bluuebunny/crossref_metadata_2025_split huggingface dataset:
Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group
Authors: Litzow Mark R. , Othus Megan , Cripe Larry D. , Gore Steven D. , Lazarus Hillard M. , Lee Sandra J. , Bennett John M. , Paietta Elisabeth M. , Dewald Gordon W. , Rowe Jacob M. , Tallman Martin S. ,   for the Eastern Cooperative Oncology Group Leukemia Committee
Published: October 2009

SummaryThe treatment of relapsed acute myeloid leukaemia (AML) remains unsatisfactory. We conducted a phase II randomized trial where patients received intermediate‐dose cytarabine for 4 d followed by gemtuzumab ozogamicin on day 5 (Arm A), or combined with liposomal daunorubicin for 3 d (Arm B), or cytarabine given for 5 d combined with cyclophosphamide for 3 d and topotecan by continuous infusion for 5 d (Arm C). Eligible patients had primary refractory AML, a first relapse after a remission of <1 year, or a second or greater relapse. The primary objective of this trial was attainment of a conventional complete remission (CR) or a CR without platelet recovery (CRp) in at least 40% of patients. The CR/CRp rates for the 82 eligible patients were 3/26 (12%) in Arm A, 2/29 (7%) in Arm B, and 1/27 (4%) in Arm C. No patients who had relapsed within 6 months of initial CR or who had suffered multiple relapses responded. More than 95% of patients subsequently died of AML. No unexpected toxicities were encountered. We conclude that none of these three regimens were effective enough in the treatment of high‐risk relapsed or refractory AML to warrant further study. This trial was registered at http://www.clinicaltrials.gov as #NCT00005962.
Combination of KIT gene silencing and tocopherol succinate may offer improved therapeutic approaches for human mastocytosis
Authors: Ruano Irene , Gargini Ricardo , Izquierdo Marta 
Published: October 2009

SummaryGain‐of‐function mutations of kit tyrosine kinase receptor are associated with mastocytosis. Two subclones of the HMC1 mast leukaemia cell line were used; both express an identical KIT allele‐specific regulatory type mutation (V560G), but differ in that one also expresses an enzymatic site type mutation (D816V) that confers on them resistance to imatinib mesylate tyrosine kinase inhibitor. In both cell lines, proliferation was suppressed and apoptosis induced by the combination of KIT gene silencing and α‐tocopherol succinate (α‐TOS), a derivate of α‐tocopherol, also known as vitamin E. Furthermore, HMC1 cells with decreased kit levels by KIT silencing, failed to form tumours when xenotransplanted into immunocompromised mice and the animals were treated systemically with α‐TOS. Targeting kit in the presence of α‐TOS represents a new approach against proliferation of human mast leukaemia cell lines.
Hearing the child
Authors: Archard David , Skivenes Marit 
Published: October 2009

ABSTRACTGiven that in our view the child has a fundamental right to be heard in all collective deliberative processes determining his or her future, we set out, firstly, what is required of such processes to respect this right – namely that the child's authentic voice is heard and makes a difference – and, secondly, the distance between this ideal and practice exemplified in the work of child welfare and child protection workers in Norway and the UK, chiefly in their display of an instrumental attitude to children's views.
Relationships matter: the problems and prospects for social workers’ relationships with young children in care
Authors: Winter Karen 
Published: October 2009

ABSTRACTOne of the key lessons learnt in the UK from the Laming Inquiry into the death of Victoria Climbié was the importance of social workers developing consistent and long‐term relationships with young children in whose lives they are involved. This issue is now informing policy developments, including the proposed Social Work Practices which, based on a similar model to General Practitioner practices, aim to provide a lead professional to act as a parental figure and an advocate for every child in care. This paper begins by confirming the importance of developing relationships between social workers and young children, but questions the ability of the new policy developments to facilitate these. Drawing upon data from research involving interviews with social workers, the paper outlines the factors which hinder social workers’ relationships with young children and argues that while the new proposals address some of the more surface structural and organizational factors, they do not address the deeper factors regarding attitudes, values and emotional competence which are crucial if social workers are to successfully build relationships with young children in care.
Communication with parents in child welfare: skills, language and interaction
Authors: Hall Christopher , Slembrouck Stef 
Published: October 2009

