lbrutinib (lmbruvica™) for Treatment of Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a rare and moderately aggressive form of non-Hodgkin\u27s lymphoma (NHL) that predominantly presents at an advanced stage in older males. Patients often present with multiple involvement in the lymph nodes, blood, spleen, bone marrow and gastrointestinal tract (GIT). Some patients may be asymptomatic in early stages or present with an incurable, indolent (slow progressing) form, while other patients display rapid growth of more aggressive lymphomas. Overall survival for patients diagnosed with MCL is four to five years and treatment should be initiated in those who are symptomatic. Mantle cell lymphoma responds well to first-line treatment, but recurrent relapses are common, and no regimen has been proven superior for relapsed or refractory MCL. The U.S. Food and Drug Administration (FDA) has recently approved ibrutinib (lmbruvica™) as breakthrough MCL therapy. lbrutinib is a Bruton\u27s tyrosine kinase (BTK) inhibitor that interferes with malignant B-cell proliferation and survival. In a recent clinical study, ibrutinib proved to be a highly active monotherapy with a favorable toxicity profile in 111 patients with relapsed or refractory MCL. As an oral chemotherapy drug, ibrutinib has the potential to improve patient compliance. Additionally, specialty pharmacies dispensing ibrutinib will be able to play an important role in patient counseling and monitoring

A comparison of protocols for passive and discriminative avoidance learning tasks in the domestic chick

A one-trial learning task where chicks learn that a bead of a particular shape and/or colour has a bitter taste (100% Methyl anthranilate – MeA) and subsequently avoids it on test has been widely used by research groups across the world. However, there are some differences in the results reported by different research laboratories. One important difference is found when chicks are trained on a diluted bitter taste (10 or 20% MeA) such that memory is not consolidated and fades, e.g. memory lasts for 30 min at Monash University versus 4-6 hours at the Open University (OU). Differences in protocol that may explain this apparent discrepancy are whether the chicks have seen the bead before (novelty), and whether the colour or the shape of the bead is a more important feature. In this review, we discuss these and other factors that may contribute to the differences in the characteristics of memory processing between Monash and the OU, e.g. strain, hatchery or laboratory incubated chicks, age at training. It is clear that there is a difference between passive avoidance and discriminative avoidance and this may explain the differences in duration of the memory and the different stages. Is the OU task a more salient experience because of the novelty of the bead and therefore a 'stronger' learning experience? The different protocols may allow different questions to be addressed

A method for the objective selection of landscape-scale study regions and sites at the national level

1. Ecological processes operating on large spatio-temporal scales are difficult to disentangle with traditional empirical approaches. Alternatively, researchers can take advantage of ‘natural’ experiments, where experimental control is exercised by careful site selection. Recent advances in developing protocols for designing these ‘pseudo-experiments’ commonly do not consider the selection of the focal region and predictor variables are usually restricted to two. Here, we advance this type of site selection protocol to study the impact of multiple landscape scale factors on pollinator abundance and diversity across multiple regions. 2. Using datasets of geographic and ecological variables with national coverage, we applied a novel hierarchical computation approach to select study sites that contrast as much as possible in four key variables, while attempting to maintain regional comparability and national representativeness. There were three main steps to the protocol: (i) selection of six 100 9 100 km2 regions that collectively provided land cover representative of the national land average, (ii) mapping of potential sites into a multivariate space with axes representing four key factors potentially influencing insect pollinator abundance, and (iii) applying a selection algorithm which maximized differences between the four key variables, while controlling for a set of external constraints. 3. Validation data for the site selection metrics were recorded alongside the collection of data on pollinator populations during two field campaigns. While the accuracy of the metric estimates varied, the site selection succeeded in objectively identifying field sites that differed significantly in values for each of the four key variables. Between-variable correlations were also reduced or eliminated, thus facilitating analysis of their separate effects. 4. This study has shown that national datasets can be used to select randomized and replicated field sites objectively within multiple regions and along multiple interacting gradients. Similar protocols could be used for studying a range of alternative research questions related to land use or other spatially explicit environmental variables, and to identify networks of field sites for other countries, regions, drivers and response taxa in a wide range of scenarios

Genetic influence on scar height and pliability after burn injury in individuals of European ancestry: A prospective cohort study

After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and % total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings

Genetic diversity and evolution of human metapneumovirus fusion protein over twenty years

<p>Abstract</p> <p>Background</p> <p>Human metapneumovirus (HMPV) is an important cause of acute respiratory illness in children. We examined the diversity and molecular evolution of HMPV using 85 full-length F (fusion) gene sequences collected over a 20-year period.</p> <p>Results</p> <p>The F gene sequences fell into two major groups, each with two subgroups, which exhibited a mean of 96% identity by predicted amino acid sequences. Amino acid identity within and between subgroups was higher than nucleotide identity, suggesting structural or functional constraints on F protein diversity. There was minimal progressive drift over time, and the genetic lineages were stable over the 20-year period. Several canonical amino acid differences discriminated between major subgroups, and polymorphic variations tended to cluster in discrete regions. The estimated rate of mutation was 7.12 × 10^-4substitutions/site/year and the estimated time to most recent common HMPV ancestor was 97 years (95% likelihood range 66-194 years). Analysis suggested that HMPV diverged from avian metapneumovirus type C (AMPV-C) 269 years ago (95% likelihood range 106-382 years).</p> <p>Conclusion</p> <p>HMPV F protein remains conserved over decades. HMPV appears to have diverged from AMPV-C fairly recently.</p

