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Purpose – Adolescent pregnancy stands as a societal challenge, compelling young individuals to prematurely discontinue their education. Conversely, an expansion of high school education can potentially diminish rates of adolescent pregnancy, given that educational attainment stands as the foremost risk factor influencing sexual initiation, the use of contraceptive methods during initial sexual encounters and fertility. The aim of this paper is to analyze the impact of the implementation of the public educational policy introducing full-time schools (FTS) for high schools in the state of Ceará, Brazil, on early pregnancy rates. Design/methodology/approach – Using the difference-in-differences method with multiple time periods, we measured the average effect of this staggered treatment on the treated municipalities. Findings – The main result indicates a reduction of 0.849 percentage points in the teenage pregnancy rate. Concerning dynamic effects, the establishment of FTS in treated municipalities results in a 1.183–1.953 percentage point decrease in teenage pregnancy rates, depending on the timing of exposure. We explored heterogeneous effects within socioeconomically vulnerable municipalities, yet discerned no impact on this group. Rigorous tests confirm the robustness of the results. Originality/value – This paper aims to contribute to: (1) the consolidation of research on the subject, given the absence of such research in Brazil to the best of our knowledge; (2) the advancement and analysis of evidence-based public policy and (3) the utilization of novel longitudinal data and methodology to evaluate adolescent pregnancy rates.

PEDOT:PSS has found numerous applications in the field of advanced materials, especially in the development of organic electronics. Embedding nanoparticles into the polymer matrix has emerged as an effective strategy to modify the properties of PEDOT:PSS and develop advanced functional composites. Over the past decade, Halloysite nanotubes (HNT) have garnered significant interest and utility as nanofillers and/or templates due to their unique physical-chemical properties, small size, relatively low cost, and large availability. Interestingly, pairing PEDOT:PSS with non-conductive HNT has been demonstrated to enhance the charge transport properties of the composite film. Our discoveries show how the HNT can act as scaffolding for PEDOT:PSS by improving the local ordering of PEDOT chains and enabling the formation of conductive pathways. Consequently, the mechanism responsible for the observed changes in conductivity and the correlation between PEDOT:PSS and insulating nanofillers (HNT) could be different to that previously proposed. Hence, in this work it was observed that PEDOT:PSS/HNT composite films exhibited a non-linear conductivity dependence as a function of the HNT loading. From thermogravimetric analysis, infrared and UV-Vis-NIR spectroscopies, as well as impedance spectroscopy, a more complex interaction between the polymer chains and the nanotubes is revealed. Our study includes the modification of the interaction between the PEDOT chains and the nanofillers by using the secondary doping effect and functionalization of the nanotubes, which confirms our findings. These results represent a significant progress toward a deeper understanding of the emergence of a conductive polymer network on the nanofiller surface, leading to improvements in the electrical conductivity in the composite material.

Abstract Zoonoses constitute a major risk to human health. Comprehensive assessments on the potential emergence of novel disease outbreaks are essential to ensure the effectiveness of sanitary controls and to establish mitigating actions. Through a continental‐scale survey of rural human settlements conducted over 13 years in 15 Neotropical countries, we document the vast extent of poaching to meet the local demand for pets, resulting in thousands of families living with ca. 275 species of wild animals without any sanitary controls. Parrots account for ca. 80% of wild pets, dying mostly from diseases at an average age of 1 year. This culturally rooted tradition, which dates back to pre‐Columbian times, may lead to health risks by bringing wild animals prone to carrying parasites and pathogens into close contact with humans and their exotic pets and livestock. Although animal pathogens and parasites have been transmitted to humans for centuries, the current trend of human population growth and connectivity can increase the risk of zoonotic outbreaks spreading at an unprecedented pace. Similarly, disease transmission from humans and poultry to wild animals is also expected to be facilitated via wild pets, leading to conservation problems. Several studies have highlighted the risk posed by wildlife city markets for cross‐species disease transmission, ignoring the risk associated with widespread pet ownership of wild animals poached locally in rural areas. Given its geographic and social dimensions, a holistic approach is required to reduce this illegal activity as well as to strengthen health surveillance of seized individuals and people in close contact with poached pets, which would benefit both people and wildlife. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Introduction Dolutegravir/lamivudine (DTG/3TC) and dolutegravir/rilpivirine (DTG/RPV) are fixed-dose, complete, single-tablet, two-drug regimens (2DRs) indicated for HIV-1. DTG/3TC is approved for antiretroviral therapy (ART)-naive people with HIV-1 and virologically suppressed individuals to replace current ART; DTG/RPV is indicated for virologically suppressed individuals as a switch option. Virologic efficacy and effectiveness of these DTG-based 2DRs have been demonstrated in phase 3 clinical trials and real-world cohorts, primarily from Europe. This study characterized real-world use of DTG-based 2DRs for HIV-1 treatment in the USA. Methods TANDEM was a retrospective medical chart review across 24 US sites. Individuals aged ≥ 18 years who initiated DTG/3TC or DTG/RPV before September 30, 2020, with ≥ 6 months of follow-up were included. One cohort included ART-naive people who initiated DTG/3TC (n = 126), and two other cohorts included virologically suppressed (HIV-1 RNA

Abstract Introduction Dolutegravir/lamivudine (DTG/3TC) was first approved by the US Food and Drug Administration in 2019 for the treatment of antiretroviral therapy (ART)-naive people with HIV-1 based on results from the pivotal GEMINI-1/GEMINI-2 trials. Around that time, immediate initiation of treatment upon diagnosis was recommended in the US Department of Health and Human Services guidelines. Here we report results from 126 treatment-naive people with HIV-1 who initiated DTG/3TC as part of a test-and-treat strategy (n = 61) or with high baseline viral loads (HIV-1 RNA ≥ 100,000 copies/ml; n = 16) from the TANDEM study. Methods TANDEM was a US-based, retrospective chart review study that included a cohort of 126 individuals aged ≥ 18 years with no prior history of ART who initiated DTG/3TC before September 30, 2020, and had ≥ 6 months of follow-up. Test-and-treat was defined as ART initiation shortly after diagnosis without available viral load, CD4 + cell count, or HIV-1 resistance data. Outcomes included virologic suppression (HIV-1 RNA 250,000 copies/ml: 1.0 [0.7–1.1] years), 14 (88%) achieved virologic suppression, 13 (81%) remained suppressed, and none discontinued DTG/3TC. Patient preference was the most common HCP-reported reason for initiating DTG/3TC in this subgroup. Conclusions Results demonstrate real-world effectiveness of DTG/3TC, with few discontinuations, in people with HIV-1 in test-and-treat settings or with high baseline viral loads.

