The Paget Trial:topical 5% imiquimod cream for noninvasive vulvar Paget disease

BACKGROUND: Vulvar Paget disease is an extremely rare skin disorder, which is most common in postmenopausal women. Most vulvar Paget disease cases are noninvasive; however, it may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The current treatment of choice for noninvasive vulvar Paget disease is wide local excision, which is challenging because of extensive intraepithelial spread and may cause severe morbidity. Recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. Imiquimod, a topical immune response modifier, has been shown to be effective in a few studies and case reports, and is a promising new treatment modality. OBJECTIVE: To prospectively investigate the efficacy, safety, and effect on quality of life of a standardized treatment schedule with 5% imiquimod cream in patients with noninvasive vulvar Paget disease. STUDY DESIGN: The Paget Trial is a multicenter prospective observational clinical study including 7 tertiary referral hospitals in the Netherlands. A total of 24 patients with noninvasive vulvar Paget disease were treated with topical 5% imiquimod cream 3 times a week for 16 weeks. The primary efficacy outcome was the reduction in lesion size at 12 weeks after the end of treatment. Secondary outcomes were safety, clinical response after 1 year, and quality of life. Safety was assessed by evaluation of adverse events and tolerability of treatment. Quality of life was investigated with 3 questionnaires taken before, during, and after treatment. RESULTS: Data were available for 23 patients, 82.6% of whom responded to therapy. A complete response was reported in 12 patients (52.2%), and 7 patients (30.4%) had a partial response. A histologic complete response was observed in 10 of the 12 patients with a complete response. Patients experienced side effects such as fatigue (66.7%-70.9%) and headaches (16.7%-45.8%), and almost 80% needed painkillers during treatment. Eight patients (34.8%) adjusted the treatment protocol to 2 applications a week, and 3 patients (13.0%) stopped treatment because of side effects after 4 to 11 weeks. Treatment improved quality of life, whereas a slight, temporary negative impact was observed during treatment. Two patients with a complete response developed a recurrence within 1 year after treatment. Follow-up showed 6 patients with a noninvasive recurrence after a median of 31 months (14-46 months) after the end of treatment. CONCLUSION: Topical 5% imiquimod cream can be an effective and safe treatment alternative for noninvasive vulvar Paget disease, particularly when compared with treatment with surgical excision

Ophthalmological Evaluation in Children Presenting with a Primary Brain Tumor

Background:Children with a brain tumor are prone to develop visual impairment, which to date is often underestimated and unrecognized. Our aim was to assess the prevalence of ophthalmological evaluation and abnormal ophthalmological findings, and investigate whether demographic and tumor-related characteristics are associated with abnormal ophthalmological findings in children presenting with a primary brain tumor.Methods:Medical records of all 90 children diagnosed with a primary brain tumor between June 2018 and May 2019 and treated at the Princess Máxima Center for Pediatric Oncology, a tertiary referral center in the Netherlands, were retrospectively reviewed. Univariate regression analysis was used to investigate associations between demographic, tumor-related and clinical characteristics, and abnormal ophthalmological findings.Results:Sixty children (34 male [56.7%]; median [range] age, 9.3 [0-16.9] years) underwent ophthalmological evaluation within 6 weeks before or after diagnosis, 11 children (5 male [45.5%]; median [range] age, 5.7 [0.1-17.2] years) were seen more than 6 weeks before or after diagnosis, and 19 children (7 male [36.8%]; median [range] age, 7.2 [1.9-16.6] years) did not receive ophthalmological evaluation within at least 6 months from diagnosis. A total of 19 children (21.1%) presented with visual symptoms as first sign leading to the diagnosis of a brain tumor. Children who presented with visual symptoms (odds ratio [OR], 22.52; 95% confidence interval [CI], 4.90-103.60) and/or hydrocephalus (OR, 3.60; 95% CI, 1.38-9.36) at diagnosis were more often seen for ophthalmological evaluation. The most common abnormal ophthalmological findings were eye movement disorders (66.0%), papilledema (44.1%), and visual field defects (58.1%). Eye movement disorders occurred more frequently in patients with an infratentorial tumor (OR, 4.71; 95% CI, 1.03-21.65). The risk of papilledema was associated with older age (OR, 1.19; 95% CI, 1.05-1.34), hydrocephalus (OR, 9.63; 95% CI, 2.68-34.61), and infratentorial (OR, 9.11; 95% CI, 1.77-46.78) and supratentorial (OR, 13.13; 95% CI, 1.92-89.52) tumors.Conclusions:In this study, most children with a primary brain tumor underwent ophthalmological evaluation around diagnosis, 21% of the children were not evaluated. The high prevalence of abnormal ophthalmological findings stresses the importance of early standardized ophthalmological evaluation to detect visual impairment and provide timely treatment to potentially prevent permanent visual loss

