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Abstract Background Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. Methods The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. Discussion This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. Trial registration EudraCT number: 2020–003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

Abstract Does the Halbach magnetization rotation rule that is used for designing circular magnet arrays for achieving the best homogeneity hold also for an elliptical or other non-circular cross-section? In this article, it is shown that a new numerically optimized magnetization rotation rule can provide more than three orders of magnitude improvement in field homogeneity as compared to a Halbach configuration for elliptical systems. Further it is demonstrated that such optimized magnetization rules can be easily derived in an intuitive way by studying virtual permanent magnets of a similar cross-section as the desired magnet array. This is coined as a permanent magnet hypothesis. Finally, it is shown that the applicability of this technique is not limited to circular or elliptical systems but can be applied to any arbitrarily shaped cross-section.

Abstract Objectives The Anal Cancer High-grade squamous intraepithelial lesions (HSIL) Outcomes Research (ANCHOR) Health-Related Symptom Index (A-HRSI) is a 25-item measure that assesses physical symptoms and impacts, and psychological symptoms. To promote generalizability and equity in the capture of these concepts in Spanish-speaking participants, we linguistically validated a Spanish version of A-HRSI. Methods Following independent forward translation and reconciliation of A-HRSI from English to Spanish, two rounds of cognitive interviews were completed with ANCHOR participants who had been diagnosed with anal HSIL in the prior nine months and preferred delivery of their healthcare in Spanish. Interviews were coded to highlight any items and concepts that were reported as being difficult for any reason by ≥ 3 participants, with such items revised during a research team panel discussion and tested in a second round of interviews if applicable. Results Seventeen participants representing 8 nationalities were enrolled (Round 1 n=10, Round 2 n=7); 7 participants reported not completing high school (41.2%). No difficulties were reported with respect to the theoretical concepts measured by A-HRSI. We made modifications to the Spanish translation of eight items and two response option terms in cases where participants had difficulty understanding a term, experienced problems in discriminating between terms, or preferred the use of an alternative term to represent the concept(s). Conclusion The Spanish version of A-HRSI is a linguistically valid tool that can be used to assess physical symptoms, impacts, and psychological symptoms related to anal HSIL. Plain English Summary Language is a tremendous barrier to enrolling patients to clinical trials. The anal cancer high-grade squamous intraepithelial lesions (HSIL) outcomes research [ANCHOR] trial is a randomized clinical trial that recently established that the treatment of anal HSIL, versus active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV (PLWH). The ANCHOR Health-Related Symptom Index (A-HRSI) is a 25-item patient-reported outcomes measure that was developed to assess physical symptoms, physical impacts, and psychological symptoms related to anal HSIL. As approximately 10% of ANCHOR participants preferred the delivery of their healthcare in Spanish, the purpose of the present study was to linguistically validate a Spanish version of A-HRSI. Based on feedback from interviews with 17 participants from the ANCHOR trial who had been diagnosed with anal HSIL in the prior nine months and preferred delivery of their healthcare in Spanish, we made modifications to the Spanish translation of eight items and two response option terms in cases where participants had difficulty understanding a term, experienced problems in discriminating between terms, or preferred the use of an alternative term to represent the concept(s). The Spanish version of A-HRSI is a linguistically valid tool that can be used to assess physical symptoms, impacts, and psychological symptoms related to anal HSIL as part of clinical trials or routine care.

BackgroundAccurate self-reported symptomatic toxicity documentation via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is essential throughout cancer treatment to ensure safety and understand therapeutic efficacy. However, the capture of accurate toxicities from patients undergoing radiation therapy is challenging because this is generally provided only at the time of scheduled visits. ObjectiveThis study seeks to establish the usability and feasibility of a mobile PRO-CTCAE Administration System (mPROS) to capture toxicities related to radiation therapy. MethodsEnglish-speaking adult patients who were undergoing radiation therapy for cancer were enrolled and given a brief demonstration of the Say All Your Symptoms (SAYS) and Symptom Tracking Entry Program (STEP) interfaces of the mPROS app, followed by a patient-use phase where patient actions were observed as they navigated mPROS to enter toxicities. Patient feedback was captured via a semistructured interview and brief questionnaire. ResultsWe enrolled 25 patients (age: mean 60.7 years; females: n=13, 52%; White patients: n=13; 52%; non-Hispanic patients: n=19, 76%; college graduates: n=17, 68%). Patients almost equally preferred the SAYS (n=14, 56%) or STEP (n=11, 44%) interfaces, with 21 patients (84%) agreeing that they would use mPROS to report their symptoms to their health care team and 19 patients (76%) agreeing that they would recommend mPROS to others. ConclusionsThe mPROS app is usable and feasible for facilitating the patient reporting of radiation therapy–related symptomatic toxicities. A revised version of mPROS that incorporates patient input and includes electronic health record integration is being developed and validated as part of a multicenter trial.

