Parent values and preferences underpinning treatment decision-making in poor-prognosis childhood cancer: a scoping review.

BACKGROUND: Parents of children who are diagnosed with a poor-prognosis cancer want to be involved in making treatment-related decisions for their child. They often make repeated decisions depending on their child's response to treatment and can experience decisional regret as a consequence. Understanding parent values and preferences when making treatment-related decisions may help enhance discussions with healthcare professionals and identify additional ways of providing support to this parent population. OBJECTIVES: To explore parent values and preferences underpinning treatment decision-making for children receiving cancer-directed therapy for a poor prognosis cancer. METHODS: A scoping review of research literature and systematic reviews from qualitative, quantitative, and mixed methods studies was conducted following Joanna Briggs Institute methodology. Articles which included parents of a child who received cancer-directed therapy for a poor-prognosis childhood cancer, under the age of eighteen years were considered. Four electronic databases were searched (CINAHL, Medline, PsychINFO, Web of Science Core Collections). Reference and citation lists of all included full-text articles were also searched. Summative content analysis was used to synthesise findings and develop themes. RESULTS: Twelve articles were included. Parent decision-making was affected by underpinning factors: hope for a cure, fear of their child dying and uncertainty. Influencing factors: opinions of others, child's wishes, and faith and religion had the potential to inform decision-making processes. Parents valued having enough time, being a good parent and being involved in decision-making. Preferences within these values varied resulting in the potential for conflict and 'trade-offs' in making decisions. CONCLUSIONS: Parent decision-making in poor-prognosis childhood cancer is complex and extends beyond values and preferences. Underpinning factors and values are consistent through the decision-making process with influencing factors and preferences varying between parents. Preferences can conflict when parents want to continue cancer-directed therapy whilst maintaining their child's quality of life or can change depending on a parents' cognitive state as they realise cure might be unlikely.

Further diversity of the 5' promoter region of the MHC class I-related chain B gene.

We have now found a total of 15 individual MICB promoter sequences, varying by combination of 18 polymorphic positions within the MICB minimal promoter sequence. Sequence-based typing and cloning characterized the three new 5' promoter sequences as MICB-P13, MICB-P14 and MICB-P15.

An International reference reagent for the detection of anti-human neutrophil antigen-1a.

BACKGROUND AND OBJECTIVES: Testing for neutrophil antibodies has become more common as awareness of transfusion-related acute lung injury (TRALI) has increased. However, unlike other areas of blood cell antibody testing, there are no certified reference reagents available with which laboratories can determine the sensitivity of detection of their assays. This report describes the production and evaluation of a freeze-dried preparation of human plasma, code 09/284, containing anti-human neutrophil antigen-1a (anti-HNA-1a) for use as a minimum sensitivity reagent. MATERIALS AND METHODS: One-millilitre of aliquots of plasma containing anti-HNA-1a were freeze-dried in glass ampoules. To characterize the material, 24 laboratories took part in an international collaborative study. The participants evaluated doubling dilutions of the material using their in-house routine assays and recorded the highest dilution in which the antibody could be detected. RESULTS: When diluted 1 in 4, most laboratories were able to detect the anti-HNA-1a in the material, and the participants agreed that this was an appropriate level to set as the minimum sensitivity required. CONCLUSIONS: In October 2011, the WHO Expert Committee on Biological Standardization approved the material 09/284 as an International Reference Reagent for the detection of anti-HNA-1a.

Effects of balance-focused interactive games compared to therapeutic balance classes for older women.

OBJECTIVE: The prospective pre-post control study was designed to evaluate the effect of introducing balance-focused interactive virtual-reality games to community-dwelling older women to improve their agility, balance and functional mobility. METHOD: The study was set in a senior citizens' club in Cheras, Kuala Lumpur, Malaysia. The participants were 36 community-dwelling older women. Participants were randomly divided into either a group undertaking balance-focused virtual-reality games or a group doing therapeutic balance exercises. The program lasted 6 weeks and was conducted twice a week for 40 min during each session. As the main outcome measures, the results of the Ten Step Test (TST), postural sway (overall performance index, OPI) and the Timed Up and Go test (TUG) were measured pre- and post-intervention to evaluate agility, balance and functional mobility, respectively. RESULTS: Although both groups improved in OPI (F = 4.63, p < 0.001), TST (F = 46.15, p < 0.001) and TUG (F = 52.57, p = 0.03), combined time and group interaction only improved in the TUG (F = 4.54, p < 0.05). No significant differences between the two groups were found in terms of TST (F = 0.02, p = 0.86), OPI (F = 0.66, p = 0.42), and TUG (F = 0.11, p = 0.74). CONCLUSION: Older people could improve their agility, balance and functional mobility by complementing therapeutic balance exercises with active participation in interactive virtual-reality games at home or in the community.