Avaliação do efeito antimicrobiano in vitro dos extratos etanólicos de Plectranthus neochilus e Cnidoscolus quercifolius

Avaliou-se o efeito antimicrobiano in vitro dos extratos etanólicos de Plectranthus neochilus e Cnidoscolus quercifolius de forma isolada e associadas. Na 1ª etapa, utilizaram-se os extratos em concentrações 1%, 2,5%, 5% e 10%. Na 2ª etapa, utilizaram-se apenas extratos brutos. Para o teste de sensibilidade dos extratos, utilizaram-se cepas padrão Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853. Nas duas etapas, realizaram-se os mesmos testes de sensibilidade. As placas foram semeadas e lidas após 24 horas de incubação em estufa a 37ºC. De acordo com os resultados, conclui-se que não houve atividade bacteriana dos extratos etanólicos estudados isolados, bem como associados diante das cepas padrão de Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa nas diferentes metodologias aplicadas quando comparadas com o antibiótico padrão (amicacina)

Widespread drying of European peatlands in recent centuries

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record Climate warming and human impacts are thought to be causing peatlands to dry,potentially converting them from sinks to sources of carbon. However, it is unclear whether the hydrological status of peatlands has moved beyond their natural envelope. Here we show that European peatlands have undergone substantial, widespread drying during the last ~300 years. We analyse testate amoeba-derived hydrological reconstructions from 31 peatlands across Britain, Ireland, Scandinavia and continental Europe to examine changes in peatland surface wetness during the last 2000 years. 60% of our study sites were drier during the period CE 1800-2000 than they have been for the last 600 years; 40% of sites were drier than they have been for 1000 years; and 24% of sites were drier than they have been for 2000 years. This marked recent transition in the hydrology of European peatlands is concurrent with compound pressures including climatic drying, warming and direct human impacts on peatlands, although these factors vary between regions and individual sites. Our results suggest that the wetness of many European peatlands may now be moving away from natural baselines. Our findings highlight the need for effective management and restoration of European peatlands.Natural Environment Research Council (NERC

The Debunking Handbook 2020

Published versio

B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase

We show that the enzymatic acetylation and deacetylation of a cell surface carbohydrate controls B cell development, signaling, and immunological tolerance. Mice with a mutation in sialate:O-acetyl esterase, an enzyme that specifically removes acetyl moieties from the 9-OH position of α2–6-linked sialic acid, exhibit enhanced B cell receptor (BCR) activation, defects in peripheral B cell development, and spontaneously develop antichromatin autoantibodies and glomerular immune complex deposits. The 9-O-acetylation state of sialic acid regulates the function of CD22, a Siglec that functions in vivo as an inhibitor of BCR signaling. These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage

Addressing climate change with behavioral science:A global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions' effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior-several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people's initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.</p

All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe

The All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class mission concept that will provide essential contributions to multimessenger astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in the 200 keV to 10 GeV energy range with a wide field of view, good spectral resolution, and polarization sensitivity. Therefore, AMEGO is key in the study of multimessenger astrophysical objects that have unique signatures in the gamma-ray regime, such as neutron star mergers, supernovae, and flaring active galactic nuclei. The order-of-magnitude improvement compared to previous MeV missions also enables discoveries of a wide range of phenomena whose energy output peaks in the relatively unexplored medium-energy gamma-ray band

Addressing climate change with behavioral science: a global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors

Addressing climate change with behavioral science:A global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions' effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior-several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people's initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.</p