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Purpose: Compared with photon cranial radiation therapy (X-CRT), proton cranial radiation therapy (P-CRT) offers potential advantages in limiting radiation-induced sequalae in the treatment of pediatric brain tumors. This study aims to identify cognitive, functional magnetic resonance and positron emission tomography imaging markers and molecular differences between the radiation modalities. Methods and Materials: Juvenile rats received a single faction of 10 Gy (relative biological effectiveness−weighted dose) delivered with 6 MV X-CRT or at the midspread out Bragg peak of a 100 MeV P-CRT beam. At 3, 6, and 12 months post-CRT, executive function was measured using 5-choice serial reaction time task. At ~12 months post-CRT, animals were imaged with 18F-Flurodeoxy-glucose positron emission tomography imaging followed by functional ex vivo magnetic resonance imaging and stained for markers of neuroinflammation. Results: Irradiated animals had cognitive impairment with a higher number of omissions and lower incorrect and premature responses compared with sham (P ≤ .05). The accuracy of the animals’ X-CRT was less than that of sham (P ≤ .001). No significant difference in rates of cognitive change were found between the radiation modalities. At 12 months post-CRT, glucose metabolism was significantly higher than sham in X-CRT (P = .04) but not P-CRT. Using diffusion tensor imaging, P-CRT brains were found to have higher white matter volume and fiber lengths compared with sham (P < .03). Only X-CRT animals had higher apparent diffusion coefficient values compared with sham (P = .04). P-CRT animals had more connectomic changes compared with X-CRT. Correlative analysis identified several imaging features with cognitive performance. Further-more, microgliosis (P < .05), astrogliosis (P < .01), and myelin thinning (P

Many neurodevelopmental disorders and associated learning deficits have been linked to early-life immune activation or ongoing immune dysregulation ( Laskaris et al., 2016 , Leckman, 2014 , Frick et al., 2013 ). Neuroscientists have begun to understand how the maturation of neural circuits allows for the emergence of cognitive and learning behaviors; yet we know very little about how these developing neural circuits are perturbed by certain events, including risk-factors such as early-life immune activation and immune dysregulation. To answer these questions, we examined the impact of early-life immune activation on the emergence of hippocampal-dependent learning in juvenile male and female rats using a well-characterized hippocampal-dependent learning task and we investigated the corresponding, dynamic multicellular interactions in the hippocampus that may contribute to these learning deficits. We found that even low levels of immune activation can result in hippocampal-depedent learning deficits days later, but only when this activation occurs during a sensitive period of development. The initial immune response and associated cytokine production in the hippocampus resolved within 24 h, several days prior to the observed learning deficit, but notably the initial immune response was followed by altered microglial-neuronal communication and synapse remodeling that changed the structure of hippocampal neurons during this period of juvenile brain development. We conclude that immune activation or dysregulation during a sensitive period of hippocampal development can precipitate the emergence of learning deficits via a multi-cellular process that may be initiated by, but not the direct result of the initial cytokine response. Significance Statement Many neurodevelopmental disorders have been linked to early-life immune activation or immune dysregulation; however, very little is known about how dynamic changes in neuroimmune cells mediate the transition from normal brain function to the early stages of cognitive disorders, or how changes in immune signaling are subsequently integrated into developing neuronal networks. The current experiments examined the consequences of immune activation on the cellular and molecular changes that accompany the emergence of learning deficits during a sensitive period of hippocampal development. These findings have the potential to significantly advance our understanding of how early-life immune activation or dysregulation can result in the emergence of cognitive and learning deficits that are the largest source of years lived with disability in humans.