Abstract The dipolar interaction can be attractive or repulsive, depending on the position and orientation of the dipoles. Constraining atoms to a plane with their magnetic moment aligned perpendicularly leads to a largely side-by-side repulsion and generates a dipolar barrier which prevents atoms from approaching each other. We show experimentally and theoretically how this can suppress dipolar relaxation, the dominant loss process in spin mixtures of highly magnetic atoms. Using dysprosium, we observe an order of magnitude reduction in the relaxation rate constant, and another factor of ten is within reach based on the models which we have validated with our experimental study. The loss suppression opens up many new possibilities for quantum simulations with spin mixtures of highly magnetic atoms.

Abstract The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

The article provides an introduction to the second of a pair of special issues devoted to academic filmmaking, which contains ten video essays and prose guiding texts. The article describes the variety of filmmaking practice in the academy, and some of the venues where examples of the practice are published or exhibited. It gestures at the multiple origins of academic filmmaking with special reference to the tradition of the essay film, and finds a key reflexive moment in Eric S. Faden’s (prose) “Manifesto for Critical Media” (2008), which articulated the challenge of using “image, voice, pacing, text, sound, music, montage, rhythm” to create scholarly audiovisual work. The introduction goes on to set out the aims for the special issues, and to describe the contents of the video essays and some of the features, concerns or approaches shared between and across those contents. The video essays derive from fields including videographic criticism, anthropology, experimental cinema, and participatory and activist filmmaking.

Purpose: Current monoclonal antibody-based treatment approaches for cutaneous T cell lymphoma (CTCL) rely heavily on the ability to identify a tumor specific target that is essentially absent on normal cells. Herein, we propose tumor associated glycoprotein-72 (TAG-72) as one such target. TAG-72 is a mucin-associated, truncated O-glycan that has been identified as a chimeric antigen receptor (CAR)-T cell target in solid tumor indications. To date, TAG-72 targeting has not been considered in the setting of hematological malignancies. Experimental design: CD3+ cells from patients with CTCL were analyzed for TAG-72 expression by flow cytometry. Immunohistochemistry was used to assess TAG-72 expression in CTCL patient skin lesions and a TAG-72 ELISA was employed to assess soluble TAG-72 (CA 72-4) in patient plasma. TAG-72 CAR transduction was performed on healthy donor (HD) and CTCL T cells and characterized by flow cytometry. In vitro CAR-T cell function was assessed by flow cytometry and xCELLigence® using patient peripheral blood mononuclear cells and proof-of-concept ovarian cancer cell lines. In vivo CAR-T cell function was assessed in a proof-of-concept, TAG-72+ ovarian cancer xenograft mouse model. Results: TAG-72 expression was significantly higher on total CD3+ T cells and CD4+ subsets in CTCL donors across disease stages, compared to that of HDs. TAG-72 was also present in CTCL patient skin lesions, whereas CA 72-4 was detected at low levels in both CTCL patient and HD plasma with no differences between the two groups. In vitro cytotoxicity assays showed that anti-TAG-72 CAR-T cells significantly, and specifically reduced CD3+TAG-72+ expressing CTCL cells, compared to culture with unedited T cells (no CAR). CTCL CAR-T cells had comparable function to HD CAR-T cells in vitro and CAR-T cells derived from CTCL patients eradicated cancer cells in vivo. Conclusion: This study shows the first evidence of TAG-72 as a possible target for the treatment of CTCL.

The article provides an introduction to the first of a pair of special issues devoted to academic filmmaking, which, apart from this introduction, contains eleven prose articles. The article describes the variety of filmmaking practice in the academy, and some of the venues where examples of the practice are published or exhibited. It gestures at the multiple origins of academic filmmaking with special reference to the tradition of the essay film, and finds a key reflexive moment in Eric S. Faden’s (prose) “Manifesto for Critical Media” (2008), which articulated the challenge of using “image, voice, pacing, text, sound, music, montage, rhythm” to create scholarly audiovisual work. The introduction goes on to set out the aims for the special issues, and to describe the contents of the eleven articles in the first issue and some of the features, concerns or approaches shared between and across those contents. The eleven articles deal with themes raging from academic filmmaking as activism, to vulnerability and embodiment, to the challenges of production and publishing and of institutional legitimization.

From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the Spag7 gene linked to metabolic dysfunction in mice. Here, we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure. The KO animals also display reduced exercise tolerance and muscle function due to impaired mitochondrial function. Furthermore, SPAG7-deficiency in developing embryos leads to intrauterine growth restriction, brought on by placental insufficiency, likely due to abnormal development of the placental junctional zone. This insufficiency leads to loss of SPAG7-deficient fetuses in utero and reduced birth weights of those that survive. We hypothesize that a ‘thrifty phenotype’ is ingrained in SPAG7 KO animals during development that leads to adult obesity. Collectively, these results indicate that SPAG7 is essential for embryonic development and energy homeostasis later in life.

The industrial processing of coconut to produce valuable foods, such as water and milk, generates large volumes of waste, especially the fruit shell. Despite this, material can be used in bioprocess applications, e.g., the production of enzymes, its recalcitrance hinders the cultivation of microorganisms, and low productivity is usually achieved. In this study, the production of cellulolytic enzymes through solid-state fermentation (SSF) and their extraction was investigated using the green coconut fiber pretreated by steam explosion, followed by alkali. The fungus Trichoderma reesei CCT-2768 was cultivated, using an experimental design, to study the effect of the water activity and the amount of biomass in the reactor. The combination of the pretreatment strategies yielded more porous biomass, with less hemicellulose (5.38%, compared to 10.15% of the raw biomass) and more cellulose (47.77% and 33.96% in the pretreated and raw biomasses, respectively). The water activity significantly affected the production of cellulases, with maximum activity yielded at the highest investigated value (0.995). Lastly, the extraction of the enzymes from the cultivation medium was studied, and a 9 g/L NaCl solution recovered the highest CMCase and FPase activities (5.19 and 1.19 U/g, respectively). This study provides an important contribution to the valorization of the coconut residue through (i) the application of the steam explosion technology to optimize the production of cellulases using the SSF technology and (ii) their extraction using different solvents.

