Colorectal cancer outcomes determined by mode of presentation: analysis of population data in England between 2010 and 2014.

BACKGROUND: The purpose of this study was to investigate associations between mode of presentation; categorized as emergency, suspected cancer outpatient referral pathway (2-week wait or 2WW pathway), non-cancer suspected outpatient referral (non-2-week wait pathway) or following screening, and stage of diagnosis and survival in patients with colorectal cancer in England. METHODS: This was a retrospective cohort observational study of patients diagnosed with colorectal cancer between January 2010 and December 2014 in England using data from Public Health England collated from regional cancer registries. RESULTS: The most common route to diagnosis among 167,501 patients diagnosed with colorectal cancer was via the non-cancer suspect (non-2WW) outpatient referral pathway (35.1%) followed by the suspected cancer (2WW) referral pathway (31.6%), emergency presentation (22.8%) and most infrequently following screening (10.6%) (p < 0.01). Screening confers the greatest likelihood of early-stage diagnosis (61.6%) compared to other modes of presentation. The 5-year overall survival was 81.8%, 53.3%, 53.0% and 27.6% in those diagnosed via screening, 2WW, non-2WW pathway and emergency presentation, respectively. Patients from most deprived regions were more likely to be diagnosed following emergency presentation (27.7 vs 19.7%, p < 0.01) and less likely via screening (8.1 vs 12%, p < 0.01). CONCLUSIONS: Asymptomatic individuals diagnosed following screening have earlier stage cancers and better survival, the opposite was observed in those diagnosed following emergency presentation. Patients referred via the 2WW pathway do not have better survival outcomes when compared to those referred via the non-2WW pathway. In addition, this study has identified socio-economic groups that need to be targeted with public health campaigns to improve screening uptake.

Bifunctional Role of the Sternohyoideus Muscle During Suction Feeding in Striped Surfperch, Embiotoca lateralis.

In ray-finned fishes, the sternohyoideus (SH) is among the largest muscles in the head region and, based on its size, can potentially contribute to the overall power required for suction feeding. However, the function of the SH varies interspecifically. In largemouth bass (Micropterus salmoides) and several clariid catfishes, the SH functions similarly to a stiff ligament. In these species, the SH remains isometric and transmitts power from the hypaxial musculature to the hyoid apparatus during suction feeding. Alternatively, the SH can shorten and contribute muscle power during suction feeding, a condition observed in the bluegill sunfish (Lepomis macrochirus) and one clariid catfish. An emerging hypothesis centers on SH muscle size as a predictor of function: in fishes with a large SH, the SH shortens during suction feeding, whereas in fish with a smaller SH, the muscle may remain isometric. Here, we studied striped surfperch (Embiotoca lateralis), a species in which the SH is relatively large at 8.8% of axial muscle mass compared with 4.0% for L. macrochirus and 1.7% for M. salmoides, to determine whether the SH shortens during suction feeding and is, therefore, bifunctional-both transmitting and generating power-or remains isometric and only transmits power. We measured skeletal kinematics of the neurocranium, urohyal, and cleithrum with Video Reconstruction of Moving Morphology, along with muscle strain and shortening velocity in the SH and epaxial muscles, using a new method of 3D external marker tracking. We found mean SH shortening during suction feeding strikes (n = 22 strikes from four individual E. lateralis) was 7.2 ± 0.55% (±SEM) of initial muscle length. Mean peak speed of shortening was 4.9 ± 0.65 lengths s-1, and maximum shortening speed occurred right around peak gape when peak power is generated in suction feeding. The cleithrum of E. lateralis retracts and depresses but the urohyal retracts and depresses even more, a strong indicator of a bifunctional SH capable of not only generating its own power but also transmitting hypaxial power to the hyoid. While power production in E. lateralis is still likely dominated by the axial musculature, since even the relatively large SH of E. lateralis is only 8.8% of axial muscle mass, the SH may contribute a meaningful amount of power given its continual shortening just prior to peak gape across all strikes. These results support the finding from other groups of fishes that a large SH muscle, relative to axial muscle mass, is likely to both generate and transmit power during suction feeding.

Representing virus-host interactions and other multi-organism processes in the Gene Ontology.

BACKGROUND: The Gene Ontology project is a collaborative effort to provide descriptions of gene products in a consistent and computable language, and in a species-independent manner. The Gene Ontology is designed to be applicable to all organisms but up to now has been largely under-utilized for prokaryotes and viruses, in part because of a lack of appropriate ontology terms. METHODS: To address this issue, we have developed a set of Gene Ontology classes that are applicable to microbes and their hosts, improving both coverage and quality in this area of the Gene Ontology. Describing microbial and viral gene products brings with it the additional challenge of capturing both the host and the microbe. Recognising this, we have worked closely with annotation groups to test and optimize the GO classes, and we describe here a set of annotation guidelines that allow the controlled description of two interacting organisms. CONCLUSIONS: Building on the microbial resources already in existence such as ViralZone, UniProtKB keywords and MeGO, this project provides an integrated ontology to describe interactions between microbial species and their hosts, with mappings to the external resources above. Housing this information within the freely-accessible Gene Ontology project allows the classes and annotation structure to be utilized by a large community of biologists and users.

The after-death call to family members: a clinical perspective.

In this paper, we discuss the value of an after-death telephone call made by the treating mental health clinician to family members, after the death of a geriatric patient with a psychiatric disorder. We outline the process of the after-death call including the optimal method, nature, and content. We note the psychotherapeutic value of an after-death telephone call in addressing complex emotions, and helping the family to cope with bereavement. We also discuss institutional, legal, and ethical ramifications. We conclude that an after-death call may be of sufficient benefit to be considered as a "best practice" approach in the care of every patient.

The Gene Ontology (GO) database and informatics resource.

The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.

Unravelling dispersal patterns in an expanding population of a highly mobile seabird, the northern fulmar (Fulmarus glacialis).

The northern fulmar (Fulmarus glacialis) is an abundant seabird whose Northeast Atlantic population has expanded dramatically over the past 100 years. Archaeological evidence suggests that Iceland and St Kilda were the ancestral populations from which essentially all other colonies in the region were derived. We collected samples from seven breeding colonies around the North Atlantic and used mitochondrial DNA analysis to ask whether population structure was present and, if so, where there was evidence about which colony was the dominant source population. Our data reveal a pattern consistent with isolation by distance, suggesting that, even though capable of flying great distances, most birds return to breed either at their own or neighbouring colonies. Interestingly, although most colonizers appear to have come originally from Iceland, our analysis also identifies St Kilda as a possible source. However, this secondary pattern appears to be largely an artefact, and can be attributed to the low haplotype diversity on St Kilda which yields a much clearer isolation by distance signal than that generated by birds dispersing from Iceland, where haplotype diversity is extremely high. Consequently, we urge caution when interpreting patterns in which populations vary greatly in the genetic diversity they harbour.

A prospective study of a quantitative PCR ELISA assay for the diagnosis of CMV pneumonia in lung and heart-transplant recipients.

BACKGROUND: Qualitative polymerase chain reaction (PCR) for the identification of cytomegalovirus (CMV) infection has a low predictive value for the identification of CMV pneumonia. This study prospectively evaluated the application of a quantitative PCR Enzyme-Linked Immuno-Sorbent Assay (ELISA) assay in 9 lung- and 18 heart-transplant recipients who did not receive ganciclovir prophylaxis. METHODS: DNA was collected from peripheral blood polymorphonuclear leucocytes (PMNL) posttransplantation. Oligonucleotide primers for the glycoprotein B gene (149 bp) were used in a PCR ELISA assay using an internal standard for quantitation. CMV disease was defined as histological evidence of end organ damage. RESULTS: The median level CMV genome equivalents in patients with CMV disease was 2665/2 x 10(5) PMNL (range 1,200 to 61,606) compared to 100 x 10(5) PMNL (range 20 to 855) with infection but no CMV disease (p = 0.036). All patients with CMV disease had genome equivalents levels of >1200/2 x 10(5) PMNL. A cut-off level of 1,200 PMNL had a positive predictive value for CMV disease of 100% and a negative predictive value of 100%. The first detection of levels of CMV genome equivalents above a level of 1200/2 x 10(5) PMNL was at a median of 58 days (range 47 to 147) posttransplant. CONCLUSIONS: Quantitative PCR assays for the diagnosis of CMV infection may predict patients at risk of CMV disease and thereby direct preemptive treatment to high-risk patients.

Health care issues for specific populations of employees.

Formulation of a medical treatment plan by a physician can be influenced by an individual's current and past medical conditions, gender, and socioeconomic, racial, and genetic background. This applies equally to treating work-related injuries and illnesses. Experienced workers' compensation clinicians know that treatment guidelines developed to treat one group of workers may not be effective for other populations of employees.

Workers' comp care. Part 1.

The care of an injured employee often is a significant challenge for the clinician. While workers' compensation and group health share similarities, there are differences in regulations. In addition to addressing the injury, the doctor also must supply documentation and interact with a claims adjuster and/or case manager more frequently than with an HMO or PPO patient with the identical condition.

Preemptive treatment for the prevention of cytomegalovirus disease: in lung and heart transplant recipients.

