Consensus Head Acceleration Measurement Practices (CHAMP): Origins, methods, transparency and disclosure

The use of head kinematic measurement devices has recently proliferated owing to technology advances that make such measurement more feasible. In parallel, demand to understand the biomechanics of head impacts and injury in sports and the military has increased as the burden of such loading on the brain has received focused attention. As a result, the field has matured to the point of needing methodological guidelines to improve the rigor and consistency of research and reduce the risk of scientific bias. To this end, a diverse group of scientists undertook a comprehensive effort to define current best practices in head kinematic measurement, culminating in a series of manuscripts outlining consensus methodologies and companion summary statements. Summary statements were discussed, revised, and voted upon at the Consensus Head Acceleration Measurement Practices (CHAMP) Conference in March 2022. This manuscript summarizes the motivation and methods of the consensus process and introduces recommended reporting checklists to be used to increase transparency and rigor of future experimental design and publication of work in this field. The checklists provide an accessible means for researchers to apply the best practices summarized in the companion manuscripts when reporting studies utilizing head kinematic measurement in sport and military settings

Mercury's Moment of Inertia from Spin and Gravity Data

Earth-based radar observations of the spin state of Mercury at 35 epochs between 2002 and 2012 reveal that its spin axis is tilted by (2.04 plus or minus 0.08) arc min with respect to the orbit normal. The direction of the tilt suggests that Mercury is in or near a Cassini state. Observed rotation rate variations clearly exhibit an 88-day libration pattern which is due to solar gravitational torques acting on the asymmetrically shaped planet. The amplitude of the forced libration, (38.5 plus or minus 1.6) arc sec, corresponds to a longitudinal displacement of ∼450 m at the equator. Combining these measurements of the spin properties with second-degree gravitational harmonics (Smith et al., 2012) provides an estimate of the polar moment of inertia of MercuryC/MR2 = 0.346 plus or minus 0.014, where M and R are Mercury's mass and radius. The fraction of the moment that corresponds to the outer librating shell, which can be used to estimate the size of the core, is Cm/C = 0.431 plus or minus 0.025

Haptoglobin improves shock, lung injury, and survival in canine pneumonia

During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alternative approach. Human haptoglobin binds CFH with high affinity and, therefore, can potentially reduce iron availability and oxidative activity. CFH levels are elevated over approximately 24-48 hours in our antibiotic-treated canine model of S. aureus pneumonia that simulates the cardiovascular abnormalities of human septic shock. In this 96-hour model, resuscitative treatments, mechanical ventilation, sedation, and continuous care are translatable to management in human intensive care units. We found, in this S. aureus pneumonia model inducing septic shock, that commercial human haptoglobin concentrate infusions over 48-hours bind canine CFH, increase CFH clearance, and lower circulating iron. Over the 96-hour study, this treatment was associated with an improved metabolic profile (pH, lactate), less lung injury, reversal of shock, and increased survival. Haptoglobin binding compartmentalized CFH to the intravascular space. This observation, in combination with increasing CFHs clearance, reduced available iron as a potential source of bacterial nutrition while decreasing the ability for CFH and iron to cause extravascular oxidative tissue injury. In contrast, haptoglobin therapy had no measurable antiinflammatory effect on elevations in proinflammatory C-reactive protein and cytokine levels. Haptoglobin therapy enhances normal host defense mechanisms in contrast to previously studied antiinflammatory sepsis therapies, making it a biologically plausible novel approach to treat septic shock

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease

Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: a pharmacogenomics study from the CHARGE consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10−8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

The use of standardized patients for mock oral board exams in neurology: a pilot study

BACKGROUND: Mock oral board exams, fashioned after the live patient hour of the American Board of Psychiatry and Neurology exam, are commonly part of resident assessment during residency training. Exams using real patients selected from clinics or hospitals are not standardized and do not allow comparisons of resident performance across the residency program. We sought to create a standardized patient mock oral board exam that would allow comparison of residents' clinical performance. METHODS: Three cases were created and then used for this mock oral boards exercise utilizing trained standardized patients. Residents from the University of Cincinnati and Indiana University participated in the exam. Residents were scored by attending physician examiners who directly observed the encounter with the standardized patient. The standardized patient also assessed each resident. A post-test survey was administered to ascertain participant's satisfaction with the examination process. RESULTS: Resident scores were grouped within one standard deviation of the mean, with the exception of one resident who was also subjectively felt to "fail" the exam. In exams with two faculty "evaluators", scores were highly correlated. The survey showed satisfaction with the examination process in general. CONCLUSION: Standardized patients can be used for mock oral boards in the live patient format. Our initial experience with this examination process was positive. Further testing is needed to determine if this examination format is more reliable and valid than traditional methods of assessing resident competency

c-Crk proto-oncogene contributes to transcriptional repression of p120-catenin in non-small cell lung cancer cells

As a member of adherens junction, p120-catenin (p120ctn) plays a major role in cell adhesions through stabilization of E-cadherin. p120ctn is transcriptionally down-regulated in non-small cell lung cancer (NSCLC), although the molecular mechanisms underlying p120ctn repression are incompletely defined. Here we further investigated transcriptional regulation of p120ctn in NSCLC. We prepared a promoter reporter plasmid construct that contained p120ctn promoter region from position −1082 to +320 relative to transcription start site. Through serial deletion mutation analysis of the p120ctn promoter, we pinpointed cis-acting elements involved in regulation of p120ctn. We identified transcription factor SP1 as a transcriptional repressor of p120ctn that directly binds to segment (−9 to +36) of the p120ctn promoter. SP1 can receive multiple signals from several intracellular signaling pathways. Through examination of SP1 binding partners, we identified proto-oncogene c-Crk to be involved in transcriptional down-regulation of p120ctn. RNAi mediated silencing of CRK in A549, H157 and H358 cells increased p120ctn protein levels. On the other hand, over-expression of CRK-I and CRK-II in NSCLC cells down-regulated p120ctn, an effect that was abrogated by simultaneous silencing of SP1. In summary, our data provide evidence for the role of c-Crk proto-oncogene in transcriptional repression of p120ctn that further clarifies the mechanism by which this biochemical signal promotes metastasis in NSCLC

Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand

Background: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. Methods: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%–80%) were revised and re-introduced in Phase 3, and statements with low agreement (80%) were confirmed by the Task Force in Phase 4. Conclusions: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia

Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand

Background: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. Methods: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at \u3e 80 %, and five multiple-choice questions. Statements with moderate agreement (70 % – 80 %) were revised and re-introduced in Phase 3, and statements with low agreement ( \u3c 70 %) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. Results: Topic experts from Australia (n = 62, 92.5 %) and New Zealand (n = 5, 7.5 %) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7 %) were women, 38 (56.7 %) were health professionals and 27 (40.3 % ) were researchers/academics. In Phase 2, 15 of 18 (83.3 %) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100 %) and offering tailored resistance training to people with sarcopenia (92.5 %). Forty-seven experts participated in Phase 3; 5/6 (83.3 %) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9 %) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement ( \u3e 80 %) were confirmed by the Task Force in Phase 4. Conclusions: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia