicating that LAIR-1 and PECAM-1 participate in the same inhibitory pathway. Interestingly, DKO mice exhibited normal thrombus formation in vivo due to DKO mouse platelets lacking the enhanced Src family kinase activation previously shown in platelets from LAIR-1-deficient mice. Conclusion: Findings from this study reveal that LAIR-1 and PECAM-1 act to inhibit GPVI-mediated platelet activation via the same signaling pathway. Mice lacking LAIR-1 and PECAM-1 do not however exhibit an increase in thrombus formation despite minor increase in platelet count and reactivity to collagen. This study adds to the growing evidence that immunoreceptor tyrosine-based inhibition motif-containing receptors are important regulators of platelet count and function.

Mental health symptom burden in elite ice hockey players and its association with self-reported concussive events.

BACKGROUND: Some studies suggest that elite athletes experience adverse mental health symptoms at rates commensurate with the general population, despite the well-established buffering effects of exercise. Within contact sports, such as ice-hockey, recurrent concussions may be a source of this discrepancy. We compared the point prevalence of various mental health outcomes with other athlete and general population samples, as well as investigated their relationship with concussive events. METHODS: We surveyed 648 active ice hockey players from the top two men's tiers and the top women's tier in Swedish elite ice hockey on lifetime concussive events, hazardous alcohol use, problematic social media use, depression, anxiety, and burnout. RESULTS: Hazardous alcohol use was more prevalent among male ice hockey players (29.5% AUDIT-C ≥ 6) compared to other athlete and general population samples, while other mental health symptoms were less common. Female ice hockey players reported higher hazardous alcohol consumption (36.4% AUDIT-C ≥ 4) than another athlete sample and more burnout (19.1%) than the general population. After adjusting for covariates, athletes with 3+ concussive events had 2.1 times the odds of elevated depressive symptoms and 3.5 times the odds of elevated burnout symptoms compared to those with no concussion history. Treating lifetime concussive events as a continuous predictor revealed positive correlations with all outcomes except for hazardous alcohol use. CONCLUSIONS: Mental health outcome rates among active elite ice hockey athletes differ from those of other athlete and general population samples, whilst concussive events may be particularly linked to elevated symptoms of depression and burnout.

Rise in Gender Dysphoria Diagnoses and Legal Gender Changes in Sweden: 2005-2017.

Evidence suggests the incidence of gender dysphoria (GD), a condition characterized by psychological distress caused by a mismatch between an individual's gender identity and biological sex assigned as birth, has increased since the turn of the twenty-first century. We examined trends in the number of GD diagnoses and legal gender changes in Sweden using registry data from 5007 individuals diagnosed with GD between 2005 and 2017 (53.5% assigned female at birth). GD diagnoses increased substantially over time, especially in birth-assigned females and younger age groups. One-third of all subjects with GD legally changed their gender, with an increase of 1000% from 2005 to 2018. Generally, individuals who were assigned female at birth changed their gender earlier than birth-assigned males, and most did so within one year of GD diagnosis. Our findings highlight the need to analyze the causes and correlations of rapid changes in clinical presentation and to prepare healthcare systems for rising patient demand.

Time domain characterization of nonstationary low-Mach number aeroacoustic sources using principal component analysis.

This paper presents the use of principal component analysis (PCA) for time domain microphone array denoising to characterize an impulsive aeroacoustic source, which is illustrated with the aeroacoustic emission caused by a vortex ring/edge interaction. Prior studies have used signal processing approaches that required assumptions about the source directivity or user intervention at low signal-to-noise ratio (SNR) conditions. In this context, PCA, a matrix decomposition tool which identifies the most common features across an ensemble of observations, provides a data-driven (hands-off) approach to signal processing. For microphone array time series, particular attention is paid to the temporal alignment of the signals to facilitate PCA. A time domain approach is necessary when sources are impulsive and nonstationary. Two such signal arrangements are discussed in this work. Results from this method are in good agreement with theory, validated by prior results using an ensemble averaging approach requiring user support. Furthermore, the results of this method are improved when compared to the ensemble averaging approach without user intervention. A SNR limit is identified where PCA becomes less effective for the vortex/edge interaction problem. This SNR limit is intended to aid in the design of similar future experiments.

