426 research outputs found
Patterns of Pelvic Radiotherapy in Patients with Stage II/III Rectal Cancer
High-level evidence supports adjuvant radiotherapy for rectal cancer. We examined the influence of sociodemographic factors on patterns of adjuvant radiotherapy for resected Stage II/III rectal cancer. Methods. Patients undergoing surgical resection for stage II/III rectal cancer were identified in SEER registry. Results. A total of 21,683 patients were identified. Majority of patients were male (58.8%), white (83%), and with stage III (54.9%) and received radiotherapy (66%). On univariate analysis, male gender, stage III, younger age, year of diagnosis, and higher socioeconomic status (SES) were associated with radiotherapy. Radiotherapy was delivered in 84.4% of patients 50; however, only 32.8% of those are 80 years. Logistic regression demonstrated a significant increase in the use of radiotherapy in younger patients who are 50 (OR, 10.3), with stage III (OR, 1.21), males (OR, 1.18), and with higher SES. Conclusions. There is a failure to conform to standard adjuvant radiotherapy in one-third of patients, and this is associated with older age, stage II, area-level of socioeconomic deprivation, and female sex
A high-throughput method for the detection of homoeologous gene deletions in hexaploid wheat
<p>Abstract</p> <p>Background</p> <p>Mutational inactivation of plant genes is an essential tool in gene function studies. Plants with inactivated or deleted genes may also be exploited for crop improvement if such mutations/deletions produce a desirable agronomical and/or quality phenotype. However, the use of mutational gene inactivation/deletion has been impeded in polyploid plant species by genetic redundancy, as polyploids contain multiple copies of the same genes (homoeologous genes) encoded by each of the ancestral genomes. Similar to many other crop plants, bread wheat (<it>Triticum aestivum </it>L.) is polyploid; specifically allohexaploid possessing three progenitor genomes designated as 'A', 'B', and 'D'. Recently modified TILLING protocols have been developed specifically for mutation detection in wheat. Whilst extremely powerful in detecting single nucleotide changes and small deletions, these methods are not suitable for detecting whole gene deletions. Therefore, high-throughput methods for screening of candidate homoeologous gene deletions are needed for application to wheat populations generated by the use of certain mutagenic agents (e.g. heavy ion irradiation) that frequently generate whole-gene deletions.</p> <p>Results</p> <p>To facilitate the screening for specific homoeologous gene deletions in hexaploid wheat, we have developed a TaqMan qPCR-based method that allows high-throughput detection of deletions in homoeologous copies of any gene of interest, provided that sufficient polymorphism (as little as a single nucleotide difference) amongst homoeologues exists for specific probe design. We used this method to identify deletions of individual <it>TaPFT1 </it>homoeologues, a wheat orthologue of the disease susceptibility and flowering regulatory gene <it>PFT1 </it>in Arabidopsis. This method was applied to wheat nullisomic-tetrasomic lines as well as other chromosomal deletion lines to locate the <it>TaPFT1 </it>gene to the long arm of chromosome 5. By screening of individual DNA samples from 4500 M2 mutant wheat lines generated by heavy ion irradiation, we detected multiple mutants with deletions of each <it>TaPFT1 </it>homoeologue, and confirmed these deletions using a CAPS method. We have subsequently designed, optimized, and applied this method for the screening of homoeologous deletions of three additional wheat genes putatively involved in plant disease resistance.</p> <p>Conclusions</p> <p>We have developed a method for automated, high-throughput screening to identify deletions of individual homoeologues of a wheat gene. This method is also potentially applicable to other polyploidy plants.</p
Enhanced Recovery after Surgery in a Single High-Volume Surgical Oncology Unit: Details Matter
Benefits of ERAS protocol have been well documented; however, it is unclear whether the improvement stems from the protocol or shifts in expectations. Interdisciplinary educational seminars were conducted for all health professionals. However, one test surgeon adopted the protocol. 394 patients undergoing elective abdominal surgery from June 2013 to April 2015 with a median age of 63 years were included. The implementation of ERAS protocol resulted in a decrease in the length of stay (LOS) and mortality, whereas the difference in cost was found to be insignificant. For the test surgeon, ERAS was associated with decreased LOS, cost, and mortality. For the control providers, the LOS, cost, mortality, readmission rates, and complications remained similar both before and after the implementation of ERAS. An ERAS protocol on the single high-volume surgical unit decreased the cost, LOS, and mortality
How U.S. Ocean Policy and Market Power Can Reform the Coral Reef Wildlife Trade
As the world’s largest importer of marine ornamental species for the aquaria, curio, home décor, and jewelry industries, the United States has an opportunity to leverage its considerable market power to promote more sustainable trade and reduce the effects of ornamental trade stress on coral reefs worldwide. Evidence indicates that collection of some coral reef animals for these trades has caused virtual elimination of local populations, major changes in age structure, and promotion of collection practices that destroy reef habitats. Management and enforcement of collection activities in major source countries such as Indonesia and the Philippines remain weak. Strengthening US trade laws and enforcement capabilities combined with increasing consumer and industry demand for responsible conservation can create strong incentives for improving management in source countries. This is particularly important in light of the March 2010 failure of the parties to the Convention on International Trade in Endangered Species (CITES) to take action on key groups of corals