Abstract The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and efficacy of drug formulations. This work aims to develop a novel approach for the protection of space pharmaceutical drug molecules from the radiation-induced damage to help extend or at least preserve their structural integrity and potency. To achieve this, free radical scavenging antioxidant, Trolox was conjugated on the surface of poly-lactic-co-glycolic acid (PLGA) nanoparticles for the protection of a candidate drug, melatonin that is used as a sleep aid medication in International Space Station (ISS). Melatonin-PLGA-PLL-Trolox nanoparticle as named as PolyRad was synthesized employing single oil in water (o/w) emulsion solvent evaporation method. PolyRad is spherical in shape and has an average diameter of ~600 nm with a low polydispersity index of 0.2. PolyRad and free melatonin (control) were irradiated by UV light after being exposed to a strong oxidant, hydrogen peroxide (H2O2). Bare melatonin lost ~80% of the active structure of the drug following irradiation with UV light or treatment with H2O2. In contrast, PolyRad protected >80% of the active structure of melatonin. The ability of PolyRad to protect melatonin structure was also carried out using 0, 1, 5 and 10 Gy gamma radiation. Gamma irradiation showed >98% active structures of melatonin encapsulated in PolyRads. Drug release and effectiveness of melatonin using PolyRad were evaluated on human umbilical vein endothelial cells (HUVEC) in vitro. Non-irradiated PolyRad demonstrated maximum drug release of ~70% after 72 h, while UV-irradiated and H2O2-treated PolyRad showed a maximum drug release of ~85%. Cytotoxicity of melatonin was carried out using both live/dead and MTT assays. Melatonin, non-radiated PolyRad and irradiated PolyRad inhibited the viability of HUVEC in a dose-dependent manner. Cell viability of melatonin, PolyRad alone without melatonin (PolyRad carrier control), non-radiated PolyRad, and irradiated PolyRad were ~98, 87, 75 and 70%, respectively at a concentration $$ \sim $$ ~ 0.01 $${mg}/{ml}$$ mg/ml ($$10\mu g/{ml}$$ 10μg/ml ). Taken together, PolyRad nanoparticle provides an attractive formulation platform for preventing damage to pharmaceutical drugs in potential space mission applications.

Abstract Extracellular vesicles (EVs) are important mediators of intercellular communication. However, EV biogenesis remains poorly understood. We previously defined a role for Arrdc4 (Arrestin domain containing protein 4), an adaptor for Nedd4 family ubiquitin ligases, in the biogenesis of EVs. Here we report that ubiquitination of Arrdc4 is critical for its role in EV secretion. We identified five potential ubiquitinated lysine residues in Arrdc4 using mass spectrometry. By analysing Arrdc4 lysine mutants we discovered that lysine 270 (K270) is critical for Arrdc4 function in EV biogenesis. Arrdc4K270R mutation caused a decrease in the number of EVs released by cells compared to Arrdc4WT, and a reduction in trafficking of divalent metal transporter (DMT1) into EVs. Furthermore, we also observed a decrease in DMT1 activity and an increase in its intracellular degradation in the presence of Arrdc4K270R. K270 was found to be ubiquitinated with K‐29 polyubiquitin chains by the ubiquitin ligase Nedd4‐2. Thus, our results uncover a novel role of K‐29 polyubiquitin chains in Arrdc4‐mediated EV biogenesis and protein trafficking.