On the Topotactic Phase Transition Achieving Superconducting Infinite-Layer Nickelates.

Topotactic reduction is critical to a wealth of phase transitions of current interest, including synthesis of the superconducting nickelate Nd0.8Sr0.2NiO2, reduced from the initial Nd0.8Sr0.2NiO3/SrTiO3 heterostructure. Due to the highly sensitive and often damaging nature of the topotactic reduction, however, only a handful of research groups have been able to reproduce the superconductivity results. A series of in situ synchrotron-based investigations reveal that this is due to the necessary formation of an initial, ultrathin layer at the Nd0.8Sr0.2NiO3 surface that helps to mediate the introduction of hydrogen into the film such that apical oxygens are first removed from the Nd0.8Sr0.2NiO3 / SrTiO3 (001) interface and delivered into the reducing environment. This allows the square-planar / perovskite interface to stabilize and propagate from the bottom to the top of the film without the formation of interphase defects. Importantly, neither geometric rotations in the square planar structure nor significant incorporation of hydrogen within the films is detected, obviating its need for superconductivity. These findings unveil the structural basis underlying the transformation pathway and provide important guidance on achieving the superconducting phase in reduced nickelate systems.

The angiotensin (1-7) glycopeptide PNA5 improves cognition in a chronic progressive mouse model of Parkinson's disease through modulation of neuroinflammation.

Cognitive decline in Parkinson's Disease (PD) is a prevalent and undertreated aspect of disease. Currently, no therapeutics adequately improve this aspect of disease. It has been previously shown that MAS receptor agonism via the glycosylated Angiotensin (1-7) peptide, PNA5, effectively reduces cognitive decline in models of vascular contributions to cognitive impairment and dementia (VCID). PNA5 has a brain/plasma ratio of 0.255 indicating good brain penetration. The goal of the present study was to determine if (1) systemic administration of PNA5 rescued cognitive decline in a mouse model of PD, and (2) if improvements in cognitive status could be correlated with changes to histopathological or blood plasma-based changes. Mice over-expressing human, wild-type α-synuclein (αSyn) under the Thy1 promoter (Thy1-αSyn mice, "line 61") were used as a model of PD with cognitive decline. Thy1-αSyn mice were treated with a systemic dose of PNA5, or saline (1 mg/kg/day) beginning at 4 months of age and underwent behavioral testing at 6 months, compared to WT. Subsequently, mice brains were analyzed for changes to brain pathology, and blood plasma was examined with a Multiplex Immunoassay for peripheral cytokine changes. Treatment with PNA5 reversed cognitive dysfunction measured by Novel Object Recognition and spontaneous alteration in a Y-maze in Thy1-αSyn mice. PNA5 treatment was specific to cognitive deficits, as fine-motor disturbances were unchanged. Enhanced cognition was associated with decreases in hippocampal inflammation and reductions in circulating levels of Macrophage Induced Protein (MIP-1ß). Additionally, neuronal loss was blunted within the CA3 hippocampal region of PNA5-treated αsyn mice. These data reveal that PNA5 treatment reduces cognitive dysfunction in a mouse model of PD. These changes are associated with decreased MIP-1ß levels in plasma identifying a candidate biomarker for target engagement. Thus, PNA5 treatment could potentially fill the therapeutic gap for cognitive decline in PD.

Apollo Next Generation Sample Analysis (ANGSA): an Apollo Participating Scientist Program to Prepare the Lunar Sample Community for Artemis.