BACKGROUND: Rapid quantifiable diagnostic techniques for the diagnosis of cytomegalovirus (CMV) infection may predict patients at risk of CMV pneumonitis and allow preemptive antiviral treatment. METHODS: Using CMV antigenemia as a prospective surveillance technique for CMV infection, we compared the outcome of preemptive treatment (PT) with ganciclovir, 10 mg/kg/day for 21 days directed by "high levels" of CMV antigenemia (PT group, n= 19), with the outcome in a group of historical controls (n=18) treated with ganciclovir when CMV illness occurred. Greater than 50 antigen-positive cells per 2 x 10(5) polymorphonuclear leukocytes was considered to be high-level antigenemia. RESULTS: Nine of the 18 controls developed high-level CMV antigenemia at a median of 33 days (range: 13-65 days) and 5 of the 9 developed CMV disease. Ten of the 19 PT group had high levels of CMV antigenemia detected at a median of 47 days (range: 20-63 days) and were given ganciclovir; none developed CMV disease. There was a significantly lower incidence of CMV disease in the PT group in comparison to controls (0 of 19 vs. 5 of 18: P=0.019). CONCLUSION: We have reduced the incidence of CMV disease using preemptive treatment, and because of a 100% negative predictive value, we omitted unnecessary antiviral prophylaxis for many at-risk patients.

Comparative study of three PCR assays with antigenaemia and serology for the diagnosis of HCMV infection in thoracic transplant recipients.

Three PCR assays were evaluated for the detection of human cytomegalovirus (HCMV) infection in heart and lung transplant recipients in comparison with HCMV antigenaemia and serology assay. Polymorphonuclear leucocyte (PMNL) samples taken at regular intervals after transplantation were tested for HCMV DNA using primer sets homologous to the glycoprotein B (gp58), major immediate early (IE1), and structural phosphoprotein (pp150) regions. The detection of HCMV infection at various times after transplantation showed all three primer sets to have a sensitivity of 100% and a specificity of 92.3% for the detection of HCMV infection although overall the gp58 primer set was found to be significantly more frequently associated with a positive PCR result than the IE1 (P = 0.0228) and pp150 (P = 0.0015) primer sets. The positive PCR result had a positive predictive value of 27.8% for HCMV disease. Detection of HCMV infection was first by the PCR assay, and significantly before the HCMV antigenaemia assay. Of nine patients who received antiviral therapy while PCR positive, only one patient cleared HCMV DNA from PMNLs during treatment but became positive again 17 days later. Quantitative PCR methodologies may improve the predictive value of PCR for HCMV disease and its value for monitoring antiviral therapy.

Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients.

BACKGROUND: New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS: Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS: Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS: CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment.

Apple-fruit xyloglucans: a comparative study of enzyme digests of whole cell walls and of alkali-extracted xyloglucans.

Apple cell walls or alkali-extracted xyloglucans were digested with an endo-glucanase from Trichoderma viride and the resulting oligosaccharides were isolated by chromatography on Bio-Gel P-4. Three main oligosaccharides were present in similar proportions, and their structures were shown to be [Xyl(Glc)]3-Glc, [Xyl(Glc)]2-(FucGalXyl)Glc-Glc, and XylGlc-(GalXyP)Glc-(FucGalXyl)Glc-Glc. Each non-reducing-end Glc was 6-linked, each reducing-end Glc was 4-substituted, and each other Glc was 4,6-disubstituted. The Xyl was either terminal or 2-substituted, the Fuc was terminal, and the Gal was either terminal or 2-substituted. The 1H-NMR spectra of the oligosaccharides extracted directly from the cell wall showed that they are not acetylated. Other oligosaccharides, notably GalXyl3Glc4, Xyl2Glc4, and Xyl2Glc3, were present in smaller proportions in the digest of the cell walls.

Evaluating the evaluations of psychiatry residents.

This survey assessed the perceptions of psychiatry residents and faculty about resident evaluations. Current residents, former residents, and faculty of a psychiatry residency program were asked about the value and effect of feedback in 15 specific areas and rated their preferences for evaluation methods. Residents and faculty most valued feedback that addressed practical clinical skills. Evaluations reportedly improved skills in half of the areas surveyed. Most respondents preferred face-to-face evaluations from individual faculty. This study confirms the value of resident evaluations addressing clinical skills, but it highlights discrepancies in expectations and merits of several methods of evaluation.

Characterisation of polysaccharides by in-source pyrolysis positive- and negative-ion direct chemical ionisation-mass spectrometry.

Series of oligosaccharide ions have been generated from a range of polysaccharides by the application of in-source pyrolysis mass spectrometry, using both ammonia positive-ion chemical ionisation and negative-ion chlorine-nucleophilic-addition ionisation. Glucans with alpha-(1----6), beta-(1----6), alpha-(1----4), beta-(1----4), beta-(1----3), and beta-(1----2) linkages were studied, together with pentosans, xyloglucans, and an arabinogalactan. The series of ions correspond to intact, desorbed oligosaccharides with a terminal anhydro-sugar unit, and to similar oligosaccharides with attached sugar ring-cleavage fragments. The ions generated are dependent on the position of the linkage and ring size, and retain significant information on the structure of the original polysaccharide.