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Whether disasters spur policy change remains contested. Here, the authors utilize a dataset of 10,976 natural hazard events and multiple disaster risk reduction (DRR) policy indicators across 85 countries over eight years to show that frequency and severity factors are unassociated with improved DRR policy.

Abstract To investigate bone health and body composition in young women with long-duration type 1 diabetes (T1D) in relation to matched controls. Twenty-three Swedish women, age 19.2–27.9 years, with a T1D duration of 10 years or more were recruited from the Swedish National Diabetes Registry (NDR). An age-, gender- and geography-matched control group was recruited. Bone mass and body composition were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Data was retrieved from the NDR and SWEDIABKIDS registries. T1D individuals had a mean diabetes duration of 19 years. T1D individuals had reduced lean mass (40.0 ± 6.1 kg vs. 43.9 ± 4.9 kg) and were shorter (1.66 ± 0.06 m vs. 1.71 ± 0.06 m) although comparable BMI. Subjects with T1D had lower muscle area (P = 0.0045). No differences were observed for fractures; physical activity; total, lumbar spine or femur areal bone mineral density. The cortical bone strength strain index was lower for TD1 patients (1875 ± 399 mm3 vs. 2277 ± 332 mm3). In conclusion, young women with long-term diabetes duration showed reduced cortical bone strength, decreased periosteal circumference, endosteal circumference and altered body composition. These factors contribute to the health burden of TD1, which warrants further attention for advancing bone health in women with T1D.

BackgroundThis paper describes the development of a mobile app for diabetes mellitus (DM) control and self-management and presents the results of long-term usage of this system in the Czech Republic. DM is a chronic disease affecting large numbers of people worldwide, and this number is continuously increasing. There is massive potential to increase adherence to self-management of DM with the use of smartphones and digital therapeutics interventions. ObjectiveThis study aims to describe the process of development of a mobile app, called Mobiab, for DM management and to investigate how individual features are used and how the whole system benefits its long-term users. Using at least 1 year of daily records from users, we analyzed the impact of the app on self-management of DM. MethodsWe have developed a mobile app that serves as an alternative form to the classic paper-based protocol or diary. The development was based on cooperation with both clinicians and people with DM. The app consists of independent individual modules. Therefore, the user has the possibility to use only selected features that they find useful. Mobiab was available free of charge on Google Play Store from mid-2014 until 2019. No targeted recruitment was performed to attract users. ResultsMore than 500 users from the Czech Republic downloaded and signed up for the mobile app. Approximately 80% of the users used Mobiab for less than 1 week. The rest of the users used it for a longer time and 8 of the users produced data that were suitable for long-term analysis. Additionally, one of the 8 users provided their medical records, which were compared with the gathered data, and the improvements in their glucose levels and overall metabolic stability were consistent with the way in which the mobile app was used. ConclusionsThe results of this study showed that the usability of a DM-centered self-management smartphone mobile app and server-based systems could be satisfactory and promising. Nonetheless, some better ways of motivating people with diabetes toward participation in self-management are needed. Further studies involving a larger number of participants are warranted to assess the effect on long-term diabetes management.

BackgroundeHealth interventions can help people change behavior (eg, quit smoking). Reminders sent via SMS text messaging or email may improve the adherence to web-based programs and increase the probability of successful behavior change; however, it is unclear whether their efficiency is affected by the modality of the communication channel. ObjectiveA 2-armed randomized control trial was conducted to compare the effect of providing reminders via SMS text messaging versus email on the adherence to an eHealth program for smoking cessation and on the probability to initiate a quit attempt. MethodsSmokers were recruited via an internet-based advertisement. A total of 591 participants who diverted from intended use of the program (ie, failed to log on to a session) were automatically randomized to the experimental (SMS text messaging reminder, n=304) or the active comparator (email reminder, n=287) group. ResultsUnexpectedly, we found that the mode of reminder delivery did not significantly affect either the adherence, namely the number of completed program sessions, with the SMS text messaging reminder group showing a mean of 4.30 (SD 3.24) and the email reminder group showing a mean of 4.36 (SD 3.27) (t586=0.197, P=.84, and Cohen d=0.016), or the outcome, namely the quit smoking attempt rate (34.2% in the SMS text messaging group vs 31.7% in the email group; χ21=0.4, P=.52). Secondary analyses showed that age, gender, and education had significant effects on program adherence and education on the outcome. Moreover, we found a significant interaction effect between the mode of reminder delivery and gender on program adherence, suggesting that the effectiveness of SMS text message reminders might be different for females and males. However, this particular finding should be treated with care as it was based on post hoc subgroup analysis. ConclusionsThis study indicates that the modality of user reminders to log on increased neither the program adherence nor the probability of quitting smoking. This suggests that program developers may save costs using emails instead of SMS text messaging reminders. Trial RegistrationClinicalTrials.gov NCT03276767; https://clinicaltrials.gov/ct2/show/ NCT03276767

A infiltração de água e a resistência do solo à penetração são parâmetros fundamentais para o eficiente manejo do solo e da água nos diferentes sistemas de cultivo. Objetivou-se neste estudo quantificar a infiltração de água e a resistência à penetração em um Latossolo cultivado com diferentes sistemas de cultivo integrados sobre área de pastagem degradada. Foram avaliados solos de sete tratamentos: T1 - Degradado; T2 - Pasto adubado; T3 - Convencional; T4 - ILF frutíferas e olerícolas; T5 – IPF; T6 - ILPF feno; e T7 - ILPF silagem. Foram determinadas as curvas de velocidade de infiltração de água e os respectivos valores de velocidade de infiltração básica (VIB) para as áreas dos solos em estudo. A infiltração da água no solo foi determinada “in situ” pelo método do infiltrômetro de anel e empiricamente por meio de modelos propostos por Kostiakov e Kostiakov-Lewis. A resistência do solo à penetração, até a profundidade de 0,3 m, foi realizada com o uso de penetrômetro de impacto. A maior infiltração em relação ao tempo ocorreu no tratamento T7. Os maiores valores de velocidade de infiltração básica (VIB) ocorreu no tratamento T5. O modelo proposto por Kostiakov apresentou maior ajuste aos dados de velocidade de infiltração obtidos no campo. A menor resistência do solo à penetração é proporcionada pela diversidade de espécies nos sistemas silviagrícolas.