ABSTRACTThis paper reviews the literature on communication between professionals and parents/carers in health and social care. It notes that there is considerable research on doctor–patient communication and counselling, but much less on professionals who visit families in their homes. While there is a large literature on good practice and communication skills, there is little research on the actual encounters themselves. What counts as ‘communication’ in such publications is explored. The paper suggests that there is much to be gained by considering research in discourse analysis and sociolinguistics on professional–client encounters. Examples of some of the key concepts are discussed and an engagement with this literature is recommended.
Anxiety and child protection – implications for practitioner–parent relations
Authors: Waterhouse Lorraine , McGhee Janice 
Published: October 2009

ABSTRACTSocial work practitioners face powerful existential threats in child protection. Core aspects of anxiety and their significance for practitioner–parent relations are identified. Social and psychoanalytic theories are utilized to suggest that the production of anxiety in child protection stems from multiple sources and that insufficient attention has been paid to the social context of poverty and disadvantage. Menzies' core analytic categories of primary and secondary anxiety are applied and extended to take account of specific dimensions of the social and organizational context of child protection practice for social work. Processing the anxiety is central to practitioner–parent relations that lie at the heart of the protection of children.
Alkaloids may not be responsible for endophyte‐associated reductions in tall fescue decomposition rates
Authors: Siegrist Jacob A. , McCulley Rebecca L. , Bush Lowell P. , Phillips Tim D. 
Published: October 2009

Summary 1.  Fungal endophyte – grass symbioses can have dramatic ecological effects, altering individual plant physiology, plant and animal community structure and function, and ecosystem processes such as litter decomposition and nutrient cycling. 2.
Within the tall fescue (Schedonorus arundinaceus) – fungal endophyte (Neotyphodium coenophialum) symbiosis, fungal produced alkaloids are often invoked as the putative mechanism driving these ecological responses. Yet few measurements of alkaloids exist in the ecological literature. In this study, we quantified alkaloid levels in live, standing dead and decomposing endophyte‐infected (E+) and –free (E−) plant material and simultaneously evaluated the direct and indirect effects of endophyte presence on tall fescue decomposition. 3.
Loline and ergot alkaloid levels were consistently high in live E+ (common toxic strain of N. coenophialum) tall fescue biomass throughout the sampling period (May–November 2007), whereas, E− live and standing dead material had non‐detectable alkaloid concentrations. Standing dead E+ biomass had significantly reduced alkaloid levels (6–19x lower than the levels measured in the corresponding live E+ biomass) that were equivalent to E− live and dead for loline but were still somewhat higher than E− material for ergots. 4.  In an effort to test the role of alkaloids in directly inhibiting decomposition, as has been suggested by previous studies, we conducted a litter bag experiment using green, alkaloid‐laden E+ and alkaloid‐free E− tall fescue plant material. We incubated E+ and E− litter bags in both E+ and E− tall fescue stands for 170 days, and measured mass loss, carbon and nitrogen content, and ergot and loline alkaloid concentrations over the incubation period. 5.  Consistent with previous reports, both direct and indirect effects of endophyte presence on litter decomposition were observed: endophyte presence in the litter and surrounding microenvironment significantly reduced decomposition rates. Surprisingly, despite large differences in alkaloid content between E+ and E− litter from Day 0–Day 21 of the incubation, direct effects of the endophyte on litter decomposition, while significant, were relatively small (differences in mass loss between E+ and E− litter were never >3%). Alkaloids were gone from E+ material by day 56. 6.  We propose that results from this study indicating alkaloids are largely absent in standing dead material (the typical input to the decomposition process), and that despite being present in our litter bag experiment, failed to produce large differences in mass loss between E+ and E− material questions the supposition that fungal produced alkaloids directly inhibit decomposition. Additional studies exploring the mechanisms behind the direct and indirect effects of endophytes on this ecosystem process are needed.
Effects of competition on great and blue tit reproduction: intensity and importance in relation to habitat quality
Authors: Dhondt André A. 
Published: October 2009