As a first step in preparing for the return of samples from the Moon by the Artemis Program, NASA initiated the Apollo Next Generation Sample Analysis Program (ANGSA). ANGSA was designed to function as a low-cost sample return mission and involved the curation and analysis of samples previously returned by the Apollo 17 mission that remained unopened or stored under unique conditions for 50 years. These samples include the lower portion of a double drive tube previously sealed on the lunar surface, the upper portion of that drive tube that had remained unopened, and a variety of Apollo 17 samples that had remained stored at -27 °C for approximately 50 years. ANGSA constitutes the first preliminary examination phase of a lunar "sample return mission" in over 50 years. It also mimics that same phase of an Artemis surface exploration mission, its design included placing samples within the context of local and regional geology through new orbital observations collected since Apollo and additional new "boots-on-the-ground" observations, data synthesis, and interpretations provided by Apollo 17 astronaut Harrison Schmitt. ANGSA used new curation techniques to prepare, document, and allocate these new lunar samples, developed new tools to open and extract gases from their containers, and applied new analytical instrumentation previously unavailable during the Apollo Program to reveal new information about these samples. Most of the 90 scientists, engineers, and curators involved in this mission were not alive during the Apollo Program, and it had been 30 years since the last Apollo core sample was processed in the Apollo curation facility at NASA JSC. There are many firsts associated with ANGSA that have direct relevance to Artemis. ANGSA is the first to open a core sample previously sealed on the surface of the Moon, the first to extract and analyze lunar gases collected in situ, the first to examine a core that penetrated a lunar landslide deposit, and the first to process pristine Apollo samples in a glovebox at -20 °C. All the ANGSA activities have helped to prepare the Artemis generation for what is to come. The timing of this program, the composition of the team, and the preservation of unopened Apollo samples facilitated this generational handoff from Apollo to Artemis that sets up Artemis and the lunar sample science community for additional successes.

Epidemiology of injuries in united states high school track and field jumping events from 2008 - 2019.

OBJECTIVES: Reports of injury characteristics of high school track and field athletes participating in jumping events in the United States are limited. In this descriptive epidemiological study, we report injury rates and patterns in these athletes. METHODS: Injuries and athletic exposures (AE) from the National High School Sports Related Injury Surveillance System, and High School Reporting Information Online (RIO) from 2008-2019 were analyzed. Jumping events included high jump, long jump, triple jump, and pole vault. Injury rate ratios (IRR) and injury proportion ratios (IPR) were examined by sex. RESULTS: A total of 727 injuries related to jumping events during 5,486,279 AEs occurred with the highest frequency at the thigh (20.3%) followed by the ankle (18.2%), knee (16.1%), and lower leg (11.0%). The most common types of injuries were muscle strain (29.0%) and ligament sprain (21.2%). Most athletes returned to sport within 1 week (43.1%, n = 312) or 3 weeks (34.7%, n = 243). Few jumping-related injuries resulted in surgery (4.9%, n = 35) or medical disqualification (4.4%, n = 31). The jumping-related injury rate was 1.33 injuries/10,000 AEs from 2008 to 2019. The rate of jumping-related injuries was higher in competition than in practice (IRR = 2.63, 95% confidence interval [CI]: 2.25-3.06). Injury rates were significantly higher in practice for female athletes than for males (IRR = 1.51, 95% CI: 1.23-1.86). Compared to male athletes, female athletes sustained a higher proportion of ankle injuries (IPR = 1.63, 95% CI: 1.15-2.32) and ligament sprains (IPR = 1.55, 95% CI: 1.16-2.09). CONCLUSIONS: This study describes injury characteristics of high school track and field jumping athletes from 2008 to 2019. We found an overall injury rate of 1.33 injuries per 10,000 AEs. Higher overall rates of jumping-related injuries occurred during competitions than in practice, and female athletes displayed a significantly higher rate of injuries during practices compared to male athletes.

Transcriptome- and proteome-wide association studies identify genes associated with renal cell carcinoma.

