Parents' responses to prognostic disclosure at diagnosis of a child with a high-risk brain tumor: Analysis of clinician-parent interactions and implications for clinical practice.

Background: Previous studies have found that parents of children with cancer desire more prognostic information than is often given even when prognosis is poor. We explored in audio-recorded consultations the kinds of information they seek.

Methods: Ethnographic study including observation and audio recording of consultations at diagnosis.

Research barriers in children and young people with life-limiting conditions: a survey.

Unlabelled: Studies indicate research ethics committee (REC) approval and clinician gatekeeping are two key barriers in recruiting children and young people (CYP) with life-limiting conditions (LLCs) and life-threatening illnesses (LTIs) and their families to research.

Objectives: To explore the reported experiences, difficulties and proposed solutions of chief investigators (CIs) recruiting CYP with LLCs/LTIs and families in the UK.

Methods: 61 CIs conducting studies with CYP with LLCs/LTIs and their families, identified from the UK National Institute of Health Research portfolio, completed an anonymous, web-based questionnaire, including both closed and open-ended questions.

Children's and Parents' Conceptualization of Quality of Life in Children With Brain Tumors: A Meta-Ethnographic Exploration.

The concept of quality of life (QoL) is used in consultations to plan the care and treatment of children and young people (CYP) with brain tumors (BTs). The way in which CYP, their parents, and their health care professionals (HCP) each understand the term has not been adequately investigated. This study aimed to review the current qualitative research on CYP, parents' and clinicians' concepts of QoL for CYP with BTs using meta-ethnography.

Keeping all options open: Parents' approaches to advance care planning.

Background: Early engagement in advance care planning (ACP) is seen as fundamental for ensuring the highest standard of care for children and young people with a life-limiting condition (LLC). However, most families have little knowledge or experience of ACP.

Objective: To investigate how parents of children and young people with LLCs approach and experience ACP.

Pharmacological interventions for pain in children and adolescents with life-limiting conditions.

Background: Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer. The current literature indicates that pain is not well managed, however the evidence base to guide clinicians is limited. There is a clear need for evidence from a systematic review to inform prescribing.

Inviting parents to take part in paediatric palliative care research: a mixed-methods examination of selection bias.

Background: Recruitment to paediatric palliative care research is challenging, with high rates of non-invitation of eligible families by clinicians. The impact on sample characteristics is unknown.

Aim: To investigate, using mixed methods, non-invitation of eligible families and ensuing selection bias in an interview study about parents' experiences of advance care planning (ACP).

Animal models that best reproduce the clinical manifestations of human intoxication with organophosphorus compounds.

The translational capacity of data generated in preclinical toxicological studies is contingent upon several factors, including the appropriateness of the animal model. The primary objectives of this article are: 1) to analyze the natural history of acute and delayed signs and symptoms that develop following an acute exposure of humans to organophosphorus (OP) compounds, with an emphasis on nerve agents; 2) to identify animal models of the clinical manifestations of human exposure to OPs; and 3) to review the mechanisms that contribute to the immediate and delayed OP neurotoxicity. As discussed in this study, clinical manifestations of an acute exposure of humans to OP compounds can be faithfully reproduced in rodents and nonhuman primates.

Preferred place of death for children and young people with life-limiting and life-threatening conditions: a systematic review of the literature and recommendations for future inquiry and policy.

Background: Home is often cited as preferred place of death in the United Kingdom and elsewhere. This position, however, usually relies on data concerning adults and not evidence about children. The latter data are scant, primarily retrospective and from parents.

Self-complementary AAV2.5-BMP2-coated femoral allografts mediated superior bone healing versus live autografts in mice with equivalent biomechanics to unfractured femur.

Structural allografts used for critical bone defects have limited osteogenic properties for biointegration. Although ex vivo tissue-engineered constructs expressing bone morphogenetic protein-2 (BMP2) have demonstrated efficacy in critical defect models, similar success has not been achieved with off-the-shelf acellular approaches, including allografts coated with freeze-dried single-stranded adeno-associated virus (ssAAV-BMP2). To see whether the self-complementary AAV serotype 2.

Characterization of a recombinant adeno-associated virus type 2 Reference Standard Material.

A recombinant adeno-associated virus serotype 2 Reference Standard Material (rAAV2 RSM) has been produced and characterized with the purpose of providing a reference standard for particle titer, vector genome titer, and infectious titer for AAV2 gene transfer vectors. Production and purification of the reference material were carried out by helper virus-free transient transfection and chromatographic purification. The purified bulk material was vialed, confirmed negative for microbial contamination, and then distributed for characterization along with standard assay protocols and assay reagents to 16 laboratories worldwide.

Targeting of T lymphocytes to melanoma cells through chimeric anti-GD3 immunoglobulin T-cell receptors.

Immunoglobulin T-cell receptors (IgTCRs) combine the specificity of antibodies with the potency of cellular killing by grafting antibody recognition domains onto TCR signaling chains. IgTCR-modified T cells are thus redirected to kill tumor cells based on their expression of intact antigen on cell surfaces, bypassing the normal mechanism of activation through TCR-peptide-major histocompatibility complex (MHC) recognition. Melanoma is one of the most immunoresponsive of human cancers and has served as a prototype for the development of a number of immunotherapies.