The removal of thermo-tolerant coliform bacteria by immobilized waste stabilization pond algae.

This study investigated the potential of laboratory- scale columns of immobilized micro-algae to disinfect effluents using thermo-tolerant coliforms (TTC) as a model system. Cells of a Chlorella species isolated from a waste stabilization pond complex in Northeast Brazil were immobilized in calcium alginate, packed into glass columns and incubated in contact with TTC suspensions for up to 24 hours. Five to six log removals of TTC were achieved in 6 hours and 11 log removals in 12 hours contact time. The results were similar under artificial light and shaded sunlight. However little or no TTC removal occurred in the light in columns of alginate beads without immobilized algae present or when the immobilized algae were incubated in the dark suggesting that the presence of both algae and light were necessary for TTC decay. There was a positive correlation between K(b) values for TTC and increasing pH in the effluent from the immobilized algal columns within the range pH 7.2 and 8.9. The potential of immobilized algal technology for wastewater disinfection may warrant further investigation.

Thermo-tolerant coliform bacteria decay rates in a full scale waste stabilization pond system in northeast Brazil.

This paper presents the results for thermo-tolerant coliform (TTC) decay rates (K(b)) in a full scale WSP system located in Natal-RN, northeast Brazil. The series comprises a primary facultative pond (2 m deep), followed by two maturation ponds (1.5 m deep) giving a total area of 11 ha. The influent sewage and the pond effluents were monitored weekly during a seven month period. The results showed that the K(b) values predicted by the Marais equation assuming a hydraulic regime of complete mixing overestimated TTC die-off rates. The K(b) value adopted in the project design was 6.20 d(-1) but the mean value found for the WSP system during the monitoring programme was only 0.85 d(-1). This value is low compared to the values cited in the literature for shallow ponds (<1.25 m deep) but similar to values for deeper ponds. The sub optimal TTC removal rate in this WSP system may be caused by the adoption of too high a K(b) value at the design stage and the negative influence of high wind conditions on the mixing regime in the water columns of the ponds. Thus values for K(b) adopted at the design stage of WSP systems should be coherent with the hydraulic flow model, the type of pond, pond depth, and with the surface organic loading.

The removal of ammonia from sanitary landfill leachate using a series of shallow waste stabilization ponds.

This study evaluated the efficiency of a shallow (0.5 m deep) waste stabilization pond series to remove high concentrations of ammonia from sanitary landfill leachate. The pond system was located at EXTRABES, Campina Grande, Paraiba, Northeast Brazil. The pond series was fed with sanitary landfill leachate transported by road tanker to the experimental site from the sanitary landfill of the City of Joao Pessoa, Paraiba. The ammoniacal-N surface loading on the first pond of the series was equivalent to 364 kg ha(-1) d(-1) and the COD surface loading equivalent to 3,690 kg ha(-1) d(-1). The maximum mean ammonia removal efficiency was 99.5% achieved by the third pond in the series which had an effluent concentration of 5.3 mg L(-1) ammoniacal-N for an accumulative HRT of 39.5 days. The removal process was mainly attributed to ammonia volatilization (stripping) from the pond surfaces as a result of high surface pH values and water temperatures of 22-26°C. Shallow pond systems would appear to be a promising technology for stripping ammonia from landfill leachate under tropical conditions.

Baffled primary facultative ponds with inlets and outlets set at different levels treating domestic wastewater in northeast Brazil.

