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High-strength aluminum is a good candidate for use in light-weighting applications, but forming it is difficult due to its low formability. Elevated temperatures are therefore necessary to improve formability, but this reduces lubricant performance. The use of calcium carbonate (CaCO3) as a lubricant additive in warm- and hot-forming of high-strength aluminum is evaluated by strip-drawing tests at room temperature, 225°C and 425°C. Further, the influence of tool surface roughness on the performance of the particles in reducing friction is evaluated. Lastly, the particle-additivated oil is compared to fully formulated, commercially available warm- and hot forming oils. The results show that CaCO3 particles are suitable for improving tribo-systems in warm- and hot-forming of aluminum, and that they can robustify processes where preparation and maintenance of tool surfaces is difficult as the tribo-system is less sensitive to the tool surface. The performance of the particle-additivated oil was similar to the commercial lubricants at room temperature and 225°C, but was worse at 425°C. However, due to the low cost and effort necessary to prepare the particle-additivated oil, it is a promising alternative to existing lubricant additives.

Abstract Neuroimaging with [2,2-dimethyl-3-[(2R,3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(2R,3E)-3-hydroxyiminobutan-2-yl]azanide;oxo(99Tc)technetium-99(3+) ([99mTc]HMPAO) single photon emission computed tomography (SPECT) is used in Alzheimer’s disease (AD) to evaluate regional cerebral blood flow (rCBF). Hypoperfusion in select temporoparietal regions has been observed in human AD. However, it is unknown whether AD hypoperfusion signatures are also present in the 5XFAD mouse model. The current study was undertaken to compare baseline brain perfusion between 5XFAD and wild-type (WT) mice using [99mTc]HMPAO SPECT and determine whether hypoperfusion is recapitulated in 5XFAD mice. 5XFAD and WT mice underwent a 45 min SPECT scan, 20 min after [99mTc]HMPAO administration. Whole brain and regional standardized uptake values (SUV) and regional relative standardized uptake values (SUVR) with whole brain reference were compared between groups. Brain perfusion was similar between WT and 5XFAD brains. Whole brain [99mTc]HMPAO retention revealed no significant difference in SUV (5XFAD, 0.372 ± 0.762; WT, 0.640 ± 0.955; p = 0.536). Similarly, regional analysis revealed no significant differences in [99mTc]HMPAO metrics between groups (SUV: 0.357 ≤ p ≤ 0.640; SUVR: 0.595 ≤ p ≤ 0.936). These results suggest apparent discrepancies in rCBF between human AD and the 5XFAD model. Establishing baseline perfusion patterns in 5XFAD mice is essential to inform pre-clinical diagnostic and therapeutic drug discovery programs.

Hops are among the most costly and environmentally impactful raw materials used in brewing, yet they play a crucial role in the aroma of beer. However, predicting beer aroma based on hop variety or hopping method remains arduous. This is partly because hop oils are unique for each hop variety, and they may be biotransformed by yeast enzymes during fermentation. Even slight molecular structure modifications can dramatically affect the organoleptic properties of beer. Through combined chemical and sensory analysis of dry-hopped beers prepared with different hop varieties (Azacca, Idaho-7, and Sultana), this work aimed to profile the aromas and the overall biotransformation processes taking place during fermentation. A total of 51 volatile organic compounds (VOCs) were semi-quantified and monitored: 19 esters, 13 sesquiterpenes, 7 ketones, 7 alcohols, 4 monoterpenes, and 1 volatile acid. There were significant similarities in the measured analytes and perceived aromas of these beers, but one hop variety (Sultana) delivered an increased quantity of unique aromas and an increased concentration of volatiles in the headspace for the same quantity of hop pellets added. This work provides practical information to brewers who utilize hops in beer production.

This paper introduces a new formability test based on double-action radial extrusion to characterize material formability in the three-dimensional to plane-stress material flow transitions that are found in bulk metal-formed parts. The presentation draws from a multidirectional tool, which was designed to convert the vertical press stroke into horizontal movement of the compression punches towards each other, aspects of experimental strain determination, fractography, and finite element analysis. Results show that three-dimensional to plane-stress material flow transitions at the radially extruded flanges lead to different modes of fracture (by tension and by shear) that may or may not be preceded by necking, such as in sheet metal forming. The new formability test also reveals adequate characteristics to characterize the failure limits of very ductile wrought and additively manufactured metallic materials, which cannot be easily determined by conventional upset compression tests, and to facilitate the identification of the instant of cracking and of the corresponding fracture strains by combination of the force vs. time evolutions with the in-plane strains obtained from digital image correlation.

