Paul G. Richardson

Bio: Paul G. Richardson is an academic researcher from Harvard University. The author has contributed to research in topics: Multiple myeloma & Bortezomib. The author has an hindex of 183, co-authored 1533 publications receiving 155912 citations. Previous affiliations of Paul G. Richardson include Broomfield Hospital & Dartmouth College.

A randomized phase II study of elotuzumab with lenalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

Abstract: 8020 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting CS1, a cell surface glycoprotein. CS1 is highly expressed on >95% of multiple myeloma (MM) cells, with lower expr...

Overt hepatic encephalopathy: management and prevention of recurrence

Abstract: Most patients with overt hepatic encephalopathy are managed in an acute hospital setting. The mainstays of treatment are non-absorbable disaccharides, To prevent a recurrence, and thus further hospital admission, the focus is on identifying and avoiding precipitants, optimising nutrition and prescribing medication including rifaximin-α*†.

PWE-086 Improving identification and management of alcohol-related brain injury (ARBI) in acute care settings

Abstract: Introduction Alcohol Related Brain Injury (ARBI) is a hidden harm in drinkers. The most commonly used clinical definition is given in DSM IV, however this has been shown to be vague and subjective with poor utility in acute care settings. Estimates of prevalence have been reported at 0.03% per 3 00 000 however, as no routine, standardised algorithm for assessment of ARBI exists; this is most likely an underestimate. A systematic review of brain injury confirmed neurodegenerative changes in heavy drinkers, but importantly also highlighted the potential for reversibility of these changes with sustained abstinence. Therefore, recognition of ARBI at the earliest opportunity has the potential to facilitate the implementation of comprehensive care pathways that optimise medical and psychosocial care, and prevent the cycle of readmissions for increasingly complex physical and psychological harms. Methods In April 2017 we implemented an innovative clinical pathway. Patients meeting risk criteria based on number of previous admissions or carers concerns had an automatic referral to a specialist nurse for assessment utilising the Montreal Cognitive Assessment tool (MoCA©). A score of Results Over an period of 8 months (April to Nov 2017) 163 patients met criteria for screening; 118 males and 45 females, mean age=52 years (SD=11); range 26–80 years. 60 scored ≤23 (36.8%) of which 35 (58.3%) had a confirmed diagnosis of ARBI from a psychiatrist. At 3 months 22 patients had received follow-up. Compared with baseline MoCA scores were significantly higher (improved); mean difference=3.7 (95%CI: 1.2 to 6.3; p=0.07), mean hospital attendance was reduced from 3.2 to 1.9, and mean admissions were reduced from 1.8 to 1.1. Results from family reported outcome measures (FROMS) has highlighted several outcomes that our patient families found most valuable; a) receiving an assessment to confirm or reject the presence of ARBI, b) helping them understand their loved ones condition c) helping them plan for the future. Conclusions We have demonstrated potential benefits of this point-of-care screening which can facilitate the initiation of referral and treatment pathways which can improve patient outcomes. Our Results are descriptive, but may contribute to the design of clinical trials that are needed to determine utility, acceptability and validity of our Methods and the MoCA as a screening instrument in this setting.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

The Pfam protein families database

Abstract: Pfam is a widely used database of protein families and domains. This article describes a set of major updates that we have implemented in the latest release (version 24.0). The most important change is that we now use HMMER3, the latest version of the popular profile hidden Markov model package. This software is approximately 100 times faster than HMMER2 and is more sensitive due to the routine use of the forward algorithm. The move to HMMER3 has necessitated numerous changes to Pfam that are described in detail. Pfam release 24.0 contains 11,912 families, of which a large number have been significantly updated during the past two years. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/).

The sequence of the human genome.

Abstract: A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

The Human Genome Browser at UCSC

Abstract: As vertebrate genome sequences near completion and research refocuses to their analysis, the issue of effective genome annotation display becomes critical. A mature web tool for rapid and reliable display of any requested portion of the genome at any scale, together with several dozen aligned annotation tracks, is provided at http://genome.ucsc.edu. This browser displays assembly contigs and gaps, mRNA and expressed sequence tag alignments, multiple gene predictions, cross-species homologies, single nucleotide polymorphisms, sequence-tagged sites, radiation hybrid data, transposon repeats, and more as a stack of coregistered tracks. Text and sequence-based searches provide quick and precise access to any region of specific interest. Secondary links from individual features lead to sequence details and supplementary off-site databases. One-half of the annotation tracks are computed at the University of California, Santa Cruz from publicly available sequence data; collaborators worldwide provide the rest. Users can stably add their own custom tracks to the browser for educational or research purposes. The conceptual and technical framework of the browser, its underlying MYSQL database, and overall use are described. The web site currently serves over 50,000 pages per day to over 3000 different users.