Purpose Cranial radiation therapy (CRT) is a common treatment for pediatric brain tumor patients. However, side effects include significant neurobehavioral dysfunction in survivors. This dysfunction may in part be caused by inflammation, including increased production of tumor necrosis factor alpha (TNFα) and its receptor TNFR1, which can activate the nuclear factor kappa light-chain enhancer of activated B cells (NF-κB). The TNFα blockade abrogates this inflammatory response, although it presents immunologic risks. Thus, modulation of pathway subsets may be preferable. Here, we test whether inhibition of NF-κB activation using an NF-κB essential modulator binding domain (NBD) peptide mitigates CRT-induced neuroinflammation and improves behavioral outcomes. Methods and Materials Male C57BL/6J 28-day old mice were randomized to saline (sham), 5 Gy whole-brain CRT, or CRT + NBD-peptide. Brain tissue was collected after 4 hours or 3 months for Western blot or immunohistochemistry. The cortex, corpus callosum (CC), and dentate gyrus were variably imaged for NF-κB-p65, IκBα, proliferation, apoptosis, necroptosis, TNFα, TNFR1, IBA-1, doublecortin, CD11c, and GFAP. Neurobehavioral changes were assessed by open field and elevated plus maze tests 3 months post-CRT. Results NF-κB expression increased in whole and nuclear fractions 4 hours after CRT and was abrogated by NBD treatment. Cell death increased and proliferation decreased after CRT, including within neuronal progenitors, with some loss mitigated by NBD. Increased levels of TNFα, IBA-1, and GFAP were found in the CC and cortex months after CRT and were limited by NBD. The anti-NF-κB peptide also improved neurobehavioral assessments, yielding improvements in anxiety and exploration. Conclusions Results suggest a role for NF-κB modulation by NBD peptide in the reduction of neuroinflammation and mitigation of behavioral complications after pediatric radiation therapy.

Acoustic impedance is an important property used to interpret acoustic reflection measurements in tests to determine oil film thickness, a critical parameter dictating efficiency and wear rates of lubricated components. A new method to measure acoustic impedance of solid media, based on the well-established spring model, is described. The advantage of this method over existing techniques is that it can be applied to thin, multi-layered materials where individual reflections cannot be distinguished, common in many tribological systems such as bearings, piston rings and piston liners. The method is demonstrated experimentally for a range of materials. Results compare well with values calculated independently from acoustic velocity and density. The method has been applied to a bearing test rig to determine acoustic impedance of a thin-walled bearing. This study demonstrates that the technique is capable of measurements in dynamic systems and where traditional methods of calculating acoustic impedance are not feasible.

Objective To summarise the existing knowledge base that can inform the development of a core competency profile for physiotherapists to support and deliver rehabilitation services to refugees. Method In this scoping review, a comprehensive search of peer-reviewed and grey literature was conducted. The search parameters included studies relevant to the physiotherapy profession and published between 2000 and 2019. MEDLINE, EMBASE, CINAHL, PEDro, and Ovid PsycINFO databases were searched. Grey literature was accessed through website searches, Google Scholar, and direct requests. Findings Three themes were identified in the literature. The first theme encompassed the physical and mental health of refugees. The second theme explored the cultural competence physiotherapists need to work with refugees. This theme included the cultural influences on health and healthcare and communication strategies that could be used to optimise healthcare for refugees. The last theme described refugees and the healthcare system which encompassed the challenges that refugees face in accessing healthcare and navigating the healthcare system. The main physiotherapy competencies detected in the literature were an understanding of refugee health, the administration of culturally competent care and knowledge of healthcare systems as they relate to refugees. Conclusion This comprehensive search identified three themes that can be used to inform the development of a competency profile for physiotherapists working with refugees. These themes are, however, rather vague and non-specific and signal the need for research to further examine the physiotherapy competencies necessary to provide the highest quality of care for this growing population.

Summary Background Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods This was a non-randomised matched-control study in adolescents aged 13–18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov ( NCT00289705 ). Findings Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI −7 to 16], p=0·4263) or after intervention (10% [−6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [−10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p Interpretation Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Funding Swedish Research Council, VINNOVA, Vastra Gotalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.