More research on sport for development and peace (SDP) organizations is needed to better understand their actual contributions to the United Nations (UN) Sustainable Development Goals (SDGs). Yet, the unstable, restricted, or even risky contexts in which many non-governmental organizations (NGOs) and SDP agencies sometimes operate often leave researchers to face important challenges to develop effective or feasible methods to work with such organizations. This study aimed to address the ontological and epistemological questions about what should be known about a given context in an organization before setting off on fieldwork. We propose a methodology, based on an actantial model (AM), as a method to analyze the nature and context of a project, to assess the actors involved in the project, and to establish if the global cost (i.e., material, temporal, financial, and physical) for conducting fieldwork is realistic and feasible of all the parties involved in the potential project. To illustrate this process, we analyzed the nature and context of an SDP project in Madagascar as the first step for potential collaborative research. As researchers, we do not want to invest time and energy to build up a fully developed field research project with an NGO in a context where it would not be realistic or feasible to conduct such research. Actually in this context, developing a research protocol without an implementation strategy might not only be detrimental to the researchers, but also to the NGO itself, where resources are often limited. Accordingly, the results from this preliminary field research demonstrate that an AM is a relevant analytical tool for obtaining insights about the context, the actors, and their relationships within an NGO. In conclusion, this model might be a useful instrument for conducting an initial analysis for the preliminary identification of the necessary conditions for the construction of a sustainable empirical research partnership with a given SDP project.

Purpose: The optimal treatment strategy for uveal melanoma (UM) relies on many factors, the most important being tumor size and location. Building on recent developments in high-resolution 3D ocular magnetic resonance imaging (MRI), we developed an automatic image-processing framework to create patient-specific eye models and to subsequently determine the full 3D tumor shape and size automatically. Methods and Materials: From 15 patients with UM, 3D inversion-recovery gradient-echo (T1-weighted) and 3D fat-suppressed spin-echo (T2-weighted) images were acquired with a 7T MRI scanner. First, the sclera and cornea were segmented from the T2-weighted image by mesh-fitting. The T1- and T2-weighted images were then coregistered. From the registered T1-weighted image, the lens, vitreous body, retinal detachment, and tumor were segmented. Fuzzy C-means clustering was used to differentiate the tumor from retinal detachments. The tumor model was verified and (if needed) edited by an ophthalmic MRI specialist. Subsequently, the prominence and largest basal diameter of the tumor were measured automatically based on the verified contours. These results were compared with manual assessments on the original images and with ultrasound measurements to show the errors in manual analysis. Results: The framework successfully created an eye model fully automatically in 12 cases. In these cases, a Dice similarity coefficient (mean surface distance) of 97.7%±0.84% (0.17±0.11 mm) was achieved for the sclera, 96.8%±1.05% (0.20±0.06 mm) for the vitreous body, 91.6%±4.83% (0.15±0.06 mm) for the lens, and 86.0%±7.4% (0.35±0.27 mm) for the tumor. The manual assessments deviated, on average, 0.39±0.31 mm in prominence and 1.7±1.22 mm in basal diameter from the automatic measurements. Conclusions: The described framework combined information from T1- and T2-weighted images to accurately determine tumor boundaries in 3D. The proposed process may have a direct effect on clinical workflow, as it enables an accurate 3D assessment of tumor dimensions, which directly influences therapy selection.

Aims: Aceruloplasminemia is an ultra-rare neurodegenerative disorder associated with massive brain iron deposits, of which the molecular composition is unknown. We aimed to quantitatively determine the molecular iron forms in the aceruloplasminemia brain, and to illustrate their influence on iron-sensitive MRI metrics. Methods: The inhomogeneous transverse relaxation rate (R2*) and magnetic susceptibility obtained from 7 T MRI were combined with Electron Paramagnetic Resonance (EPR) and Superconducting Quantum Interference Device (SQUID) magnetometry. The basal ganglia, thalamus, red nucleus, dentate nucleus, superior- and middle temporal gyrus and white matter of a post-mortem aceruloplasminemia brain were studied. MRI, EPR and SQUID results that had been previously obtained from the temporal cortex of healthy controls were included for comparison. Results: The brain iron pool in aceruloplasminemia detected in this study consisted of EPR-detectable Fe3+ ions, magnetic Fe3+ embedded in the core of ferritin and hemosiderin (ferrihydrite-iron), and magnetic Fe3+ embedded in oxidized magnetite/maghemite minerals (maghemite-iron). Ferrihydrite-iron represented above 90% of all iron and was the main driver of iron-sensitive MRI contrast. Although deep gray matter structures were three times richer in ferrihydrite-iron than the temporal cortex, ferrihydrite-iron was already six times more abundant in the temporal cortex of the patient with aceruloplasminemia compared to the healthy situation (162 µg/g vs. 27 µg/g), on average. The concentrations of Fe3+ ions and maghemite-iron in the temporal cortex in aceruloplasminemia were within the range of those in the control subjects. Conclusions: Iron-related neurodegeneration in aceruloplasminemia is primarily associated with an increase in ferrihydrite-iron, with ferrihydrite-iron being the major determinant of iron-sensitive MRI contrast.

