Cardiac Remodeling After Hypertensive Pregnancy Following Physician-Optimized Blood Pressure Self-Management: The POP-HT Randomized Clinical Trial Imaging Substudy.

BACKGROUND: Hypertensive pregnancy disorders are associated with adverse cardiac remodeling, which can fail to reverse in the postpartum period in some women. The Physician-Optimized Postpartum Hypertension Treatment trial demonstrated that improved blood pressure control while the cardiovascular system recovers postpartum associates with persistently reduced blood pressure. We now report the effect on cardiac remodeling. METHODS: In this prospective, randomized, open-label, blinded end point trial, in a single UK hospital, 220 women were randomly assigned 1:1 to self-monitoring with research physician-optimized antihypertensive titration or usual postnatal care from a primary care physician and midwife. Participants were 18 years of age or older, with preeclampsia or gestational hypertension, requiring antihypertensives on hospital discharge postnatally. Prespecified secondary cardiac imaging outcomes were recorded by echocardiography around delivery, and again at blood pressure primary outcome assessment, around 9 months postpartum, when cardiovascular magnetic resonance was also performed. RESULTS: A total of 187 women (101 intervention; 86 usual care) underwent echocardiography at baseline and follow-up, at a mean 258±14.6 days postpartum, of which 174 (93 intervention; 81 usual care) also had cardiovascular magnetic resonance at follow-up. Relative wall thickness by echocardiography was 0.06 (95% CI, 0.07-0.05; P<0.001) lower in the intervention group between baseline and follow-up, and cardiovascular magnetic resonance at follow-up demonstrated a lower left ventricular mass (-6.37 g/m2; 95% CI, -7.99 to -4.74; P<0.001), end-diastolic volume (-3.87 mL/m2; 95% CI, -6.77 to -0.98; P=0.009), and end-systolic volume (-3.25 mL/m2; 95% CI, 4.87 to -1.63; P<0.001) and higher left and right ventricular ejection fraction by 2.6% (95% CI, 1.3-3.9; P<0.001) and 2.8% (95% CI, 1.4-4.1; P<0.001), respectively. Echocardiography-assessed left ventricular diastolic function demonstrated a mean difference in average E/E' of 0.52 (95% CI, -0.97 to -0.07; P=0.024) and a reduction in left atrial volumes of -4.33 mL/m2 (95% CI, -5.52 to -3.21; P<0.001) between baseline and follow-up when adjusted for baseline differences in measures. CONCLUSIONS: Short-term postnatal optimization of blood pressure control after hypertensive pregnancy, through self-monitoring and physician-guided antihypertensive titration, associates with long-term changes in cardiovascular structure and function, in a pattern associated with more favorable cardiovascular outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04273854.

Steps on the Path to Clinical Translation: A workshop by the British and Irish Chapter of the ISMRM.

The British and Irish Chapter of the International Society for Magnetic Resonance in Medicine (BIC-ISMRM) held a workshop entitled "Steps on the path to clinical translation" in Cardiff, UK, on 7th September 2022. The aim of the workshop was to promote discussion within the MR community about the problems and potential solutions for translating quantitative MR (qMR) imaging and spectroscopic biomarkers into clinical application and drug studies. Invited speakers presented the perspectives of radiologists, radiographers, clinical physicists, vendors, imaging Contract/Clinical Research Organizations (CROs), open science networks, metrologists, imaging networks, and those developing consensus methods. A round-table discussion was held in which workshop participants discussed a range of questions pertinent to clinical translation of qMR imaging and spectroscopic biomarkers. Each group summarized their findings via three main conclusions and three further questions. These questions were used as the basis of an online survey of the broader UK MR community.

Artificial Intelligence for Contrast-Free MRI: Scar Assessment in Myocardial Infarction Using Deep Learning-Based Virtual Native Enhancement.