We performed a series of integrative analyses including transcriptome-wide association studies (TWASs) and proteome-wide association studies (PWASs) of renal cell carcinoma (RCC) to nominate and prioritize molecular targets for laboratory investigation. On the basis of a genome-wide association study (GWAS) of 29,020 affected individuals and 835,670 control individuals and prediction models trained in transcriptomic reference models, our TWAS across four kidney transcriptomes (GTEx kidney cortex, kidney tubules, TCGA-KIRC [The Cancer Genome Atlas kidney renal clear-cell carcinoma], and TCGA-KIRP [TCGA kidney renal papillary cell carcinoma]) identified 38 gene associations (false-discovery rate <5%) in at least two of four transcriptomic panels and identified 12 genes that were independent of GWAS susceptibility regions. Analyses combining TWAS associations across 48 tissues from GTEx identified associations that were replicable in tumor transcriptomes for 23 additional genes. Analyses by the two major histologic types (clear-cell RCC and papillary RCC) revealed subtype-specific associations, although at least three gene associations were common to both subtypes. PWAS identified 13 associated proteins, all mapping to GWAS-significant loci. TWAS-identified genes were enriched for active enhancer or promoter regions in RCC tumors and hypoxia-inducible factor binding sites in relevant cell lines. Using gene expression correlation, common cancers (breast and prostate) and RCC risk factors (e.g., hypertension and BMI) display genetic contributions shared with RCC. Our work identifies potential molecular targets for RCC susceptibility for downstream functional investigation.

Development and IND-enabling studies of a novel Cas9 genome-edited autologous CD34+ cell therapy to induce fetal hemoglobin for sickle cell disease.

Sickle cell disease (SCD) is a common, severe genetic blood disorder. Current pharmacotherapies are partially effective and allogeneic hematopoietic stem cell transplantation is associated with immune toxicities. Genome editing of patient hematopoietic stem cells (HSCs) to reactivate fetal hemoglobin (HbF) in erythroid progeny offers an alternative potentially curative approach to treat SCD. Although the FDA released guidelines for evaluating genome editing risks, it remains unclear how best to approach pre-clinical assessment of genome-edited cell products. Here, we describe rigorous pre-clinical development of a therapeutic γ-globin gene promoter editing strategy that supported an investigational new drug application cleared by the FDA. We compared γ-globin promoter and BCL11A enhancer targets, identified a potent HbF-inducing lead candidate, and tested our approach in mobilized CD34+ hematopoietic stem progenitor cells (HSPCs) from SCD patients. We observed efficient editing, HbF induction to predicted therapeutic levels, and reduced sickling. With single-cell analyses, we defined the heterogeneity of HbF induction and HBG1/HBG2 transcription. With CHANGE-seq for sensitive and unbiased off-target discovery followed by targeted sequencing, we did not detect off-target activity in edited HSPCs. Our study provides a blueprint for translating new ex vivo HSC genome editing strategies toward clinical trials for treating SCD and other blood disorders.

Early adaptive schemas, emotional regulation, and cognitive flexibility in eating disorders: subtype specific predictors of eating disorder symptoms using hierarchical linear regression.

PURPOSE: Understanding how early adaptive schemas, cognitive flexibility, and emotional regulation influence eating disorder (ED) symptoms, and whether this differs across diagnostic subtypes is critical to optimising treatment. The current study investigated the relationship between these variables and ED symptomology in individuals self-reporting an ED diagnosis and healthy controls. METHODS: A dataset of 1576 online survey responses yielded subsamples for anorexia nervosa (n = 155), bulimia nervosa (n = 55), binge eating disorder (n = 33), other specified feeding or eating disorder (n = 93), and healthy participants (n = 505). The hierarchical linear regression analysis included Eating Disorder Examination Questionnaire 6.0 Global Score as the dependent variable; Young Positive Schema Questionnaire, Emotional Regulation Questionnaire, and Cognitive Flexibility Inventory subscale scores as the independent variables; and demographic measures as the covariates. RESULTS: The number of significant predictors varied considerably by ED sub-group. Amongst the anorexia nervosa, bulimia nervosa, and healthy subsamples, the adaptive schema Self-Compassion and Realistic Expectations was associated with lower ED symptom severity. In comparison, age and body mass index were the strongest predictors for binge eating disorder, whilst the Expressive Suppression (a subscale of the Emotional Regulation Questionnaire) was the strongest predictor for other specified feeding or eating disorders. CONCLUSION: Early adaptive schemas, cognitive flexibility, and emotional regulation vary across ED subtype, suggesting the need for tailored treatment that disrupts the self-reinforcing cycle of ED psychopathology. Future research investigating how early adaptive schemas may predict or be associated with treatment response across diagnostic subtypes is needed. LEVEL OF EVIDENCE: Level IV, evidence obtained from multiple time-series with or without the intervention, such as case studies.