This study evaluates the performance of four 2.3 m deep pilot-scale, independently loaded, primary facultative ponds treating predominantly domestic sewage in northeast Brazil. The ponds contained longitudinal baffles giving different length to width ratios from 3.55 to 32.4. The ponds had mean hydraulic retention times of ~15 days, and mean surface organic loadings of 330 kg BOD(5).ha.d(-1) during the first experimental phase and 375 kg BOD(5).ha.d(-1) in the second. The vertical inlets and outlets pipes were positioned at 1.8 m and 5 cm respectively below the pond surface in the first phase and at 50 cm and 1.8 m respectively in the second. All the ponds functioned as efficient primary facultative ponds but statistical analysis demonstrated no differences in effluent quality for most of the parameters measured for the various configurations of baffles and inlet and outlet depths. All behaved similarly to the unbaffled pond. The only exceptions were suspended solids and chlorophyll a concentrations which tended to be lower for all combinations of baffles with the outlets set 1.8 m below the surface. This study suggested that the longitudinal baffling of primary facultative ponds when using vertical inlets and outlets may well not significantly improve pond performance.

Report on the 14th International Society of Blood Transfusion Platelet Immunology Workshop.

BACKGROUND AND OBJECTIVES: The aims of the 14th ISBT Platelet Immunology Workshop were to evaluate in-house methods for detection of antibodies to human platelet antigens, to compare the sensitivity and specificity of antibody detection using a panel of monoclonal antibodies and to evaluate genotyping methods and establish procedures for drug-dependent antibody detection. MATERIALS AND METHODS: Forty-two laboratories from 23 countries participated. Samples and reagents provided for the five different exercises. RESULTS: The ability of participating laboratories to correctly identify the HPA antibody specificity in the nine samples ranged from 20% to 97%. The greatest difficulty was observed with samples that contained antibodies against HPA-3b and GPIV. The significant differences in optical density values by monoclonal antibody of immobilization of platelet antigens (MAIPA) assay were observed when testing the same platelet-specific antibodies. HPA genotyping of DNA with novel mutations did not significantly affect the results. The overall average discrepancy rate was 2·15% for genotyping of 10 DNA samples from well-characterized Epstein­Barr virus transformed cell lines. For detection of drug-dependent antibodies, excellent results for specificity and sensitivity were obtained by the laboratories using the MAIPA and flow cytometry. CONCLUSIONS: Most laboratories were able to identify the majority of HPA antibodies; however, significant disparities were observed in proficiency testing. MAIPA assay sensitivity is influenced by the monoclonal antibody clone used. DNA with new mutations and EBV cell lines are valuable samples to ensure accurate genotyping. A sensitive and specific drug-dependent antibody assay performed well in the hands of participants.

Evidence of heterogeneity in the antibody response against the platelet antigen 3a; recognition of an 11-mer peptide carrying the HPA-3a polymorphic determinant.

BACKGROUND: The immune processes involved in the development of alloantibodies against the human platelet antigens in alloimmune disorders remain unclear. Antibody recognition of the platelet antigens on their respective platelet glycoproteins has been shown to be dependent on glycoprotein conformation. Furthermore, the post-translational modification of glycoproteins adds complexity to the alloantigenic determinants. METHODS: Nine anti-HPA-3a sera along with several control sera were tested for reactivity to an 11-mer peptide straddling the HPA-3a/b polymorphism. Sera found to specifically recognize the 3a peptide were further assessed by platelet pre-exposure and immunoblotting. RESULTS: Three of the nine antisera were found to specifically recognize an 11-mer synthetic 3a peptide by ELISA. Further analysis of all anti-HPA-3a sera by Western blot showed that only those reactive to the 3a peptide were able to bind both reduced and non-reduced GPIIb. CONCLUSION: The results presented in this study provide the first known evidence for the identification of an antibody population capable of recognizing a linear and non-glycosylated form of the HPA-3a epitope.

Posttranscriptional defects in beta-globin messenger RNA metabolism in beta-thalassemia: abnormal accumulation of beta-messenger RNA precursor sequences.