Enhanced activity of the glutamatergic system has been linked to migraine pathophysiology. The present study aimed to assess the involvement of the glutamatergic system in the onset of attacks. We provoked attacks by infusion of glyceryl trinitrate (GTN; 0.5 µg/kg/min over 20 min) in 24 female episodic migraineurs without aura and 13 female age-matched healthy controls. Over the course of a single day participants were scanned three times at fixed time slots (baseline before GTN infusion, 90 min and 270 min after start of GTN infusion). Single-volume proton magnetic resonance spectra (1H–MRS) were acquired at 7 Tesla from a volume of interest (VOI, 2x2x3 cm) in the visual cortex. We assessed the concentrations of glutamate, its major precursor glutamine, and its product gamma-aminobutyric acid (GABA) over the course of a provoked attack. The preictal state was defined as the period after GTN infusion until the migraine-like headache started, independent of possible experienced premonitory symptoms, and the ictal state was defined as the period with provoked migraine-like headache. Data were analyzed using a linear mixed-effect model for repeated measures. Glutamate and glutamine levels did not change from interictal to the preictal and ictal state. GABA levels increased from interictal towards the preictal state for migraine patients compared with healthy controls. We conclude that high resolution 7T MRS is able to show changes in the glutamatergic system towards a triggered migraine attack, by revealing an increased GABA concentration associated with the onset of a migraine attack.

Background: Effects of short-term interventions on large artery stiffness assessed by pulse wave velocity (PWV) have mainly been explained by concomitant changes in blood pressure (BP). However, lower body negative pressure (LBNP), which increases sympathetic activity (SA) has a specific effect on PWV in healthy volunteers [1]. Methods: We examined effects of lower limb venous occlusion (LVO), a similar intervention to LBNP that reduces BP but increases SA and device guided breathing (DBG), which reduces both BP and SA, on PWV in patients with essential hypertension (n = 70 after LVO, n = 45 after DGB and LVO in random order). The short acting calcium channel antagonist nifedipine was used as a control for changes in BP. Results: LVO produced a small but significant reduction in mean arterial pressure of 1.8 (95% confidence-intervals, 0.3–3.4) mmHg. Despite this, aortic and carotid-femoral PWV increased during LVO by 0.8 (0.2–1.4) m/s and 0.7 (0.3–1.05) m/s respectively. When comparing effects of DGB with nifedipine (n = 19), nifedipine produced a greater reduction in mean arterial pressure compared to DGB (reduction of 13.4 (10.2–17.7) mmHg and 7.7 (6.4–9.0) mmHg respectively, p = 0.009 between the two) but the decrease in PWV was less than that observed with DGB (0.7 (0.1–1.5) m/s and 1.3 (0.8–1.8) m/s respectively, p = 0.022 between the two). Conclusion: Arterial stiffness can be modulated independently of BP in patients with hypertension. The mechanism could involve alterations in SA influencing the tone of smooth muscle in the aortic wall.

BAX and BAK are pro-apoptotic proteins whose activity is essential for the action of many anti-cancer drugs and to suppress tumorigenesis. Here, the authors perform a genome-wide CRISPR/Cas9 screen and identify VDAC2 as a promoter of BAX-mediated apoptosis that is important for an efficient chemotherapeutic response and to suppress tumor formation.

