Reading Success in the Primary Years: An Evidence-Based Interdisciplinary Approach to Guide Assessment and Intervention

This open access book describes the Reading Success project, in which a 5-step, assessment-to- intervention process, based on the Simple View of Reading, was used within a primary school setting in Australia to better support those students who struggle with reading. It provides an easily accessible overview of each step of the process involved in implementing this approach and highlights the crucial importance of collaboration between professionals involved in the teaching of reading within a school setting. It focuses on the decision-making processes used, such as rich dialogue with the leadership team and teachers, and shares participants’ perspectives gathered throughout the project. Using case studies, the book describes how the 5-step approach assists in creating detailed profiles of students’ strengths and weaknesses in spoken and written language skills that can be used to guide targeted intervention. This book offers valuable insights for educators, speech pathologists, researchers, and pre-service teacher education students interested in the teaching of reading

Reading Success in the Primary Years

This open access book describes the Reading Success project, in which a 5-step, assessment-to- intervention process, based on the Simple View of Reading, was used within a primary school setting in Australia to better support those students who struggle with reading. It provides an easily accessible overview of each step of the process involved in implementing this approach and highlights the crucial importance of collaboration between professionals involved in the teaching of reading within a school setting. It focuses on the decision-making processes used, such as rich dialogue with the leadership team and teachers, and shares participants’ perspectives gathered throughout the project. Using case studies, the book describes how the 5-step approach assists in creating detailed profiles of students’ strengths and weaknesses in spoken and written language skills that can be used to guide targeted intervention This book offers valuable insights for educators, speech pathologists, researchers, and pre-service teacher education students interested in the teaching of readin

Accelerated BEP : a phase I trial of dose-dense BEP for intermediate and poor prognosis metastatic germ cell tumour

Background: We used bleomycin, etoposide, cisplatin (BEP), the most effective regimen in the treatment of germ cell tumours (GCTs) and increased dose-density by using pegfilgrastim to shorten cycle length. Our aim was to assess safety and tolerability. Methods: Sixteen male patients with intermediate or poor prognosis metastatic GCT were treated with four cycles of 3-day BEP with G-CSF on a 14-day cycle for a planned relative dose-density of 1.5 compared with standard BEP. Results: Eleven intermediate and five poor prognosis patients were treated. In all, 14 of 16 patients completed the study treatment. Toxicities were comparable to previous studies using standard BEP, except for mucositis and haematological toxicity that were more severe. The overall relative dose-density for all 16 patients was mean 1.38 (range 0.72–1.5; median 1.46). Complete response was achieved after chemotherapy alone in two patients (13%) and following chemotherapy plus surgery in nine additional patients (56%). Four patients (25%) had a partial response and normalised their marker levels. At a median follow-up of 4.4 years (range 2.1–6.8) the estimated 5-year progression-free survival probability is 81% (95% CI 64–100%). Conclusion: Accelerated BEP is tolerable without major additional toxicity. A randomised controlled trial will be required to obtain comparative efficacy data

Tanzania’s Countdown to 2015: an analysis of two decades of progress and gaps for reproductive, maternal, newborn, and child health, to inform priorities for post-2015