BACKGROUND: Myocardial scars are assessed noninvasively using cardiovascular magnetic resonance late gadolinium enhancement (LGE) as an imaging gold standard. A contrast-free approach would provide many advantages, including a faster and cheaper scan without contrast-associated problems. METHODS: Virtual native enhancement (VNE) is a novel technology that can produce virtual LGE-like images without the need for contrast. VNE combines cine imaging and native T1 maps to produce LGE-like images using artificial intelligence. VNE was developed for patients with previous myocardial infarction from 4271 data sets (912 patients); each data set comprises slice position-matched cine, T1 maps, and LGE images. After quality control, 3002 data sets (775 patients) were used for development and 291 data sets (68 patients) for testing. The VNE generator was trained using generative adversarial networks, using 2 adversarial discriminators to improve the image quality. The left ventricle was contoured semiautomatically. Myocardial scar volume was quantified using the full width at half maximum method. Scar transmurality was measured using the centerline chord method and visualized on bull's-eye plots. Lesion quantification by VNE and LGE was compared using linear regression, Pearson correlation (R), and intraclass correlation coefficients. Proof-of-principle histopathologic comparison of VNE in a porcine model of myocardial infarction also was performed. RESULTS: VNE provided significantly better image quality than LGE on blinded analysis by 5 independent operators on 291 data sets (all P<0.001). VNE correlated strongly with LGE in quantifying scar size (R, 0.89; intraclass correlation coefficient, 0.94) and transmurality (R, 0.84; intraclass correlation coefficient, 0.90) in 66 patients (277 test data sets). Two cardiovascular magnetic resonance experts reviewed all test image slices and reported an overall accuracy of 84% for VNE in detecting scars when compared with LGE, with specificity of 100% and sensitivity of 77%. VNE also showed excellent visuospatial agreement with histopathology in 2 cases of a porcine model of myocardial infarction. CONCLUSIONS: VNE demonstrated high agreement with LGE cardiovascular magnetic resonance for myocardial scar assessment in patients with previous myocardial infarction in visuospatial distribution and lesion quantification with superior image quality. VNE is a potentially transformative artificial intelligence-based technology with promise in reducing scan times and costs, increasing clinical throughput, and improving the accessibility of cardiovascular magnetic resonance in the near future.

Postpartum blood pressure self-management following hypertensive pregnancy: protocol of the Physician Optimised Post-partum Hypertension Treatment (POP-HT) trial.

INTRODUCTION: New-onset hypertension affects approximately 10% of pregnancies and is associated with a significant increase in risk of cardiovascular disease in later life, with blood pressure measured 6 weeks postpartum predictive of blood pressure 5-10 years later. A pilot trial has demonstrated that improved blood pressure control, achevied via self-management during the puerperium, was associated with lower blood pressure 3-4 years postpartum. Physician Optimised Post-partum Hypertension Treatment (POP-HT) will formally evaluate whether improved blood pressure control in the puerperium results in lower blood pressure at 6 months post partum, and improvements in cardiovascular and cerebrovascular phenotypes. METHODS AND ANALYSIS: POP-HT is an open-label, parallel arm, randomised controlled trial involving 200 women aged 18 years or over, with a diagnosis of pre-eclampsia or gestational hypertension, and requiring antihypertensive medication at discharge. Women are recruited by open recruitment and direct invitation around time of delivery and randomised 1:1 to, either an intervention comprising physician-optimised self-management of postpartum blood pressure or, usual care. Women in the intervention group upload blood pressure readings to a 'smartphone' app that provides algorithm-driven individualised medication-titration. Medication changes are approved by physicians, who review blood pressure readings remotely. Women in the control arm follow assessment and medication adjustment by their usual healthcare team. The primary outcome is 24-hour average ambulatory diastolic blood pressure at 6-9 months post partum. Secondary outcomes include: additional blood pressure parameters at baseline, week 1 and week 6; multimodal cardiovascular assessments (CMR and echocardiography); parameters derived from multiorgan MRI including brain and kidneys; peripheral macrovascular and microvascular measures; angiogenic profile measures taken from blood samples and levels of endothelial circulating and cellular biomarkers; and objective physical activity monitoring and exercise assessment. An additional 20 women will be recruited after a normotensive pregnancy as a comparator group for endothelial cellular biomarkers. ETHICS AND DISSEMINATION: IRAS PROJECT ID 273353. This trial has received a favourable opinion from the London-Surrey Research Ethics Committee and HRA (REC Reference 19/LO/1901). The investigator will ensure that this trial is conducted in accordance with the principles of the Declaration of Helsinki and follow good clinical practice guidelines. The investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Authors will acknowledge that the study was funded by the British Heart Foundation Clinical Research Training Fellowship (BHF Grant number FS/19/7/34148). Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be acknowledged. TRIAL REGISTRATION NUMBER: NCT04273854.