Summary 1. In studies on the effect of competition in plant communities two terms are used to describe its effects: the absolute reduction in growth of an individual as a consequence of the presence of another one is called intensity, while the relative impact of competition on an individual as a proportion of the impact of the whole environment is called importance. One school of thought is that the role of competition remains constant across productivity gradients, while the other is that it decreases with increasing severity. J.B. Grace (1991. A clarification of the debate between grime and tilman. Functional Ecology, 5, 583–587.) suggested that the apparent contradiction might be solved if we acknowledge that the two schools are discussing different aspects of competition: the intensity of competition might remain constant while its importance declines with increasing severity. 2. There are no studies that compare intensity and importance of competition in bird populations between areas that differ in quality or productivity and hence it is not possible to make predictions how intensity or importance of competition would vary between them. 3. I compared variation in intensity and importance of competition of three demographic variables between five plots that differ strongly in quality for great Parus major L. and blue tit Cyanistes caeruleus (L.). 4. Both intensity and importance of competition are larger in great than in blue tit populations meaning that the effect of competition on demographic variables is stronger in great than in blue tits and that the contribution of competition to variation in these variables is relatively higher in great than in blue tits. 5. Intensity of competition is higher in low quality than in high quality plots for both species, a result not expected from studies in plant communities. 6. Importance of competition varies strongly between plots. It is larger in oak‐dominated plots than in mixed deciduous plots. 7. In birds breeding density increases with habitat quality but is limited by territorial behaviour. As a result competition for food is reduced in high quality habitats resulting in a reduction of competition intensity in high quality sites in which birds breed at high densities. 8. It can be predicted that in studies of territorial species density dependent effects on reproduction are more likely to be detected in low quality sites explaining in part differences in results between studies.
Multiyear multiple paternity and mate fidelity in the American alligator,Alligator mississippiensis
Authors: LANCE S. L. , TUBERVILLE T. D. , DUECK L. , HOLZ‐SCHIETINGER C. , TROSCLAIR P. L. , ELSEY R. M. , GLENN T. C. 
Published: October 2009

AbstractWe examined multiple paternity during eight breeding events within a 10‐year period (1995–2005) for a total of 114 wild American alligator nests in Rockefeller Wildlife Refuge in south‐west Louisiana. Our goals included examining (i) within population variation in multiple paternity among years, (ii) variation in multiple paternity in individual females and (iii) the potential for mate fidelity. To accomplish this, in the current study, eggs were sampled from 92 nests over 6 years and analysed along with 22 nests from a previous 2‐year study. Genotypes at five microsatellite loci were generated for 1802 alligator hatchlings. Multiple paternity was found in 51% of clutches and paternal contributions to these clutches were highly skewed. Rates of multiple paternity varied widely among years and were consistently higher in the current study than previously reported for the same population. Larger females have larger clutches, but are not more likely to have multiply sired nests. However, small females are unlikely to have clutches with more than two sires. For 10 females, nests from multiple years were examined. Seven (70%) of these females exhibited long‐term mate fidelity, with one female mating with the same male in 1997, 2002 and 2005. Five females exhibiting partial mate fidelity (71%) had at least one multiple paternity nest and thus mated with the same male, but not exclusively. These patterns of mate fidelity suggest a potential role for mate choice in alligators.
Nuclear and mitochondrial DNA reveals isolation of imperilled grey nurse shark populations (Carcharias taurus)
Authors: AHONEN H. , HARCOURT R. G. , STOW A. J. 
Published: October 2009

AbstractLoss of sharks and other upper‐trophic marine predators has sparked worldwide concern for the stability of ocean ecosystems. The grey nurse (ragged‐tooth or sand tiger) shark (Carcharias taurus) is Vulnerable on a global scale, Critically Endangered in Australia and presumed extinct in parts of its historical range. We used 193 muscle and fin samples collected from six extant populations to assess global mtDNA and microsatellite diversity and the degree of global population genetic structure. Control region mtDNA diversity was low in every population, and two populations (eastern Australia and Japan) contained only a single mtDNA haplotype. Genetic signatures of recent losses of genetic variation were not yet apparent at microsatellite loci, indicating that this low mtDNA variation is not a result of anthropogenic population declines. Population differentiation was substantial between each population pair except Brazil and South Africa, FST values ranged from 0.050 to 0.699 and 0.100 to 1.00 for microsatellite and mitochondrial data respectively. Bayesian analysis clearly partitioned individuals into five of the populations from which they were sampled. Our data imply a low frequency of immigrant exchange among each of these regions and we suggest that each be recognized as a distinct evolutionary significant unit. In contrast to pelagic species such as whale shark and white shark that may cross ocean basins and where cooperative international efforts are necessary for conservation, grey nurse shark, like many coastal species, need to be managed regionally.
Matrix metalloproteinases‐7, ‐8, ‐9 and TIMP‐1 in the follow‐up of diisocyanate‐induced asthma
Authors: Piirilä P. , Lauhio A. , Majuri M.‐L. , Meuronen A. , Myllärniemi M. , Tervahartiala T. , Vuorinen K. , Laitinen A. , Alenius H. , Kinnula V. L. , Sorsa T. 
Published: October 2009

