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Purpose\ud To systematically map available evidence for school-based interventions led by allied health (i.e., occupational therapy, physiotherapy, and/or speech and language therapy).\ud \ud Materials and methods\ud We searched for studies in pre-school, primary, secondary, or post-secondary settings, published 2004–2020. We coded study, population, and intervention characteristics. Outcomes were coded inductively, categorised, and linked to the International Classification of Functioning, Disability, and Health.\ud \ud Results\ud We included 337 studies (33 countries) in an interactive evidence map. Participants were mainly pre-school and primary-aged, including individuals with neurodisability and whole-school populations. Interventions targeted wide-ranging outcomes, including educational participation (e.g., writing, reading) and characteristics of school environments (e.g., educators’ knowledge and skills, peer support). Universal, targeted, and intensive interventions were reported in 21.7%, 38.9%, and 60.2% of studies, respectively. Teachers and teaching assistants delivered interventions in 45.4% and 22.6% of studies, respectively. 43.9% of studies conducted early feasibility testing/piloting and 54.9% had ≤30 participants. Sixty-two randomised controlled trials focused on intervention evaluation or implementation.\ud \ud Conclusions\ud In the United Kingdom, future research should take forward school-based allied health interventions that relate directly to agreed research priorities. Internationally, future priorities include implementation of tiered (universal, targeted, intensive) intervention models and appropriate preparation and deployment of the education workforce.\ud \ud IMPLICATIONS FOR REHABILITATION\ud Allied health professionals (occupational therapists, physiotherapists, and speech and language therapists) work in schools supporting children and young people affected by neurodisability but the content, impact, and cost-effectiveness of their interventions are not well-understood.\ud \ud We systematically mapped the available evidence and identified that allied health school-based interventions target highly diverse health-related outcomes and wider determinants of children and young people’s health, including educational participation (e.g., literacy) and characteristics of the school environment (e.g., educators’ knowledge and skills).\ud \ud Our interactive evidence map can be used to help stakeholders prioritise the interventions most in need of further evaluation and implementation research, including tiered models of universal, targeted, and intensive allied health support.\ud \ud Teachers and teaching assistants play a central role in delivering allied health interventions in schools – appropriate preparation and deployment of the education workforce should therefore be a specific priority for future international allied health research.

Achieving success as an integrated care system can be fraught with challenges. Rob Webster CBE, CEO Lead for the West Yorkshire and Harrogate Health and Care Partnership, explains why trust is integral to overcoming these challenges and making a real difference to local communities.

In this paper, the guest editors consider the direction of research on teaching assistants (TAs), and how academics can elevate the field within the spheres of education and the social sciences. We begin by unpicking, and endorsing, Giangreco’s idea of applying the ‘Maslow’s Hammer test’ (expressed in this special issue) to manuscripts about studies of TAs and inclusion to journal editorship and peer review processes. The purpose of the test is to address the disproportionate attention paid by researchers to a set of narrow and recurring interests, and to open up new lines of inquiry and discussions about the innovative methodological approaches required to operationalise them. Secondly, we describe a persistent and urgent research gap: the shortage of international data on TAs. Given the pre-eminence of TA deployment as a means to facilitate access to and participation in mainstream education for pupils with special educational needs, we argue that the continued lack of large-scale data on TAs’ characteristics, experiences, practices and impact poses a risk to advancing the global inclusion agenda. Finally, we make a call for expressions of interest in establishing an international research network to help expand, empower and raise the esteem the field of scholarship on TAs.

This article identifies the factors that characterise effective interpersonal partnerships between teachingassistants (TAs) and teachers working in inclusive schools in Catalonia (Spain). This phenomenologicalstudy, based on 40 semi-structured interviews with 22 TAs and 18 teachers revealed that the maininterpersonal factors affecting partnerships were: feeling at ease; trust; respect; and valuing one another.Participants detailed key aspects such as personal affinity, professional compatibility, open communi-cation, a sense of belonging to a class-group, and teamwork, as additionally important for successfulpartnerships. Thefindings provide insight into how schools can support the development of effective TA-teacher partnerships. Implications are discussed. This work was supported by the Spanish Ministry of Educationand Vocational Training [grant number: FPU16/00284 and EST18/00695]

Quantitative modeling is increasingly utilized in the drug discovery and development process, from the initial stages of target selection, through clinical studies. The modeling can provide guidance on three major questions–is this the right target, what are the right compound properties, and what is the right dose for moving the best possible candidate forward. In this manuscript, we present a site-of-action modeling framework which we apply to monoclonal antibodies against soluble targets. We give a comprehensive overview of how we construct the model and how we parametrize it and include several examples of how to apply this framework for answering the questions postulated above. The utilities and limitations of this approach are discussed.