Coupling CD28 co-stimulation to immunoglobulin T-cell receptor molecules: the dynamics of T-cell proliferation and death.

Immunoglobulin T-cell receptor (IgTCR) molecules are potentially potent immune response modifiers because they allow T cells to bypass tolerance. Tolerance to self antigens has been one of the major barriers to the development of effective adoptive immunotherapies for treating cancer. In vitro studies in several laboratories have shown that cross-linking IgTCR molecules with the target antigen leads to cytolytic activity, cytokine release, and T-cell proliferation in model systems.

Dynamics of tumor cell killing by human T lymphocytes armed with an anti-carcinoembryonic antigen chimeric immunoglobulin T-cell receptor.

Chimeric immunoglobulin T-cell receptors (IgTCR) join the antigen-binding portion of an antibody to one of the signaling chains of the TCR. A previous report described the construction and functional testing of an IgTCR gene directed against the carcinoembryonic tumor antigen (CEA). These preclinical studies showed the proper assembly and cell surface expression of anti-CEA IgTCR molecules, specific target antigen binding, and activation of T-cell effector functions.

Bypassing immunization: optimized design of "designer T cells" against carcinoembryonic antigen (CEA)-expressing tumors, and lack of suppression by soluble CEA.

Tumor-associated antigens are typically nonimmunogenic in cancer patients, "immune surveillance" having manifestly failed. The fact that most tumor antigens are normal human proteins presents significant obstacles to current cancer immunization approaches that researchers are presently striving to overcome. An alternative strategy bypasses immunization altogether by direct genetic alteration of autologous patient T cells, to create "designer T cells" specific to a particular antigen.

Less repair of pyrimidine dimers and single-strand breaks in genes by scid cells.

Severe combined immunodeficient (Scid) mice have a mutation in the catalytic subunit of the DNA binding protein kinase that is involved in repair of double-strand breaks in DNA. To determine if the protein also influences repair of single-strand breaks, we examined the ability of Scid cells to repair lesions introduced by ultraviolet light and gamma-ray irradiation. DNA repair was measured both in total genomic DNA and in specific genes from murine Scid and wildtype fibroblast cell lines.

Decoupling of DNA excision repair and RNA transcription in translocation breaksite regions of plasmacytoma-susceptible BALB/cAnPt mice.

Preferential repair of pyrimidine dimers in rodent cells is thought to be directly coupled to the RNA transcription machinery. The most compelling evidence for this notion is the finding that excision repair occurs more rapidly in the template strand of DNA of transcribed genes than in the non-template strand. A thorough test of this coupling concept by careful comparison of the rate of repair to the rate of transcription of a gene and its regulatory region has not been reported.

DNA repair in the endogenous and episomal amplified c-myc oncogene loci in human tumor cells.

We have studied the repair of u.v.-induced cyclobutane pyrimidine dimers (CPDs) in amplified c-myc oncogene loci in human colon cancer cells to better understand the relationship between chromatin structure, transcription and DNA repair.

DNA repair defects associated with chromosomal translocation breaksite regions.

Using an assay that measures the removal of UV-induced pyrimidine dimers in specific DNA sequences, we have found that the Pvt-1, immunoglobulin H-C alpha (IgH-C alpha), and IgL-kappa loci are poorly repaired in normal B lymphoblasts from plasmacytoma-susceptible BALB/cAnPt mice. Breaksites in these genes are associated with the chromosomal translocations that are found in > 95% of BALB/cAnPt plasmacytomas. In contrast to those from BALB/cAnPt mice, B lymphoblasts from plasmacytoma-resistant DBA/2N mice rapidly repair Pvt-1, IgH-C alpha, and IgL-kappa.

Repair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells.

Using methodology recently developed to assess gene-specific DNA repair, we have demonstrated that it is possible not only to study mitochondrial DNA repair, but also directly to compare mitochondrial and nuclear DNA repair in the same biological sample. Complex enzymatic mechanisms recognize and repair nuclear DNA damage, but it has long been thought that there was no DNA repair in mitochondria. Therefore, in an attempt to delineate more clearly which DNA repair mechanisms, if any, are functioning in mitochondria, we have investigated the repair of several specific DNA lesions in mitochondrial DNA.

DNA repair in the c-myc proto-oncogene locus: possible involvement in susceptibility or resistance to plasmacytoma induction in BALB/c mice.

This report describes an unexpected difference in the efficiency of removal of UV-induced DNA damage in the c-myc locus in splenic B lymphoblasts from two inbred strains of mice. In cells from plasmacytoma-resistant DBA/2N mice, 35% of UV-induced damage in the regulatory and 5' flank of c-myc is removed by 12 h. However, in cells from plasmacytoma-susceptible BALB/cAn mice, damage is not removed from this region.

DNA damage induced by phorbol ester-stimulated neutrophils is augmented by extracellular cofactors. Role of histidine and metals.

Activated neutrophils cause extensive DNA damage in neighboring nonphagocytic cells. To determine whether compounds in the extracellular milieu participate in the DNA damage process, murine neutrophils were cocultivated with target tumor cells in media of varying composition. Using the alkaline elution assay, it was found that the level of strand breaks induced was significantly higher (2.