In this article, we utilize the Collaborative Governance Databank to empirically explore core theoretical assumptions about collaborative governance in the context of crisis management. By selecting a subset of cases involving episodes or situations characterized by the combination of urgency, threat, and uncertainty, we conduct a plausibility probe to garner insights into a number of central assumptions and dynamics fundamental to understanding collaborative crisis management. Although there is broad agreement among academics and practitioners that collaboration is essential for managing complex risks and events that no single actor can handle alone, in the literature, there are several unresolved claims and uncertainties regarding many critical aspects of collaborative crisis management. Assumptions investigated in the article relate to starting-points and triggers for collaboration, level of collaboration, goal-formulation, adaptation, involvement and role of non-state actors, and the prevalence and impact of political infighting. The results confirm that crises represent rapidly moving and dynamic events that raise the need for adaptation, adjustment, and innovation by diverse sets of participants. We also find examples of successful behaviours where actors managed, despite challenging conditions, to effectively contain conflict, formulate and achieve shared goals, adapt to rapidly changing situations and emergent structures, and innovate in response to unforeseen problems.

Malignant melanoma is the most deadly skin cancer, associated with rising incidence and mortality rates. Most of the patients with melanoma, treated with current targeted therapies, develop a drug resistance, causing tumor relapse. The attainment of a better understanding of novel cancer-promoting molecular mechanisms driving melanoma progression is essential for the development of more effective targeted therapeutic approaches. Recent studies, including the research previously conducted in our laboratory, reported that the histone methyltransferase SETDB1 contributes to melanoma pathogenesis. In this follow-up study, we further elucidated the role of SETDB1 in melanoma, showing that SETDB1 modulated relevant transcriptomic effects in melanoma, in particular, as activator of cancer-related secreted (CRS) factors and as repressor of melanocyte-lineage differentiation (MLD) and metabolic enzymes. Next, we investigated the effects of SETDB1 inhibition via compounds belonging to the mithramycin family, mithramycin A and mithramycin analog (mithralog) EC-8042: melanoma cells showed strong sensitivity to these drugs, which effectively suppressed the expression of SETDB1 and induced changes at the transcriptomic, morphological, and functional level. Moreover, SETDB1 inhibitors enhanced the efficacy of mitogen-activated protein kinase (MAPK) inhibitor-based therapies against melanoma. Taken together, this work highlights the key regulatory role of SETDB1 in melanoma and supports the development of SETDB1-targeting therapeutic strategies for the treatment of melanoma patients.

Abstract After drilling oil wells using oil-based drilling fluid, there is the occurrence of a formation of a thin layer of solids adsorbed on the surface, called filter cake, which must be removed to obtain satisfactory well cementation. The present work developed microemulsion systems from sodium dodecyl sulfate, a biodegradable surfactant, with kerosene as oil phase, n-butanol as cosurfactant and distilled water, in order to evaluate its efficiency in removing the filter cake. The results showed that the microemulsion systems composed of inverse and bicontinuous micelles removed 100% of the filter cake regardless of the content of the constituents in the formulation, while the direct micelles only reached 100% with the formulation composed by 10% kerosene and cosurfactant/surfactant ratio = 4. It was observed that the cosurfactant/surfactant ratio is a determining variable for direct micelles to remove 100% of the filter cake and that they are compatible with cement, offering desirable thermal stability and improving the wettability of the rock in water.

Abstract Background ERF-related craniosynostosis are a rare, complex, premature trisutural fusion associated with a broad spectrum of clinical features and heterogeneous aetiology. Here we describe two cases with the same pathogenic variant and a detailed description of their clinical course. Case presentation Two subjects; a boy with a BLSS requiring repeated skull expansions and his mother who had been operated once for sagittal synostosis. Both developed intracranial hypertension at some point during the course, which was for both verified by formal invasive intracranial pressure monitoring. Exome sequencing revealed a pathogenic truncating frame shift variant in the ERF gene. Conclusions Here we describe a boy and his mother with different craniosynostosis patterns, but both with verified intracranial hypertension and heterozygosity for a truncating variant of ERF c.1201_1202delAA (p.Lys401Glufs*10). Our work provides supplementary evidence in support of previous phenotypic descriptions of ERF-related craniosynostosis, particularly late presentation, an evolving synostotic pattern and variable expressivity even among affected family members.

Abstract All approaches currently used to study finite baryon density lattice QCD suffer from uncontrolled systematic uncertainties in addition to the well-known sign problem. We formulate and test an algorithm, sign reweighting, that works directly at finite μ = μ B /3 and is yet free from any such uncontrolled systematics. With this algorithm the only problem is the sign problem itself. This approach involves the generation of configurations with the positive fermionic weight |Re det D(μ)| where D(μ) is the Dirac matrix and the signs sign(Re det D(μ)) = ±1 are handled by a discrete reweighting. Hence there are only two sectors, +1 and −1 and as long as the average 〈±1〉 ≠ 0 (with respect to the positive weight) this discrete reweighting by the signs carries no overlap problem and the results are reliable. The approach is tested on N t = 4 lattices with 2 + 1 flavors and physical quark masses using the unimproved staggered discretization. By measuring the Fisher (sometimes also called Lee-Yang) zeros in the bare coupling on spatial lattices L/a = 8, 10, 12 we conclude that the cross-over present at μ = 0 becomes stronger at μ > 0 and is consistent with a true phase transition at around μ B /T ∼ 2.4.

Abstract We revisit the semi-classical calculation of the size distribution of instantons at finite temperature in non-abelian gauge theories in four dimensions. The relevant functional determinants were first calculated in the seminal work of Gross, Pisarski and Yaffe and the results were used for a wide variety of applications including axions most recently. In this work we show that the uncertainty on the numerical evaluations and semi-analytical expressions are two orders of magnitude larger than claimed. As a result various quantities computed from the size distribution need to be reevaluated, for instance the resulting relative error on the topological susceptibility at arbitrarily high temperatures is about 5% for QCD and about 10% for SU(3) Yang-Mills theory. With higher rank gauge groups this discrepancy is even higher. We also provide a simple semi-analytical formula for the size distribution with absolute error 2 · 10 −4. In addition we also correct the over-all constant of the instanton size distribution in the MS ¯ $$ \overline{\mathrm{MS}} $$ scheme which was widely used incorrectly in the literature if non-trivial fermion content is present.

ABSTRACTThe variegated squirrel bornavirus 1 (VSBV-1), a member of the family Bornaviridae, was discovered in 2015 in a series of lethal human infections. Screening approaches revealed kept exotic squirrels as the putative source of infection.Infectious virus was successfully isolated by co-cultivation of infected primary squirrel cells with permanent cell lines. For in vivo characterization, neonatal and adult Lewis rats were inoculated either intracranially, intranasally or subcutaneously. After 4.5 months, three out of fifteen neonatal intracranially inoculated rats were VSBV-1 genome positive in the central nervous system without showing clinical signs. Pathohistological examination revealed a non-purulent encephalitis. While infection of immune incompetent rats (neonatal) using the type species of mammalian bornaviruses, the Borna disease virus 1, proceed to an immune tolerant status, VSBV-1 infection could result in inflammation of neuronal tissue. Sequencing showed minor adaptations within the VSBV-1 genome comparing to the viral genomes from infected squirrels, cell cultures or rat tissues.In conclusion, we were able to generate the first VSBV-1 isolates and provide in vivo animal model data in Lewis rats revealing substantial differences between VSBV-1 and BoDV-1. Furthermore, the presented data are a precondition for insights into the transmission and pathogenesis of this novel zoonotic pathogen.