Background: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. Objectives: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. Design: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. Setting: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. Participants: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. Interventions: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. Main outcome measures: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. Results: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n = 3035; 6-month analysis, n = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand–foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years (p

Abstract We present a quantitative study of different molecular iron forms found in the temporal cortex of Alzheimer (AD) patients. Applying the methodology we developed in our previous work, we quantify the concentrations of non-heme Fe(III) by Electron Paramagnetic Resonance (EPR), magnetite/maghemite and ferrihydrite by SQUID magnetometry, together with the MRI transverse relaxation rate $$({{\rm{R}}}_{2}^{\ast })$$ (R2⁎) , to obtain a systematic view of molecular iron in the temporal cortex. Significantly higher values of $${{\rm{R}}}_{2}^{\ast }$$ R2⁎ , a larger concentration of ferrihydrite, and a larger magnetic moment of magnetite/maghemite particles are found in the brain of AD patients. Moreover, we found correlations between the concentration of the iron detected by EPR, the concentration of the ferrihydrite mineral and the average iron loading of ferritin. We discuss these findings in the framework of iron dis-homeostasis, which has been proposed to occur in the brain of AD patients.

En relación con los liceos de la Región de la Araucanía con alta composición indígena, este artículo explora los modos en que los significados y las conductas acerca de la blanquitud son reproducidos en y a través de la educación. Nos focalizamos en las intersecciones entre criterios socioeconómicos, geográficos y raciales para entender cómo los privilegios de la blanquitud son naturalizados, en el marco del suministro de educación existente en la región y entre los alumnos indígenas mapuches. Aunque se reconocen las desigualdades socio-económicas producidas desde la reforma educativa en 1980, nosotros resaltamos la naturaleza omnipresente y no distintiva de la blanquitud en el sistema educativo, en relación con la segregación socio-espacial de alumnos Mapuches, los textos escolares, las actitudes de los docentes, y el auto-posicionamiento de los jóvenes respecto al logro individual y la normalización del racismo en sus escuelas. Estos aspectos de racismo institucional se combinan de una manera tal que marginalizan y le restan poder a las poblaciones Mapuches en un conjunto de liceos rurales en la región de la Araucanía

Abstract Developments in metamaterials and related structures such as metasurfaces have opened up new possibilities in designing materials and devices with unique properties. Here we report a new hybrid metasurface structure, comprising a two-dimensional metamaterial surface and a very high permittivity dielectric substrate, that has been designed to enhance the local performance of an ultra-high field MRI scanner. This new flexible and compact resonant structure is the first metasurface which can be integrated with multi-element close-fitting receive coil arrays that are used for all clinical MRI scans. We demonstrate the utility of the metasurface acquiring in-vivo human brain images and proton MR spectra with enhanced local sensitivity on a commercial 7 Tesla system.

Background Effects of short‐term interventions on large‐artery stiffness assessed by pulse wave velocity (PWV) have mainly been explained by concomitant changes in blood pressure (BP). However, lower body negative pressure, which increases sympathetic activity and has other hemodynamic effects, has a specific effect on PWV in healthy volunteers. Methods and Results We examined effects of lower‐limb venous occlusion (LVO), a similar intervention to lower‐body negative pressure that reduces BP but increases sympathetic activity and device‐guided breathing (DGB), which reduces both BP and sympathetic activity, on PWV in patients with essential hypertension (n=70 after LVO, n=45 after DGB and LVO in random order). The short‐acting calcium channel antagonist nifedipine was used as a control for changes in BP. LVO produced a small but significant reduction in mean arterial pressure of 1.8 (95% CI 0.3–3.4) mm Hg. Despite this, aortic and carotid‐femoral PWV increased during LVO by 0.8 (0.2–1.4) m/s and 0.7 (0.3–1.05) m/s, respectively. DGB reduced PWV by 1.2 (0.9–1.4) m/s, to a greater extent than did nifedipine 10 mg (reduction of 0.7 [0.1–1.3] m/s, P

Electrical properties tomography (EPT) is an imaging method that uses a magnetic resonance (MR) system to non-invasively determine the spatial distribution of the conductivity and permittivity of the imaged object. This manuscript starts by providing clear definitions about the data required for, and acquired in, EPT, followed by comprehensively formulating the physical equations underlying a large number of analytical EPT techniques. This thorough mathematical overview of EPT harmonizes several EPT techniques in a single type of formulation and gives insight into how they act on the data and what their data requirements are. Furthermore, the review describes machine learning-based algorithms. Matlab code of several differential and iterative integral methods is available upon request.