The production of beta-globin messenger RNA (mRNA) in beta-thalassemic erythroblasts was studied during pulse-chase incubations with [3H]uridine. Globin [3H]mRNA was quantitated by molecular hybridization to recombinant DNA probes complementary to globin mRNA and mRNA precursor sequences. Each of six patients with beta +-thalassemia produced normal amounts of globin alpha and beta [3H]mRNA during a 20-min pulse incubation, but the beta/alpha [3H]mRNA ratio declined to steady-state levels during a chase incubation, suggesting posttranscriptional defects in beta-globin mRNA metabolism. beta-globin mRNA precursor production was estimated by measurement of [3H]RNA sequences hybridizing to a pure DNA probe containing only the large intervening sequence (intron) of the beta-mRNA precursor. Four of the patients exhibited abnormal accumulation of 3H-beta-intron sequences (2-10 times normal), indicating abnormal posttranscriptional processing. In the remaining two patients, one of whom is known to carry a mutation in the small intron of the beta-globin gene, accumulation of large 3H beta-intron RNA and beta-globin [3H]mRNA was normal in nuclei, but the ratio of beta/alpha [3H]mRNA in cytoplasm was reduced, suggesting a different posttranscriptional defect in beta-mRNA processing. These findings imply the existence of heterogeneous posttranscriptional abnormalities in beta-globin mRNA metabolism in different patients with beta-thalassemia. The initial rates of gamma- and delta-mRNA synthesis were low in all patients, suggesting that the low level of expression of these genes in adults is mediated at the transcriptional level.

Amyloid peptides mediate hypoxic increase of L-type Ca2+ channels in central neurones.

Prolonged hypoxia, encountered in individuals suffering from various cardiorespiratory diseases, enhances the likelihood of subsequently developing Alzheimer's disease (AD). However, the underlying mechanisms are unknown, as are the mechanisms of neurodegeneration of amyloid beta peptides (AbetaPs), although the latter involves disruption of Ca2+ homeostasis. Here, immunohistochemistry demonstrated that hypoxia increased production of AbetaPs, an effect which was prevented by inhibition of either beta or gamma secretase, the enzymes required for liberation of AbetaP from its precursor protein. Whole-cell patch clamp recordings showed that hypoxia selectively increased functional expression of L-type Ca2+ channels. This was prevented by inhibition of either beta or gamma secretase, indicating that hypoxic channel up-regulation is dependent upon AbetaP formation. Our results indicate for the first time that hypoxia promotes AbetaP formation in central neurons, and show that this leads to abnormally high selective expression of L-type Ca2+ channels whose blockade has previously been shown to be neuroprotective in AD models. These findings provide a cellular basis for understanding the increased incidence of AD following prolonged hypoxia.

Hypoxic regulation of Ca2+ signalling in astrocytes and endothelial cells.

Acute hypoxia is well known to modulate plasmalemmal ion channels in specific tissue types, thereby modulating [Ca2+]i. Alternative mechanisms by which acute hypoxia could modulate [Ca2+]i are less well explored, particularly in non-excitable cells. Here, we describe experiments employing microfluorimetric recordings from Fura-2-loaded rat cortical astrocytes and human saphenous vein endothelial cells designed to explore any effects of hypoxia (pO2 20-30 mmHg) on [Ca2+]i. In both cell types, hypoxia evoked small rises of [Ca2+]i in the majority of cells during perfusion with a Ca(2+)-free solution, indicating hypoxia can release Ca2+ from an intracellular pool. Capacitative Ca2+ entry was observed when Ca2+ was subsequently restored to the extracellular solution. These effects were abolished by pre-treatment of cells with thapsigargin or prior application of inositol 1,4,5-trisphosphate (IP3)-generating agonists. Antioxidants fully prevented this effect of hypoxia in both cell types. Mitochondrial uncoupling significantly enhanced the effects of hypoxia in astrocytes, yet markedly suppressed the effects of hypoxia in endothelial cells. Our findings indicate that hypoxia can modulate [Ca2+]i in non-excitable cells; most importantly, it can evoke Ca2+ release from intracellular stores via a mechanism which involves reactive oxygen species. The involvement of mitochondria in this effect appears to be tissue specific.

Increasing polymorphism of the RAET1E/ULBP4 gene in humans.

Description of three novel RAET1E/ULBP4 allele and promoter polymorphisms identified by sequence-based typing.

Is the way an oil spill response is reported in the media important for the final perception of the clean-up?