‘Candidatus Phytoplasma ulmi’ (Ca. P. ulmi) belongs to the ribosomal subgroup 16SrV-A and is associated with dieback, shoot proliferation and yellows disease on various Ulmus spp. Other plant species, such as Carpinus betulus and Prunus spp. have also been reported infected by the same pathogen. In 2021, in the frame of research activities focused on grapevine’s Flavescence dorée (FD), one specimen of Orientus ishidae - an East Palearctic leafhopper that was identified as an alternative vector of FD phytoplasmas - was found harboring Ca. P. ulmi in southern Switzerland. No phytoplasmas were detected in plant samples taken in the same location. Orientus ishidae has already been reported to be able to acquire diverse phytoplasmas associated with other plant diseases, such as Peach X-disease. This is the first report of Ca. P. ulmi in Switzerland, as well as in O. ishidae. Ca. P. ulmi may potentially be present in the wild compartment of the Swiss Pre-alpine and Alpine range, but no dedicated survey has so far been conducted. In the case of O. ishidae, this finding highlights the broad affinity of such a species for the acquisition of several phytoplasmas. This calls for a further investigation regarding its potential role as a vector on various pathosystems of agronomic importance.

Abstract Digital pathology has seen a proliferation of deep learning models in recent years, but many models are not readily reusable. To address this challenge, we developed WSInfer: an open-source software ecosystem designed to streamline the sharing and reuse of deep learning models for digital pathology. The increased access to trained models can augment research on the diagnostic, prognostic, and predictive capabilities of digital pathology.

The eight-toothed spruce bark-beetle Ips typographus is the most damaging insect pest of Norway spruce in Europe, and it poses a serious risk to spruce in other countries where it is not currently present but might be introduced. The beetle is not native to the UK and before 2018 it had not been found established anywhere within the country. In November 2018, however, several adult Ips typographus were found in a billet trap set up as part of annual surveys that the UK carries out to monitor for this and other quarantine bark beetle pests. The finding of adult beetles in the billet trap, a few miles south of Ashford in Kent, led to the discovery of a breeding population in an adjacent woodland. Delimiting surveys to 1 km and further surveys to 50 km showed that the infestation was confined to a single stand of Norway spruce. The stand was felled in January and February 2019, and the material destroyed, and beetles emerging on the site were trapped out using pheromone traps, billet piles and trap trees. These prompt actions eradicated the breeding population, but small numbers of adult Ips typographus continued to be caught on the outbreak site in 2020 and 2021. These captures, and numerous adult Ips typographus caught in pheromone traps set up across the region in response to the outbreak, indicate that incursions of adult Ips typographus are occurring on a regular basis, most likely from source populations in northern France and Belgium. The arrival of adult Ips typographus over a wide area and the potential for further outbreaks represents a continuing threat to spruce woodlands in south-east England, and has important implications for surveillance and monitoring and the management of spruce in this part of the UK.

Cell-to-cell gene expression variability is an inherent feature of complex biological systems, such as immunity and development. Single-cell RNA sequencing is a powerful tool to quantify this heterogeneity, but it is prone to strong technical noise. In this article, we describe a step-by-step computational workflow that uses the BASiCS Bioconductor package to robustly quantify expression variability within and between known groups of cells (such as experimental conditions or cell types). BASiCS uses an integrated framework for data normalisation, technical noise quantification and downstream analyses, propagating statistical uncertainty across these steps. Within a single seemingly homogeneous cell population, BASiCS can identify highly variable genes that exhibit strong heterogeneity as well as lowly variable genes with stable expression. BASiCS also uses a probabilistic decision rule to identify changes in expression variability between cell populations, whilst avoiding confounding effects related to differences in technical noise or in overall abundance. Using a publicly available dataset, we guide users through a complete pipeline that includes preliminary steps for quality control, as well as data exploration using the scater and scran Bioconductor packages. The workflow is accompanied by a Docker image that ensures the reproducibility of our results.

En México, como derecho humano, se ha procurado la cobertura universal en salud. Consecuencia de la transición demográfica y el incremento en la expectativa de vida, se estima que entre el 30 y 70% de los pacientes con cáncer son adultos mayores. Relacionado con el envejecimiento, el adulto mayor con cáncer es considerado social y médicamente vulnerable, lo que hace imperativa la necesidad de una atención multidisciplinaria como parte del estándar de cuidado y atención, mismas que no han sido consideradas un tema prioritario en salud. Las disparidades para recibir una atención oportuna y adecuada en el adulto mayor con cáncer, suelen ser producto de las barreras en el acceso a este tipo de servicios, por lo que el objetivo de este artículo es: identificar las barreras de acceso para la atención en oncología geriátrica; barreras relacionadas a la fragmentación y barreras propias del sistema de salud en México.

Malbranchea is a genus within the order Onygenales (phylum Ascomycota) that includes predominantly saprobic cosmopolitan species. Despite its ability to produce diverse secondary metabolites, no genomic data for Malbranchea spp. are currently available in databases. Therefore, in this study, we obtained, assembled, and annotated the genomic sequence of the ex-type strain of Malbranchea zuffiana (CBS 219.58). For the genomic sequencing, we employed both the Illumina and PacBio platforms, followed by hybrid assembly using MaSuRCA. Quality assessment of the assembly was performed using QUAST and BUSCO tools. Annotation was conducted using BRAKER2, and functional annotation was completed with InterProScan. The resulting genome was of high quality, with a size of 26.46 Mbp distributed across 38 contigs and a BUSCO completion rate of 95.7%, indicating excellent contiguity and assembly completeness. A total of 8248 protein-encoding genes were predicted, with functional annotations assigned to 73.9% of them. Moreover, 82 genes displayed homology with entries in the Pathogen Host Interactions (PHI) database, while 494 genes exhibited similarity to entries in the Carbohydrate-Active Enzymes (CAZymes) database. Furthermore, 30 biosynthetic gene clusters (BGCs) were identified, suggesting significant potential for the biosynthesis of diverse secondary metabolites. Comparative functional analysis with closely related species unveiled a considerable abundance of domains linked to enzymes involved in keratin degradation, alongside a restricted number of domains associated with enzymes engaged in plant cell wall degradation in all studied species of the Onygenales. This genome-based elucidation not only enhances our comprehension of the biological characteristics of M. zuffiana but also furnishes valuable insights for subsequent investigations concerning Malbranchea species and the order Onygenales.

