bluuebunny/crossref_metadata_2025_split huggingface dataset:
An empirical evaluation of the MATRICS Consensus Cognitive Battery in bipolar disorder
Authors: Van Rheenen Tamsyn E , Rossell Susan L 
Published: October 2013

ObjectivesThere is a large body of evidence to indicate that neurocognitive impairments in bipolar disorder (BD) may represent viable endophenotypes; however, a standard consensus‐based battery of cognitive tests used to measure them is yet to appear. There is potential for a neurocognitive battery which was developed for use in the related disorder, schizophrenia – the MATRICS Consensus Cognitive Battery (MCCB) – to provide a consistent measurement tool with a standard to which the cognitive capacity of BD can be compared to other disorders. However, its suitability for capturing neurocognitive impairment in BD cohorts is not well established. Moreover, neurocognitive tests recently recommended by the International Society for Bipolar Disorders (ISBD) for inclusion in a consensus neurocognitive battery for BD have not been evaluated in the context of the MCCB. An evaluation of (i) the clinical efficacy of the MCCB and (ii) the tests recommended by the ISBD in a BD cohort were the aims of the current study.MethodsA total of 50 patients with BD (mean age = 38 years) and 52 healthy controls (mean age = 34 years) completed all of the MCCB subtests, in addition to the well‐recognized Trail Making Test–Part B and the Colour–Word Stroop.ResultsMultivariate analyses of variance of the MCCB domains revealed a significant group effect for overall cognition, and significantly reduced patient performance on speed of processing, working memory, and visual and verbal learning. A second multivariate analysis of variance using a newly created composite score called executive function, comprising scores on an existing MCCB subtest in addition to TMT‐B and Colour–Word Stroop, revealed significant differences on this domain as well. Subgroup analysis indicated that there were no differences in any domain score performance between symptomatic and euthymic patients, or bipolar I and II disorder patient groups.ConclusionsOur findings suggest that the MCCB and two additionally recommended ISBD executive function measures form a promising consensus‐based research tool for examining neurocognition in BD.
A Neglected Aspect of Conscience: Awareness of Implicit Attitudes
Authors: Fitzgerald Chloë 
Published: October 2013

AbstractThe conception of conscience that dominates discussions in bioethics focuses narrowly on private regulation of behaviour resulting from explicit attitudes. It neglects to mention implicit attitudes and the role of social feedback in becoming aware of one's implicit attitudes. But if conscience is a way of ensuring that a person's behaviour is in line with her moral values, it must be responsive to all aspects of the mind that influence behaviour. There is a wealth of recent psychological work demonstrating the influence of implicit attitudes on behaviour. A necessary part of having a well‐functioning conscience must thus be awareness and regulation of one's implicit attitudes in addition to one's explicit attitudes; this cannot be done by an individual in isolation. On my revised conception of conscience, heeding social feedback, being emotionally self‐aware and engaging in self‐monitoring are important for the possession of a well‐functioning conscience. Health professionals may need specific training to help them develop and maintain a well‐functioning conscience, which should involve cultivation of awareness of implicit attitudes, emphasis on social feedback and techniques to enable better control over them.
Standard of Care, Institutional Obligations, and Distributive Justice
Authors: MacKay Douglas 
Published: October 2013

AbstractThe problem of standard of care in clinical research concerns the level of treatment that investigators must provide to subjects in clinical trials. Commentators often formulate answers to this problem by appealing to two distinct types of obligations: professional obligations and natural duties. In this article, I investigate whether investigators also possess institutional obligations that are directly relevant to the problem of standard of care, that is, those obligations a person has because she occupies a particular institutional role. I examine two types of institutional contexts: (1) public research agencies – agencies or departments of states that fund or conduct clinical research in the public interest; and (2) private‐for‐profit corporations. I argue that investigators who are employed or have their research sponsored by the former have a distinctive institutional obligation to conduct their research in a way that is consistent with the state's duty of distributive justice to provide its citizens with access to basic health care, and its duty to aid citizens of lower income countries. By contrast, I argue that investigators who are employed or have their research sponsored by private‐for‐profit corporations do not possess this obligation nor any other institutional obligation that is directly relevant to the ethics of RCTs. My account of the institutional obligations of investigators aims to contribute to the development of a reasonable, distributive justice‐based account of standard of care.
Phase I, multicentre, dose‐escalation trial of monotherapy with milatuzumab (humanized anti‐CD74 monoclonal antibody) in relapsed or refractory multiple myeloma
Authors: Kaufman Jonathan L. , Niesvizky Ruben , Stadtmauer Edward A. , Chanan‐Khan Asher , Siegel David , Horne Heather , Wegener William A. , Goldenberg David M. 
Published: October 2013

SummaryCD74, expressed in multiple myeloma (MM), was evaluated as a target for immunotherapy with milatuzumab (a humanized anti‐CD74 antibody). In a multicentre dose escalation study, 25 patients with advanced MM received milatuzumab doses of 1·5 (N = 8), 4·0 (N = 9), 8·0 (N = 4) or 16·0 mg/kg (N = 4) administered twice weekly x 4. They had a median of 5 prior treatments (17 post ≥1 stem cell transplantation) and were refractory (N = 7) or relapsed (N = 18) with generally short‐lived responses to last treatment (median 4·0 months). After increasing prophylactic medications and slowing administration, infusions were well tolerated (National Cancer Institute‐Common Terminology Criteria v3 toxicity Grades 1–2) with no dose‐limiting toxicity at higher doses. Only one patient developed borderline positive human anti‐milatuzumab antibody titres of uncertain clinical significance. Although milatuzumab was rapidly cleared from circulation with little serum accumulation and low trough levels, B‐cell levels were moderately decreased with treatment (median decrease, 34%). There were no objective responses by European Group for Blood and Marrow Transplantation criteria, but 5 of 19 patients (26%) who completed treatment in this heavily pretreated and generally refractory group had stable disease for ≥3 months post‐treatment (one continuing for 17 months). Disease stabilization and evidence of pharmacodynamic activity support further development for use in combination with other agents or as a drug conjugate. (Clinicaltrials.gov identifier: NCT00421525)
Erythroid‐extrinsic regulation of normal erythropoiesis by retinoic acid receptors
Authors: Dewamitta Sita R. , Joseph Chacko , Purton Louise E. , Walkley Carl R. 
Published: October 2013

SummaryVitamin A and its derivatives (retinoids) are important regulators of haematopoiesis, acting via retinoic acid receptors (RARs). Epidemiological studies indicated an association of vitamin A deficiency with anaemia in humans. To define the requirements of RARs in erythropoiesis, we evaluated erythroid parameters in RAR germ‐line deficient and conditional knock out mice with erythroid specific deletion of RARs. Adult RARγ−/− mice were anaemic, however, Epor‐Cre Rarafl/fl, Epor‐Cre Rargfl/fl and Epor‐Cre Rarafl/flgfl/fl mice were normal, indicating a lack of an erythroid intrinsic RAR function. Therefore, erythroid‐specific RAR function is dispensable for erythropoiesis and RARγ plays an erythroid extrinsic role in erythropoiesis.
Chronic myeloproliferative neoplasms and risk of osteoporotic fractures; a nationwide population‐based cohort study
Authors: Farmer Sarah , Horváth‐Puhó Erzsébet , Vestergaard Hanne , Hermann Anne Pernille , Frederiksen Henrik 
Published: October 2013

SummaryPatients with systemic mastocytosis have an increased risk of osteoporosis, however, the risk of osteoporotic fractures among the classic chronic myeloproliferative neoplasms (CMPN), including essential thrombocythaemia (ET), polycythaemia vera (PV) and chronic myeloid leukaemia (CML), is unknown. We conducted a population‐based cohort study to determine the risk of osteoporotic fractures among three cohorts of patients with newly diagnosed ET, PV, and CML. Patients were identified in medical registers including all Danish hospitals during 1980–2010 and were followed until first osteoporotic fracture. Fracture risk was compared to cohorts from the general population matched on age, sex and calendar year. We followed 7595 CMPN patients and 338 974 comparison cohort members. We found that the risk of femoral fracture after 5 years was consistently higher than the general population, being 3·01% (95% confidence interval (CI): 2·20–4·10), 4·74% (95%CI: 4·06–5·52) and 4·64% (95%CI: 3·29–6·53) among ET, PV, and CML patients respectively. Adjusted hazard ratio for femoral fracture was increased 1·19‐fold (95% CI: 0·94–1·51) for ET patients, 1·82‐fold (95% CI: 1·62–2·04) for PV patients, and 2·67‐fold (95% CI: 1·97–3·62) for CML patients. We conclude that CMPN patients are at higher risk of osteoporotic fractures than the general population.
How I treat children and adolescents with acute promyelocytic leukaemia
Authors: Abla Oussama , Ribeiro Raul C. 
Published: October 2013

SummaryAcute promyelocytic leukaemia (APL) is a rare subtype of acute myeloid leukaemia. The outcome of paediatric APL has improved substantially over the past 20 years; cure rates above 80% are expected when all‐trans retinoic acid (ATRA) is given with anthracycline‐based regimens. The presenting features of paediatric APL may include severe bleeding and thrombotic complications, which contribute to the high early death rate. The incidence of leucocytosis and the microgranular subtype is greater in paediatric than adult APL, and children experience greater ATRA‐related toxicity. It is crucial to begin ATRA therapy and intensive platelet and fibrinogen replacement on first suspicion of APL. Recent risk‐adapted therapeutic trials have shown that patients at greater risk of relapse benefit from the introduction of high‐dose cytarabine during consolidation. Combination therapy with ATRA and arsenic trioxide provides very effective frontline treatment and may reduce the need for subsequent anthracycline therapy.
Impact of glucose‐6‐phosphate dehydrogenase deficiency on sickle cell anaemia expression in infancy and early childhood: a prospective study
Authors: Benkerrou Malika , Alberti Corinne , Couque Nathalie , Haouari Zinedine , Ba Aissatou , Missud Florence , Boizeau Priscilla , Holvoet Laurent , Ithier Ghislaine , Elion Jacques , Baruchel André , Ducrocq Rolande 
Published: October 2013

SummaryIn patients with sickle cell anaemia (SCA), concomitant glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is usually described as having no effect and only occasionally as increasing severity. We analysed sequential clinical and biological data for the first 42 months of life in SCA patients diagnosed by neonatal screening, including 27 G6PD‐deficient patients, who were matched on sex, age and parents' geographic origin to 81 randomly selected patients with normal G6PD activity. In the G6PD‐deficient group, steady‐state haemoglobin was lower (−6·2 g/l, 95% confidence interval (CI), [−10·1; −2·3]) and reticulocyte count higher (247 × 109/l, 95%CI, [97; 397]). The acute anaemic event rate was 3 times higher in the G6PD‐deficient group (P < 10−3). A higher proportion of G6PD‐deficient patients required blood transfusion (20/27 [74%] vs. 37/81 [46%], P < 10−3), for acute anaemic events, and also vaso‐occlusive and infectious events. No significant between‐group differences were found regarding the rates of vaso‐occlusive, infectious, or cerebrovascular events. G6PD deficiency in babies with SCA worsens anaemia and increases blood transfusion requirements in the first years of life. These effects decrease after 2 years of age, presumably as the decline in fetal haemoglobin levels leads to increased sickle cell haemolysis and younger red blood cells with higher G6PD activity.
A common novel splice variant of SLC22A1 (OCT1) is associated with impaired responses to imatinib in patients with chronic myeloid leukaemia
Authors: Grinfeld Jacob , Gerrard Gareth , Alikian Mary , Alonso‐Dominguez Juan , Ale Sakuntala , Valgañon Mikel , Nteliopoulos Georgios , White Deborah , Marin David , Hedgley Corinne , O'Brien Stephen , Clark Richard , Goldman John M. , Milojkovic Dragana , Apperley Jane F. , Foroni Letizia 
Published: October 2013

SummaryApproximately one‐third of patients with chronic myeloid leukaemia will fail to achieve or maintain responses to imatinib. Changes in solute carrier family 22 (organic cation transporter), member 1 (SLC22A1, also termed OCT1), the main transporter for imatinib, have been proposed as a possible predictive factor. We analysed SLC22A1 mRNA levels and single nucleotide polymorphisms (SNPs) located in exon 7 in 153 diagnostic whole blood samples from two patient cohorts. The level of SLC22A1 expression did not significantly correlate with imatinib failure or achievement of molecular remission. The SNP 408V>M (g.1222G>A) was present in 65% of patients and was associated in all cases with an eight base‐pair insertion (8+ allele) at the 3′ end of exon 7. The latter generates an alternative splice site, leading to a premature stop codon. M420del was found in 33% of patients and never in cis with 8+ (the 3− allele). Significantly longer times to 1% and 0·1% molecular responses (by quantitative reverse transcription polymerase chain reaction) were seen in patients with 8+8+ or 8+N compared to those with the remaining four genotypes (N = no insertion or deletion). Patients lacking 8+ and 3− (NN, 18%) showed the best outcomes overall. Thus, while SLC22A1 expression does not appear to affect response, alterations in its splicing or amino acid sequence may do so.
Secondary cancers among children with acute lymphoblastic leukaemia treated by the Tokyo Children's Cancer Study Group protocols: a retrospective cohort study
Authors: Ishida Yasushi , Maeda Miho , Urayama Kevin Y. , Kiyotani Chikako , Aoki Yuki , Kato Yoko , Goto Shoko , Sakaguchi Sachi , Sugita Kenichi , Tokuyama Mika , Nakadate Naoya , Ishii Eizaburo , Tsuchida Masahiro , Ohara Akira ,   The QOL committee of Tokyo Children's Cancer Study Group (TCCSG)
Published: October 2013

SummaryWith improvement in survival, it is important to evaluate the impact of treatment on secondary cancers in acute lymphoblastic leukaemia (ALL) survivors. A retrospective cohort study comprising 2918 children diagnosed with ALL and enrolled on Tokyo Children's Cancer Study Group (TCCSG) protocols between 1984 and 2005 was conducted to evaluate the incidence of secondary cancers and associated factors including treatment protocol, cranial irradiation and other characteristics of the primary ALL. Thirty‐seven patients developed secondary cancers, including acute myeloid leukaemia (n = 11), myelodysplastic syndrome (n = 5), non‐Hodgkin lymphoma (n = 2), brain tumours (n = 13) and other solid carcinomas (n = 6) within a median follow‐up duration of 9·5 years. The cumulative incidence of any secondary cancers was 1·0% (95% confidence interval (CI), 0·7–1·4%) at 10 years and 2·4% (95% CI, 1·5–3·7%) at 20 years, respectively. Standardized incidence rate ratio of secondary cancers was 9·3 (95% CI, 6·5–12·8). Multivariate analyses showed an increased risk of secondary cancers associated with the recent treatment protocol and cranial irradiation. There was no evidence of a reduction in secondary cancer incidence despite marked decreases in cranial irradiation use in the recent protocols.
Concerns about unintended negative consequences of informing the public about multifactorial risks may be premature for young adult smokers
Authors: Waters Erika A. , Kincaid Caroline , Kaufman Annette R. , Stock Michelle L. , Peterson Laurel M. , Muscanell Nicole L. , Guadagno Rosanna E. 
Published: October 2013

BackgroundMany health risks are associated with both genetic and behavioural factors. Concerns have been raised that learning about such multifactorial risks might have detrimental effects on health‐related beliefs, cognitions, and affect. However, experimental evidence is sparse.ObjectiveTo explore the effects of reading an online news article about the discovery of a genetic basis for nicotine addiction.MethodsSmokers (N = 333) were recruited from the psychology subject pools of two major universities. Participants were randomly assigned to read one of three news articles: one describing a genetic basis for nicotine addiction and lung cancer obtained from a national news source, one altered to indicate no genetic basis for nicotine addiction and lung cancer, or one unrelated attention control. Participants then completed an online questionnaire, which assessed smoking‐related cognitions and affect, and beliefs about nicotine addiction, quitting smoking, and whether the harms of tobacco use are delayed.ResultsThere was no statistically significant influence of experimental condition on smoking‐related cognitions/affect (ps > .05, η2 < .002), beliefs about addiction and quitting (Wilks' λ = .98, p = .66, η2 = .01), or delayed harm (ps > .05, η2 < .002).ConclusionReading an online news article about the presence or absence of a genetic basis for nicotine addiction was not found to change smoking‐related cognitions/affect or beliefs among young adult smokers. Concerns about negative effects of multifactorial risk information on health beliefs may be premature. Nevertheless, to effectively translate basic genomics research into effective public health practice, further research should investigate these issues in different populations, via different communication modalities, and for different health outcomes.Statement of contribution

What is already known on this subject?

