Let a Thousand Teachers Bloom. A Response to Creating Communities

Public education in the United States is nominally inclusive and open to all, but is also nuanced and complicated, particularly for students with special learning needs or for English language learners. For refugee students, who may also belong to either or both these two groups, the challenge can be compounded by previous traumas to themselves and their families. Roxas’s description of teacher Patricia Engler illustrates how complicated, but ultimately doable, is the work of educating refugee youth. The key strategy that the article illustrated was the need for attention to connections between school and home life. The students experienced these and other cultural intersections as affirming and consistent, further strengthening the community-school linkages

Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms : revival of an old drug

BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. CONCLUSIONSIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launche

Orally active antischistosomal early leads identified from the open access malaria box.

BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development

Activity of antiandrogens against juvenile and adult Schistosoma mansoni in mice

Objectives The antischistosomal properties of the marketed antiandrogens bicalutamide, flutamide, nilutamide and cyproterone acetate were studied both in vivo and in vitro. Methods Schistosoma mansoni-infected mice were treated orally with 50-400 mg/kg of the antiandrogens 3 and 7 weeks post-infection. In addition, three drug combinations of nilutamide and praziquantel (200/100, 100/100 and 100/50 mg/kg) were administered to mice harbouring adult S. mansoni. Drug effects were also monitored in vitro following exposure to antiandrogen concentrations of 1, 10 and 100 µg/mL. Results Low total worm burden reductions (5%-37%) and low to moderate female worm burden reductions (13%-75%) were achieved with the antiandrogens in the S. mansoni juvenile infection model. While flutamide and cyproterone acetate lacked activity against adult S. mansoni in vivo, low to moderate total and female worm burden reductions (0%-47%) were observed with bicalutamide. The highest total and female worm burden reductions (85% and 71%, respectively) (P < 0.001) were documented following a single 400 mg/kg dose of nilutamide. Statistically significant total (91%) and female (85%) worm burden reductions were achieved with the combination of nilutamide (200 mg/kg) and praziquantel (100 mg/kg). Schistosomes incubated with 100 µg/mL cyproterone acetate in vitro died after 15 h. Incubation with bicalutamide, nilutamide and flutamide at 100 µg/mL resulted in decreased movement of S. mansoni adults. Conclusions Our data indicate that the hydantoin derivative nilutamide has interesting antischistosomal properties, confirming previous results of schistosomicidal activities of this drug clas

Analysis of global routine immunisation coverage shows disruption and stagnation during the first two-years of the COVID-19 pandemic with tentative recovery in 2022

Whilst it is now widely recognised that routine immunisation (RI) was disrupted by the COVID-19 pandemic in 2020, and further so in 2021, the extent of continued interruptions in 2022 and/or rebounds to previous trends remains unclear. We modelled country-specific RI trends using validated estimates of national coverage from the World Health Organisation and United Nation Children's Fund for 182 countries (accounting for > 97% of children globally), to project expected diphtheria, tetanus, and pertussis-containing vaccine first-dose (DTP1), third-dose (DTP3) and measles-containing vaccine first-dose (MCV1) coverage for 2020-2022 based on pre-pandemic trends (from 2000 to 2019). We provide further evidence of peak pandemic immunisation disruption in 2021, followed by tentative recovery in 2022. We report a 3.4% (95 %CI: [2.5%; 4.4%]) decline in global DTP3 coverage in 2021 compared to 2000-2019 trends, from an expected 89.8% to reported 86.4%. This coverage gap reduced to a 2.7% (95 %CI: [1.8%; 3.6%]) decline in 2022, with reported coverage rising to 87.2%. Similar results were seen for DTP1 and MCV1. Whilst partial rebounds are encouraging, global coverage decline translates to a 17-year setback in RI to 2005 levels, and the majority of countries retain coverage at or lower than pre-pandemic levels. The Americas, Africa, and Asia were the most impacted regions; and low- and middle-income countries the most affected income groups. The number of annual Zero Dose (ZD) children - indicating those receiving no immunisations - increased from 12.1 million (M) globally in 2019 to a peak of 16.7 M in 2021, then reduced to 13.1 M in 2022. Overall, we estimate an excess of 8.8 M ZD children cumulatively in 2020-2022 compared to pre-pandemic levels. This work can be used as an objective baseline to inform future interventions to prioritise and target interventions, and facilitate catch-up of growing populations of under- and un-immunised children