COVID-19 laboratory diagnosis primarily relies on molecular tests, highly sensitive during early infection stages with high viral loads. As the disease progresses, sensitivity decreases, requiring antibody detection. Since the beginning of the pandemic, serological tests have been developed and made available in Brazil, but their diagnostic performance varies. This study evaluated the IBMP ELISA IgA/IgM/IgG COVID-19 kit performance in detecting SARS-CoV-2 antibodies. A total of 90 samples, including 64 from COVID-19 patients and 26 pre-pandemic donors, were assessed based on time post symptom onset (0–7, 8–14, and 15–21 days). The kit showed 61% sensitivity, 100% specificity, and 72% accuracy overall. Sensitivity varied with time, being 25%, 57%, and 96% for 0–7, 8–14, and 15–21 days, respectively. Similar variations were noted in other commercial tests. The Gold ELISA COVID-19 (IgG/IgM) had sensitivities of 31%, 71%, and 100%, while the Anti-SARS-CoV-2 NCP ELISA (IgG) and Anti-SARS-CoV-2 NCP ELISA (IgM) showed varying sensitivities. The IBMP ELISA kit displayed high diagnostic capability, especially as the disease progressed, complementing COVID-19 diagnosis. Reproducibility assessment revealed minimal systematic and analytical errors. In conclusion, the IBMP ELISA IgA/IgM/IgG COVID-19 kit is a robust tool for detecting anti-SARS-CoV-2 antibodies, increasing in efficacy over the disease course, and minimizing false negatives in RT-PCR COVID-19 diagnosis.

Abstract Introduction Dolutegravir/lamivudine (DTG/3TC) is a 2-drug regimen for HIV-1 treatment with long-term efficacy and good tolerability comparable to 3- or 4-drug regimens. This study evaluated DTG/3TC cost versus other standard single-tablet regimens during its first year of approval. Methods This retrospective study analyzed US claims data from adults with HIV-1. Eligibility criteria included ≥ 1 dispensing of DTG/3TC, DTG/abacavir (ABC)/3TC, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF, and darunavir (DRV)/COBI/FTC/TAF (index date was first dispensing) and ≥ 6 months of continuous eligibility before index date (baseline period). All-cause and HIV-related healthcare costs were evaluated during the observation period (index date until earliest of end of continuous eligibility or data availability). Adjusted cost differences and adjusted cost ratios were estimated using multivariable regression models controlling for differences in baseline characteristics between cohorts. Results Overall, 22,061 individuals with HIV-1 and dispensed treatment with DTG/3TC (n = 590), DTG/ABC/3TC (n = 4355), BIC/FTC/TAF (n = 9068), EVG/COBI/FTC/TAF (n = 7081), or DRV/COBI/FTC/TAF (n = 967) were included. Most claims data were from men (mean age ~ 46 years). Mean unadjusted all-cause total healthcare costs per patient per month were significantly lower for DTG/3TC versus BIC/FTC/TAF and DRV/COBI/FTC/TAF, and mean unadjusted HIV-related healthcare costs per patient per month were significantly lower for DTG/3TC versus DRV/COBI/FTC/TAF. Cost differences were primarily driven by significantly lower pharmacy costs for DTG/3TC versus other regimens (P

IntroductionTesticular cancer is among the most common malignancies in men under the age of 50 years. Most testicular symptoms are linked to benign diseases. Men's awareness of testicular diseases and testicular self-examination behaviours are suboptimal. In this pilot feasibility study and process evaluation we examine the feasibility of conducting a future definitive randomised controlled trial (RCT) to test the effect of the Enhancing Men's Awareness of Testicular Diseases using Virtual Reality intervention (E-MATVR) compared to the Enhancing Men's Awareness of Testicular Diseases using Electric information control (E-MATE). The study protocol is registered on ClinicalTrials.gov (NCT05146466).MethodsMale athletes, engaged in Gaelic games, and aged 18 to 50 years were included. Recruitment was via FacebookTM, XTM (formerly TwitterTM), and posters. Participants were individually randomised to either E-MATVR or E-MATE. Data were collected at baseline (T0), immediately post-test (T1), and three months post-test (T2) using surveys. Qualitative interviews were conducted with participants and researchers.ResultsData were collected from 74 participants. Of those, 66 were retained. All E-MATVR participants and most E-MATE participants (n = 33, 89.2%) agreed/strongly agreed that the device was easy to use and that they were engaged to learn by the device. Most E-MATVR participants (n = 34, 91.9%) and all E-MATE participants agreed/strongly agreed that the time it took them to complete the intervention was reasonable. All 74 participants were extremely satisfied/somewhat satisfied with their overall participation in the study. E-MATVR was described as interactive, easy, fun, and close to real life. Initial difficulty using VR equipment, nausea, and technical issues were identified as challenges to engaging with E-MATVR. Recommendations were made to make VR more accessible, shorten the survey, and incorporate more interactivity. Across all participants, mean testicular knowledge scores (range 0-1) increased from 0.4 (SD 0.2) at T0 to 0.8 (SD 0.2) at T1. At T2, overall mean scores for participants were 0.7 (SD 0.2). Mean knowledge scores did not differ by trial arm at any timepoint. At T2, all E-MATVR participants and 29/32 E-MATE participants (90.6%) reported purposefully examining their testes within the past three months.ConclusionFindings are promising, highlighting the feasibility of using VR to promote young athletes' awareness of testicular diseases. Considering the strengths, limitations, and lessons learned from this study, some modifications are required prior to conducing an RCT. These include but are not limited to shortening survey questions, incorporating more interactivity and visual content, and targeting more heterogenous male-dominated environments.

Objectives. Rare metabolic bone diseases can present with symptoms mimicking more common rheumatological conditions including spondyloarthritis, osteoarthritis, and fibromyalgia. Increasing awareness of these rare diseases within the rheumatology community is vital to ensure that affected patients are diagnosed and appropriately treated. The literature includes several reports of tumour-induced osteomalacia initially diagnosed as rheumatic disease, but other rare diseases such as X-linked hypophosphatemia (XLH) and hypophosphatasia (HPP) also deserve attention. Here, we describe two cases of adult patients incorrectly diagnosed with ankylosing spondylitis and osteoarthritis who, upon referral to a metabolic bone disease specialist, were subsequently diagnosed with XLH and HPP, respectively, profoundly altering their management. Methods. The cases were collected from Brigham and Women’s Hospital, Boston, MA, USA, and Vanderbilt University Medical Center, Nashville, TN, USA. Results. Details of the patients’ respective medical and family histories are presented, and the clinical and biochemical investigations undertaken to reach the correct diagnoses are described. Conclusion. Rheumatologists should be encouraged to think beyond common rheumatological diseases when faced with symptoms such as bone pain, muscle pain, and stiffness, especially when accompanied by manifestations including atraumatic fractures, poor dentition, and hearing loss. In cases where one of these rare diseases is suspected, referral to a metabolic bone disease specialist for confirmation of diagnosis is encouraged as effective treatment options have recently become available.