Abstract Background The astonishing variety of sounds that birds can produce has been the subject of many studies aiming to identify the underlying anatomical and physical mechanisms of sound production. An interesting feature of some bird vocalisations is the simultaneous production of two different frequencies. While most work has been focusing on songbirds, much less is known about dual-sound production in non-passerines, although their sound production organ, the syrinx, would technically allow many of them to produce “two voices”. Here, we focus on the king penguin, a colonial seabird whose calls consist of two fundamental frequency bands and their respective harmonics. The calls are produced during courtship and for partner and offspring reunions and encode the birds’ identity. We dissected, μCT-scanned and analysed the vocal tracts of six adult king penguins from Possession Island, Crozet Archipelago. Results King penguins possess a bronchial type syrinx that, similarly to the songbird’s tracheobronchial syrinx, has two sets of vibratory tissues, and thus two separate sound sources. Left and right medial labium differ consistently in diameter between 0.5 and 3.2%, with no laterality between left and right side. The trachea has a conical shape, increasing in diameter from caudal to cranial by 16%. About 80% of the king penguins’ trachea is medially divided by a septum consisting of soft elastic tissue (septum trachealis medialis). Conclusions The king penguins’ vocal tract appears to be mainly adapted to the life in a noisy colony of a species that relies on individual vocal recognition. The extent between the two voices encoding for individuality seems morphologically dictated by the length difference between left and right medial labium. The septum trachealis medialis might support this extent and could therefore be an important anatomical feature that aids in the individual recognition process.

Abstract Background The majority of emerging infectious diseases are zoonotic in nature and originate from wildlife reservoirs. Borna disease, caused by Borna disease virus 1 (BoDV-1), is an infectious disease affecting mammals, but recently it has also been shown to cause fatal encephalitis in humans. The endemic character of Borna disease points towards a nature-bound reservoir, with only one shrew species identified as reservoir host to date. Bats have been identified as reservoirs of a variety of zoonotic infectious agents. Endogenous borna-like elements in the genome of certain bat species additionally point towards co-evolution of bats with bornaviruses and therefore raise the question whether bats could serve as a potential reservoir of orthobornaviruses. Methods Frozen brain samples (n = 257) of bats of seven different genera from Germany were investigated by orthobornaviral RT-PCR. Additionally, tissue slides of formalin-fixed paraffin-embedded material of a subset of these bats (n = 140) were investigated for orthobornaviral phosphoprotein by immunohistochemistry. Results The brain samples were tested by RT-PCR without any evidence of orthobornavirus specific amplicons. Immunohistochemistry revealed a faint immunoreaction in 3/140 bats but with an untypical staining pattern for viral antigen. Conclusions RT-PCR-screening showed no evidence for orthobornaviral RNA in the investigated bats. However, immunohistochemistry results should be investigated further to elucidate whether the reaction might be associated with expressed endogenous bornaviral elements or other so far unknown bornaviruses.

Myelofibrosis is a myeloproliferative neoplasm. Here, the authors show the clonal evolution of myelofibrosis during JAK inhibitor therapy, revealing how the treatment results in an increase in clonal complexity and a gain of RAS pathway mutations.

Introdução: o Diabetes Mellitus tipo 2 (DM2) é condição crônica que frequentemente cursa com baixa adesão ao tratamento. Objetivo: o presente estudo avaliou a prevalência de adesão à terapêutica medicamentosa e fatores associados em pessoas com DM2 assistidas pela Estratégia Saúde da Família (ESF). Método: trata-se de estudo observacional transversal realizado na ESF da zona urbana de um município de médio porte de Minas Gerais, com amostra randômica de 190 participantes. Foram utilizados dois instrumentos validados: Medida de Adesão ao Tratamento (MAT), que avalia o uso diário de medicamentos prescritos, e teste de Batalla, que avalia adesão através do conhecimento em DM2. O perfil socioeconômico e clínico foi coletado por questionário elaborado pelos autores. Principais resultados: a adesão avaliada pelo MAT (84,2%) se contrapôs àquela estimada pelo teste de Batalla (44,2%). Maiores valores apresentados pelo MAT obtiveram associação significativa com polifarmácia (OR=2,7; IC 95%=1,2-6,1). Melhor adesão pelo teste de Batalla obteve associação com idade abaixo de 60 anos (OR=3,7; IC 95%=1,9-7,1), presença de companheiro (OR=2,2; IC 95%=1,1-4,1), associação de antidiabético oral à insulina (OR=2,2; IC 95%=1,2-4,0) e cumprimento da meta de atividade física (OR=2,6; IC 95%=1,2-5,6). Conclusão: os índices de adesão ao uso diário de medicamentos e conhecimento em DM2 verificados pelo estudo são concordantes com a literatura. Piores resultados presentes na população idosa e sem companheiro evidenciam grupo vulnerável que deve receber especial atenção das equipes de saúde.

Category: Ankle Arthritis; Ankle Introduction/Purpose: Both total ankle arthroplasty (TAA) and ankle arthrodesis (AA) are effective treatments for ankle arthritis. This study sought to use a statistical modeling approach to determine factors associated with success following either surgery. While a number of studies have explored risk factors associated with complications, our aim was to guide management based on factors which may be predictive of success. Methods: We retrospectively analyzed data from a prospective multicenter cohort study conducted between May 2012 and May 2015. We compared outcomes in 448 patients who had follow-up of at least 4 years and were treated for ankle arthritis with either TAA or AA. We collected baseline factors including demographics, pre- and post-operative outcome scores including the Foot and Ankle Ability Measure (FAAM), Short Form-36 (SF-36) Physical and Mental Component Summary scores, pain, ankle related adverse events, and radiographs (coronal tilt and sagittal subluxation). We defined fully Successful as an increase in the FAAM ADL score by the minimum clinically important difference (MCID) and the absence of post-operative complications. We performed a multivariate logistic regression model adjusted for age, sex, BMI, and surgery type to identify associations with success. Results: Of the 517 patients who consented, had surgery and completed post-operative surveys, 414 (80.0%) underwent TAA and 103 (19.9%) underwent AA. Of the 517 patients, 448 patients (86.7%) had a minimum of 4-year follow-up. Of the 448 patients, 331 (73.9%) were successful) outcome and 117 (26.1%) were not fully successful. Out multivariable logistic model found female sex (0.83 +- 0.03, p=0.002), treatment with TAA (0.80 +- 0.020, p=0.001), and no previous surgery (0.82 +- 0.03, p=0.030) as variable significantly associated with success. Notably, mental health factors and pre-operative radiographic measurements, including coronal tilt and sagittal subluxation, were not significantly associated with success. Conclusion: Surgeons treating patients with ankle arthritis have two viable surgical alternatives. Recognizing the factors associated with mid-term success may be as valuable as knowing risk factors associated with failure. In addition, we also find variables thought to affect outcomes, mental health and pre-operative radiographic measurements such as coronal plane misalignment, were not found to significantly affect outcomes.