Prospective Assessment of Tumour Burden and Bone Disease in Plasma Cell Dyscrasias Using DW-MRI and Exploratory Bone Biomarkers.

Novel biomarkers for tumour burden and bone disease are required to guide clinical management of plasma cell dyscrasias. Recently, bone turnover markers (BTMs) and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) have been explored, although their role in the prospective assessment of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) is unclear. Here, we conducted a pilot observational cohort feasibility study combining serum BTMs and DW-MRI in addition to standard clinical assessment. Fifty-five patients were recruited (14 MGUS, 15 smouldering MM, 14 new MM and 12 relapsed MM) and had DW-MRI and serum biomarkers (P1NP, CTX-1, ALP, DKK1, sclerostin, RANKL:OPG and BCMA) measured at baseline and 6-month follow-up. Serum sclerostin positively correlated with bone mineral density (r = 0.40-0.54). At baseline, serum BCMA correlated with serum paraprotein (r = 0.42) and serum DKK1 correlated with serum free light chains (r = 0.67); the longitudinal change in both biomarkers differed between International Myeloma Working Group (IMWG)-defined responders and non-responders. Myeloma Response Assessment and Diagnosis System (MY-RADS) scoring of serial DW-MRI correlated with conventional IMWG response criteria for measuring longitudinal changes in tumour burden. Overall, our pilot study suggests candidate radiological and serum biomarkers of tumour burden and bone loss in MM/MGUS, which warrant further exploration in larger cohorts to validate the findings and to better understand their clinical utility.

Toward Replacing Late Gadolinium Enhancement With Artificial Intelligence Virtual Native Enhancement for Gadolinium-Free Cardiovascular Magnetic Resonance Tissue Characterization in Hypertrophic Cardiomyopathy.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for noninvasive myocardial tissue characterization but requires intravenous contrast agent administration. It is highly desired to develop a contrast agent-free technology to replace LGE for faster and cheaper CMR scans. METHODS: A CMR virtual native enhancement (VNE) imaging technology was developed using artificial intelligence. The deep learning model for generating VNE uses multiple streams of convolutional neural networks to exploit and enhance the existing signals in native T1 maps (pixel-wise maps of tissue T1 relaxation times) and cine imaging of cardiac structure and function, presenting them as LGE-equivalent images. The VNE generator was trained using generative adversarial networks. This technology was first developed on CMR datasets from the multicenter Hypertrophic Cardiomyopathy Registry, using hypertrophic cardiomyopathy as an exemplar. The datasets were randomized into 2 independent groups for deep learning training and testing. The test data of VNE and LGE were scored and contoured by experienced human operators to assess image quality, visuospatial agreement, and myocardial lesion burden quantification. Image quality was compared using a nonparametric Wilcoxon test. Intra- and interobserver agreement was analyzed using intraclass correlation coefficients (ICC). Lesion quantification by VNE and LGE were compared using linear regression and ICC. RESULTS: A total of 1348 hypertrophic cardiomyopathy patients provided 4093 triplets of matched T1 maps, cines, and LGE datasets. After randomization and data quality control, 2695 datasets were used for VNE method development and 345 were used for independent testing. VNE had significantly better image quality than LGE, as assessed by 4 operators (n=345 datasets; P<0.001 [Wilcoxon test]). VNE revealed lesions characteristic of hypertrophic cardiomyopathy in high visuospatial agreement with LGE. In 121 patients (n=326 datasets), VNE correlated with LGE in detecting and quantifying both hyperintensity myocardial lesions (r=0.77-0.79; ICC=0.77-0.87; P<0.001) and intermediate-intensity lesions (r=0.70-0.76; ICC=0.82-0.85; P<0.001). The native CMR images (cine plus T1 map) required for VNE can be acquired within 15 minutes and producing a VNE image takes less than 1 second. CONCLUSIONS: VNE is a new CMR technology that resembles conventional LGE but without the need for contrast administration. VNE achieved high agreement with LGE in the distribution and quantification of lesions, with significantly better image quality.