Engineered cytokine/antibody fusion proteins improve IL-2 delivery to pro-inflammatory cells and promote antitumor activity.

Progress in cytokine engineering is driving therapeutic translation by overcoming these proteins' limitations as drugs. The IL-2 cytokine is a promising immune stimulant for cancer treatment but is limited by its concurrent activation of both pro-inflammatory immune effector cells and antiinflammatory regulatory T cells, toxicity at high doses, and short serum half-life. One approach to improve the selectivity, safety, and longevity of IL-2 is complexing with anti-IL-2 antibodies that bias the cytokine toward immune effector cell activation. Although this strategy shows potential in preclinical models, clinical translation of a cytokine/antibody complex is complicated by challenges in formulating a multiprotein drug and concerns regarding complex stability. Here, we introduced a versatile approach to designing intramolecularly assembled single-agent fusion proteins (immunocytokines, ICs) comprising IL-2 and a biasing anti-IL-2 antibody that directs the cytokine toward immune effector cells. We optimized IC construction and engineered the cytokine/antibody affinity to improve immune bias. We demonstrated that our IC preferentially activates and expands immune effector cells, leading to superior antitumor activity compared with natural IL-2, both alone and combined with immune checkpoint inhibitors. Moreover, therapeutic efficacy was observed without inducing toxicity. This work presents a roadmap for the design and translation of cytokine/antibody fusion proteins.

Ionizable Drugs Enable Intracellular Delivery of Co-Formulated siRNA.

Targeting complementary pathways in diseases such as cancer can be achieved with co-delivery of small interfering ribonucleic acid (siRNA) and small molecule drugs; however, current formulation strategies are typically limited to one, but not both. Here, ionizable small molecule drugs and siRNA are co-formulated in drug-rich nanoparticles. Ionizable analogs of the selective estrogen receptor degrader fulvestrant self-assemble into colloidal drug aggregates and cause endosomal disruption, allowing co-delivery of siRNA against a non-druggable target. siRNA is encapsulated in lipid-stabilized, drug-rich colloidal nanoparticles where the ionizable lipid used in conventional lipid nanoparticles is replaced with an ionizable fulvestrant analog. The selection of an appropriate phospholipid and formulation buffer enables endocytosis and potent reporter gene knockdown in cancer cells. Importantly, siRNA targeting cyclin E1 is effectively delivered to drug-resistant breast cancer cells, demonstrating the utility of this approach. This strategy opens the possibility of using ionizable drugs to co-deliver RNA and ultimately improve therapeutic outcomes.

The Kinematics of Proal Chewing in Rats.