In this paper, we draw on the concepts of figurations, capital, and hegemonic masculinity to analyse a bullying relation involving two fifth-grade boys at a Swedish comprehensive school. The findings are based on ethnographic fieldwork, which included participant observations and group interviews with eight teachers and fourteen students (seven girls and seven boys) from the same class. Our findings demonstrate the complexity of the relation between the boys and suggest that rather than constituting a straight-forward bullying "situation" involving a problematically aggressive 'bully' targeting a less powerful 'victim', it is part of a more complex "figuration" involving interdependent social relations that are tenuously balanced in terms of power dynamics and where the boys position themselves and are positioned in relation to the long-term symbolic norms of status dominant within their specific school field.

Background: Precancerous anal high-grade squamous intraepithelial lesions (HSIL) and its associated treatments have the potential to reduce health-related quality of life (HRQoL) in impacted individuals. The ANCHOR (ANal Cancer HSIL Outcomes Research) trial aims to determine whether treating anal HSIL, versus active monitoring, is effective in reducing incidence of anal cancer in HIV-infected individuals. The present study sought to establish preliminary psychometric evidence of the 25-item ANCHOR Health-Related Symptom Inventory (A-HRSI). Methods: Eligible ANCHOR participants recruited within two-weeks post-treatment or randomization to active surveillance completed the A-HRSI and well-established legacy HRQoL measures (i.e., Functional Assessment of Cancer Therapy – General [FACT-G] and MD Anderson Symptom Inventory [MDASI]) via telephone. Construct validity was assessed using an exploratory factor analysis (EFA). Pearson correlations were then calculated between summed items within the resulting A-HRSI latent factors and legacy measure outcome subscales to establish convergent and divergent validity. Results: 200 participants were enrolled. EFA provided initial confirmation that the A-HRSI items are best represented by the proposed broad three-factor structure (e.g., physical symptoms, physical impacts, psychological symptoms). These three factors had fair to moderate Pearson correlations with FACT-G Total and MDASI Symptom Severity and Interference subscales. Conclusions: Preliminary psychometric evidence exists to support the construct validity of the A-HRSI, indicating this measure can capture disease- and treatment-related physical and psychological symptoms and physical impacts. Clinical responsiveness and Spanish-translation of this measure will be completed prior to ultimately deploying this measure in the ANCHOR trial to facilitate participant reporting of their HRQoL to inform clinical decision-making.

Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5-deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza.

The main objective of electrical-property tomography (EPT) is to retrieve dielectric tissue parameters from B ^ 1 + data as measured by a magnetic-resonance (MR) scanner. This is a so-called hybrid inverse problem in which data are defined inside the reconstruction domain of interest. In this paper, we discuss recent and new developments in EPT based on the contrast-source inversion (CSI) method. After a short review of the basics of this method, two- and three-dimensional implementations of CSI⁻EPT are presented along with a very efficient variant of 2D CSI⁻EPT called first-order induced current EPT (foIC-EPT). Practical implementation issues that arise when applying the method to measured data are addressed as well, and the limitations of a two-dimensional approach are extensively discussed. Tissue-parameter reconstructions of an anatomically correct male head model illustrate the performance of two- and three-dimensional CSI⁻EPT. We show that 2D implementation only produces reliable reconstructions under very special circumstances, while accurate reconstructions can be obtained with 3D CSI⁻EPT.

Detection limits of the changes in absorption and reduced scattering coefficients were investigated using a frequency-domain near-infrared system in a realistic head phantom. The results were quantified in terms of the maximum detectable depth for different activation volumes in the range of 0.8–20 microliters. The non-linear relation between the maximum detectable depth and the magnitude of changes in the absorption coefficient conform well with the Born approximation to the diffusion equation. The minimal detectable changes in the reduced scattering coefficient measured in terms of the phase signal were found to be approximately twice as large as that of the absorption coefficient using the AC signal for the same volume and at the same depth. The phase delay, which can be used to quantify the fast neuronal optical response in the human brain, showed a linear dependence on the reciprocal of the reduced scattering coefficient, as predicted by the Rytov approximation.