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

BACKGROUND: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. METHODS: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FINDINGS: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). INTERPRETATION: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. FUNDING: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.

Crazy-Paving: A Computed Tomographic Finding of Coronavirus Disease 2019.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 first occurred in Wuhan, China, in December 2019, and by March 2020 COVID-19 was declared a global pandemic. CASE PRESENTATION: We describe a case of a 52-year-old female with past medical history of asthma, type 2 diabetes, and previous tobacco use who presented to the emergency department with dyspnea and was found to be positive for COVID-19. We discuss the computed tomographic finding of "crazy-paving" pattern in the patient's lungs and the significance of this finding in COVID-19 patients. DISCUSSION: Emergency providers need to be aware of the different imaging characteristics of various stages of COVID-19 to appropriately treat, isolate, and determine disposition of COVID-19 infected patients. Ground-glass opacities are the earliest and most common imaging finding for COVID-19. Crazy-paving pattern is defined as thickened interlobular septa and intralobular lines superimposed on diffuse ground-glass opacities and should be recognized by emergency providers as a radiographic finding of progressive COVID-19.

CSA-90 reduces periprosthetic joint infection in a novel rat model challenged with local and systemic Staphylococcus aureus.

Infection of orthopedic implants is a growing clinical challenge to manage due to the proliferation of drug-resistant bacterial strains. In this study, we aimed to investigate whether the treatment of implants with ceragenin-90 (CSA-90), a synthetic compound based on endogenous antibacterial peptides, could prevent infection in a novel rat model of periprosthetic joint infection (PJI) challenged with either local or systemic Staphylococcus aureus. A novel preclinical model of PJI was created using press-fit porous titanium implants in the distal femur of male Wistar rats. Sterile implants were pre-treated with 500 µg CSA-90 in saline. S. aureus was applied either directly at the time of surgery or administered via tail vein injection immediately afterward. Animals were monitored daily for clinical and radiographic evidence of infection for a total of 6 weeks. Post-study microbiological, radiographic, and histological analysis were performed to determine the incidence of PJI and assess osseointegration. CSA-90 treated groups demonstrated a reduced rate of PJI as confirmed by deep tissue swab culture at the time of cull compared with untreated groups with both local (33% vs 100%; P = .009) and systemic (10% vs 90%; P < .0001) S. aureus inoculation. Median survival time also increased from 8 to 17 days and from 8 to 42 days, respectively. In conclusion, this study describes a novel preclinical model of local and hematogenous PJI using a porous metal implant. CSA-90 reduced the incidence of PJI in this model supporting its further development as an antimicrobial coating for orthopedic implants.

The application of ceragenins to orthopedic surgery and medicine.

Osteomyelitis and infections associated with orthopedic implants represent a significant burden of disease worldwide. Ceragenins (CSAs) are a relatively new class of small-molecule antimicrobials that target a broad range of Gram-positive and Gram-negative bacteria as well as fungi, viruses, and parasites. This review sets the context of the need for new antimicrobial strategies by cataloging the common pathogens associated with orthopedic infection and highlighting the increasing challenges of managing antibiotic-resistant bacterial strains. It then comparatively describes the antimicrobial properties of CSAs with a focus on the CSA-13 family. More recently developed members of this family such as CSA-90 and CSA-131 may have a particular advantage in an orthopedic setting as they possess secondary pro-osteogenic properties. In this context, we consider several new preclinical studies that demonstrate the utility of CSAs in orthopedic models. Emerging evidence suggests that CSAs are effective against antibiotic-resistant Staphylococcus aureus strains and can prevent the formation of biofilms. There remains considerable scope for developing CSA-based treatments, either as coatings for orthopedic implants or as local or systemic antibiotics to prevent bone infection.