Purpose There is limited qualitative research on the experience of patients undergoing lower limb amputation due to chronic limb threatening ischemia (CLTI) and their participation in amputation-level decisions. This study was performed to understand patient lived experiences related to amputation and patient involvement in shared decision making. Materials and methods Phenomenological interviews were conducted with Veterans 6–12 months post transtibial or transmetatarsal amputation due to CLTI. Interviews were read and summarized by two analysts who discussed the contents of each interview and relationships between interviews to identify emergent, cross-cutting elements of patient experience. Results Twelve patients were interviewed between March and August 2019. Three cross cutting elements of patient lived experience and participation in shared decision making were identified: 1) Lacking a sense of decision making; 2) Actively working towards recovery as response to a perceived loss of independence; and 3) Experiencing amputation as a Veteran. Conclusions Patients did not report a high level of involvement in shared decision making about their amputation or amputation level. Understanding patient experiences and priorities is crucial to supporting shared decision making for Veterans with amputation due to CLTI.

The Earth mover’s distance (EMD) is a useful metric for image recognition and classification, but its usual implementations are not differentiable or too slow to be used as a loss function for training other algorithms via gradient descent. In this paper, we train a convolutional neural network (CNN) to learn a differentiable, fast approximation of the EMD and demonstrate that it can be used as a substitute for computing-intensive EMD implementations. We apply this differentiable approximation in the training of an autoencoder-inspired neural network (encoder NN) for data compression at the high-luminosity LHC at CERN The goal of this encoder NN is to compress the data while preserving the information related to the distribution of energy deposits in particle detectors. We demonstrate that the performance of our encoder NN trained using the differentiable EMD CNN surpasses that of training with loss functions based on mean squared error.

Coronal bright points (CBPs) are sets of small-scale coronal loops, connecting opposite magnetic polarities, primarily characterized by their enhanced extreme-ultraviolet (EUV) and X-ray emission. Being ubiquitous, they are thought to play an important role in heating the solar corona. We aim at characterizing the barely explored chromosphere underneath CBPs, focusing on the related spicular activity and on the effects of small-scale magnetic flux emergence on CBPs. We used high-resolution observations of a CBP in H β and Fe i 617.3 nm from the Swedish 1 m Solar Telescope in coordination with the Solar Dynamics Observatory. This work presents the first high-resolution observation of spicules imaged in H β . The spicules were automatically detected using advanced image processing techniques, which were applied to the Dopplergrams derived from H β . Here we report their abundant occurrence close to the CBP “footpoints” and find that the orientation of such spicules is aligned along the EUV loops, indicating that they constitute a fundamental part of the whole CBP magnetic structure. Spatiotemporal analysis across multiple channels indicates that there are coronal propagating disturbances associated with the studied spicules, producing transient EUV intensity variations of the individual CBP loops. Two small-scale flux emergence episodes appearing below the CBP were analyzed, one of them leading to quiet-Sun Ellerman bombs and enhancing the nearby spicular activity. This paper presents unique evidence of the tight coupling between the lower and upper atmosphere of a CBP, thus helping to unravel the dynamic phenomena underneath CBPs and their impact on the latter.

Optimizing production in the mature fields of heavy oil reservoirs is still challenging. In most cases, conventional recovery techniques are not effective, although they are suitable for applying thermal recovery methods. Steam injection involves injecting steam into the reservoir where the heat exchange with the oil occurs. This promotes a reduction in oil viscosity and thus increases its mobility. One of the challenges of the EOR project is understanding how the presence of regions with contrasting properties, such as fractures, caves, and barriers, could affect the steam flow. This work investigates the impact of low-permeability barriers in the steam injection process. The barriers were created on a semi-synthetic reservoir characteristic of Brazilian onshore mature fields. We used the three-phase pseudo-compositional reservoir simulation STARS (Steam Thermal Advanced Processes Reservoir Simulation) for simulations. Our results show that the shape, number, and arrangement of barriers in a porous medium can affect the amount of oil recovered. They may also be able to anticipate or delay oil production.

The erythroferrone gene (ERFE), also termed CTRP15, belongs to the C1q tumor necrosis factor-related protein (CTRP) family. Despite multiple reports about the involvement of CTRPs in cancer, the role of ERFE in cancer progression is largely unknown. We previously found that ERFE was upregulated in erythroid progenitors in myelodysplastic syndromes and strongly predicted overall survival. To understand the potential molecular interactions and identify cues for further functional investigation and the prognostic impact of ERFE in other malignancies, we performed a pan-cancer in silico analysis utilizing the Cancer Genome Atlas datasets. Our analysis shows that the ERFE mRNA is significantly overexpressed in 22 tumors and affects the prognosis in 11 cancer types. In certain tumors such as breast cancer and adrenocortical carcinoma, ERFE overexpression has been associated with the presence of oncogenic mutations and a higher tumor mutational burden. The expression of ERFE is co-regulated with the factors and pathways involved in cancer progression and metastasis, including activated pathways of the cell cycle, extracellular matrix/tumor microenvironment, G protein-coupled receptor, NOTCH, WNT, and PI3 kinase-AKT. Moreover, ERFE expression influences intratumoral immune cell infiltration. Conclusively, ERFE is aberrantly expressed in pan-cancer and can potentially function as a prognostic biomarker based on its putative functions during tumorigenesis and tumor development.

Laryngeal dystonia (LD), or spasmodic dysphonia (SD), is a chronic, task-specific, focal movement disorder affecting the larynx. It interferes primarily with the essential functions of phonation and speech. LD affects patients’ ability to communicate effectively and significantly diminishes their quality of life. Botulinum neurotoxin was first used as a therapeutic agent in the treatment of LD four decades ago and remains the standard of care for the treatment of LD. This article provides an overview of the clinical application of botulinum neurotoxin in the management of LD, focusing on the classification for this disorder, its pathophysiology, clinical assessment and diagnosis, the role of laryngeal electromyography and a summary of therapeutic injection techniques, including a comprehensive description of various procedural approaches, recommendations for injection sites and dosage considerations.