Objectives Tailored models of home-based palliative care aimed to support death at home, should also ensure optimal symptom control. This study aimed to explore symptom occurrence and distress over time in Palliative Extended And Care at Home (PEACH) model of care recipients.Design This was a prospective cohort study.Setting and participants Participants were consecutive recipients of the PEACH rapid response nurse-led model of care in metropolitan Sydney (December 2013–January 2017) who were in the last weeks of life with a terminal or deteriorating phase of illness and had a preference to be cared or die at home.Outcome measures Deidentified data including sociodemographic and clinical characteristics, and symptom distress scores (Symptom Assessment Score) were collected at each clinical visit. Descriptive statistics and forward selection logistic regression analysis were used to explore influence of symptom distress levels on mode of separation ((1) died at home while still receiving a PEACH package, (2) admitted to a hospital or an inpatient palliative care unit or (3) discharged from the package (alive and no longer requiring PEACH)) across four symptom distress level categories.Results 1754 consecutive clients received a PEACH package (mean age 70 years, 55% male). 75.7% (n=1327) had a home death, 13.5% (n=237) were admitted and 10.8% (n=190) were still alive and residing at home when the package ceased. Mean symptom distress scores improved from baseline to final scores in the three groups (p

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Abstract Sustained multisensory integration over long inter-stimulus time delays is typically found in older adults, particularly those with a history of falls. However, the extent to which the temporal precision of audio-visual integration is associated with longitudinal fall or fall risk trajectories is unknown. A large sample of older adults (N = 2319) were grouped into longitudinal trajectories of self-reported fall incidents (i.e., decrease, stable, or increase in number) and, separately, their performance on a standard, objective measure of fall risk, Timed Up and Go (TUG; stable, moderate decline, severe decline). Multisensory integration was measured once as susceptibility to the Sound-Induced Flash Illusion (SIFI) across three stimulus onset asynchronies (SOAs): 70 ms, 150 ms and 230 ms. Older adults with an increasing fall number showed a significantly different pattern of performance on the SIFI than non-fallers, depending on age: For adults with increasing incidents of falls, those aged 53–59 years showed a much smaller difference in illusion susceptibility at 70 ms versus 150 ms than those aged 70 + years. In contrast, non-fallers showed a more comparable difference between these SOA conditions across age groups. There was no association between TUG performance trajectories and SIFI susceptibility. These findings suggests that a fall event is associated with distinct temporal patterns of multisensory integration in ageing and have implications for our understanding of the mechanisms underpinning brain health in older age.

Tissue engineering strategies for tendon repair and regeneration rely heavily on the use of tendon derived cells. However, these cells frequently undergo phenotypic drift in vitro, which compromises their therapeutic potential. In order to maintain the phenotype of tendon derived cells in vitro, microenvironmental cues (biophysical, biochemical and/or biological in origin) have been used to better imitate the complex tendon microenvironment. Herein, the influence of planar and grooved (groove width of ∼1.0 µm, groove depth of ∼1.4 µm and distance between groves of ∼1.7 µm) poly(glycolide-co-ε-caprolactone) substrates with elastic modulus of 7 kPa and poly(lactide-co-trimethylene carbonate) substrates with elastic modulus of 12 kPa on human tendon derived cell response was assessed, using planar tissue culture plastic substrates of 3 GPa elastic modulus as control, in both basal and tenogenic media. At day 17, the grooved 12 kPa poly(lactide-co-trimethylene carbonate) substrate induced the highest deposition and alignment of collagen type I in tenogenic media. At day 17, the grooved 12 kPa poly(lactide-co-trimethylene carbonate) substrate and the tissue culture plastic induced the highest deposition and the tissue culture plastic and the planar 7 kPa poly(glycolide-co-ε-caprolactone) induced the lowest alignment of tenascin C in tenogenic media. Also at day 17 in tenogenic media, the grooved 12 kPa poly(lactide-co-trimethylene carbonate) substrate induced the upregulation of most tenogenic genes (COL1A1, COL3A1, MKX, TNMD). Our data further support the notion of multifactorial tissue engineering for effective control over cell fate in vitro setting.

Abstract Background Mifepristone, also known as RU-486, is an anti-progestational steroid with similar chemical structure to anabolic steroids. Given as a single dose in conjunction with misoprostol, mifepristone is used to induce medical abortion. Mifepristone administered chronically at a higher dose is also approved for the management of hypercortisolism. There have been only 2 reported cases of mifepristone associated liver injury, in both cases, in the setting of Cushing syndrome. We report a third patient with Cushing syndrome with mifepristone induced liver injury with unique histological findings that provide insight to the pathophysiology of liver injury in mifepristone and anabolic steroids. Case presentation Patient is a 63-year-old Caucasian female Cushing disease with no prior history of liver disease. She was started on mifepristone and semaglutide. Ninety days after initiating mifepristone, she developed deep jaundice, severe pruritus, fatigue, and nausea. Liver tests revealed a mixed hepatocellular/cholestatic pattern. Viral and autoimmune serologies were negative and there was no biliary dilatation on imaging. Liver biopsy showed severe cholestasis but no bile duct injury. Focal endothelialitis was present within a central venule. Cholestatic symptoms persisted for one month after presentation before slowly subsiding. Four months after stopping mifepristone, the patient’s symptoms completely resolved, and liver tests became normal. Compilation of Roussell Uclaf Causality Assessment Method score indicated probable causality. Conclusions Mifepristone shares a similar chemical structure as synthetic anabolic/androgenic steroids and there are many similarities in the clinical presentation of liver injury. This case and the 2 other reported cases share similar clinical characteristics. The observation of endothelialitis in our patient may provide a mechanistic link between mifepristone, or anabolic steroids in general, and the development of vascular complications such as peliosis.

Tumor-induced osteomalacia (TIO) is a rare form of osteomalacia caused by fibroblast growth factor-23 (FGF23)- secreting tumors. Most of these tumors are phosphaturic mesenchymal tumors (PMTs) typically involving soft tissue in the extremities and bone of the appendicular skeleton and cranium. We report the case of a 60-year-old woman with about 3 years of persistent bone pain and multiple fractures, initially diagnosed as osteoporosis, who was found to have hypophosphatemia with low 1,25-dihydroxyvitamin D and elevated alkaline phosphatase and inappropriately normal FGF23 consistent with TIO. Her symptoms improved with phosphate supplementation, vitamin D and calcitriol. 68Ga-DOTATATE imaging revealed a T12 vertebral body lesion confirmed on biopsy to be a PMT. She underwent resection of the PMT with resolution of TIO and increased bone density. This rare case of TIO secondary to a PMT of the thoracic spine highlights some of the common features of PMT-associated TIO and draws attention to PMT-associated TIO as a possible cause of unexplained persistent bone pain, a disease entity that often goes undiagnosed and untreated for years.