Over 90% of preterm neonates are, often empirically, exposed to antibiotics as a potentially life-saving measure against sepsis. Long-term outcome in association with antibiotic exposure (NABE) has insufficiently been studied after preterm birth. We investigated the association of NABE-duration with early-childhood developmental and health outcomes in preterm-born children and additionally assessed the impact of GA on outcomes. Preterm children (GA < 30 weeks) participating in a multicenter cohort study were approached for follow-up. General expert-reviewed health questionnaires on respiratory, atopic and gastrointestinal symptoms were sent to parents of children > 24 months’ corrected age (CA). Growth and developmental assessments (Bayley Scales of Infant and Toddler Development (BSID) III) were part of standard care assessment at 24 months’ CA. Uni- and multivariate regressions were performed with NABE (per 5 days) and GA (per week) as independent variables. Odds ratios (OR) for health outcomes were adjusted (aOR) for confounders, where appropriate. Of 1079 infants whose parents were approached, 347 (32%) responded at a mean age of 4.6 years (SD 0.9). In children with NABE (97%), NABE duration decreased by 1.6 days (p < 0.001) per week of gestation. Below-average gross-motor development (BSID-III gross-motor score < 8) was associated with duration of NABE (aOR = 1.28; p = 0.04). The aOR for constipation was 0.81 (p = 0.04) per gestational week. Growth was inversely correlated with GA. Respiratory and atopic symptoms were not associated with NABE, nor GA. We observed that prolonged NABE after preterm birth was associated with below-average gross-motor development at 24 months’ CA, while a low GA was associated with lower weight and stature Z-scores and higher odds for constipation.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Abstract Introduction A new generation of large‐scale studies is using neuroimaging to investigate adolescent brain development across health and disease. However, imaging artifacts such as head motion remain a challenge and may be exacerbated in pediatric clinical samples. In this study, we assessed the scan–rescan reliability of multimodal MRI in a sample of youth enriched for risk of mental illness. Methods We obtained repeated MRI scans, an average of 2.7 ± 1.4 weeks apart, from 50 youth (mean age 14.7 years, SD = 4.4). Half of the sample (52%) had a diagnosis of an anxiety disorder; 22% had attention‐deficit/hyperactivity disorder (ADHD). We quantified reliability with the test–retest intraclass correlation coefficient (ICC). Results Gray matter measurements were highly reliable with mean ICCs as follows: cortical volume (ICC = 0.90), cortical surface area (ICC = 0.89), cortical thickness (ICC = 0.82), and local gyrification index (ICC = 0.85). White matter volume reliability was excellent (ICC = 0.98). Diffusion tensor imaging (DTI) components were also highly reliable. Fractional anisotropy was most consistently measured (ICC = 0.88), followed by radial diffusivity (ICC = 0.84), mean diffusivity (ICC = 0.81), and axial diffusivity (ICC = 0.78). We also observed regional variability in reconstruction, with some brain structures less reliably reconstructed than others. Conclusions Overall, we showed that developmental MRI measures are highly reliable, even in youth at risk for mental illness and those already affected by anxiety and neurodevelopmental disorders. Yet, caution is warranted if patterns of results cluster within regions of lower reliability.

Abstract Background Oil emulsions are commonly used as vaccine delivery platforms to facilitate slow release of antigen by forming a depot at the injection site. Antigen is trapped in the aqueous phase and as the emulsion degrades in vivo the antigen is passively released. DepoVax™ is a unique oil based delivery system that directly suspends the vaccine components in the oil diluent that forces immune cells to actively take up components from the formulation in the absence of passive release. The aim of this study was to use magnetic resonance imaging (MRI) with additional biological markers to evaluate and understand differences in clearance between several different delivery systems used in peptide-based cancer vaccines. Methods C57BL/6 mice were implanted with a cervical cancer model and vaccinated 5 days post-implant with either DepoVax (DPX), a water-in-oil emulsion (w/o), a squalene oil-in-water emulsion (squal o/w) or a saponin/liposome emulsion (sap/lip) containing iron oxide-labeled targeted antigen. MRI was then used to monitor antigen clearance, the site of injection, tumour and inguinal lymph node volumes and other gross anatomical changes. HLA-A2 transgenic mice were also vaccinated to evaluate immune responses of human directed peptides. Results We demonstrated differences in antigen clearance between DPX and w/o both in regard to how quickly the antigen was cleared and the pattern in which it was cleared. We also found differences in lymph node responses between DPX and both squal o/w and sap/lip. Conclusions These studies underline the unique mechanism of action of this clinical stage vaccine delivery system.