Aims Craniosynostosis is a congenital condition characterised by premature fusion of one or more cranial sutures. The aim of this study was to analyse ophthalmic function before and after cranial surgery, in children with various types of non-syndromic craniosynostosis.Methods Children referred to Uppsala University Hospital for surgery of non-syndromic craniosynostosis were examined preoperatively. Visual acuity was measured with Preferential Looking tests or observation of fixation and following. Strabismus and eye motility were noted. Refraction was measured in cycloplegia and funduscopy was performed. Follow-up examinations were performed 6–12 months postoperatively at the children’s local hospitals.Results One hundred twenty-two children with mean age 6.2 months were examined preoperatively. Refractive values were similar between the different subtypes of craniosynostosis, except for astigmatism anisometropia which was more common in unicoronal craniosynostosis. Strabismus was found in seven children, of which four had unicoronal craniosynostosis.Postoperatively, 113 children were examined, at mean age 15.9 months. The refractive values decreased, except for astigmatism and anisometropia in unicoronal craniosynostosis. Strabismus remained in unicoronal craniosynostosis. Two new cases with strabismus developed in unicoronal craniosynostosis and one in metopic, all operated with fronto-orbital techniques. No child had disc oedema or pale discs preoperatively or postoperatively.Conclusion Ophthalmic dysfunctions were not frequent in children with sagittal craniosynostosis and preoperative ophthalmological evaluation may not be imperative. Children with unicoronal craniosynostosis had the highest prevalence of strabismus and anisometropia. Fronto-orbital techniques used to address skull deformity may be related to a higher prevalence of strabismus postoperatively.

Voice tremor is a common, yet debilitating symptom for patients suffering from a number of tremor-associated disorders. The key to targeting effective treatments for voice tremor requires a fundamental understanding of the pathophysiology that underpins the tremor mechanism and accurate identification of the disease in affected patients. An updated review of the literature detailing the current understanding of voice tremor (with or without essential tremor), its accurate diagnosis and targeted treatment options was conducted, with a specific focus on the role of botulinum neurotoxin. Judicious patient selection, following detailed characterisation of voice tremor qualities, is essential to optimising treatment outcomes for botulinum neurotoxin therapy, as well as other targeted therapies. Further focused investigation is required to characterise the response to targeted treatment in voice tremor patients and to guide the development of innovative treatment options.

BackgroundSelf-reported mood is a valuable clinical data source regarding disease state and course in patients with mood disorders. However, validated, quick, and scalable digital self-report measures that can also detect relapse are still not available for clinical care. ObjectiveIn this study, we aim to validate the newly developed ASERT (Aktibipo Self-rating) questionnaire—a 10-item, mobile app–based, self-report mood questionnaire consisting of 4 depression, 4 mania, and 2 nonspecific symptom items, each with 5 possible answers. The validation data set is a subset of the ongoing observational longitudinal AKTIBIPO400 study for the long-term monitoring of mood and activity (via actigraphy) in patients with bipolar disorder (BD). Patients with confirmed BD are included and monitored with weekly ASERT questionnaires and monthly clinical scales (Montgomery-Åsberg Depression Rating Scale [MADRS] and Young Mania Rating Scale [YMRS]). MethodsThe content validity of the ASERT questionnaire was assessed using principal component analysis, and the Cronbach α was used to assess the internal consistency of each factor. The convergent validity of the depressive or manic items of the ASERT questionnaire with the MADRS and YMRS, respectively, was assessed using a linear mixed-effects model and linear correlation analyses. In addition, we investigated the capability of the ASERT questionnaire to distinguish relapse (YMRS≥15 and MADRS≥15) from a nonrelapse (interepisode) state (YMRS

Resumo Objetivo: Descrever a adequação da conservação de imunobiológicos nas salas de imunização dos municípios da macrorregião de saúde Oeste do estado de Minas Gerais, Brasil. Métodos: Estudo descritivo, pautado em uma escala validada, com escore máximo de 15 pontos. Realizou-se análise descritiva e teste de associação entre os escores obtidos pelos municípios e variáveis do contexto externo. Resultados: Foram avaliadas 275 do total de 295 salas de imunização existentes. A conservação de imunobiológicos na macrorregião Oeste obteve um escore médio de 4 pontos (escore-padrão de 0 a 15). Evidenciou-se ausência ou carência de insumos destinados à conservação de imunobiológicos, e processos de trabalho que requerem aprimoramento. Municípios de pequeno porte apresentaram melhor conservação de imunobiológicos (p=0,011). Conclusão: A conservação de imunobiológicos nas salas de imunização da macrorregião de saúde Oeste de Minas Gerais foi considerada inadequada.

Previous research has shown the value of the sense of embodiment, i.e., being able to integrate objects into one's bodily self-representation, and its connection to (assistive) robotics. Especially, tactile interfaces seem essential to integrate assistive robots into one's body model. Beyond functional feedback, such as tactile force sensing, the human sense of touch comprises specialized nerves for affective signals, which transmit positive sensations during slow and low-force tactile stimulations. Since these signals are extremely relevant for body experience as well as social and emotional contacts but scarcely considered in recent assistive devices, this review provides a requirement analysis to consider affective touch in engineering design. By analyzing quantitative and qualitative information from engineering, cognitive psychology, and neuroscienctific research, requirements are gathered and structured. The resulting requirements comprise technical data such as desired motion or force/torque patterns and an evaluation of potential stimulation modalities as well as their relations to overall user experience, e.g., pleasantness and realism of the sensations. This review systematically considers the very specific characteristics of affective touch and the corresponding parts of the neural system to define design goals and criteria. Based on the analysis, design recommendations for interfaces mediating affective touch are derived. This includes a consideration of biological principles and human perception thresholds which are complemented by an analysis of technical possibilities. Finally, we outline which psychological factors can be satisfied by the mediation of affective touch to increase acceptance of assistive devices and outline demands for further research and development.

The bone marrow (BM) microenvironment, also called the BM niche, is essential for the maintenance of fully functional blood cell formation (hematopoiesis) throughout life. Under physiologic conditions the niche protects hematopoietic stem cells (HSCs) from sustained or overstimulation. Acute or chronic stress deregulates hematopoiesis and some of these alterations occur indirectly via the niche. Effects on niche cells include skewing of its cellular composition, specific localization and molecular signals that differentially regulate the function of HSCs and their progeny. Importantly, while acute insults display only transient effects, repeated or chronic insults lead to sustained alterations of the niche, resulting in HSC deregulation. We here describe how changes in BM niche composition (ecosystem) and structure (remodeling) modulate activation of HSCs in situ. Current knowledge has revealed that upon chronic stimulation, BM remodeling is more extensive and otherwise quiescent HSCs may be lost due to diminished cellular maintenance processes, such as autophagy, ER stress response, and DNA repair. Features of aging in the BM ecology may be the consequence of intermittent stress responses, ultimately resulting in the degeneration of the supportive stem cell microenvironment. Both chronic stress and aging impair the functionality of HSCs and increase the overall susceptibility to development of diseases, including malignant transformation. To understand functional degeneration, an important prerequisite is to define distinguishing features of unperturbed niche homeostasis in different settings. A unique setting in this respect is xenotransplantation, in which human cells depend on niche factors produced by other species, some of which we will review. These insights should help to assess deviations from the steady state to actively protect and improve recovery of the niche ecosystem in situ to optimally sustain healthy hematopoiesis in experimental and clinical settings.