The long-term, international trend towards the inclusion of pupils with special educational needs (SEN) has been accompanied and enabled by an increase in the employment and deployment of a parapro...

The early 21st century has seen a considerable increase in both the number and presence of teaching assistants (TAs) and learning support staff in classrooms. In the United Kingdom and elsewhere, TAs have assumed responsibility for teaching lower-attaining pupils and especially those with special educational needs or disabilities (SEND). This drift has occurred in a largely uncritical way and has attracted little attention because of the attendant benefits additional adult support has for teachers. However, evidence from research in the United Kingdom and the United States have revealed troubling and unintended consequences of this arrangement in terms of impeding pupil progress and increasing the likelihood of pupils’ dependency on adult support. Of particular concern are research findings that show how a high amount of support from TAs for pupils with high-level SEND leads to a qualitatively different experience of schooling compared to pupils without SEND, particularly in terms of having fewer interactions with teachers and peers. Heavy reliance on the employment and deployment of TAs to facilitate the inclusion of pupils with often complex learning difficulties in mainstream settings can be seen as a proxy for long-standing and unresolved questions about how teachers are prepared and trained to meet the learning needs of those with SEND and the priority school leaders give to SEND. Future efforts to meaningfully educate pupils with SEND in mainstream schools must attend to teachers’ confidence and competence in respect of this aim. In addition, extensive and collaborative work with schools in the United Kingdom is offering a more hopeful model of how TAs can supplement this endeavor. Improving how teachers deploy TAs and how TAs interact with pupils, together with addressing persistent problems relating to the way TAs are trained and prepared for their roles in classrooms, schools can unlock the potential of the TA workforce as part of a wider, more inclusive approach for disadvantaged pupils.

Monoclonal antibodies (mAbs) can be engineered to have “extended half‐life” and “catch and release” properties to improve target coverage. We have developed a mAb physiologically‐based pharmacokinetic model that describes intracellular trafficking, neonatal Fc receptor (FcRn) recycling, and nonspecific clearance of mAbs. We extended this model to capture target binding as a function of target affinity, expression, and turnover. For mAbs engineered to have an extended half‐life, the model was able to accurately predict the terminal half‐life (82% within 2‐fold error of the observed value) in the human FcRn transgenic (Tg32) homozygous mouse and human. The model also accurately captures the trend in pharmacokinetic and target coverage data for a set of mAbs with differing catch and release properties in the Tg32 mouse. The mechanistic nature of this model allows us to explore different engineering techniques early in drug discovery, potentially expanding the number of “druggable” targets.

This paper reports on results from a descriptive study of the nature and quality of the day-to-day educational experiences of 49 13–14 year olds with special education needs and/or disabilities (SEND). All pupils had either an Education Health and Care Plan (EHCP) or a Statement, and attended in mainstream secondary school in England. Pupils involved in the SEN in Secondary Education study were shadowed for several days over a school week. Researchers prepared pupil-level case studies on the basis of data from qualitative observations and semi-structured interviews with pupils and key school staff involved in their learning and development. The case studies were subjected to a thematic analysis. Results are presented in terms of two inter-related themes – (i) teaching and support; and (ii) differentiation – which address approaches to, and expressions of, inclusive practice; the roles of teachers and teaching assistants; and the defining features of teaching and support for SEND. The results are considered in view of the inclusiveness, appropriateness and effectiveness of provision on offer to pupils with high-level SEND. We conclude there has been a systemic and long-standing failure to fully address the educational needs of such pupils, and suggest what schools could do to provide higher quality experiences.

Coast redwood (Sequoia sempervirens) is a productive conifer that has considerable potential as a plantation species within New Zealand where radiata pine (Pinus radiata) comprises 90% of plantations. However, little research has compared volume productivity on the same basis between radiata pine and promising species such as redwood. Radiata pine volume productivity can be described by 300 Index, which quantifies its mean annual increment at age 30 for a stand density of 300 stems ha−1. Using New Zealand redwood growth data from 130 plots, the objectives of this study were to (i) develop a model of redwood 300 Index productivity, (ii) compare fine scale (25 m) spatial predictions of 300 Index from this model with previous national predictions of 300 Index for radiata pine and (iii) undertake species comparisons of volume productivity across a broader age range for contrasting stand densities and values of 300 Index. Measurements made within the plot dataset demonstrated the high productivity of New Zealand grown redwood with maximum mean top height and volume reaching, respectively, 59.1 m and 4,293 m3 ha−1 for an 84 year old stand. Redwood 300 Index ranged 15-fold within the dataset from 4.36 – 64.8 m3 ha−1 yr−1 (mean = 22.8 m3 ha−1 yr−1; SD = 11.7 m3 ha−1 yr−1). The multiple regression model that was developed to predict 300 Index from environmental and stand variables fitted the data well (R2 = 0.66, RMSD = 6.80 m3 ha−1 yr−1). The 300 Index surfaces show that redwood volume productivity was on average 8% higher than radiata pine within the North Island, but on average 33% lower than radiata pine in the South Island. Species comparisons of volume over time, for three contrasting site qualities (300 Indices), showed that redwood markedly outperformed radiata pine, at ages older than 30 years for final crop stand densities of 300 stems ha−1 and this species divergence in volume increased at 600 stems ha−1. The developed surfaces highlight the potential of redwood for further afforestation within New Zealand.

Objectives The objective of this study was to describe seasonality, demographics, presentations, treatments, complications and outcomes for cats with Ixodes holocyclus causing tick paralysis, and to identify risk factors for mortality. Methods This was a retrospective single cohort study with 2077 cases occurring between 2008 and 2016, and presenting to one of four emergency clinics in south-eastern Queensland, Australia. Case mortality at 5 days post-presentation could be determined for 1742 cases, and potential risk factors for mortality were assessed using random-effects logistic regression. Results Cases occurred all year round, but there was a marked seasonal pattern with more cases presenting in spring than any other season. Overall, 54/1742 cases (3%) died by 5 days after presentation. Five day mortality incidence for cases that received polyclonal canine tick antitoxin serum (TAS) and recommended treatment was 28/1410 (2%) vs 4/52 (8%) for cases that did not receive TAS ( P Conclusions and relevance The overall mortality risk for cats treated for tick paralysis caused by I holocyclus is low. Risk factors for mortality include advanced gait and respiratory scores, and hypothermia at presentation. Coat clipping and TAS reduce the risk of mortality, whereas the occurrence of a TAS reaction increases the risk. Mechanical ventilation reduces mortality risk in cats with respiratory failure due to tick paralysis.

FXaI16L is a recombinant human FXa variant which is currently being evaluated in the clinic for treating intracerebral hemorrhage. The aim of our studies is to investigate overall pharmacokinetics, pharmacodynamics, and distribution of FXaI16L in preclinical species, and to understand its potential implication in human. Pharmacokinetics of FXaI16L was examined using active site probes and the results showed that FXaI16L displayed fast clearance, low volume of distribution, and a very short plasma resident time in mice, rats, and monkeys. When pharmacodynamics was examined in monkeys, concentration effects of FXaI16L on shortening of active partial prothrombin time and formation of thrombin-antithrombin complex were observed. Furthermore, biodistribution study was conducted in mice using radiolabeled FXaI16L, and showed that 125I-FXaI16L has high plasma protein binding and significant liver and kidney distribution. Human pharmacokinetic prediction for first-in-human dosing was evaluated using allometric scaling, liver blood flow, and a fixed coefficient method, and single species allometric scaling using monkey data was most predictive for human pharmacokinetics of FXaI16L.