Learning Melanocytic Cell Masks from Adjacent Stained Tissue

Melanoma is one of the most aggressive forms of skin cancer, causing a large proportion of skin cancer deaths. However, melanoma diagnoses by pathologists shows low interrater reliability. As melanoma is a cancer of the melanocyte, there is a clear need to develop a melanocytic cell segmentation tool that is agnostic to pathologist variability and automates pixel-level annotation. Gigapixel-level pathologist labeling, however, is impractical. Herein, we propose a means to train deep neural networks for melanocytic cell segmentation from hematoxylin and eosin (H&E) stained slides using paired immunohistochemical (IHC) slides of adjacent tissue sections, achieving a mean IOU of 0.64 despite imperfect ground-truth labels.Comment: {Medical Image Learning with Limited & Noisy Data Workshop at MICCAI 202

Leadership Dispositions and Skills for Ethnically Diverse Schools

Quality educational leadership is especially critical today in the era of school improvement, student achievement, and teacher accountability. Leaders help meet ever-changing contexts and opportunities. Senge (1990) observed, “The new view of leadership in learning organizations centers on subtler and more important tasks. In learning organizations, leaders are designers, stewards, and teachers” (p. 340). In addition to these new leadership challenges, this is a time when school resources—human as well as financial--are limited not only in PK-12 schools but to universities as well (Price, 2008). While American educators today are serving an increasingly diverse community, educators are still predominately middle-class, European American, and English-only speakers (Banks et al., 2005; Jazzar & Algozzine, 2006; Swartz, 2003). Not only must school leaders understand students’ communities and experience, they also need the willingness, attitudes, and ethics or dispositions to work well with diversity and to teach these skills to others (Lindsey, Robins, & Terrell, 2003). Dispositions may be defined as, “values, commitments, and professional ethics that influence behaviors toward students, families, colleagues, and communities” (NCATE, 2002, p. 53). More specifically, diversity dispositions include the skills, beliefs and connections to be successful within the community (Schulte, Edwards, & Edick, 2008). For school administrators, the objective is to become a leader who “promotes the success of students by collaborating with families and community members, responding to the diverse community interests and needs, and mobilizing community resources” (CCSSO, 2007, p. 16) More than ever before, those who train educators need to assist candidates in cultivating their positive dispositions in order to help all students succeed (Keiser & Smith, 2009)

The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica

Objectives: The trematocidal properties of a synthetic peroxide, 1,2,4-trioxolane (OZ78) were determined both in vivo and in vitro. Methods: Two weeks post-infection Echinostoma caproni-infected mice were administered single oral doses of 400-1000 mg/kg OZ78. Fasciola hepatica-infected rats were treated orally with 50-400 mg/kg OZ78 3 and 8-9 weeks post-infection. Worm burden reductions were assessed against untreated control animals. Adult F. hepatica were observed by scanning electron microscopy (SEM) after recovery from the bile duct of a rat 3 days after administration of a single oral dose of 100 mg/kg OZ78 and after in vitro exposure to concentrations of 1, 10 and 100 μg/mL OZ78. Results: In the E. caproni-mouse model 100% worm burden reductions were achieved with a single oral dose of 1000 mg/kg OZ78. A single dose of 100 mg/kg OZ78 resulted in worm burden reductions of 100% against juvenile and adult F. hepatica. F. hepatica recovered from rats 3 days post-treatment displayed feeble activity and some flukes had died. Typical features revealed by SEM included extensive blebbing and sloughing. Exposure of F. hepatica to 10-100 μg/mL OZ78 in vitro resulted in the death of all trematodes. F. hepatica showed focal blebbing and sloughing of the tegument at all concentrations investigated. Conclusions: Our data indicate that OZ78 is highly efficacious against F. hepatica and E. caproni and provide a sound platform for identification of a synthetic peroxide drug development candidate against major trematode infection