A high temperature gas flow environment for neutron total scattering studies of complex materials.

We present the design and capabilities of a high temperature gas flow environment for neutron diffraction and pair distribution function studies available at the Nanoscale Ordered Materials Diffractometer instrument at the Spallation Neutron Source. Design considerations for successful total scattering studies are discussed, and guidance for planning experiments, preparing samples, and correcting and reducing data is defined. The new capabilities are demonstrated with an in situ decomposition study of a battery electrode material under inert gas flow and an in operando carbonation/decarbonation experiment under reactive gas flow. This capability will aid in identifying and quantifying the atomistic configurations of chemically reactive species and their influence on underlying crystal structures. Furthermore, studies of reaction kinetics and growth pathways in a wide variety of functional materials can be performed across a range of length scales spanning the atomic to the nanoscale.

RHEGAL: Resistive heating gas enclosure loadframe for in situ neutron scattering.

In situ neutron scattering is a powerful tool to reveal materials atomic structural response such as phase transformation, lattice straining, and texture under external stimuli. The advent of a high flux neutron source such as the Spallation Neutron Source (SNS) allows fast measurement in even non-equilibrium conditions, i.e., phase transformation in steels. However, the commercial fast heating apparatus such as commercial physical simulation equipment is not designed for in situ neutron scattering, which limits its application to in situ materials research by using neutrons. Here we present a resistive heating gas enclosure loadframe (RHEGAL) for non-equilibrium phase transformation studies by using in situ neutron scattering, which takes the advantage of high flux neutron sources like SNS. RHEGAL enables fast resistive heating of metal samples to 1200 °C at a rate up to 60 °C/s in an inert atmosphere. It provides both horizontal and vertical positions for scattering optimization. The mechanical loading capability also allows in situ high temperature tension above the oxidation temperature limit. The optimized translucent neutron scattering window by silicon allows both reflection and transmission measurements, making this equipment applicable for neutron diffraction, small angle scattering, and imaging. To demonstrate the fast heating capability, the phase transformations of an example of advanced high strength steel heated at 3 °C/s and 30 °C/s were measured with the VULCAN engineering diffractometer, and the different phase transformation kinetics by neutron diffraction were presented.

CSA-90 Promotes Bone Formation and Mitigates Methicillin-resistant Staphylococcus aureus Infection in a Rat Open Fracture Model.