Chewing kinematics are well-documented in several mammal species with fused mandibular symphyses, but relatively understudied in mammals with an unfused symphysis, despite the fact that more than half of extant Mammalia have an unfused mandibular symphysis. The Wistar brown rat (Rattus norvegicus) is widely used in human health research, including studies of mastication or neurological studies where mastication is the output behavior. These animals are known to have unfused mandibular symphyses and proal jaw (rostrocaudal) motion during occlusion, but the lack of high resolution, 3-dimensional analysis of rat chewing leaves the functional significance of symphyseal mobility unknown. We used biplanar fluoroscopy and the X-ray reconstruction of moving morphology workflow to quantify chewing kinematics in 3 brown rats, quantifying overall jaw kinematics, including motions about the temporomandibular joint and unfused mandibular symphysis. During occlusion, the teeth and the mandibular condyle translate almost exclusively anteriorly (proal) during occlusion, with little motion in any other degrees of freedom. At the symphysis, we observed minimal flexion throughout the chew cycle. Overall, there are fundamental differences in jaw kinematics between rats and other mammals and therefore rats are not an appropriate proxy for ancestral mammal jaw mechanics. Additionally, differences between humans and rat chewing kinematics must be considered when using rats as a clinical model for pathological feeding research.

Revealing the Structural Intricacies of Biomembrane-Interfaced Emulsions with Small- and Ultra-Small-Angle Neutron Scattering.

Utilizing cell membranes from diverse cell types for biointerfacing has demonstrated significant advantages in enhancing colloidal stability and incorporating biological properties, tailored specifically for various biomedical applications. However, the structures of these materials, particularly emulsions interfaced with red blood cell (RBC) or platelet (PLT) membranes, remain an underexplored area. This study systematically employs small- and ultra-small-angle neutron scattering (SANS and USANS) with contrast variation to investigate the structure of emulsions containing perfluorohexane within RBC (RBC/PFH) and PLT membranes (PLT/PFH). The findings reveal that the scattering length density of RBC and PLT membranes is 1.5 × 10-6 Å-2, similar to 30% (w/w) deuterium oxide. Using this solvent as a cell membrane-matching medium, estimated droplet diameters are 770 nm (RBC/PFH) and 1.5 µm (PLT/PFH), based on polydispersed sphere model fitting. Intriguingly, calculated patterns and invariant analysis reveal native droplet architectures featuring entirely liquid PFH cores, differing significantly from the observed bubble-droplet core system in electron microscopy. This highlights the advantage of SANS and USANS in differentiating genuine colloidal structures in complex dispersions. In summary, this work underscores the pivotal role of SANS and USANS in characterizing biointerfaced colloids and in uncovering novel colloidal structures with significant potential for biomedical applications and clinical translation.

Venous thromboembolic events associated with blood product administration in an era of whole blood use.

BACKGROUND: The risks associated with blood product administration and venous thromboembolic events remains unclear. We sought to determine which blood products were associated with the development of deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: We analyzed data from patients ≥18 years of age in the Trauma Quality Improvement Program (TQIP) database that received ≥1 blood product and survived ≥24 â€‹h. RESULTS: There were 42,399 that met inclusion, of whom, 2086 had at least one VTE event. In our multivariable logistic regression model, we found that WB had a unit odds ratio (uOR) of 1.05 (95 â€‹% CI 1.02-1.08) for DVT and 1.08 (1.05-1.12) for PE. Compared to WB, platelets had a higher uOR for DVT of 1.09 (1.04-1.13) but similar uOR for PE of 1.08 (1.03-1.14). CONCLUSIONS: We found an association of both DVT and PE with early whole blood and platelets.

Controlling a new plasma regime.

Success of the UK's Spherical Tokamak for Energy Production (STEP) programme requires a robust plasma control system. This system has to guide the plasma from initiation to the burning phase, maintain it there, produce the desired fusion power for the desired duration and then terminate the plasma safely. This has to be done in a challenging environment with limited sensors and without overloading plasma-facing components. The plasma parameters and the operational regime in the STEP prototype will be very different from tokamaks, which are presently in operation. During fusion burn, the plasma regime in STEP will be self-organizing, adding further complications to the plasma control system design. This article describes the work to date on the design of individual controllers for plasma shape and position, magneto hydrodynamic instabilities, heat load and fusion power. Having studied 'normal' operation, the article discusses the philosophy of how the system will handle exceptions, when things do not go exactly as planned. This article is part of the theme issue 'Delivering Fusion Energy - The Spherical Tokamak for Energy Production (STEP)'.