Background Leadless pacemaker is a novel technology, and evidence supporting its use is uncertain. We performed a systematic review and meta‐analysis to examine the safety and efficacy of leadless pacemakers implanted in the right ventricle. Methods and Results We searched PubMed and Embase for studies published before June 6, 2020. The primary safety outcome was major complications, whereas the primary efficacy end point was acceptable pacing capture threshold (≤2 V). Pooled estimates were calculated using the Freedman‐Tukey double arcsine transformation. Of 1281 records screened, we identified 36 observational studies of Nanostim and Micra leadless pacemakers, with most (69.4%) reporting outcomes for the Micra. For Micra, the pooled incidence of complications at 90 days (n=1608) was 0.46% (95% CI, 0.08%–1.05%) and at 1 year (n=3194) was 1.77% (95% CI, 0.76%–3.07%). In 5 studies with up to 1‐year follow‐up, Micra was associated with 51% lower odds of complications compared with transvenous pacemakers (3.30% versus 7.43%; odds ratio [OR], 0.49; 95% CI, 0.34–0.70). At 1 year, 98.96% (95% CI, 97.26%–99.94%) of 1376 patients implanted with Micra had good pacing capture thresholds. For Nanostim, the reported complication incidence ranged from 6.06% to 23.54% at 90 days and 5.33% to 6.67% at 1 year, with 90% to 100% having good pacing capture thresholds at 1 year (pooled result not estimated because of the low number of studies). Conclusions Most studies report outcomes for the Micra, which is associated with a low risk of complications and good electrical performance up to 1‐year after implantation. Further data from randomized controlled trials are needed to support the widespread adoption of these devices in clinical practice.

RESUMO Objetivo: Avaliar as estratégias de educação em grupo e intervenção telefônica em relação às variáveis empoderamento, práticas de autocuidado e controle glicêmico da pessoa com diabetes. Método: Ensaio clínico com oito clusters randomizados, realizado entre 2015 e 2016, com 208 usuários com diabetes mellitus tipo 2 alocados para educação em grupo, intervenção telefônica ou grupo controle. Foram coletados dados sociodemográficos, hemoglobina glicada, empoderamento e práticas de autocuidado. Resultados: A média de idade dos usuários era de 63,5 anos (DP = 8,9 anos), com participação de 124 mulheres, equivalente a 59,6% desses usuários. As estratégias levaram a uma redução estatisticamente significante nos níveis de hemoglobina glicada (p < 0,001). Observou-se também que a intervenção telefônica apresentou resultados estatisticamente significantes quanto às práticas de autocuidado (p < 0,001) e ao empoderamento em diabetes (p < 0,001) quando comparada à educação em grupo. Conclusão: A intervenção telefônica apresentou resultados estatisticamente significantes de empoderamento e de práticas de autocuidado se comparada à educação em grupo. Registro Brasileiro de Ensaios Clínicos RBR-7gb4wm.

Abstract Conventional treatment of drill cuttings, as drying and thermal desorption, is failing to meet environmental and economic standards; therefore, new alternatives for the treatment of this waste must be developed. The purpose of this study was to remove n-paraffin from drill cuttings using microemulsion systems (MES). The extraction percentage (%) of n-paraffin was quantified by gas chromatography with a flame ionization detector. The optimization of extraction parameters showed that the extraction percentage (%) is directly proportional to the stirring speed and contact time and inversely proportional to the HLB of the surfactant used in the microemulsion system. Results for MES using Alkonat® L90 and Renex® 95 were similar, but Alkonat® L90 was chosen as the best system considering the environmental issue. The MES/cuttings ratio did not influence the percentage of n-paraffin extracted, reaching 55.03% and 56.32% for the ratios of 0.5 and 2.0, respectively. The reuse of MES in multiple extractions showed that MES can be reused in up to two extractions, obtaining up to 86% extraction. The optimal parameters for Alkonat® L90 microemulsion systems were MES/cuttings ratio of 1.0, stirring speed of 132 strokes, and contact time of 80 min, achieving 86.27% extraction. Results obtained in this study may help to better understand n-paraffin removal from drill cuttings by MES, considering the future use of this technology in the design of an industrial treatment plant for both onshore and offshore operations.

Abstract Background The separate design concepts of dual-mobility cups and triple-taper femoral stems were developed to improve survivorship following total hip replacement (THR) by reducing instability/dislocation and enabling enhanced fixation. Successful outcomes at over two decades have been reported with earlier-generation devices based on these concepts. The current study aimed to provide the first long-term results with a unique pairing of later-generation dual-mobility cup and triple-taper cementless femoral stem after a decade of use in patients undergoing THR. Methods In this retrospective analysis, records were reviewed for all subjects implanted with this dual-mobility cup/cementless femoral stem combination at three centers between 2002 and 2005. Any subject who had not already had follow-up visit beyond 10 years, was not previously revised, and still living were invited for a single follow-up visit consisting of Merle d’Aubgine Scores, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, and standard radiographs. Results There were 244 THRs available for analysis. At a mean follow-up of 11.9 years, the Kaplan-Meier survivorship (endpoint: revision for any reason) was 99.1% (95% CI, 97.6–99.7) for the stem and 95.9% (95% CI, 93.1–97.6) for the cup. Merle d’Aubigne Scores were significantly improved from baseline and WOMAC scores were in the satisfactory range at the final follow-up. Radiographic analysis revealed no cases of stem subsidence, no cases of bone hypertrophy, 1 (0.4%) case of bone atrophy, and 3 (1.2%) cases of osteolysis around the stem. No subjects had radiolucent lines greater than 1 mm in any femoral Gruen zone. Evidence of cup migration was seen in 1 (0.4%) subject and 1 (0.4%) subject had evidence of osteolysis that was seen in Gruen zones I, II, IV, and V. Conclusions This combination of a later-generation dual-mobility cup and cementless triple-taper stem was associated with excellent survivorship and satisfactory functional outcomes at over 10 years follow-up. Trial registration ClinicalTrials.gov, NCT02648152. Date of registration: January 6, 2016. Retrospectively registered.

Although the safety of valve-in-valve transcatheter aortic valve replacement has improved, coronary ostium obstruction remains a significant complication, with chimney stenting a possible solution to circumvent this complication. In this case, we discuss the failure of a chimney stent in a case of valve-in-valve transcatheter aortic valve replacement resulting in cardiogenic shock. (Level of Difficulty: Advanced.)