AbstractBackground:  Diisocyanate‐induced asthma (DIA) is known to be associated with poor prognosis. We wished to clarify if matrix metalloproteinases (MMP)‐7, ‐8 or ‐9 or tissue inhibitor of matrix metalloproteinases (TIMP‐1) are associated with the functional or inflammatory outcome in DIA patients.Methods:  This is a longitudinal study where 17 patients with DIA diagnosed by a specific challenge test to diisocyanates were monitored. Exposure to diisocyanates was terminated seven (mean) months before the challenge test. The studies included spirometry, histamine challenge test and bronchoscopy. MMP‐7, MMP‐8, TIMP‐1 [Enzyme‐linked immunosorbent assay (ELISA)‐ and immunofluorometric assay‐methods], MMP‐9 (ELISA and zymography), interferon‐gamma, tumour necrosis factor‐alpha, interleukin‐6, ‐8, ‐15, ‐17, CXCL‐5/ENA‐78, monocyte chemoattractant protein‐1 and macrophage inhibitory factor (MIF) (ELISA) were assayed from bronchoalveolar lavage (BAL) fluid. Inhaled steroid therapy was initiated after the examinations, which were repeated at 6 months and at 3 years during the treatment. The results were compared with those of 15 healthy controls.Results:  Inhaled steroid medication increased BAL levels of MMP‐9 and MMP‐9/TIMP‐1 and decreased MMP‐7 and MMP‐7/TIMP‐1. The increase in MMP‐9 levels was associated with a decline in the TH‐2 type inflammation.Conclusions:  Our data suggest that reduced TH‐2 type inflammation in DIA after inhaled steroid medication is reflected as elevated MMP‐9 and MMP‐9/TIMP‐1 levels in BAL. MIF may be the inducer of MMP‐9. This might point to some protective role for MMP‐9 in DIA.
Temperature modulated histamine‐itch in lesional and nonlesional skin in atopic eczema – a combined psychophysical and neuroimaging study
Authors: Pfab F. , Valet M. , Sprenger T. , Huss‐Marp J. , Athanasiadis G. I. , Baurecht H. J. , Konstantinow A. , Zimmer C. , Behrendt H. , Ring J. , Tölle T. R. , Darsow U. 
Published: October 2009

AbstractBackground: Itch is the major symptom of many allergic diseases; yet it is still difficult to measure objectively. The aim of this study was to use an evaluated itch stimulus model in lesional (LS) and nonlesional (NLS) atopic eczema (AE) skin and to characterize cerebral responses using functional magnetic resonance imaging (fMRI).Methods: Thermal modulation was performed on a histamine stimulus in randomized order on LS or NLS in rapid alternating order from 32°C (warm) to 25°C (cold). Subjective itch ratings were recorded. Additionally, fMRI measurements were used to analyze the cerebral processing (n = 13). Healthy skin (HS) of age‐matched volunteers served as control (n = 9).Results: Mean VAS itch intensity was significantly (P < 0.0001) higher during the relative cold [55.2 ± 8.3% (LS); 48.6 ± 8.2% (NLS)] compared to the relative warm blocks [36.0 ± 7.3% (LS); 33.7 ± 7.6% (NLS)]. Compared to HS, the itch response was delayed in LS and NLS. Itch intensity was perceived highest in LS, followed by NLS and HS. For NLS, fMRI revealed at the beginning of the itch provocation a cerebral deactivation pattern in itch processing structures (thalamus, prefrontal, cingulate, insular, somatosensory and motor cortex). During the course of stimulation, the cerebral deactivation was reduced with time and instead an activation of the basal ganglia occurred. In contrast LS showed an activation instead of deactivation pattern already at the beginning of the stimulation in the above mentioned structures.Conclusions: Moderate short‐term temperature modulation led to a reproducible, significant enhancement of histamine‐induced itch with the strongest effect in LS. The differences in itch perception and itch kinetics between healthy volunteers and NLS in patients point towards an ongoing central inhibitory activity patients with AE, especially at the beginning of the itch provocation.
The allergen specificity of the late asthmatic reaction
Authors: Hatzivlassiou M. , Grainge C. , Kehagia V. , Lau L. , Howarth P. H. 
Published: October 2009