Assessing discards in an illegal small-scale fishery using fisher-led reporting

Funding: Newton Fund (IL 2018-Grant Agreement 414695818 James PER), Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica (PE) (FONDECYT 2018-222).About a third of all marine fish in the world are caught in Small-Scale Fisheries (SSF). SSF are increasingly recognised as essential for food security and livelihoods for vulnerable and economically fragile communities globally. Although individual SSF vessels are usually perceived as having little impact on the ecosystem, the cumulative impact of gear type and number of vessels may be substantial. Bottom trawling is a common fishing method that can greatly influence the marine ecosystem by damaging the seafloor and generating high levels of discards. However, appropriate sampling coverage using on-board observer programmes to collect these data from SSF are rare, as they are expensive and pose logistical constraints. A mobile App was used to assess whether self-reporting by fishers could provide reliable fine-scale information on fishing effort and discards over time in an illegal shrimp trawling fishery in northern Peru. Maps depicting the spatial distribution of trawling effort and the proportion of discards from observers and fishers were compared using the Similarity in Means (SIM) Index, which ranges from 0 when spatial patterns differ completely to 1 when spatial patterns are very similar. High levels of agreement between spatio-temporal patterns of effort (SIM Index = 0.81) and discards (0.96) were found between fisher and observer maps. Moreover, far greater spatial coverage was accomplished by fishers, suggesting that self-reporting via an App represents a useful approach to collect reliable fisheries data as an initial step for effective monitoring and management of these fisheries.Publisher PDFPeer reviewe

An AzTEC 1.1 mm survey of the GOODS-N field – I. Maps, catalogue and source statistics

This article has been accepted for publication in Monthly Notices Of The Royal Astronomical Society ©: 2008 T. A. Perera et al. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.We have conducted a deep and uniform 1.1 mm survey of the Great Observatories Origins Deep Survey-North (GOODS-N) field with AzTEC on the James Clerk Maxwell Telescope. Here, we present the first results from this survey including maps, the source catalogue and 1.1 mm number counts. The results presented here were obtained from a 245 arcmin2 region with a near uniform coverage to a depth of 0.96–1.16 mJy beam−1. Our robust catalogue contains 28 source candidates detected with S/N ≥ 3.75, only ∼1– 2 of which are expected to be spurious detections. Of these source candidates, eight are also detected by Submillimetre Common-User Bolometer Array (SCUBA) at 850 μm in regions where there is a good overlap between the two surveys. The major advantage of our survey over that with SCUBA is the uniformity of coverage. We calculate number counts using two different techniques: the first using a frequentist parameter estimation and the second using a Bayesian method. The two sets of results are in good agreement. We find that the 1.1 mm differential number counts are well described in the 2–6 mJy range by the functional form dN/dS=N′(S′/S) exp(−S/S′) with fitted parameters S′= 1.25 ± 0.38 mJy and dN/dS= 300 ± 90 mJy−1deg−2 at 3 mJy

Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a prospective cohort study

© 2017 Elsevier Ltd Background Clinical decision rules can help to determine the need for CT imaging in children with head injuries. We aimed to validate three clinical decision rules (PECARN, CATCH, and CHALICE) in a large sample of children. Methods In this prospective observational study, we included children and adolescents (age

A prospective observational study to assess the diagnostic accuracy of clinical decision rules for children presenting to emergency departments after head injuries (protocol): The Australasian Paediatric Head Injury Rules Study (APHIRST)

Background: Head injuries in children are responsible for a large number of emergency department visits. Failure to identify a clinically significant intracranial injury in a timely fashion may result in long term neurodisability and death. Whilst cranial computed tomography (CT) provides rapid and definitive identification of intracranial injuries, it is resource intensive and associated with radiation induced cancer. Evidence based head injury clinical decision rules have been derived to aid physicians in identifying patients at risk of having a clinically significant intracranial injury. Three rules have been identified as being of high quality and accuracy: the Canadian Assessment of Tomography for Childhood Head Injury (CATCH) from Canada, the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) from the UK, and the prediction rule for the identification of children at very low risk of clinically important traumatic brain injury developed by the Pediatric Emergency Care Applied Research Network (PECARN) from the USA. This study aims to prospectively validate and compare the performance accuracy of these three clinical decision rules when applied outside the derivation setting.Methods/design: This study is a prospective observational study of children aged 0 to less than 18 years presenting to 10 emergency departments within the Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network in Australia and New Zealand after head injuries of any severity. Predictor variables identified in CATCH, CHALICE and PECARN clinical decision rules will be collected. Patients will be managed as per the treating clinicians at the participating hospitals. All patients not undergoing cranial CT will receive a follow up call 14 to 90 days after the injury. Outcome data collected will include results of cranial CTs (if performed) and details of admission, intubation, neurosurgery and death. The performance accuracy of each of the rules will be assessed using rule specific outcomes and inclusion and exclusion criteria.Discussion: This study will allow the simultaneous comparative application and validation of three major paediatric head injury clinical decision rules outside their derivation setting.Trial registration: The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)- ACTRN12614000463673 (registered 2 May 2014). © 2014 Babl et al.; licensee BioMed Central Ltd