Urachal cyst is a rare condition that is typically asymptomatic and will often have symptomatology that is misdiagnosed or missed. A urachal cyst occurs in 1 out of 5000 live-births, but is only clinically relevant in 1 out of 150,000 of the population often as an incidental finding. The urachus is the embryological remnant of the allantois, which connects the apex of the bladder to the umbilicus, and usually fully obliterates to become the median umbilical ligament.Urachal defects are uncommon and cysts are usually asymptomatic until infection results. An infected cyst may present mimicking a wide range of intra-abdominal and pelvic disorders, and accurate diagnosis is often delayed. Children may present with umbilical discharge; adults often have hematuria. Computed tomography (CT) and ultrasound are ideally suited for demonstrating urachal remnant diseases; however, infected urachal cysts commonly display increased echogenicity with ultrasoundsography and thick-walled cystic or mixed attenuation with CT. Drainage and excision of the urachal remnant is the definitive treatment. Keywords: Pediatric radiology, Diagnostic radiology, Ultrasound, Urology

Abstract Background Remote ischemic conditioning (RIC) is a procedure applied in a limb for triggering endogenous protective pathways in distant organs, namely brain or heart. The underlying mechanisms of RIC are still not fully understood, and it is hypothesized they are mediated either by humoral factors, immune cells and/or the autonomic nervous system. Herein, heart rate variability (HRV) was used to evaluate the electrophysiological processes occurring in the heart during RIC and, in turn to assess the role of autonomic nervous system. Methods Healthy subjects were submitted to RIC protocol and electrocardiography (ECG) was used to evaluate HRV, by assessing the variability of time intervals between two consecutive heart beats. This is a pilot study based on the analysis of 18 ECG from healthy subjects submitted to RIC. HRV was characterized in three domains (time, frequency and non-linear features) that can be correlated with the autonomic nervous system function. Results RIC procedure increased significantly the non-linear parameter SD2, which is associated with long term HRV. This effect was observed in all subjects and in the senior (> 60 years-old) subset analysis. SD2 increase suggests an activation of both parasympathetic and sympathetic nervous system, namely via fast vagal response (parasympathetic) and the slow sympathetic response to the baroreceptors stimulation. Conclusions RIC procedure modulates both parasympathetic and sympathetic autonomic nervous system. Furthermore, this modulation is more pronounced in the senior subset of subjects. Therefore, the autonomic nervous system regulation could be one of the mechanisms for RIC therapeutic effectiveness.

In recent years, social media platforms such as Facebook, Twitter, and Instagram have become major players in sports communication. In this study, we focus on the motives for athletes’ use of social media. Applying a mediatization approach, we conceptualize social media as a possible means to bypass traditional (sports) journalism. For sport disciplines that receive minor media coverage, social media provides the opportunity to increase public visibility. Consequently, our study focuses on indoor volleyball as such a marginalized sport. The online survey results from all players of the 24 either all-male or all-female teams of the German first volleyball leagues are combined with a quantitative content analysis of the players’ social media activities. Results indicate that athletes evaluate traditional media coverage of their sport as negative and social media as extremely influential. Still, their postings on social media seem neither to aim at bypassing sports journalism nor to address sports fans directly. Instead, they use social media primarily to connect with friends and family. In conclusion, volleyball players have so far not embraced social media as a tool to promote themselves as sportspersons. At the moment, they do not exploit social media’s potential as channels for professional sports communication.

Abstract We calculate the m ϱ /f π ratio in the chiral and continuum limit for SU(3) gauge theory coupled to N f = 2, 3, 4, 5, 6 fermions in the fundamental representation. Keeping all systematic effects under full control we find no statistically significant N f -dependence; m ϱ /f π = 7.95(15). Assuming the KSRF-relations we conclude that 3 other low energy quantities related to the vector meson are also N f -independent within errors including the ϱππ coupling g ϱππ . If the model is thought of as a strong dynamics inspired composite Higgs model our results indicate that the experimentally most easily accessible new composite particle, the vector meson, and its properties may be robust and independent of the fermion content of the model as long as the gauge group is SU(3), provided N f -independence extends all the way to the conformal window.

Abstract Background This work presents a comparison and selection of different machine learning classification techniques applied in the identification of objects using data collected by an instrumented glove during a grasp process. The selected classifiers techniques can be applied to e-rehabilitation and e-training exercises for different pathologies, as in aphasic patients. Methods The adopted method uses the data from a commercial instrumented glove. An experiment was carried out, where three subjects using an instrumented glove had to grasp eight objects of common use. The collected data were submitted to nineteen different classification techniques (available on the scikit-learn library of Python) used in two classifier structures, with the objective of identifying the grasped object. The data were organized into two dataset scenarios: one with data from the three users and another with individual data. Results As a result of this work, three classification techniques presented similar accuracies for the classification of objects. Also, it was identified that when training the models with individual dataset the accuracy improves from 96 to 99%. Conclusions Classification techniques were used in two classifier structures, one based on a single model and the other on a cascade model. For both classifier structure and scenarios, three of the classification techniques were selected due to the high reached accuracies. The highest results were obtained using the classifier structure that employed the cascade models and the scenario of individual dataset.

Increasing student motivation and engagement in classroom (and during the study in general) is the aim of every lecturer. Never stopping development of new digital tools and media present a new challenge in the educational process. The goal of this research is to increase the knowledge and understanding of the influence of Bring Your Own Device (BYOD) approach (and use of the mobile devices in classrooms in general) on: teachers’ practice and students’ classroom activities, students’ attitude about bringing the mobile phones in the class and mobile phone applications in education processes. This research focuses on undergraduate and postgraduate mechanical engineering students. Personal reflection of the lecturers and online survey for students was used as a tool to investigate participants’ attitude towards mobile applications as a method of promotion of active learning in engineering education.

Internet usage has grown dramatically since the early years of its inception. The rich field of data provided by internet users in interaction with digital media content can provide insight into web-based navigation behavior and underlying psychological dimensions. Human-computer interaction in the web is an underutilized source of data for understanding human online behavior. While researchers and usability testing services do use these sources to analyze human behavior and user experience, access to the diverse range of other potentially useful data available during web-based interaction for research is limited. In this paper, we propose a novel tool in the form of a web browser extension, referred to as Latent, which can be used to simultaneously capture information from different sources while users interact with digital content. The data acquisition capabilities of Latent makes it suitable for various research purposes, ranging from studies of usability to decision-making and personality. A particular advantage of Latent is that the method and control of data acquisition is completely transparent to the user. We present the architecture of the web browser extension, describe the data that can be acquired, and report on the residual impact of the tool on the user's computer processing resources.