This paper presents a systemic investigation of ADA development and ADA impact of a human coagulation factor in nonclinical species during drug development and provides insights into potential implications in human if a similar ADA occurs. FXaI16L-induced ADA response was characterized in monkey, mouse, rat, and dog in different studies, and ADA effects on pharmacokinetic and/or pharmacodynamics of FXaI16L were further examined in ADA-negative and ADA-positive animals. After repeated administrations, FXaI16L elicited a dose and exposure day-dependent ADA response which ranged from no response to a transient or persistent response. Increase in exposure day and increase in dose generally enhanced ADA incidence except for a decrease in ADA incidence was observed in monkeys after repeated high-dose administrations. The observable ADA impact on pharmacokinetics was only found in some ADA+ animals and included decrease in clearance and increase in systemic exposure but no increase in half-life. In addition, no or limited effect on pharmacodynamics by ADA was observed. The earliest ADA response was observed after three exposure days, marked elevation of drug exposure was observed in some animals at log titer > 2.0, and the highest antibody titer excited was about 4 (Log10) in all species. A correlation between ADA induction and accumulative exposure after various repeat treatments in different species was found for FXaI16L. In addition, potential immunogenicity risk and mitigation of ADA in clinics are discussed.

The Mary Warnock Enquiry remains the most comprehensive review of special educational needs and disabilities (SEND) ever commissioned by a UK government. In November 1971, a Labour backbencher asked the then secretary of state for education and science, Margaret Thatcher, to consider an enquiry into ‘the whole field of special education’. The Warnock Report is sometimes credited as introducing inclusion, but in reality, it was a catalyst. The Warnock Report consolidated and brought together many different strands of thinking and practice in special education and employment in one place, and articulated a cohesive and expansive plan for lifelong inclusion for those with SEND. The SEND enquiry, launched in April 2018, and ongoing at the time of writing, ‘is intended to review the success of reforms, how they have been implemented, and what impact they are having in meeting the challenges faced by children and young people with special educational needs and disabilities’.

This chapter discusses how – against the backdrop of some particular contemporary challenges – the education system in England might successfully educate, and not just accommodate, pupils with special educational needs and disabilities (SEND). While the free school model might serve the needs of some parents – whose children may or may not have SEND – it is poorly aligned to the reality of planning and providing local special education. In an appearance at an Education Committee hearing in July 2018, Baroness Warnock observed that Ofsted’s focus on ‘academic excellence’ meant that it had a ‘contradictory role’ with respect to inclusion. Special education must be seen as a form of educational activity no less important, no less demanding and no less rewarding than any other, and teachers, administrators and other professionals engaged in it must have the same commitment to children with special needs as they have to all other children.

This paper presents a systemic investigation of ADA development and ADA impact of a human coagulation factor in nonclinical species during drug development and provides insights into potential implications in human if a similar ADA occurs. FXa

The emergence of genetic data linking Nav1.7 sodium channel over- and under- expression to human pain signalling has led to an interest in the treatment of chronic pain through inhibition of Nav1.7 channels. We describe the pharmacokinetic (PK) results of a clinical microdose study performed with four potent and selective Nav1.7 inhibitors and the subsequent modelling resulting in the selection of a single compound to explore Nav1.7 pharmacology at higher doses. A clinical microdose study to investigate the intravenous and oral PK of four compounds (PF-05089771, PF-05150122, PF-05186462 and PF-05241328) was performed in healthy volunteers. PK parameters were derived via noncompartmental analysis. A physiologically-based PK (PBPK) model was used to predict exposure and multiples of Nav1.7 50 % inhibitory concentration (IC50) for each compound at higher doses. Plasma clearance, volume of distribution and bioavailability ranged from 45 to 392 mL/min/kg, 13 to 36 L/kg and 38 to 110 %, respectively. The PBPK model for PF-05089771 predicted a 1 g oral dose would be required to achieve exposures of approximately 12× Nav1.7 IC50 at maximum concentration (C max), and approximately 3× IC50 after 12 h (minimum concentration [C min] for a twice-daily regimen). Lower multiples of Nav1.7 IC50 were predicted with the same oral doses of PF-05150122, PF-05186462, and PF-05241328. In a subsequent single ascending oral dose clinical study, the predictions for PF-05089771 compared well with observed data. Based on the human PK data obtained from the microdose study and subsequent modelling, PF-05089771 provided the best opportunity to explore Nav1.7 blockade for the treatment of acute or chronic pain conditions.