Background Tanzania is on track to meet Millennium Development Goal (MDG) 4 for child survival, but is making insuffi cient progress for newborn survival and maternal health (MDG 5) and family planning. To understand this mixed progress and to identify priorities for the post-2015 era, Tanzania was selected as a Countdown to 2015 case study. Methods We analysed progress made in Tanzania between 1990 and 2014 in maternal, newborn, and child mortality, and unmet need for family planning, in which we used a health systems evaluation framework to assess coverage and equity of interventions along the continuum of care, health systems, policies and investments, while also considering contextual change (eg, economic and educational). We had fi ve objectives, which assessed each level of the health systems evaluation framework. We used the Lives Saved Tool (LiST) and did multiple linear regression analyses to explain the reduction in child mortality in Tanzania. We analysed the reasons for the slower changes in maternal and newborn survival and family planning, to inform priorities to end preventable maternal, newborn, and child deaths by 2030. Findings In the past two decades, Tanzania’s population has doubled in size, necessitating a doubling of health and social services to maintain coverage. Total health-care fi nancing also doubled, with donor funding for child health and HIV/AIDS more than tripling. Trends along the continuum of care varied, with preventive child health services reaching high coverage (≥85%) and equity (socioeconomic status diff erence 13–14%), but lower coverage and wider inequities for child curative services (71% coverage, socioeconomic status diff erence 36%), facility delivery (52% coverage, socioeconomic status diff erence 56%), and family planning (46% coverage, socioeconomic status diff erence 22%). The LiST analysis suggested that around 39% of child mortality reduction was linked to increases in coverage of interventions, especially of immunisation and insecticide-treated bednets. Economic growth was also associated with reductions in child mortality. Child health programmes focused on selected high-impact interventions at lower levels of the health system (eg, the community and dispensary levels). Despite its high priority, implementation of maternal health care has been intermittent. Newborn survival has gained attention only since 2005, but high-impact interventions are already being implemented. Family planning had consistent policies but only recent reinvestment in implementation. Interpretation Mixed progress in reproductive, maternal, newborn, and child health in Tanzania indicates a complex interplay of political prioritisation, health fi nancing, and consistent implementation. Post-2015 priorities for Tanzania should focus on the unmet need for family planning, especially in the Western and Lake regions; addressing gaps for coverage and quality of care at birth, especially in rural areas; and continuation of progress for child health

A first insight into the developability of an IgG3 : a combined computational and experimental approach

Immunoglobulin G 3 (IgG3) monoclonal antibodies (mAbs) are high value scaffolds for developing novel therapies. Despite their wide-ranging therapeutic potential, IgG3 physicochemical properties and developability characteristics remain largely under-characterised. Protein-protein interactions elevate solution viscosity in high-concentration formulations impacting physico-chemical stability, manufacturability, and injectability of mAbs. Therefore, in this manuscript, the key molecular descriptors and biophysical properties of a model anti-IL-8 IgG1 and its IgG3 ortholog are characterised. A computational and experimental framework was applied to measure molecular descriptors impacting on their downstream developability. Findings from this approach underpin a detailed understanding of the molecular characteristics of IgG3 mAbs as potential therapeutic entities. This work is the first report examining the manufacturability of IgG3 for high concentration mAb formulations. While poorer conformational and colloidal stability, and elevated solution viscosity was observed for IgG3, future efforts controlling surface potential through sequence-engineering of solvent-accessible patches can be used to improve biophysical parameters that dictate mAb developability

Tanzania's countdown to 2015: an analysis of two decades of progress and gaps for reproductive, maternal, newborn, and child health, to inform priorities for post-2015.

BACKGROUND: Tanzania is on track to meet Millennium Development Goal (MDG) 4 for child survival, but is making insufficient progress for newborn survival and maternal health (MDG 5) and family planning. To understand this mixed progress and to identify priorities for the post-2015 era, Tanzania was selected as a Countdown to 2015 case study. METHODS: We analysed progress made in Tanzania between 1990 and 2014 in maternal, newborn, and child mortality, and unmet need for family planning, in which we used a health systems evaluation framework to assess coverage and equity of interventions along the continuum of care, health systems, policies and investments, while also considering contextual change (eg, economic and educational). We had five objectives, which assessed each level of the health systems evaluation framework. We used the Lives Saved Tool (LiST) and did multiple linear regression analyses to explain the reduction in child mortality in Tanzania. We analysed the reasons for the slower changes in maternal and newborn survival and family planning, to inform priorities to end preventable maternal, newborn, and child deaths by 2030. FINDINGS: In the past two decades, Tanzania's population has doubled in size, necessitating a doubling of health and social services to maintain coverage. Total health-care financing also doubled, with donor funding for child health and HIV/AIDS more than tripling. Trends along the continuum of care varied, with preventive child health services reaching high coverage (≥85%) and equity (socioeconomic status difference 13-14%), but lower coverage and wider inequities for child curative services (71% coverage, socioeconomic status difference 36%), facility delivery (52% coverage, socioeconomic status difference 56%), and family planning (46% coverage, socioeconomic status difference 22%). The LiST analysis suggested that around 39% of child mortality reduction was linked to increases in coverage of interventions, especially of immunisation and insecticide-treated bednets. Economic growth was also associated with reductions in child mortality. Child health programmes focused on selected high-impact interventions at lower levels of the health system (eg, the community and dispensary levels). Despite its high priority, implementation of maternal health care has been intermittent. Newborn survival has gained attention only since 2005, but high-impact interventions are already being implemented. Family planning had consistent policies but only recent reinvestment in implementation. INTERPRETATION: Mixed progress in reproductive, maternal, newborn, and child health in Tanzania indicates a complex interplay of political prioritisation, health financing, and consistent implementation. Post-2015 priorities for Tanzania should focus on the unmet need for family planning, especially in the Western and Lake regions; addressing gaps for coverage and quality of care at birth, especially in rural areas; and continuation of progress for child health. FUNDING: Government of Canada, Foreign Affairs, Trade, and Development; US Fund for UNICEF; and the Bill & Melinda Gates Foundation