BACKGROUND: Infection of open fractures remains a significant cause of morbidity and mortality to patients worldwide. Early administration of prophylactic antibiotics is known to improve outcomes; however, increasing concern regarding antimicrobial resistance makes finding new compounds for use in such cases a pressing area for further research. CSA-90, a synthetic peptidomimetic compound, has previously demonstrated promising antimicrobial action against Staphylococcus aureus in rat open fractures. However, its efficacy against antibiotic-resistant microorganisms, its potential as a therapeutic agent in addition to its prophylactic effects, and its proosteogenic properties all require further investigation. QUESTIONS/PURPOSES: (1) Does prophylactic treatment with CSA-90 reduce infection rates in a rat open fracture model inoculated with S aureus, methicillin-resistant S aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis (MRSE) as measured by survival, radiographic union, and deep tissue swab cultures? (2) Does CSA-90 reduce infection rates when administered later in the management of an open fracture as measured by survival, radiographic union, and deep tissue swab cultures? (3) Does CSA-90 demonstrate a synergistic proosteogenic effect with bone morphogenetic protein 2 (BMP-2) in a noninfected rat ectopic bone formation assay as assessed by micro-CT bone volume measurement? (4) Can CSA-90 elute and retain its antimicrobial efficacy in vitro when delivered using clinically relevant agents measured using a Kirby-Bauer disc diffusion assay? METHODS: All in vivo studies were approved by the local animal ethics committee. In the open fracture studies, 12-week-old male Wistar rats underwent open midshaft femoral fractures stabilized with a 1.1-mm Kirschner wire and 10 µg BMP-2 ± 500 µg CSA-90 was applied to the fracture site using a collagen sponge along with 1 x 10 colony-forming units of bacteria (S aureus/MRSA/MRSE; n = 10 per group). In the delayed treatment study, débridement and treatment with 500 µg CSA-90 were performed at Day 1 and Day 5 after injury and bacterial insult (S aureus). All animals were reviewed daily for signs of local infection and/or sepsis. An independent, blinded veterinarian reviewed twice-weekly radiographs, and rats showing osteolysis and/or declining overall health were culled at his instruction. The primary outcome of both fracture studies was fracture infection, incorporating survival, radiographic union, and deep tissue swab cultures. For the ectopic bone formation assay, 0 to 10 µg BMP-2 and 0 to 500 µg CSA-90 were delivered on a collagen sponge into bilateral quadriceps muscle pouches of 8-week-old rats (n = 10 per group). Micro-CT quantification of bone volume and descriptive histologic analysis were performed for all in vivo studies. Modified Kirby-Bauer disc diffusion assays were used to quantify antimicrobial activity in vitro using four different delivery methods, including bone cement. RESULTS: Infection was observed in none of the MRSA inoculated open fractures treated with CSA-90 with 10 of 10 deep tissue swab cultures negative at the time of cull. Median survival was 43 days (range, 11-43 days) in the treated group versus 11 days (range, 8-11 days) in the untreated MRSA inoculated group (p < 0.001). However, delayed débridement and treatment of open fractures with CSA-90 at either Day 1 or Day 5 did not prevent infection, resulting in early culls by Day 21 with positive swab cultures (10 of 10 for each time point). Maximal ectopic bone formation was achieved with 500 µg CSA-90 and 10 µg BMP-2 (mean volume, 9.58 mm; SD, 7.83), creating larger bone nodules than formed with 250 µg CSA-90 and 10 µg BMP-2 (mean volume, 1.7 mm; SD, 1.07; p < 0.001). Disc diffusion assays showed that CSA-90 could successfully elute from four potential delivery agents including calcium sulphate (mean zone of inhibition, 11.35 mm; SD, 0.957) and bone cement (mean, 4.67 mm; SD, 0.516). CONCLUSIONS: CSA-90 shows antimicrobial action against antibiotic-resistant Staphylococcal strains in vitro and in an in vivo model of open fracture infection. CLINICAL RELEVANCE: The antimicrobial properties of CSA-90 combined with further evidence of its proosteogenic potential make it a promising compound to develop further for orthopaedic applications.

Preclinical models for orthopedic research and bone tissue engineering.

In this review, we broadly define and discuss the preclinical rodent models that are used for orthopedics and bone tissue engineering. These range from implantation models typically used for biocompatibility testing and high-throughput drug screening, through to fracture and critical defect models used to model bone healing and severe orthopedic injuries. As well as highlighting the key methods papers describing these techniques, we provide additional commentary based on our substantive practical experience with animal surgery and in vivo experimental design. This review also briefly touches upon the descriptive and functional outcome measures and power calculations that are necessary for an informative study. Obtaining informative and relevant research outcomes can be very dependent on the model used, and we hope this evaluation of common models will serve as a primer for new researchers looking to undertake preclinical bone studies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:832-840, 2018.

Correlation and comparison of syndesmosis dimension on CT and MRI.