Background Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are effective for weight loss in adolescents with severe obesity. However, little is known about adverse gastrointestinal symptoms (GIS) following these operations in adolescents. The objective was to examine GIS over 5 years after surgery and differences by surgery type. Methods We prospectively studied 228 adolescents (161 RYGB, 67 VSG) undergoing bariatric surgery. Gastrointestinal symptoms were assessed before surgery, at 6-months, and yearly to 5 years after surgery. Symptom severity was dichotomized for analysis. Analysis of post-surgery symptoms involved linear models adjusting for baseline symptoms, BMI, early post-operative complication, sex, and race. Results Participants at surgery were 17 ± 1.6 years with preoperative BMI 53 ± 9.4 kg/m2. From 6 months to 5 years, gastroesophageal reflux symptoms (GERS), nausea, bloating, and diarrhea increased. Crude prevalence rates of GERS increased from 4% (1% RYGB, 11% VSG) at 6-months post-surgery to 14% (10% RYGB, 26% VSG) at 5-years. In adjusted analyses, the VSG group experienced 4-fold (4.85 95% CI 2.63, 8.91, p Conclusions Adolescents who underwent VSG experienced greater risk of GERS compared to those undergoing RYGB. Adolescents undergoing VSG should be counseled preoperatively about GERS and objectively monitored postoperatively for gastroesophageal reflux when indicated. Clinical trial registration ClinicalTrials.gov , Identifier: NCT00474318 , https://clinicaltrials.gov/ct2/show/NCT00474318?term=Teen-LABS&rank=1 . Type of Study Treatment Study. Level of Evidence Level II.

Highlights • The binding of anti-Vi mAb and polyclonal immune sera correlated with the level of O-acetylation. • C. freundii Vi resists de-O-acetylation and is more viscous than S. Typhi Vi. • Sera from human vaccine recipients contains IgG that recognizes the backbone of Vi. • Simulations show O-acetyls are exposed on the surface of Vi and confer rigidity. • MD gives conformational rationale for effect of O-acetylation on Vi antigenicity and viscosity., In this work, we explore the effects of O-acetylation on the physical and immunological characteristics of the WHO International Standards of Vi polysaccharide (Vi) from both Citrobacter freundii and Salmonella enterica serovar Typhi. We find that, although structurally identical according to NMR, the two Vi standards have differences with respect to susceptibility to de-O-acetylation and viscosity in water. Vi standards from both species have equivalent mass and O-acetylation-dependent binding to a mouse monoclonal antibody and to anti-Vi polyclonal antisera, including the WHO International Standard for human anti-typhoid capsular Vi PS IgG. This study also confirms that human anti-Vi sera binds to completely de-O-acetylated Vi. Molecular dynamics simulations provide conformational rationales for the known effect of de-O-acetylation both on the viscosity and antigenicity of the Vi, demonstrating that de-O-acetylation has a very marked effect on the conformation and dynamic behavior of the Vi, changing the capsular polysaccharide from a rigid helix into a more flexible coil, as well as enhancing the strong interaction of the polysaccharide with sodium ions. Partial de-O-acetylation of Vi revealed hidden epitopes that were recognized by human and sheep anti-Vi PS immune sera. These findings have significance for the manufacture and evaluation of Vi vaccines.

Beta-cell dedifferentiation as shown by cellular colocalization of insulin with glucagon and/or vimentin, and decreased expression of MAFA and/or urocortin3 has been suggested to contribute to metabolic decompensation in type 2 diabetes, and was recently described postimplantation in islet allotransplant patients. Dysglycaemia and diabetes mellitus are often encountered preoperatively in patients undergoing pancreatectomy and islet autotransplantation (PIAT). In this series of case reports, we document variation in islet phenotypic identity in three patients with chronic pancreatitis (CP) without diabetes or significant insulin resistance who subsequently underwent PIAT. Pancreas histology was examined using colocalization of endocrine hormones, mesenchymal and pan-endocrine markers in islets, and the relative expression of MAFA and urocortin3 in insulin-expressing cells as compared to that of nondiabetic and type 2 diabetic donors. We present results of pre- and posttransplant clinical metabolic testing. Varying degrees of islet-cell dedifferentiation are identified in nondiabetic patients with CP at the time of PIAT, and may need further investigation.

Multinational enterprises (MNEs) use the regional aggregation and integration of their foreign direct investments as an important part of their internationalization. Internationalization decisions are integrated at the region level; however, little work has focused on explaining the extent of this regional integration. We develop theoretical arguments and test new hypotheses about MNEs’ general international experience and international geographic scope (i.e., institutional diversity and international dispersion) as predictors of their extent of regional integration. The results from a sample of Japanese MNEs validate these different effects, suggesting these MNE level variables are important for regional influences on their internationalization decisions. The results further our understanding of how MNEs organize their internationalization and strategic geographic foci.