Abstract The combined effect of surface topography and substrate rigidity in stem cell cultures is still under‐investigated, especially when biodegradable polymers are used. Herein, we assessed human bone marrow stem cell response on aliphatic polyester substrates as a function of anisotropic grooved topography and rigidity (7 and 12 kPa). Planar tissue culture plastic (TCP, 3 GPa) and aliphatic polyester substrates were used as controls. Cell morphology analysis revealed that grooved substrates caused nuclei orientation/alignment in the direction of the grooves. After 21 days in osteogenic and chondrogenic media, the 3 GPa TCP and the grooved 12 kPa substrate induced significantly higher calcium deposition and alkaline phosphatase (ALP) activity and glycosaminoglycan (GAG) deposition, respectively, than the other groups. After 14 days in tenogenic media, the 3 GPa TCP upregulated four and downregulated four genes; the planar 7 kPa substrate upregulated seven genes and downregulated one gene; and the grooved 12 kPa substrate upregulated seven genes and downregulated one gene. After 21 days in adipogenic media, the softest (7 kPa) substrates induced significantly higher oil droplet deposition than the other substrates and the grooved substrate induced significantly higher droplet deposition than the planar. Our data pave the way for more rational design of bioinspired constructs.

Understanding the role teachers must play in fostering social justice is one of many tasks student teachers learn on practicum. This self-study is a collaborative endeavour between eight Brazilian teacher-researchers who work in multiple teaching positions and settings in different regions of the country. Our assumption within the broader research scope is that being a teacher-researcher has commonalities related to social justice whether teaching in K-12 schools or higher education. We have reconfigured a collaborative, four-stage methodological approach to practitioner research. In this paper, we investigate how one teacher-researcher and university professor – Luiz, the first author – has been transforming his practice towards social justice through the self-study of teacher education practices. His initial dilemma concerned his students’ practicum experiences. Through the prompting of his co-authors and critical friends, Luiz reflected on his decisions and assumptions. He presented his analysis to the group which generated the discussion which forms the basis of this paper. The contribution this paper makes is two-fold. One is to exemplify the rigorous method we used to generate alternative perspectives through self-study. The other is to explore the impact of deeply seated social injustices on our teacher education practices.

Due to their inherent plasticity, dermal fibroblasts hold great promise in regenerative medicine. Although biological signals have been well-established as potent regulators of dermal fibroblast function, it is still unclear whether physiochemical cues can induce dermal fibroblast trans-differentiation. Herein, we evaluated the combined effect of surface topography, substrate rigidity, collagen type I coating and macromolecular crowding in human dermal fibroblast cultures. Our data indicate that tissue culture plastic and collagen type I coating increased cell proliferation and metabolic activity. None of the assessed in vitro microenvironment modulators affected cell viability. Anisotropic surface topography induced bidirectional cell morphology, especially on more rigid (1,000 kPa and 130 kPa) substrates. Macromolecular crowding increased various collagen types, but not fibronectin, deposition. Macromolecular crowding induced globular extracellular matrix deposition, independently of the properties of the substrate. At day 14 (longest time point assessed), macromolecular crowding downregulated tenascin C (in 9 out of the 14 groups), aggrecan (in 13 out of the 14 groups), osteonectin (in 13 out of the 14 groups), and collagen type I (in all groups). Overall, our data suggest that physicochemical cues (such surface topography, substrate rigidity, collagen coating and macromolecular crowding) are not as potent as biological signals in inducing dermal fibroblast trans-differentiation.

A pedagogia crítica é uma abordagem dinâmica e transformadora da educação que deve continuar a se adaptar aos contextos sociais e históricos em rápida mudança. Neste artigo, defendemos que práticas pedagógicas baseadas em saberes e princípios indígenas possibilitam uma pedagogia crítica para a Saúde e Educação Física que questione os efeitos da precariedade. Com base especificamente no contexto de Aotearoa Nova Zelândia, descrevemos os princípios de Kaupapa Māori, uma perspectiva indígena que expressa as aspirações Māori e os valores Māori específicos, e como esses princípios são articulados em Saúde e Educação Física. Argumentamos que as práticas de Saúde e Educação Física sustentadas por Kaupapa Māori têm o potencial de reduzir a raiva, a ansiedade e a alienação por meio do fortalecimento de conexões entre alunos, entre alunos e professores, com a terra e com identidades emergentes.

Abstract Illegal wildlife trade remains highly active in the Neotropics, as indicated by the thousands of parrots annually sold in illicit city markets. However, little is known about where parrots are poached, whether certain parrot species are selected among those available in the wild, their trade routes, and potential conservation impacts. We conducted a large‐scale survey in Peru and southern Ecuador to simultaneously estimate the relative abundance of parrots in the wild and as household pets in rural areas, determine their origin (locally poached or bought at city markets), and measured the shortest distances to their native ranges and markets through the existing grid of roads. Household‐poached native parrots were found in 96% of the rural localities surveyed. Most pets were locally poached, with only 14% of them bought at markets. Parrot poaching was highly selective, with preferred species (mainly Amazon parrots and large macaws) being collected much more than expected given their abundances in the wild and attaining higher prices than the other species. Individuals that were moved away from their native ranges or bought at distant markets were of those species most preferred by people, and covered large distances (up to 1010 km), even crossing country boundaries. Our results differ from those previously obtained from city markets and seizures of illegally traded parrots in Peru, where preferred species were underrepresented. Local poaching and rural trade activities act at very large spatial scales and negatively affect the population trends of preferred parrot species. This unsustainable scenario is a challenge to the application of effective conservation actions aimed at halting poaching and illegal trade. These actions should focus on very extensive and remote rural areas throughout the Neotropics rather than just on well‐known markets located in large cities.