Enhancing viscosity control in antibody formulations : a framework for the biophysical screening of mutations targeting solvent-accessible hydrophobic and electrostatic patches

The formulation of high-concentration monoclonal antibody (mAb) solutions in low dose volumes for autoinjector devices poses challenges in manufacturability and patient administration due to elevated solution viscosity. In the current study, we present a systematic experimental framework for the computational screening of molecular descriptors to guide the design of mutants with modified viscosity profiles accompanied by experimental evaluation. Our observations using a model anti-IL8 antibody reveal that the reduction in viscosity is influenced by the location of hydrophobic interactions, while targeting positively charged patches in mAb1 leads to the most significant viscosity increase compared to the wild-type mAb. We conclude that existing in silico predictions of physicochemical properties exhibit poor correlation with experimental parameters for antibodies with suboptimal developability characteristics, emphasizing the necessity for comprehensive case-by-case evaluations of mAbs. This approach aids in the rational design of mAbs with tailored solution viscosities, ensuring improved manufacturability and patient convenience in self-administration scenarios

Transcriptome-wide Mendelian randomization study prioritising novel tissue-dependent genes for glioma susceptibility.

Genome-wide association studies (GWAS) have discovered 27 loci associated with glioma risk. Whether these loci are causally implicated in glioma risk, and how risk differs across tissues, has yet to be systematically explored. We integrated multi-tissue expression quantitative trait loci (eQTLs) and glioma GWAS data using a combined Mendelian randomisation (MR) and colocalisation approach. We investigated how genetically predicted gene expression affects risk across tissue type (brain, estimated effective n = 1194 and whole blood, n = 31,684) and glioma subtype (all glioma (7400 cases, 8257 controls) glioblastoma (GBM, 3112 cases) and non-GBM gliomas (2411 cases)). We also leveraged tissue-specific eQTLs collected from 13 brain tissues (n = 114 to 209). The MR and colocalisation results suggested that genetically predicted increased gene expression of 12 genes were associated with glioma, GBM and/or non-GBM risk, three of which are novel glioma susceptibility genes (RETREG2/FAM134A, FAM178B and MVB12B/FAM125B). The effect of gene expression appears to be relatively consistent across glioma subtype diagnoses. Examining how risk differed across 13 brain tissues highlighted five candidate tissues (cerebellum, cortex, and the putamen, nucleus accumbens and caudate basal ganglia) and four previously implicated genes (JAK1, STMN3, PICK1 and EGFR). These analyses identified robust causal evidence for 12 genes and glioma risk, three of which are novel. The correlation of MR estimates in brain and blood are consistently low which suggested that tissue specificity needs to be carefully considered for glioma. Our results have implicated genes yet to be associated with glioma susceptibility and provided insight into putatively causal pathways for glioma risk