RESUMEN Objetivo: analizar el riesgo de aparición y la prevalencia de lesión por presión en personas encamadas asistidas por las unidades de atención primaria en el domicilio, además de describir las características sociodemográficas de los participantes del estudio, así como las condiciones clínicas y de tratamiento de los pacientes con lesiones por presión. Método: se trata de un estudio transversal, con 79 participantes encamados y englobados en el programa Estrategia de Salud Familiar. Los datos fueron recogidos mediante entrevista semiestructurada, y el riesgo de aparición de lesiones por presión se estimó mediante la aplicación de la escala de Braden. Resultados: se verificó que la condición clínica de los usuarios que necesitaron cuidados en el domicilio supone un riesgo significativo para el desarrollo de la úlcera por presión o agravamiento de estas lesiones, especialmente en los ancianos. Se evidenció la presencia de lesión por presión en el 15,1%. Conclusión: el estudio pone de relieve el elevado riesgo para el desarrollo de úlcera por presión en la población del municipio.

Fluorescence microscopy provides an unparalleled tool for imaging biological samples. However, producing high-quality volumetric images quickly and without excessive complexity remains a challenge. Here, we demonstrate a four-camera structured illumination microscope (SIM) capable of simultaneously imaging multiple focal planes, allowing for the capture of 3D fluorescent images without any axial movement of the sample. This setup allows for the acquisition of many different 3D imaging modes, including 3D time lapses, high-axial-resolution 3D images, and large 3D mosaics. We imaged mitochondrial motions in live cells, neuronal structure in Drosophila larvae, and imaged up to 130 µm deep into mouse brain tissue. After SIM processing, the resolution measured using one of the four cameras improved from 357 nm to 253 nm when using a 30×/1.05 NA objective.

Despite the advances of modern medicine and the development of innovative and promising new therapeutic strategies for the treatment of the numerous types of cancer, far too many patients still lose the battle against these devastating diseases [...]

The majority of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC) (R/M) do not benefit from anti-PD-1 therapy. Hypoxia induced immunosuppression may be a barrier to immunotherapy. Therefore, we examined the metabolic effect of anti-PD-1 therapy in a murine MEER HNSCC model as well as intratumoral hypoxia in R/M patients. In order to characterize the tumor microenvironment in PD-1 resistance, a MEER cell line was created from the parental line that are completely resistant to anti-PD-1. These cell lines were then metabolically profiled using seahorse technology and injected into C57/BL6 mice. After tumor growth, mice were pulsed with pimonidazole and immunofluorescent imaging was performed to analyze hypoxia and T cell infiltration. To validate the preclinical results, we analyzed tissues from R/M patients (n=36) treated with anti-PD-1 mAb, via immunofluorescent imaging for number of CD8+ T cells (CD8), Tregs and the percent area (CAIX) and mean intensity (I) of carbonic anhydrase IX in tumor. We analyzed disease control rate (DCR), progression free survival (PFS), and overall survival (OS) using proportional odds and proportional hazards (Cox) regression. We found that anti-PD-1 resistant MEER has significantly higher oxidative metabolism, while there was no difference in glycolytic metabolism. Intratumoral hypoxia was significantly increased and CD8+ T cells decreased in anti-PD-1 resistant tumors compared with parental tumors in the same mouse. In R/M patients, lower tumor hypoxia by CAIX/I was significantly associated with DCR (p=0.007), PFS, and OS, and independently associated with response (p=0.028) and PFS (p=0.04) in a multivariate model including other significant immune factors. During PD-1 resistance, tumor cells developed increased oxidative metabolism leading to increased intratumoral hypoxia and a decrease in CD8+ T cells. Lower tumor hypoxia was independently associated with increased efficacy of anti-PD-1 therapy in patients with R/M HNSCC. To our knowledge this is the first analysis of the effect of hypoxia in this patient population and highlights its importance not only as a predictive biomarker but also as a potential target for therapeutic intervention.

The ability to effectively resolve complex environmental problems hinges upon the capacity to address several different challenges in concert. These challenges, what we refer to as policy issues, often relate to one another – they interdepend. Policy issue interdependency has been extensively theorised in the literature, yet few methodological approaches and little empirical evidence exist to translate the concept of policy issue interdependency to the on-the-ground realities facing policy actors in specific cases and contexts. We build from previous studies to develop a methodological procedure that investigates policy issue interdependencies in ways that take into account what measures and possible solutions policy actors have at their disposal in specific cases for specific environmental problems. By applying our methodological procedure to a case of water governance in Sweden, four insights emerged. First, validation by stakeholders confirms that our procedure produces reliable results. Second, we find that many, but certainly not all, policy issues are interdependent. More specifically, different patterns of policy issue interdependencies are associated with the biophysical and the governance spheres, respectively. Third, our results suggest that policy issue interdependencies are most important to consider when the overall level of interdependency is moderate. Last, our study raises new questions about policy actors’ perception of policy issue interdependencies. In particular, a key question for future research would be if reinforcing (win-win) or counteracting (trade-off) interdependencies are easier to comprehend and act on for policy actors.

Abstract Urban flooding is a perennial problem, especially in developing countries with relatively weak infrastructure under ever‐increasing stress due to climate change and human activities. We simulate the temporally variable flood‐water depth and inundation area under four designed rainfall patterns in the typical tropical rainforest city of Hue, Vietnam. The four rainfall types are R1 (peak at fifth hour), R2 (peak at 20th hour), R3 (peak at first hour), and R4 (peak at 13th hour). Results show that temporal rainfall pattern R4 with peak rainfall in the middle of the total period yielded the maximum water depth of 1.88 m. R3, with peak rainfall in the first hour, yields the shallowest maximum water depth and the largest inundation extent. When the water depth for R3 is 0.1–0.2 m, the inundated area caused by R3 is 3–4 times that of the other three patterns. Analysis of urban flood inundation in Hue provides a management tool to facilitate flood risk management in the context of extreme rainfall.

A complexidade do transtorno do espectro autista tem mobilizado, no contexto escolar, o fazer docente. Nesse âmbito, faz-se necessário refletir acerca da formação do professor para lidar com o ensino de alunos com esse diagnóstico. Este artigo, resultado de uma pesquisa de mestrado realizada em uma escola de educação especial localizada no interior do estado de São Paulo, objetiva discutir como o professor, que se torna pesquisador de sua prática, articula as relações entre o referencial teórico histórico-cultural e a prática pedagógica. Os participantes foram o professor, formado em Pedagogia e mestrando em Educação, e seu aluno, com espectro autista. Durante o ano letivo, o professor registrou suas aulas em videogravações que foram posteriormente transcritas. Ao fundamentar sua prática na referida teoria, o professor passou a considerar atividades que favorecessem a imersão do aluno na esfera simbólica tendo, como primordial, o papel da linguagem sígnica. As análises, de cunho microgenético, trazem indícios de que: 1. A mudança na prática docente foi um processo (in)tenso; 2. As idas e vindas do processo de (trans)formação desvelam as tensões entre a apropriação de um referencial teórico e o modo de se realizar a prática pedagógica; 3. A produção de um saber pedagógico é oriunda do movimento da teoria com a prática.