The symptoms of addictive eating are often debated, with some overlap in symptoms with substance addictions or other disorders such as binge eating disorder. This study explored the levels of agreement with symptoms of addictive eating among different health professions, the conditions they provide advice for, and the population group/s they work with. An online cross-sectional survey was conducted in February–April 2020 including 142 health professionals (87% female, 65% residing in Australia, 28% each working in private practice/hospital settings). Of these, 47% were dietitians, 20% psychologists/psychotherapists/counsellors, 16% other health practitioners (e.g., social workers), 13% health researchers, and 5% medical professionals. Agreement with 11 statements relating to addictive eating symptoms was assessed on a scale of 1/strongly disagree to 5/strongly agree (e.g., certain foods produce physiological effects in the brain rewards system). Differences in agreement by health profession were assessed by one-way analysis of variance. There were significant differences in agreement with individual statements between health professions. Psychologists, psychotherapists, and counsellors reported lower agreement to statements relating to physiological effects in the reward system, withdrawal symptoms, and over-eating to alleviate stress/anxiety, than other professions (p < 0.05). Those providing advice for disordered eating only reported lower agreement across statements compared with those providing advice for overweight/obesity or both (p < 0.001). There were minimal differences based on the population group/s that health professionals work with. There is some agreement among health professionals regarding addictive eating symptoms, however, this differs by profession and the conditions they treat. This study provides a novel perspective on health professionals’ views on addictive eating symptoms, and there is a need for more research to explore the concepts further.

Despite increasing research on the concept of addictive eating, there is currently no published evidence on the views of health professionals who potentially consult with patients presenting with addictive eating behaviours, or of students training to become health professionals. This study aimed to explore the views and understanding of addictive eating behaviours among health professionals and health professionals in training and to identify potential gaps in professional development training. An international online cross-sectional survey was conducted in February–April 2020. The survey (70 questions, 6 key areas) assessed participants’ opinions and clinical experience of addictive eating; opinions on control, responsibility, and stigma relating to addictive eating; and knowledge of addictive eating and opinions on professional development training. In total, 142 health professionals and 33 health professionals in training completed the survey (mean age 38.1 ± 12.5 years, 65% from Australia/16% from the U.K.) Of the health professionals, 47% were dietitians and 16% were psychologists. Most participants (n = 126, 72%) reported that they have been asked by individuals about addictive eating. Half of the participants reported that they consider the term food addiction to be stigmatising for individuals (n = 88). Sixty percent (n = 105) reported that they were interested/very interested in receiving addictive eating training, with the top two preferred formats being online and self-paced, and face-to-face. These results demonstrate that addictive eating is supported by health professionals as they consult with patients presenting with this behaviour, which supports the views of the general community and demonstrates a need for health professional training.

A new joining by forming process that combines lancing and shearing with sheet-bulk compression is utilized to assemble thin-walled crash boxes utilized as energy absorbers. Process design and fabrication of the new crash boxes are analyzed by finite elements and experimentation. Axial crush tests were performed to compare the overall crashworthiness performance of the new crash boxes against that of conventional crash boxes assembled by resistance spot-welding. Results show that the joining process is a good alternative to resistance spot-welding because the new crash boxes can absorb the same crushing energy, and because the new process helps to overcome typical manufacturing problems of welding.

Western Alaska’s Yukon-Kuskokwim Delta (YKD) spans nearly 67,200 km2 and is among the largest and most productive coastal wetland ecosystems in the pan-Arctic. Permafrost currently forms extensive elevated plateaus on abandoned floodplain deposits of the outer delta, but is vulnerable to disturbance from rising air temperatures, inland storm surges, and salt-kill of vegetation. As pan-Arctic air and ground temperatures rise, accurate baseline maps of permafrost extent are critical for a variety of applications including long-term monitoring, understanding the scale and pace of permafrost degradation processes, and estimating resultant greenhouse gas dynamics. This study assesses novel, high-resolution techniques to map permafrost distribution using LiDAR and IKONOS imagery, in tandem with field-based parameterization and validation. With LiDAR, use of a simple elevation threshold provided a permafrost map with 94.9% overall accuracy; this approach was possible due to the extremely flat coastal plain of the YKD. The addition of high spatial-resolution IKONOS satellite data yielded similar results, but did not increase model performance. The methods and the results of this study enhance high-resolution permafrost mapping efforts in tundra regions in general and deltaic landscapes in particular, and provide a baseline for remote monitoring of permafrost distribution on the YKD.