To cite this article: Hatzivlassiou M, Grainge C, Kehagia V, Lau L, Howarth PH. The allergen specificity of the late asthmatic reaction. Allergy 2010; 65: 355–358.AbstractBackground:  Allergen inhalation challenge in asthma may induce both early (EAR) and late (LAR) asthmatic reactions. The EAR is IgE and mast cell dependent. The mechanism of the LAR is less well defined and we have hypothesized may be allergen dependent. The aim of this study was to investigate the allergen specificity of the LAR to allergen inhalation in asthma.Methods:  In a randomized, double‐blind, crossover design six asthmatic volunteers with dual sensitization to house dust mite (HDM) allergen and grass pollen (GP) allergen underwent inhalation allergen challenge with these separate allergens on two occasions separated by 14 days. Lung function changes were followed for 8‐h postchallenge. Bronchial reactivity (histamine PC20) and airway inflammation, assessed by induced sputum differential cell count, were measured 24‐h pre and postallergen challenge. The allergen inhalation challenges were matched to achieve the same magnitude of EAR.Results:  Despite comparable group mean EAR percent falls in FEV1 (25.8% following GP and 28.0% following HDM (P = 0.917), the LAR was statistically greater on the HDM challenge day (13.0%vs 22.8% [P = 0.046]) and was associated with a significant airway eosinophil recruitment (mean (SD) of 5.4 (4.8)% to 22.1 (18.2)% (P = 0.028) that was not evident on the GP allergen challenge day.Conclusions:  These findings identify the allergen specificity of the LAR and indicate that factors independent of IgE contribute to the LAR. Such findings have relevance both to the understanding of the allergen‐induced airway responses in asthma and the need for homogeneity in inhaled‐allergen challenge studies in asthma.
Steroid sparing effects of intranasal corticosteroids in asthma and allergic rhinitis
Authors: Nair A. , Vaidyanathan S. , Clearie K. , Williamson P. , Meldrum K. , Lipworth B. J. 
Published: October 2009

To cite this article: Nair A, Vaidyanathan S, Clearie K, Williamson P, Meldrum K, Lipworth BJ. Steroid sparing effects of intranasal corticosteroids in asthma and allergic rhinitis. Allergy 2010; 65: 359–367.AbstractBackground:  Treating allergic rhinitis may have a downstream anti‐inflammatory effect on the lower airways. We conducted a dose ranging study in asthma and persistent allergic rhinitis to evaluate if intranasal corticosteroids exhibit a sparing effect on the dose of inhaled corticosteroid.Methods:  Twenty five participants were randomized to receive two weeks of 100 μg/day (Low dose) or 500 μg/day (High dose) of inhaled fluticasone propionate both with intranasal placebo; or inhaled fluticasone 100 μg/day with intranasal fluticasone 200 μg/day (Combined) in a double‐blind cross‐over fashion.Results:  Low dose fluticasone produced a shift of 1.20 doubling‐dilutions (95% CI, 0.63, 1.77); Combined fluticasone, 1.79 doubling‐dilutions (95% CI, 0.77, 2.80) and high dose fluticasone, 2.01 doubling‐dilutions (95% CI, 1.42, 2.61) in methacholine PC20 from respective baselines. There was a significant difference between high and low doses: 0.82 doubling dilutions (95%CI, 0.12, 1.50) but not between combined and low dose 0.58 doubling dilutions (95% CI, –0.78, 1.95). Combined treatment alone produced improvements in peak nasal inspiratory flow (P < 0.001), rhinitis quality of life (P = 0.004) and nasal NO (P = 0.01); reduced blood eosinophil count (P = 0.03), and serum eosinophil cationic protein (P = 0.02). All treatments significantly improved tidal NO, FEV1 and asthma quality of life.Conclusions:  High‐dose fluticasone was superior to low dose fluticasone for methacholine PC20, demonstrating room for further improvement. Combined treatment was not significantly different from low dose fluticasone and we could not demonstrate a steroid sparing effect on methacholine PC20. Combined treatment alone produced improvements in upper airway outcomes and suppressed systemic inflammation but not adrenal function.