We investigate the relationship between multinational enterprise parent-subsidiary governance (MNEPSG), host country governance quality (HCGQ), and foreign subsidiary survival. We draw upon agency theory, MNEPSG literature, and institutional theory to develop a holistic conceptual model. We test our hypotheses using a large longitudinal sample of 1,711 MNEs and 13,398 subsidiaries in 63 countries from 1990-2013. We find that key MNEPSG mechanisms (Ownership, Expatriates, and Regional Headquarters) positively impact foreign subsidiary survival, whereas HCGQ negatively impacts it; and that increasing Ownership and Expatriates is more effective in high HCGQ contexts. We discuss important implications for research and practice.

A novel sheet metal forming process, by manufacturing parts in a single sheet with varying thickness, has been employed in this work. It combines hot forming and cold-die quenching, also known as HFQ®, and the use of aluminium tailor welded blanks (TWBs) into a hybrid process. A series of hot stamping tests on the AA6082 TWBs were performed to investigate the deformation behaviour and failure features. Two failure modes, i.e. circumferential necking and parallel weld necking have been observed in the formed parts depending on the forming speed and thickness ratio of the TWBs. An advanced forming limit prediction model has been developed and further integrated into finite element simulation via a cloud-based multi-objective platform 1 to investigate the failure/necking features of AA6082 TWBs. The model incorporates the theories of Hosford yield function, the anisotropic nature of plastic deformation in sheet metals and the Marciniak-Kaczynski (M-K) theory. According to the theories, the incremental work per unit volume ratio ( d e ¯ B ∙ σ ¯ B / d e ¯ A ∙ σ ¯ A ) between Zone B (thickness imperfect zone) and Zone A (the remainder of the material) is a key parameter determining the formability, by which the complex failure features have been fundamentally studied. The transition of failure mode in a TWB was attributed to the joint effects of temperature, strain rate and loading path changes. Strain rate could accelerate the development of localised necking in the TWBs when the failure mode was in transition from the circumferential mode to parallel mode.

Changes in food availability during the early marine phase of wild Chinook Salmon (O. tshawytscha) are being investigated as a cause of their recent declines in the Salish Sea. The marine survival of hatchery smolts, in particular, has been poor. This part of the Salish Sea Marine Survival Project examined the diet of young out-migrating Chinook Salmon for four consecutive years in the Cowichan River estuary and in Cowichan Bay, British Columbia, Canada. Local zooplankton communities were monitored during the final year of the study in the Cowichan River estuary, Cowichan Bay, and eastward to the Salish Sea to better understand the bottom-up processes that may be affecting Chinook Salmon survival. Rearing environment affected body size, diet, and distribution in the study area. Clipped smolts (hatchery-reared) were larger than the unclipped smolts (primarily naturally-reared), ate larger prey, spent very little time in the estuary, and disappeared from the bay earlier, likely due to emigration or mortality. Their larger body size may be a disadvantage for hatchery smolts if it necessitates their leaving the estuary prematurely to meet energy needs; the onset of piscivory began at a forklength of approximately 74 mm, which was less than the average forklength of the clipped fish in this study. The primary zooplankton bloom occurred during the last week of April/first week of May 2013, whereas the main release of hatchery-reared Chinook Salmon smolts occurs each year in mid-May—this timing mismatch may reduce their survival. Gut fullness was correlated with zooplankton biomass; however, both the clipped and unclipped smolts were not observed in the bay until the bloom of harmful Noctiluca was finished—20 days after the maximum recorded zooplankton abundance. Jellyfish medusa flourished in nearshore areas, becoming less prevalent towards the deeper waters of the Salish Sea. The sizable presence of Noctiluca and jellyfish in the zooplankton blooms may be repelling young salmon from a critical early marine food source and reducing their survival.

Introduction Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines. Methods A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise. Results 42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items. Conclusion We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery., Highlights • In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, STROCSS 2019 guidelines were updated through a DELPHI consensus exercise. • 42 people participated in the development of STROCSS 2021 guidelines and there was a high level of agreement among the DELPHI group members with the proposed changes to all the items. • Updated STROCSS 2021 guideline is presented.