Purpose/ background/ objectives: People with or at risk of Type II diabetes (T2DM) are at increased risk of vascular disease and arterial stiffness (AS). We hypothesized that spironolactone and dietary nitrate (beetroot juice) separately and together would reduce AS, measured as cardiac-ankle vascular index (CAVI Fukuda Denshi, Japan mainly BP-independent) or aortic pulse wave velocity (PWV). Methods: 126 (60% T2DM) were randomized, double-blind to spironolactone (≤50mg) or doxazosin (control ≤16mg) and active/ placebo juice (≤9/0mmol) daily. AS and echocardiographic measures (on a subgroup) were performed. Intention-to-treat analysis adjusted for between-group blood pressure (BP) change over time was performed using SAS. Results: Change in (Δ)BP was not different between spironolactone and doxazosin (mean -6.7mmHg), nor between the juices. ΔCAVI was marginally reduced on doxazosin compared to spironolactone (−0.11[−0.30,0.08] vs. 0.14[−0.06,0.34] units, p=0.080) but more for aortic PWV (−0.44 [−0.69,−0.20] vs. −0.07 [−0.32,0.18]ms−2, p=0.04). Dietary nitrate had no impact, but did rise in plasma. Spironolactone improved Δrelative wall thickness vs. doxazosin (0.01[−0.02,−0.0], p

Objective: To assess if 24h urinary cortisol metabolite (UCM) profiles are related to structural cardiac and arterial parameters in those with or at risk of Type 2 diabetes mellitus (T2DM). Design and method: 32 participants, 25-77 years, eGFR> 45 mL/min and no serious illness. Urine was collected over 24 hours. 2D echocardiography and arterial stiffness measures [aortic pulse wave velocity (aPWV) by Arteriograph and cardio-ankle vascular index (CAVI) by VaSera] were performed on the collection day. Steroids were extracted from urine and hydrolysed; derivatives were analysed by GC-MS. Results: Seven UCMs were quantified [tetrahydrocortisol (THF), allo-tetrahydrocortisol (a-THF), tetrahydrocortisone (THE), α-cortol (α-col), β-cortol (β-col), α-cortolone (α-cone), β-cortolone (β-cone)]. Left ventricular mass index (LVMI) correlated positively with 24h cortisol:cortisone metabolites (THF+aTHF+αcol+βcol/THE+αcortolone+βcortolone) and negatively with α:β metabolites (αcol+αcortol/βcol+βcortol), when indexed for body surface area (BSA) and height (r=0.37, 0.48 and r=−0.34, −0.49 respectively). Further, there was a positive relationship between LVMIBSA and THF:THE (r=0.35). aPWV but not CAVI was also related to 24h cortisol:cortisone metabolites (r=0.45). All p

The assessment of mitochondrial properties in skeletal muscle is important in clinical research, for instance in the study of diabetes. The gold standard to measure mitochondrial capacity non-invasively is the phosphocreatine (PCr) recovery rate after exercise, measured by (31)P Magnetic Resonance spectroscopy ((31)P MRS). Here, we sought to expand the evidence base for an alternative method to assess mitochondrial properties which uses (31)P MRS measurement of the Pi content of an alkaline compartment attributed to mitochondria (Pi2; as opposed to cytosolic Pi (Pi1)) in resting muscle at high magnetic field. Specifically, the PCr recovery rate in human quadriceps muscle was compared with the signal intensity of the Pi2 peak in subjects with varying mitochondrial content of the quadriceps muscle as a result of athletic training, and the results were entered into a mechanistic computational model of mitochondrial metabolism in muscle to test if the empirical relation between Pi2/Pi1 ratio and the PCr recovery was consistent with theory. Localized (31)P spectra were obtained at 7T from resting vastus lateralis muscle to measure the intensity of the Pi2 peak. In the endurance trained athletes a Pi2/Pi1 ratio of 0.07 ± 0.01 was found, compared to a significantly lower (p