Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project

A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project

Positive practices : solution-focused and narrative therapeutic techniques with children with sexually harmful behaviours

This article explores the use of solution-focused and Narrative Therapeutic approaches with a boy who had sexually harmful behaviours. The paper will highlight the practical challenges of working with someone who is 'problem-saturated' through institutionalisation and who is also subjected to powerful discourses claiming the 'truth' about him. The use of solution-focused and Narrative Therapeutic principles and approaches will be demonstrated in the work described, in a way that allows the reader to reflect on how these may differ from modernist understandings and responses to this behaviour

The 25th Anniversary of the Baby Doe Rules: Perspectives from the Fields of Law, Health Care, Ethics, and Disability Policy

A highly publicized and controversial case involving the withholding of medical treatment from a “Baby Doe” with Down syndrome gave rise in 1984 to the federal law known as the Baby Doe Rules, which went into effect the following year. The law conditions the grant of federal funds for any state’s child protective services program on the state’s assurance that it can respond to reports of medical neglect, which may include the withholding of medical treatment from disabled infants with life-threatening conditions. Leading scholars and practitioners from the fields of health care, law, ethics, and disability policy who are experts in the field of neonatal medicine and decision-making involving very premature and other medically at-risk infants gathered to provide thoughtful commentary and debate on the occasion of the 25th Anniversary of the Baby Doe Rules. The Georgia State University Law Review will publish a symposium volume on the topic in Fall 2009

The 25th Anniversary of the Baby Doe Rules: Perspectives from the Fields of Law, Health Care, Ethics, and Disability Policy

A highly publicized and controversial case involving the withholding of medical treatment from a “Baby Doe” with Down syndrome gave rise in 1984 to the federal law known as the Baby Doe Rules, which went into effect the following year. The law conditions the grant of federal funds for any state’s child protective services program on the state’s assurance that it can respond to reports of medical neglect, which may include the withholding of medical treatment from disabled infants with life-threatening conditions. Leading scholars and practitioners from the fields of health care, law, ethics, and disability policy who are experts in the field of neonatal medicine and decision-making involving very premature and other medically at-risk infants gathered to provide thoughtful commentary and debate on the occasion of the 25th Anniversary of the Baby Doe Rules. The Georgia State University Law Review will publish a symposium volume on the topic in Fall 2009

Massively parallel sequencing of the mouse exome to accurately identify rare, induced mutations: an immediate source for thousands of new mouse models

Accurate identification of sparse heterozygous single-nucleotide variants (SNVs) is a critical challenge for identifying the causative mutations in mouse genetic screens, human genetic diseases and cancer. When seeking to identify causal DNA variants that occur at such low rates, they are overwhelmed by false-positive calls that arise from a range of technical and biological sources. We describe a strategy using whole-exome capture, massively parallel DNA sequencing and computational analysis, which identifies with a low false-positive rate the majority of heterozygous and homozygous SNVs arising de novo with a frequency of one nucleotide substitution per megabase in progeny of N-ethyl-N-nitrosourea (ENU)-mutated C57BL/6j mice. We found that by applying a strategy of filtering raw SNV calls against known and platform-specific variants we could call true SNVs with a false-positive rate of 19.4 per cent and an estimated false-negative rate of 21.3 per cent. These error rates are small enough to enable calling a causative mutation from both homozygous and heterozygous candidate mutation lists with little or no further experimental validation. The efficacy of this approach is demonstrated by identifying the causative mutation in the Ptprc gene in a lymphocyte-deficient strain and in 11 other strains with immune disorders or obesity, without the need for meiotic mapping. Exome sequencing of first-generation mutant mice revealed hundreds of unphenotyped protein-changing mutations, 52 per cent of which are predicted to be deleterious, which now become available for breeding and experimental analysis. We show that exome sequencing data alone are sufficient to identify induced mutations. This approach transforms genetic screens in mice, establishes a general strategy for analysing rare DNA variants and opens up a large new source for experimental models of human disease

Life design and career counseling: contributions to social justice

The chapter begins with the presentation of LDC framework. In the second section, considerations are given on LDC possibilities for enhancing decent work and social justice. From this perspective of social exclusion, designated social integrationist, participation in paid work is viewed as the key to social inclusion (Watts, 2001). At the end of this section the relevance of contextual factors in career development of disadvantaged populations is referred to highlight the importance of these interventions not be exclusively focused on inter- and intrapersonal career development factors, but also take into consideration social action at the institutional, community, public policy and international/global levels (Cook, 2017). In the next section, the process of balancing the focus on the self-determination of the individual with a focus on a transformation of contextual factors that reinforce the disadvantaged position (Blustein, et al., 2005; Prilleltensky, 1997) is illustrated by presenting an intervention in which LDC was integrated into supported employment approach. Our proposal focuses exclusively on collaborative activities at the individual, institutional and communal level, with these being the tiers which the counselor can more easily influence as part of their more routine interaction with disadvantaged populations in general. The chapter concludes with an overview of the subject and a reference on LDC limitations for the intervention with disadvantaged populations in general

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe