Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg(®)) in children with relapsed/refractory myeloid leukemia

BACKGROUND: Gemtuzumab ozogamicin (GO) is a cytotoxic anti-CD33 monoclonal antibody that has given promising preliminary results in adult myeloid CD33+ AML. We conducted a retrospective multicenter study of 12 children treated with GO on a compassionate basis (median age 5.5 y). Three patients (2 MDS/AML, 1 JMML) were refractory to first-line treatment, 8 patients with de novo AML were in refractory first relapse, and one patient with de novo AML was in 2(nd )relapse after stem cell transplantation (SCT). CD33 expression exceeded 20% in all cases. METHODS: GO was administered alone, at a unit dose of 3–9 mg/m(2), once (3 patients), twice (3 patients), three (5 patients) or five times (1 patient). Mean follow-up was 128 days (8–585 d). RESULTS: There were three complete responses (25%) leading to further curative treatment (SCT). Treatment failed in the other nine patients, and only one patient was alive at the end of follow-up. NCI-CTC grade III/IV adverse events comprised hematological toxicity (n = 12), hypertransaminasemia (n = 2), allergy and hyperbilirubinemia (1 case each). There was only one major adverse event (grade IV allergy). No case of sinusoidal obstruction syndrome occurred. CONCLUSION: These results warrant a prospective trial of GO in a larger population of children with AML

Entropy-driven liquid-liquid separation in supercooled water

Twenty years ago Poole et al. (Nature 360, 324, 1992) suggested that the anomalous properties of supercooled water may be caused by a critical point that terminates a line of liquid-liquid separation of lower-density and higher-density water. Here we present an explicit thermodynamic model based on this hypothesis, which describes all available experimental data for supercooled water with better quality and with fewer adjustable parameters than any other model suggested so far. Liquid water at low temperatures is viewed as an 'athermal solution' of two molecular structures with different entropies and densities. Alternatively to popular models for water, in which the liquid-liquid separation is driven by energy, the phase separation in the athermal two-state water is driven by entropy upon increasing the pressure, while the critical temperature is defined by the 'reaction' equilibrium constant. In particular, the model predicts the location of density maxima at the locus of a near-constant fraction (about 0.12) of the lower-density structure.Comment: 7 pages, 6 figures. Version 2 contains an additional supplement with tables for the mean-field equatio

A study protocol of a randomised controlled trial incorporating a health economic analysis to investigate if additional allied health services for rehabilitation reduce length of stay without compromising patient outcomes

Background Reducing patient length of stay is a high priority for health service providers. Preliminary information suggests additional Saturday rehabilitation services could reduce the time a patient stays in hospital by three days. This large trial will examine if providing additional physiotherapy and occupational therapy services on a Saturday reduces health care costs, and improves the health of hospital inpatients receiving rehabilitation compared to the usual Monday to Friday service. We will also investigate the cost effectiveness and patient outcomes of such a service. Methods/Design A randomised controlled trial will evaluate the effect of providing additional physiotherapy and occupational therapy for rehabilitation. Seven hundred and twelve patients receiving inpatient rehabilitation at two metropolitan sites will be randomly allocated to the intervention group or control group. The control group will receive usual care physiotherapy and occupational therapy from Monday to Friday while the intervention group will receive the same amount of rehabilitation as the control group Monday to Friday plus a full physiotherapy and occupational therapy service on Saturday. The primary outcomes will be patient length of stay, quality of life (EuroQol questionnaire), the Functional Independence Measure (FIM), and health utilization and cost data. Secondary outcomes will assess clinical outcomes relevant to the goals of therapy: the 10 metre walk test, the timed up and go test, the Personal Care Participation Assessment and Resource Tool (PC PART), and the modified motor assessment scale. Blinded assessors will assess outcomes at admission and discharge, and follow up data on quality of life, function and health care costs will be collected at 6 and 12 months after discharge. Between group differences will be analysed with analysis of covariance using baseline measures as the covariate. A health economic analysis will be carried out alongside the randomised controlled trial. Discussion This paper outlines the study protocol for the first fully powered randomised controlled trial incorporating a health economic analysis to establish if additional Saturday allied health services for rehabilitation inpatients reduces length of stay without compromising discharge outcomes. If successful, this trial will have substantial health benefits for the patients and for organizations delivering rehabilitation services

Facilitating the development of controlled vocabularies for metabolomics technologies with text mining

BACKGROUND: Many bioinformatics applications rely on controlled vocabularies or ontologies to consistently interpret and seamlessly integrate information scattered across public resources. Experimental data sets from metabolomics studies need to be integrated with one another, but also with data produced by other types of omics studies in the spirit of systems biology, hence the pressing need for vocabularies and ontologies in metabolomics. However, it is time-consuming and non trivial to construct these resources manually. RESULTS: We describe a methodology for rapid development of controlled vocabularies, a study originally motivated by the needs for vocabularies describing metabolomics technologies. We present case studies involving two controlled vocabularies (for nuclear magnetic resonance spectroscopy and gas chromatography) whose development is currently underway as part of the Metabolomics Standards Initiative. The initial vocabularies were compiled manually, providing a total of 243 and 152 terms. A total of 5,699 and 2,612 new terms were acquired automatically from the literature. The analysis of the results showed that full-text articles (especially the Materials and Methods sections) are the major source of technology-specific terms as opposed to paper abstracts. CONCLUSIONS: We suggest a text mining method for efficient corpus-based term acquisition as a way of rapidly expanding a set of controlled vocabularies with the terms used in the scientific literature. We adopted an integrative approach, combining relatively generic software and data resources for time- and cost-effective development of a text mining tool for expansion of controlled vocabularies across various domains, as a practical alternative to both manual term collection and tailor-made named entity recognition methods

Weak Responses to Auditory Feedback Perturbation during Articulation in Persons Who Stutter: Evidence for Abnormal Auditory-Motor Transformation

Previous empirical observations have led researchers to propose that auditory feedback (the auditory perception of self-produced sounds when speaking) functions abnormally in the speech motor systems of persons who stutter (PWS). Researchers have theorized that an important neural basis of stuttering is the aberrant integration of auditory information into incipient speech motor commands. Because of the circumstantial support for these hypotheses and the differences and contradictions between them, there is a need for carefully designed experiments that directly examine auditory-motor integration during speech production in PWS. In the current study, we used real-time manipulation of auditory feedback to directly investigate whether the speech motor system of PWS utilizes auditory feedback abnormally during articulation and to characterize potential deficits of this auditory-motor integration. Twenty-one PWS and 18 fluent control participants were recruited. Using a short-latency formant-perturbation system, we examined participants’ compensatory responses to unanticipated perturbation of auditory feedback of the first formant frequency during the production of the monophthong [ε]. The PWS showed compensatory responses that were qualitatively similar to the controls’ and had close-to-normal latencies (~150 ms), but the magnitudes of their responses were substantially and significantly smaller than those of the control participants (by 47% on average, p<0.05). Measurements of auditory acuity indicate that the weaker-than-normal compensatory responses in PWS were not attributable to a deficit in low-level auditory processing. These findings are consistent with the hypothesis that stuttering is associated with functional defects in the inverse models responsible for the transformation from the domain of auditory targets and auditory error information into the domain of speech motor commands

Early Developing Pig Embryos Mediate Their Own Environment in the Maternal Tract

The maternal tract plays a critical role in the success of early embryonic development providing an optimal environment for establishment and maintenance of pregnancy. Preparation of this environment requires an intimate dialogue between the embryo and her mother. However, many intriguing aspects remain unknown in this unique communication system. To advance our understanding of the process by which a blastocyst is accepted by the endometrium and better address the clinical challenges of infertility and pregnancy failure, it is imperative to decipher this complex molecular dialogue. The objective of the present work is to define the local response of the maternal tract towards the embryo during the earliest stages of pregnancy. We used a novel in vivo experimental model that eliminated genetic variability and individual differences, followed by Affymetrix microarray to identify the signals involved in this embryo-maternal dialogue. Using laparoscopic insemination one oviduct of a sow was inseminated with spermatozoa and the contralateral oviduct was injected with diluent. This model allowed us to obtain samples from the oviduct and the tip of the uterine horn containing either embryos or oocytes from the same sow. Microarray analysis showed that most of the transcripts differentially expressed were down-regulated in the uterine horn in response to blastocysts when compared to oocytes. Many of the transcripts altered in response to the embryo in the uterine horn were related to the immune system. We used an in silico mathematical model to demonstrate the role of the embryo as a modulator of the immune system. This model revealed that relatively modest changes induced by the presence of the embryo could modulate the maternal immune response. These findings suggested that the presence of the embryo might regulate the immune system in the maternal tract to allow the refractory uterus to tolerate the embryo and support its development

Metabolomic analysis of human disease and its application to the eye

Metabolomics, the analysis of the metabolite profile in body fluids or tissues, is being applied to the analysis of a number of different diseases as well as being used in following responses to therapy. While genomics involves the study of gene expression and proteomics the expression of proteins, metabolomics investigates the consequences of the activity of these genes and proteins. There is good reason to think that metabolomics will find particular utility in the investigation of inflammation, given the multi-layered responses to infection and damage that are seen. This may be particularly relevant to eye disease, which may have tissue specific and systemic components. Metabolomic analysis can inform us about ocular or other body fluids and can therefore provide new information on pathways and processes involved in these responses. In this review, we explore the metabolic consequences of disease, in particular ocular conditions, and why the data may be usefully and uniquely assessed using the multiplexed analysis inherent in the metabolomic approach