Genome structural variation in Escherichia coli O157:H7
The human zoonotic pathogen Escherichia coli O157:H7 is defined by its extensive prophage repertoire including those that encode Shiga toxin, the factor responsible for inducing life-threatening pathology in humans. As well as introducing genes that can contribute to the virulence of a strain, prophage can enable the generation of large-chromosomal rearrangements (LCRs) by homologous recombination. This work examines the types and frequencies of LCRs across the major lineages of the O157:H7 serotype. We demonstrate that LCRs are a major source of genomic variation across all lineages of E. coli O157:H7 and by using both optical mapping and Oxford Nanopore long-read sequencing prove that LCRs are generated in laboratory cultures started from a single colony and that these variants can be recovered from colonized cattle. LCRs are biased towards the terminus region of the genome and are bounded by specific prophages that share large regions of sequence homology associated with the recombinational activity. RNA transcriptional profiling and phenotyping of specific structural variants indicated that important virulence phenotypes such as Shiga-toxin production, type-3 secretion and motility can be affected by LCRs. In summary, E. coli O157:H7 has acquired multiple prophage regions over time that act to continually produce structural variants of the genome. These findings raise important questions about the significance of this prophage-mediated genome contingency to enhance adaptability between environments
The Fusarium crown rot pathogen Fusarium pseudograminearum triggers a suite of transcriptional and metabolic changes in bread wheat (Triticum aestivum L.)
Background and Aims: Fusarium crown rot caused by the fungal pathogen Fusarium pseudograminearum is a disease of wheat and barley, bearing significant economic cost. Efforts to develop effective resistance to this disease have been hampered by the quantitative nature of resistance and a lack of understanding of the factors associated with resistance and susceptibility. Here, we aimed to dissect transcriptional responses triggered in wheat by F. pseudograminearum infection. Methods: We used an RNA-seq approach to analyse host responses during a compatible interaction and identified >2700 wheat genes differentially regulated after inoculation with F. pseudograminearum. The production of a few key metabolites and plant hormones in the host during the interaction was also analysed. Key Results: Analysis of gene ontology enrichment showed that a disproportionate number of genes involved in primary and secondary metabolism, signalling and transport were differentially expressed in infected seedlings. A number of genes encoding pathogen-responsive uridine-diphosphate glycosyltransferases (UGTs) potentially involved in detoxification of the Fusarium mycotoxin deoxynivalenol (DON) were differentially expressed. Using a F. pseudograminearum DON-non-producing mutant, DON was shown to play an important role in virulence during Fusarium crown rot. An over-representation of genes involved in the phenylalanine, tryptophan and tyrosine biosynthesis pathways was observed. This was confirmed through metabolite analyses that demonstrated tryptamine and serotonin levels are induced after F. pseudograminearum inoculation. Conclusions: Overall, the observed host response in bread wheat to F. pseudograminearum during early infection exhibited enrichment of processes related to pathogen perception, defence signalling, transport and metabolism and deployment of chemical and enzymatic defences. Additional functional analyses of candidate genes should reveal their roles in disease resistance or susceptibility. Better understanding of host responses contributing to resistance and/or susceptibility will aid the development of future disease improvement strategies against this important plant pathogen
Prevention and early detection of prostate cancer
This Review was sponsored and funded by the International Society of Cancer Prevention (ISCaP), the European Association of Urology (EAU), the National Cancer Institute, USA (NCI) (grant number 1R13CA171707-01), Prostate Cancer UK, Cancer Research UK (CRUK) (grant number C569/A16477), and the Association for International Cancer Research (AICR
Use of genome sequencing to investigate the molecular basis of bacteriaphage interaction of the Escherichia coli O157 typing phages and the elucidation of the biological and public health significance of phage type
Background
Shiga toxin producing Escherichia coli (STEC) O157 causes severe gastrointestinal
disease and haemolytic uremic syndrome, and has a major impact on public health
worldwide with regular outbreaks and sporadic infection. Phage typing, i.e. the
susceptibility of STEC O157 strains to a bank of 16 bacteriophages, has been used in the UK to differentiate STEC O157 for the past 25 years and the phage type (PT)
can be an epidemiological marker of strains associated with severe disease or
associated with cases that occur from foreign travel. However, little is known
about the molecular interactions between the typing phages (TP) and STEC O157.