Repetitive mild traumatic brain injury in American football players has garnered increasing public attention following reports of chronic traumatic encephalopathy, a progressive tauopathy. While the mechanisms underlying repetitive mild traumatic brain injury-induced neurodegeneration are unknown and antemortem diagnostic tests are not available, neuropathology studies suggest a pathogenic role for microvascular injury, specifically blood-brain barrier dysfunction. Thus, our main objective was to demonstrate the effectiveness of a modified dynamic contrast-enhanced MRI approach we have developed to detect impairments in brain microvascular function. To this end, we scanned 42 adult male amateur American football players and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. MRI scans were also performed in 51 patients with brain pathologies involving the blood-brain barrier, namely malignant brain tumours, ischaemic stroke and haemorrhagic traumatic contusion. Based on data from prolonged scans, we generated maps that visualized the permeability value for each brain voxel. Our permeability maps revealed an increase in slow blood-to-brain transport in a subset of amateur American football players, but not in sex- and age-matched controls. The increase in permeability was region specific (white matter, midbrain peduncles, red nucleus, temporal cortex) and correlated with changes in white matter, which were confirmed by diffusion tensor imaging. Additionally, increased permeability persisted for months, as seen in players who were scanned both on- and off-season. Examination of patients with brain pathologies revealed that slow tracer accumulation characterizes areas surrounding the core of injury, which frequently shows fast blood-to-brain transport. Next, we verified our method in two rodent models: rats and mice subjected to repeated mild closed-head impact injury, and rats with vascular injury inflicted by photothrombosis. In both models, slow blood-to-brain transport was observed, which correlated with neuropathological changes. Lastly, computational simulations and direct imaging of the transport of Evans blue-albumin complex in brains of rats subjected to recurrent seizures or focal cerebrovascular injury suggest that increased cellular transport underlies the observed slow blood-to-brain transport. Taken together, our findings suggest dynamic contrast-enhanced-MRI can be used to diagnose specific microvascular pathology after traumatic brain injury and other brain pathologies.

Background: Cortical folding is essential for healthy brain development. Previous studies have found regional reductions in cortical folding in adult patients with psychotic illness. It is unknown whether these neuroanatomical markers are present in youth with subclinical psychotic symptoms. Methods: We collected MRIs and examined the local gyrification index in a sample of 110 youth (mean age [+ or -] standard deviation 14.0 [+ or -] 3.7 yr; range 9-25 yr) with a family history of severe mental illness: 48 with psychotic symptoms and 62 without. Images were processed using the Human Connectome Pipeline and FreeSurfer. We tested for group differences in local gyrification index using mixed-effects generalized linear models controlling for age, sex and familial clustering. Sensitivity analysis further controlled for intracranial volume, IQ, and stimulant and cannabis use. Results: Youth with psychotic symptoms displayed an overall trend toward lower cortical folding across all brain regions. After adjusting for multiple comparisons and confounders, regional reductions were localized to the frontal and occipital lobes. Specifically, the medial (B = -0.42, [p.sub.FDR] = 0.04) and lateral (B = -0.39, [p.sub.FDR] = 0.04) orbitofrontal cortices as well as the cuneus (B = -0.47, [p.sub.FDR] = 0.03) and the pericalcarine (B = -0.45, [p.sub.FDR] = 0.03) and lingual (B = -0.38, [p.sub.FDR] = 0.04) gyri. Limitations: Inference about developmental trajectories was limited by the cross-sectional data. Conclusion: Psychotic symptoms in youth are associated with cortical folding deficits, even in the absence of psychotic illness. The current study helps clarify the neurodevelopmental basis of psychosis at an early stage, before medication, drug use and other confounds have had a persistent effect on the brain., Introduction Psychosis is marked by hallucinations, delusions and disturbances of affect and behaviour. It manifests in major depressive disorder, bipolar disorder and most notably, schizophrenia. Although psychotic disorders are a [...]