Based on S-parameter measurements, the effect of dynamic trapping and de-trapping of charge in the gate oxide, the increase of dielectric loss due to polarization, and the impact of leakage current on the small-signal input impedance at RF is analyzed and represented. This is achieved by systematically extracting the corresponding model parameters from single device measurements at different frequency ranges, and then the methodology is applied to analyze the evolution of these parameters when the device is submitted to non-conducting electrical stress. This approach not only allows to inspect the impact of effects not occurring under DC conditions, such as the current due to the time varying dielectric polarization, but also to clearly distinguish effects in accordance with the functional form of their contribution to the device’s impedance. In fact, it is shown that minor changes in the model of the gate capacitance by including additional resistive and capacitive components allows for an excellent model-experiment correlation up to 30 GHz. Moreover, the accuracy of the correlation is shown to be maintained when applying the proposal to the device under different gate-to-source bias conditions and at several stages during off-state degradation.

Abstract Objective Our primary objective was to evaluate how the Indigenous Healing and Seeking Safety (IHSS) model impacted residential addiction treatment program completion rates. Our secondary objective was to evaluate health service use 6 months before and 6 months after residential treatment for clients who attended the program before and after implementing IHSS. Methods We observed clients of the Benbowopka Residential Treatment before IHSS implementation (from April 2013 to March 31, 2016) and after IHSS implementation (from January 1, 2018 – March 31, 2020). The program data were linked to health administration data, including the Ontario Health Insurance Plan (OHIP) physician billing, the Registered Persons Database (RPDB), the National Ambulatory Care Reporting System (NACRS), and the Discharge Abstract Database (DAD). Chi-square tests were used to compare patient characteristics in the no-IHSS and IHSS groups. We used logistic regression to estimate the association between IHSS and treatment completion. We used generalized estimating equation (GEE) regression model to evaluate health service use (including primary care visits, ED visits overall and for substance use, hospitalizations and mental health visits), Results: There were 266 patients in the no-IHSS group and 136 in the IHSS group. After adjusting for individual characteristics, we observed that IHSS was associated with increased program completion rates (odds ratio = 1.95, 95% CI 1.02-3.70). There was no significant association between IHSS patients’ health service use at time one or time two. Primary care visits time 1: aOR 0.55, 95%CI 0.72-1.13, time 2: aOR 1.13, 95%CI 0.79-1.23; ED visits overall time 1: aOR 0.91, 95%CI 0.67-1.23, time 2: aOR 1.06, 95%CI 0.75-1.50; ED visits for substance use time 1: aOR 0.81, 95%CI 0.47-1.39, time 2: aOR 0.79, 95%CI 0.37-1.54; Hospitalizations time 1: aOR 0.78, 95%CI 0.41-1.47, time 2: aOR 0.76, 95%CI 0.32-1.80; Mental health visits time 1: aOR 0.66, 95%CI 0.46-0.96, time 2: aOR 0.92 95%CI 0.7-1.40. Conclusions Our results indicate that IHSS positively influenced program completion but had no significant effect on health service use. Trial registration This study was registered with clinicaltrials.gov (identifier number NCT04604574). First registration 10/27/2020.

Abstract Colorectal cancer (CRC) is characterised by heritable risk that is not well understood. Heritable, genetic variation at 11q23.1 is associated with increased colorectal cancer (CRC) risk, demonstrating eQTL effects on 3 cis- and 23 trans-eQTL targets. We sought to determine the relationship between 11q23.1 cis- and trans-eQTL target expression and test for potential cell-specificity. scRNAseq from 32,361 healthy colonic epithelial cells was aggregated and subject to weighted gene co-expression network analysis (WGCNA). One module (blue) included 19 trans-eQTL targets and was correlated with POU2AF2 expression only. Following unsupervised clustering of single cells, the expression of 19 trans-eQTL targets was greatest and most variable in cluster number 11, which transcriptionally resembled tuft cells. 14 trans-eQTL targets were found to demarcate this cluster, 11 of which were corroborated in a second dataset. Intra-cluster WGCNA and module preservation analysis then identified twelve 11q23.1 trans-eQTL targets to comprise a network that was specific to cluster 11. Finally, linear modelling and differential abundance testing showed 11q23.1 trans-eQTL target expression was predictive of cluster 11 abundance. Our findings suggest 11q23.1 trans-eQTL targets comprise a POU2AF2-related network that is likely tuft cell-specific and reduced expression of these genes correlates with reduced tuft cell abundance in silico.

Significant research has been conducted in identifying optimal recovery and adaptation decisions in disruptive scenarios using engineering models. In this context, an aspect that has been target of limited research is that of response times. Modelling is expected to grow progressively more complex as it becomes more accurate. Such complexity increases modelling efforts, and the promise of optimal adaptation and recovery may become hindered. The present work discusses the role of modelling fidelities in adaptation and recovery of systems, and in particular that of using a lower fidelity model that enables zero-time analyses of a system. A framework is proposed for using different fidelities in adaptation and recovery, considering system’s decision time requirements. The relevance of this analysis is researched in two traffic networks and results show that multi-fidelity models should be expected to play a key role in increasing the efficiency of optimal adaptation and recovery decisions.

In this work, an innovative and cheap electrochemical sensor for hydrogen peroxide quantification in exhaled breath was developed. H2O2 is the most used biomarker among the Reactive Oxygen Species (ROS) for monitoring the level of oxidative stress in the respiratory system. This is due to its stability and ability to cross biological membranes and also because it is detectable in extracellular space. The electrochemical sensor was obtained using the silver layer of wasted compact discs (CDs). All three electrodes, working (WE), counter (CE), and pseudo-reference electrode (RE), were fabricated using a laser cutter. The working electrode was used directly, while an Ag/AgCl paste and a graphite paste were applied respectively on the RE and the CE. In addition, a chitosan layer was deposited by Electro-Phoretic Deposition (EPD) on the surface of the sensor. This biopolymer improves the wettability of the sensor in presence of a humid atmosphere such as that given by exhaled air. The sensor was tested in both liquid and nebulized solutions containing different concentrations of hydrogen peroxide. The detection of H2O2 was evaluated using Linear Sweep Voltammetry (LSV) as electrochemical technique. The results show that the peak current increases linearly with hydrogen peroxide concentration from 100 to 500 µM with a sensitivity of 0.068 µA µM-1 cm-2 and 0.108 µA µM-1 cm-2, a Limit Of Detection (LOD) of 60 µM and 30 µM respectively for liquid and nebulized solutions. Therefore, the use of the electrochemical sensor can allow the monitoring of hydrogen peroxide in real time with good results.