The aims of this thesis were to use whole genome sequencing to elucidate the
genetic basis for phage typing of STEC O157 and through this understand genetic
differences between strains relevant to disease severity and epidemiology.
Results
Sequencing the STEC O157 TPs revealed that they were clustered into 4 groups
based on sequence similarity that corresponded with their infectivity. Long read
sequencing revealed microevolutionary events occuring in STEC O157 genomes
over a short time period (approximately 1 year), evidenced by the loss and gain of
prophage regions and plasmids. An IncHI2 plasmid was found responsible for a
change in Phage Type (PT) from PT8 to PT54 during two related outbreaks at the
same restaurant. These changes resulted in a strain (PT54) that was fitter under
certain growth conditions and associated with a much larger outbreak (140 as
opposed to 4 cases). TraDIS (Transposon directed Insertion site sequencing) was
used to identify 114 genes associated with phage sensitivity and 44 genes involved
in phage resistance, emphasising the complex nature of identifying specific
genetic markers of phage susceptibility or resistance. Further work is required to
prove their phage-related functions but several are likely to encode novel phage
receptors. Deletion of a Stx2a prophage from a PT21/28 strain led to a strain that
typed as PT32, supporting the concept that the highly pathogenic PT21/28 lineage
I strains emerged from Stx2c+ PT32 strains in the last two decades by acquisition
of Stx2a-encoding prophages.
Conclusions
This body of work has highlighted the complexity of bacteriophage interaction and
investigated the genetic basis for susceptibility and resistance in E. coli. The
grouping of the TPs showed that resistance or susceptibility to all members of a
typing group was likely to be caused by one mechanism. IncHI2 was identified as
one of the markers for the PT54 phenotype. The Stx2a prophage region was
associated with the switch from PT32 to PT21/28, although PT32 strains
containing both Stx2a and Stx2c-encoding prophages have been isolated and can
provide insights into phage variation underpinning the susceptibility to the
relevant typing phages. The TraDIS results indicated that susceptibility or
resistance was governed by multiple genetic factors and not controlled by a single
gene. The significance of LPS for initial protection from phage adsorption was
evident and a number of novel genes controlling phage susceptibility and
resistance identified including the Sap operon and stringent starvation protein A
respectively. While SNP-based typing provides an excellent indication of the
evolution and relatedness of strains, phage typing can provide real insights into
short term evolution of the bacteria as PTs can be altered by mobile elements
such as prophages and plasmids. This study has shown that, although complex,
genetic determinants for PT can be mined from the genome and allow us to
understand the evolution of this zoonotic pathogen between host species and
during outbreaks
Surveying Nearby Brown Dwarfs with HGCA: Direct Imaging Discovery of a Faint, High-Mass Brown Dwarf Orbiting HD 176535 A
Brown dwarfs with well-measured masses, ages and luminosities provide direct
benchmark tests of substellar formation and evolutionary models. We report the
first results from a direct imaging survey aiming to find and characterize
substellar companions to nearby accelerating stars with the assistance of the
Hipparcos-Gaia Catalog of Accelerations (HGCA). In this paper, we present a
joint high-contrast imaging and astrometric discovery of a substellar companion
to HD 176535 A, a K3.5V main-sequence star aged approximately
Gyrs at a distance of pc. In advance of
our high-contrast imaging observations, we combined precision HARPS RVs and
HGCA astrometry to predict the potential companion's location and mass. We
thereafter acquired two nights of KeckAO/NIRC2 direct imaging observations in
the band, which revealed a companion with a contrast of mag at a projected separation of 0.\!\!''35
(13 AU) from the host star. We revise our orbital fit by incorporating
our dual-epoch relative astrometry using the open-source MCMC orbit fitting
code . HD 176535 B is a new benchmark dwarf useful for constraining
the evolutionary and atmospheric models of high-mass brown dwarfs. We found a
luminosity of and a model-dependent
effective temperature of K for HD 176535 B. Our dynamical mass
suggests that some substellar evolutionary models may be underestimating
luminosity for high-mass T dwarfs. Given its angular separation and luminosity,
HD 176535 B would make a promising candidate for Aperture Masking
Interferometry with JWST and GRAVITY/KPIC, and further spectroscopic
characterization with instruments like the CHARIS/SCExAO/Subaru integral field
spectrograph
Influenza, Winter Olympiad, 2002
Prospective surveillance for influenza was performed during the 2002 Salt Lake City Winter Olympics. Oseltamivir was administered to patients with influenzalike illness and confirmed influenza, while their close contacts were given oseltamivir prophylactically. Influenza A/B was diagnosed in 36 of 188 patients, including 13 athletes. Prompt management limited the spread of this outbreak
- …