INTRODUCTION: Various methods using CT scan have been described to diagnose distal tibiofibular syndesmotic injuries. However, CT scan does not take into account the amount of cartilage within the distal tibiofibular joint and could therefore lead to false positive results. We present the first study correlating the findings of the distal tibiofibular syndesmosis on CT and MRI scans. METHODS: CT and MRI scan of consecutive patients over a period of 18 months, and of a time lapsed less than 12 months between the two imaging modalities, were reviewed. Measurements of the distal tibiofibular syndesmosis were taken according to a previously published study at the level of the distal tibial physeal scar. RESULTS: Twenty-six ankles from 25 patients were included in this study for analysis. Significant difference between CT and MRI assessments in the overall distal tibiofibular dimensions and in the posterior distal tibiofibular distance for those ankles with evidence of osteoarthritis was found. Interclass correlation coefficients suggest that such methodology was reproducible and reliable. CONCLUSION: When the widening found on a CT scan is minor or the diagnosis is equivocal, a contralateral comparative CT or an ipsilateral MRI scan is recommended to prevent misdiagnosis. LEVEL OF EVIDENCE: Level IV.

Targeted expression of HvHMA2 increases the mineral content of the inner endosperm in barley.

Cereals are a major source of dietary energy and protein but are nutritionally poor in micronutrients. Zinc (Zn) biofortification of staple crops has been proposed as a promising strategy to combat the global challenge of human Zn-deficiency. The aim of this study was to improve the Zn content in the edible part of the barley (Hordeum vulgare L.) grain by enhancing Zn translocation into the developing seeds. We demonstrate that the barley plasma membrane P-type ATPase Zn transporter, HvHMA2 is an efficient candidate for mineral biofortification of crops. Following a cisgenic approach to produce transgenic homozygous barley line over-expressing HvHMA2 in the transfer cells of the grain, resulted in a doubling of a wide range of nutrients including Zn, iron (Fe), and magnesium (Mg) in the inner endosperm. This article is protected by copyright. All rights reserved.

Detection of light and vibration modulates bioluminescence intensity in the glowworm, Arachnocampa flava.

Glowworms are larval fungus gnats that emit light from a specialised abdominal light organ. The light attracts small arthropod prey to their web-like silk snares. Larvae glow throughout the night and can modulate their bioluminescence in response to sensory input. To better understand light output regulation and its ecological significance, we examined the larvae's reaction to light exposure, vibration and sound. Exposure to a 5-min light pulse in the laboratory causes larvae to exponentially decrease their light output over 5-10 min until they completely switch off. They gradually return to pre-exposure levels but do not show a rebound. Larvae are most sensitive to ultraviolet light, then blue, green and red. Vibration of the larval snares results in a several-fold increase in bioluminescence over 20-30 s, followed by an exponential return to pre-exposure levels over 15-30 min. Under some conditions, larvae can respond to vibration by initiating bioluminescence when they are not glowing; however, the response is reduced compared to when they are glowing. We propose that inhibitory and excitatory mechanisms combine to modulate bioluminescence intensity by regulating biochemical reactions or gating the access of air to the light organ.

Onset of Cooperative Dynamics in an Equilibrium Glass-Forming Metallic Liquid.

Onset of cooperative dynamics has been observed in many molecular liquids, colloids, and granular materials in the metastable regime on approaching their respective glass or jamming transition points, and is considered to play a significant role in the emergence of the slow dynamics. However, the nature of such dynamical cooperativity remains elusive in multicomponent metallic liquids characterized by complex many-body interactions and high mixing entropy. Herein, we report evidence of onset of cooperative dynamics in an equilibrium glass-forming metallic liquid (LM601: Zr51Cu36Ni4Al9). This is revealed by deviation of the mean effective diffusion coefficient from its high-temperature Arrhenius behavior below TA ≈ 1300 K, i.e., a crossover from uncorrelated dynamics above TA to landscape-influenced correlated dynamics below TA. Furthermore, the onset/crossover temperature TA in such a multicomponent bulk metallic glass-forming liquid is observed at approximately twice of its calorimetric glass transition temperature (Tg ≈ 697 K) and in its stable liquid phase, unlike many molecular liquids.

The South Asian genome.

The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.