The electrochemical multiplexed sensing has been gaining attention since this approach allows one to merge several sensing areas into a single compact chip. Here, we show several routes for the successful wafer scale microfabrication of a multiplexed silicon chip consisting of six ultramicro single gold (Au) bands (1 × 45 μm) as sensing electrodes. We have also developed a simple, low cost method to increase the roughness of the ultramicro sensing electrode surfaces (the roughness factor –RMS– increased from 1.6 to 2.3 nm) with high reproducibility via an electrochemical potassium hydroxide treatment. We show the application the fabricated ultramicro sensing surface via hydrogen bubble template to achieve copper foam (CuFoam) depositions. The resulting CuFoam microarchitectures were used to demonstrate a multi-purpose multiplexed platform, which was capable of catalysing glucose from serum samples and from river water to determine the chemical oxygen demand (COD). We also show the impact of the CuFoam as reference electrode to improve the electroanalytical performance of the device. The resulting sensing platform showed a superior sensitivity of 121 mA/mM cm2 and a wide linear range, 0.05 mM–22.15 mM. Herein, we clearly demonstrate the intimate link between microfabrication and engineering micro-interfaces for high performance sensing tools in fields of chemical and biological applications.

Background:. The gracilis muscle flap is a popular choice in reconstructive surgery to repair soft tissue defects or for functional restoration. Little is known on the influence of postoperative application of VAC (vacuum-assisted closure; Kinetic Concepts Inc., San Antonio, Tex.) therapy on perfusion and postoperative flap edema of free gracilis muscle flaps. Methods:. In total, 26 patients with soft tissue defects of lower extremity underwent gracilis muscle flap reconstruction. The study group (VAC, n = 13) was supplied with postoperative negative pressure therapy as a dressing; the control group (NVAC, n = 13) was supplied with conventional fat gauze dressing. Postoperative measurements of micro- and macroperfusion were performed intraoperatively, on postoperative day (POD) 3 and POD 5. Flap edema measurement was performed intraoperatively, on POD 5 and 2 weeks after operation. Results:. The VAC group showed significantly better macroflow during intraoperative VAC treatment, as well on POD 3 and POD 5. Venous outflow was also better with lower hemoglobin levels. Microflow was better in the NVAC group with higher measured oxygen levels. All gracilis muscle flaps of the VAC group showed significantly less flap edema compared with the control group. Conclusions:. VAC application on free gracilis muscle flaps leads to significantly less postoperative flap edema, improved arterial macroflow, and improved venous outflow. VAC therapy can be used without any danger for patient’s safety, as flap survival is not endangered, and presents an easy to handle and pleasant dressing regimen for nursing staff and patients.

IntroductionWilms Tumor (WT), or nephroblastoma, is the most common pediatric kidney cancer. Most WTs display a “favorable” triphasic histology, in which the tumor is comprised of blastemal, stromal, and epithelial cell types. Blastemal predominance after neoadjuvant chemotherapy or diffuse anaplasia (“unfavorable” histology; 5-8%) portend a worse prognosis. Blastema likely provide the putative cancer stem cells (CSCs), which retain molecular and histologic features characteristic of nephron progenitor cells (NPCs), within WTs. NPCs arise in the metanephric mesenchyme (MM) and populate the cap mesenchyme (CM) in the developing kidney. WT blastemal cells, like NPCs, similarly express markers, SIX2 and CITED1. Tumor xenotransplantation is currently the only dependable method to propagate tumor tissue for research or therapeutic screening, since efforts to culture tumors in vitro as monolayers have invariably failed. Therefore, a critical need exists to propagate WT stem cells rapidly and efficiently for high-throughput, real-time drug screening.MethodsPreviously, our lab developed niche conditions that support the propagation of murine NPCs in culture. Applying similar conditions to WTs, we assessed our ability to maintain key NPC "stemness" markers, SIX2, NCAM, and YAP1, and CSC marker ALDHI in cells from five distinct untreated patient tumors.ResultsAccordingly, our culture conditions maintained the expression of these markers in cultured WT cells through multiple passages of rapidly dividing cells.DiscussionThese findings suggest that our culture conditions sustain the WT blastemal population, as previously shown for normal NPCs. As a result, we have developed new WT cell lines and a multi-passage in vitro model for studying the blastemal lineage/CSCs in WTs. Furthermore, this system supports growth of heterogeneous WT cells, upon which potential drug therapies could be tested for efficacy and resistance.

The hornworts are a small group of land plants, consisting of only 11 families and approximately 220 species. Despite their small size as a group, their phylogenetic position and unique biology are of great importance. Hornworts, together with mosses and liverworts, form the monophyletic group of bryophytes that is sister to all other land plants (Tracheophytes). It is only recently that hornworts became amenable to experimental investigation with the establishment of Anthoceros agrestis as a model system. In this perspective, we summarize the recent advances in the development of A. agrestis as an experimental system and compare it with other plant model systems. We also discuss how A. agrestis can help to further research in comparative developmental studies across land plants and to solve key questions of plant biology associated with the colonization of the terrestrial environment. Finally, we explore the significance of A. agrestis in crop improvement and synthetic biology applications in general.

Abstract Floods represent one of the major challenges facing human societies. The impacts caused by them are extensive, and efficient flood adaptation will play a key role in the current century. The present work proposes a new approach to decision‐making in flood adaptation aimed at achieving robust adaptation decisions. It consists in evaluating decisions on a triaxial basis that considers expectation, probability quantile and investment in a so‐called expectation–quantile–investment (EQI) evaluation. With such approach it is possible to understand the influence of uncertainties in the probabilistic response of adaptation. While adaptation should minimise expected total costs, it needs also to be robust for competitive levels of investment. Transfer curves that relate events with outcomes are used to infer on the probabilistic character of decisions in a case study of a vulnerable location. Results show that EQI‐informed decisions can distinguish optimality in apparently competitive measures. It is shown that decisions based on one‐dimensional or two‐dimensional aspects of this triaxial rationale may fail to identify important probabilistic outcomes of adaptation, such as, the possibility of large losses with relevant probability of occurrence; and that are of high relevance when uncertainty considerations need to be enclosed in the analysis of adaptation.

Information graphics or infographics combine visual representations of information or data with text. They have been used in health research to disseminate research findings, translate knowledge and address challenges in health communication to lay audiences. There is emerging evidence of the design of infographics with the involvement of patients and the public in health research. Approaches to involvement include public and patient involvement, patient engagement and participatory research approaches. To date, there has been no comprehensive review of the literature on the design of infographics with patients and the public in health research. This paper presents a protocol and methodological framework for a scoping review to identify and map the available evidence for the involvement of patients and the public in infographics design in health research. It has been informed by preliminary searches and discussions and will guide the conduct and reporting of this review.