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Nearly all anti-tumour antibodies are of a single class—namely, IgG. Efficacy might be improved by development of tumour-specific IgE antibodies, which have higher affinities for effector cell receptors and perform potent immune functions. MOv18IgE, which targets folate receptor α (FRα), is a novel system to model this hypothesis. Human chimeric MOv18 IgE has shown superior efficacy in two murine xenograft models compared with MOv18 IgG1. Our aim was to examine the potential of this antibody class to activate monocytes. We developed an immunocompetent rat model system of rat tumour lung metastases expressing human FRα, and engineered surrogate rat MOv18 IgE and IgG antibodies to assess their efficacy and ability to recruit monocytes in the rat model system. In-vivo assessment of the efficacy of rat MOv18 IgE demonstrated superior tumour growth restriction compared with rat MOv18 IgG (tumour occupancy 6·8% [SE 1·6] vs 16·0 [1·7]; p<0·0001). We measured significant CD68-positive (CD68+) macrophage infiltration of tumours after MOv18 IgE treatment (mean ratio of CD68+ cells in tumour vs periphery 3·6 [0·5] for MOv18 IgE-treated tumours vs 2·3 [0·3] for MOv18 IgG-treated tumours; p=0·03). Our in-vivo studies using rat MOv18 IgE show the importance of monocyte recruitment in the efficacy of this antibody, and provide further evidence that tumour-specific IgE antibodies might offer improved efficacy against cancer by recruiting key immune effector cells. Academy of Medical Sciences Starter Grant, Cancer Research UK New Agents Committee Grant.

All antibodies approved for cancer therapy are monoclonal IgGs but the biology of IgE, supported by comparative preclinical data, offers the potential for enhanced effector cell potency. Here we report a Phase I dose escalation trial (NCT02546921) with the primary objective of exploring the safety and tolerability of MOv18 IgE, a chimeric first-in-class IgE antibody, in patients with tumours expressing the relevant antigen, folate receptor-alpha. The trial incorporated skin prick and basophil activation tests (BAT) to select patients at lowest risk of allergic toxicity. Secondary objectives were exploration of anti-tumour activity, recommended Phase II dose, and pharmacokinetics. Dose escalation ranged from 70 μg–12 mg. The most common toxicity of MOv18 IgE is transient urticaria. A single patient experienced anaphylaxis, likely explained by detection of circulating basophils at baseline that could be activated by MOv18 IgE. The BAT assay was used to avoid enrolling further patients with reactive basophils. The safety profile is tolerable and maximum tolerated dose has not been reached, with evidence of anti-tumour activity observed in a patient with ovarian cancer. These results demonstrate the potential of IgE therapy for cancer. IgE antibodies have shown anti-tumor activity, even superior to IgG, in preclinical models. However, all monoclonal antibodies in clinical use for cancer therapy are members of the IgG class. Here the authors report the results of a phase I clinical trial of a chimeric monoclonal IgE antibody, specific for the folate receptor-alpha, in patients with advanced solid cancer.

The majority of dogs enjoy travelling by car, once they've got over the puppy stage of vomiting before you get to the end of the driveway. After that, the slightest hint of a car door opening, and they're in there, bombing around, waiting to pass the first other dog so they can bark at it. Half the fun of a trip for a lot of dogs is barking at things, and for some dogs that means every tree, house, person and car, as well as other dogs. These dogs usually ride in the back of pick-up trucks, for obvious reasons. For the few dogs that are bad travellers and become nauseous or nervous, there are a few options: For nausea, you can use child's liquid gravol at a dose of 1 tsp per 10 pounds of body weight; however, for puppies under 3 months of age or for dogs older than seven, or with medical problems, consult your veterinarian first.

One needs good quality data on current enrolment, dropout and repetition in order to evaluate the possible implications of different repetition and dropout decisions by school authorities, learners and parents for enrolment numbers and for the composition of classes in 2021. We obtained learner level data from LURITS, a relative recent way of organising and managing enrolment data that has superseded the Annual National Census of Schools. Though far from perfect, this data give good information about the extremely high levels of repetition. High repetition leads to many learners being over-aged and to dropout being quite common in secondary school. Assessing various alternative scenarios about learners returning to school, repetition and dropout, we conclude that the most likely outcome for 2021 is that considerably more learners would be promoted to grades 11 and 12 in particular, with implications for allocations of classrooms, books and teachers, with a decline of repetition in Grade 10. Learners in all grades would have a learning deficit compared to previous years, but in addition, the heterogeneity of academic backgrounds would be even greater than usual in 2021 in the final two grades, confronting teachers with an even more difficult task than usual.

An almost unnoticed problem in the South African education system is the high rate of grade repetition. In this report, a combination of household and administrative datasets is used to identify patterns in learner repetition and dropout in South African schooling and the costs associated with these issues. According to the most conservative estimate, the number of learners in public schools repeating in grades 1 to 12 could have been 1 180 000. In monetary terms, this implies that the cost of having repeaters in the public education system was at least R20 billion (in 2018 prices), absorbing 8% of the total national budget allocated to basic education in 2018/2019. At least a half of these repetition costs is attributed to the high prevalence of repetition in the secondary school phase, with the largest number of repeaters located in grade 10 (at least 1 in every 5 grade 10 learners repeat). Despite the promulgation of repetition policy that limits the number of times learners can repeat a school phase, repetition trends in the past decade display a strong inertia, especially in higher grades. To monitor these trends better, and to track the implementation of these policies, significant improvements will need to be made to the quality of reporting on repeaters and dropout in EMIS data. While repetition is a problem, it is merely a symptom of a weakly functioning education system. The repetition debate is thus secondary to the need to address the quality of the education provided in our schools, and particularly in the foundation phase. Quality improvements will also make it easier to implement sensible policies on repetition and to provide remediation and support where these are needed. Moreover, by freeing resources currently needed to deal with repetition, improved education quality would also make remediation more feasible.

This paper analyses the SA-SAMS school administration data that the Michael and Susan Dell Foundation in partnership with the Department of Basic Education collects quarterly from schools in order to assess its usefulness for better understanding the school system. The disaggregated SA-SAMS data housed in the Data Driven Districts operational data store is typically provided in the form of data dashboards for analytical purposes to the education authorities. Although only non-random samples of the data are available in longitudinal form, the analysis shows that this can already be used to investigate important relationships and features of the education system. These include the relationship between performance in earlier grades and performance in matric, the relationship between performance, repetition and subsequent dropout, the choice between Mathematics and Mathematical Literacy, and the utility of using school-based assessments in investigating later educational outcomes. The SA-SAMS data also contains much better information on the number of disabled learners in schools than previous Annual Survey of Schools (ASS or EMIS) data. Expanding such analysis in the future with lengthened longitudinal data and larger samples as data collection improves should be very fruitful for an improved understanding of the school system.

The NHS is on the brink of a major programme of change, beginning in April, intended to put market forces at the centre of the health service. Our first article in a major new series on the implications for personnel looks at what the reforms mean for healthcare in general and for the personnel function in particular, and at how one health authority has already been trying to revolutionise its approach to human resource strategy.