The same coal at different moisture contents will reach thermal runaway at different times. There is also the possibility that if the coal has a sufficiently high moisture content it cannot reach thermal runaway due to the moisture moderating effects combined with the non-Arrhenius kinetics behaviour at low ambient temperatures. The moisture removal and evaporation processes that occur during coal self-heating are remodeled in this paper based on the definitions of moisture in the coal. These model projections of self-heating behavior of a specific coal in an adiabatic environment have been compared with the experimentally measured time–temperature curves of the coal. The results obtained emphasise the importance of the shape of the self-heating curve in terms of understanding the incubation behaviour of the coal that either leads to thermal runaway or continues to remain in a safe state for practical purposes.

Technology transfer (TT) between academia and industry is an important source of innovation and economic development and is becoming increasingly relevant across a diversity of research fields. Successful TT depends on effective communication between academic and external partners. This is best facilitated by an academic intermediary who can provide meaningful interactions. An academic intermediary can ensure expertise and knowledge are communicated using a common language and that goals and expectations are clear between partners. In the field of remote sensing where complex technologies, datasets and analyses are required to develop user friendly products, intermediaries play a particularly essential role. The rapid expansion of the remote sensing sector over the last decade, including sensor technologies and the volume of freely available data, has created a bottleneck between available data and technology and ready to use products. In an effort to address this bottleneck and establish a long-term innovation platform and thematic TT infrastructure, FERN.Lab, Remote Sensing for Sustainable Use of Resources Helmholtz Innovation Lab was founded at the Geodesy Department of the German Centre for Geosciences (GFZ) in January 2020. FERN.Lab is funded by the Helmholtz Association, the largest scientific organization in Germany. The goal of FERN.Lab is to facilitate TT and deliver remote sensing products to commercial and non-commercial partners by acting as an expert intermediary platform. FERN.Lab will improve the TT activities of GFZ from two distinct approaches. The first is a “pull” approach where tailor-made technologies are developed for and funded by external third parties. The second is a “push” approach where existing departmental technologies with high market potential are promoted. The pull and push of technologies to external partners is accomplished by a set of competencies and services delivered by the core FERN.Lab team. Competencies include business development, scientific development, software development, and public relations which directly address institutional, financial and skills gap that can cause the TT process to fail. By implementing a robust TT framework for remote sensing products, the impact of research has the potential to be much broader and farther reaching. Additionally, these efforts can improve the acceptance of remote sensing outside of academia improving and modernizing methods used in diverse sectors which in turn can benefit not only individual partners but also politics, society, and the environment. As application-oriented innovation platform, with a close interaction with partners and customers, FERN.Lab will be a crucial part of modern TT at GFZ.

The national baseline aeromagnetic survey of Britain allows a uniform assessment of the shallow and deep magnetic properties of the British tectonic terranes. The most significant is that associated with destruction of early Palaeozoic oceanic lithosphere across the Iapetus Suture separating Baltica and Avalonia from the Laurentian terranes. Here a formal 3D inversion of a continuous swathe of the data is considered. The study provides a uniform volumetric whole crust assessment extending for over 1000 km. Normally a 3D inversion of magnetic data is controlled using a variety of constraints however this is not appropriate at the crustal scale due to our increasingly imprecise knowledge of lithology at increasingly greater depths. The main crustal interface encountered occurs at the Curie isotherm depth. We demonstrate the behaviour of introducing different magnetic crustal depths and suggest the crustal ‘magnetic depth’ of our models can be independently constrained using global or regional studies of the deep geotherm. Static magnetic data have no inherent depth resolution. Here an empirical ‘1D depth’ weighting and a more formal ‘3D distance’ weighting are assessed. The inversion procedure is regularised to provide stable models appropriate to the data and their errors. To gain confidence when using such a ‘geologically-unconstrained’ inversion, we compare our 3D inversion results with an existing geologically-constrained 2.5D profile inversion across northern Britain. A surprising agreement in the 3D susceptibility magnitudes is observed. The chosen study area traverses 10 British terranes and images their tectonic fabric by way of non-magnetic zones (i.e. susceptibilities