Information about the health implications of the interaction between genetics and behaviour is becoming prevalent.

Learning about these interactions may reduce perceived risk and intentions to engage in health behaviours.

What does this study add?

Informing young adult smokers about the genetic basis for nicotine addiction does not affect health beliefs negatively.
Responses are not moderated by endorsing the idea of genetic causation or current/experimenter smoking status.
The protective role of coenzyme Q10 in renal injury associated with extracorporeal shockwave lithotripsy: a randomised, placebo‐controlled clinical trial
Authors: Carrasco Julia , Anglada Francisco J. , Campos Juan P. , Muntané Jordi , Requena Maria J. , Padillo Javier 
Published: October 2013

Objective
To determine the efficacy of coenzyme Q10 (CoQ10) in preventing renal injury in patients with lithiasis undergoing extracorporeal shockwave lithotripsy (ESWL).
Patients and Methods
Prospective, randomised, double‐blind, placebo‐controlled clinical trial of 100 patients with renal lithiasis who were treated with ESWL.
The patients were distributed randomly into two groups receiving either placebo or CoQ10 (200 mg/day), a powerful antioxidant with vasoactive properties, orally administered during the week before ESWL and for 1 week after.
Renal dysfunction markers, vasoactive hormones, oxidative stress, plasma levels of several interleukins and vascular resistance index (VRI) using Doppler ultrasound were evaluated the week before ESWL, 2 h before ESWL and at 2 h, 24 h and 7 days after ESWL.
Results
There was a significant increase in glomerular filtration (P = 0.013), as well as a decrease in the albumin/creatinine ratio and the β2‐microglobulin level (P = 0.02) after 1 week of treatment in the CoQ10 group. These changes were maintained at the follow‐up after ESWL.
The administration of CoQ10 was associated with improvement in vasoactive hormone parameters, VRI and interleukin levels. These improvements were maintained until the end of the follow‐up period.
However, the administration of CoQ10 was not associated with significant changes in the oxidative stress parameters.
Conclusion
Our results indicate that CoQ10 administration improves renal function and vasoactive and inflammation parameter values, allowing for preconditioning before the tissue insult caused by ESWL.
Cadmium disorganises the scaffolding of gap and tight junction proteins in the hepatic cell line WIF B9
Authors: Boucherie Sylviane , Decaens Catherine , Verbavatz Jean‐Marc , Grosse Brigitte , Erard Marie , Merola Fabienne , Cassio Doris , Combettes Laurent 
Published: October 2013

Background InformationHepatocytes, which perform the main functions of the liver, are particularly vulnerable to toxic agents such as cadmium, an environmental pollutant. To identify the molecular targets for cadmium in hepatocytes, we have studied the effects of CdCl2 on the hybrid cell line WIF‐B9 that exhibits stable structural and functional hepatocytic polarity.ResultsWe showed that the toxicity of CdCl2 (1 µM, 24 h) resulted in a reduction in direct intercellular communication (via gap junctions) and in an increase in paracellular permeability (decrease in the sealing of tight junctions). These effects were not related to changes in the expression of the key proteins involved, Cx32 and claudin 2, the first being constitutive of gap junctions and the second of tight junctions in this cell line. Using immunofluorescence experiments, we observed a change in the location of Cx32 and claudin 2: these two proteins were less often found in the tight junction network that closes the bile canaliculi (BC). In control cells, ‘Proximity Ligation Assay’ (PLA Duolink®) has confirmed in situ that molecules of claudin 2 and Cx32 are very close to each other at the BC (probably less than 16 nm). This was no longer the case after treatment with CdCl2. Localisation of occludin and Cx32 relative to each other was not modified by CdCl2, but CdCl2 increased the PLA signal between molecules of JAM‐A and Cx32. Finally, examination of freeze‐fracture replicas obtained from cultures treated with CdCl2 showed the disruption of the network of tight junctions and the depletion or the disintegration of the junctional plaques associated with tight junctions.ConclusionsThis study demonstrates in situ the changes induced by cadmium on the organisation of cell–cell junctions and points out the importance of the association Cx32/claudin 2 for the maintenance of normal hepatocyte functions.