This research investigates the media coverage during the C/V Rena grounding in New Zealand (NZ), in 2011, to analyze if information reported in printed media is important for the final perception of the overall oil spill response. We took all articles available from NZ's largest circulated newspaper and the regional newspaper closest to the incident and analyzed the themes within each article; the article's tone (positive, neutral or negative); the time of the report relative to incident events and any differences between the regional and national papers. This analysis indicates that oil spills are reported and perceived as inherently negative incidents. However, along with coordinating an effective spill response, fast, factual and frequent media releases and increased effect in media liaison in areas of response with high public intrinsic value such as oiled wildlife response can significantly influence tone of media coverage and likely overall public perception.

Proteogenomic-based discovery of minor histocompatibility antigens with suitable features for immunotherapy of hematologic cancers.

Pre-clinical studies have shown that injection of allogeneic T cells primed against a single minor histocompatibility antigen (MiHA) could cure hematologic cancers (HC) without causing any toxicity to the host. However, translation of this approach in humans has been hampered by the paucity of molecularly defined human MiHAs. Using a novel proteogenomic approach, we have analyzed cells from 13 volunteers and discovered a vast repertoire of MiHAs presented by the most common HLA haplotype in European Americans: HLA-A*02:01;B*44:03. Notably, out of >6000 MiHAs, we have identified a set of 39 MiHAs that share optimal features for immunotherapy of HCs. These 'optimal MiHAs' are coded by common alleles of genes that are preferentially expressed in hematopoietic cells. Bioinformatic modeling based on MiHA allelic frequencies showed that the 39 optimal MiHAs would enable MiHA-targeted immunotherapy of practically all HLA-A*02:01;B*44:03 patients. Further extension of this strategy to a few additional HLA haplotypes would allow treatment of almost all patients.

The intravenous intralipid tolerance test.

The half-life of an intravenously injected bolus of intralipid 20% was measured in normal rats in order to asess its relationship to reticuloendothelial system (RES) activity. Groups of animals were studied following various treatments, and the results compared to measurement of carbon clearance in similar groups. The RES effects of silica and C parvum were confirmed by the carbon clearance test, but no effect was seen on the half-life of intralipid. Intralipid clearance was shortened by fasting and the administration of intravenous heparin, neither of which affected carbon clearance. It is concluded that the intravenous intralipid test has no place in the asessment of RES function.

Implications for physical design: The effect of depth on the performance of waste stabilization ponds.

Studies on experimental primary facultative ponds showed that varying the depth from 1.25 m to 2.3 m had no effect on the rates of BOD removal. In contrast k values for FC removal rates were higher in the shallower (1.25 m) facultative ponds. The risk of odour release via H2S production was higher in the 2.2 m ponds than the 1.25 m ponds and NH3 removal was much better in the 1.25 m facultative ponds. A comparison of the efficiency of shallow 5-pond series (1.0 m and 0.61 m deep) with a 2.2 m deep series showed that the shallow systems were more efficient at FC removal, but the deeper series actually saved land area for the same FC final effluent quality under tropical conditions. However, efficient nutrient removal (N and P) only occurred in the shallow series and effluent standards for nutrient concentrations are unlikely to be met by 2.2 m deep 5-pond series in contrast to the norms for pathogen removal.

Variations in BOD, algal biomass and organic matter biodegradation constants in a wind-mixed tropical facultative waste stabilization pond.

This study considered the impact of wind mixing on the efficiency of BOD removal and the first order biodegradation constant for organic matter in a primary facultative pond. Wind speeds of 1-4 m/s blowing from the effluent end of the pond towards the influent created surface-water flows of up to 0.94 m/s as determined by orange and coconut drogues moving in the opposite direction to the bulk hydraulic flow of 0.217 m/s. This was sufficient to cause mixing of the water column resulting in loss of stratification in terms of chlorophyll a, temperature and dissolved oxygen. BOD and chlorophyll a concentrations were spatially and temporally homogeneous throughout this large pond. BOD removal efficiency was only 50.30% as opposed to a projected value of 79% despite an acceptable surface organic loading of 350 kgBOD5/ha/d and an actual k value for BOD removal using influent sewage samples of 0.29 d-1 close to the projected value of 0.30 d-1. It would seem that wind mixing reduced pond efficiency by destroying stratification and thus reducing the microbial activity necessary to consume organic material. Mixing also increased the mean chlorophyll a concentration compared to stratified facultative ponds receiving similar loads and non-motile algae dominated the water column.