Meta-analysis of the impact of postoperative infective complications on oncological outcomes in colorectal cancer surgery.

BACKGROUND: Cancer outcomes are complex, involving prevention, early detection and optimal multidisciplinary care. Postoperative infection and surgical site-infection (SSI) are not only uncomfortable for patients and costly, but may also be associated with poor oncological outcomes. A meta-analysis was undertaken to assess the oncological effects of SSI in patients with colorectal cancer. METHODS: An ethically approved PROSPERO-registered meta-analysis was conducted following PRISMA guidelines. PubMed and Scopus databases were searched for studies published between 2007 and 2017 reporting the effects of postoperative infective complications on oncological survival in colorectal cancer. Results were separated into those for SSI and those concerning anastomotic leakage. Articles with a Methodological Index for Non-Randomized Studies score of at least 18 were included. Hazard ratios (HRs) with 95 per cent confidence intervals were computed for risk factors using an observed to expected and variance fixed-effect model. RESULTS: Of 5027 articles were reviewed, 43 met the inclusion criteria, with a total of 154 981 patients. Infective complications had significant negative effects on overall survival (HR 1·37, 95 per cent c.i. 1·28 to 1·46) and cancer-specific survival (HR 2·58, 2·15 to 3·10). Anastomotic leakage occurred in 7·4 per cent and had a significant negative impact on disease-free survival (HR 1·14, 1·09 to 1·20), overall survival (HR 1·34, 1·28 to 1·39), cancer-specific survival (HR 1·43, 1·31 to 1·55), local recurrence (HR 1·18, 1·06 to 1·32) and overall recurrence (HR 1·46, 1·27 to 1·68). CONCLUSION: This meta-analysis identified a significant negative impact of postoperative infective complications on overall and cancer-specific survival in patients undergoing colorectal surgery.

ANTECEDENTES: Los resultados del cáncer son complejos, implican prevención, detección precoz y atención multidisciplinaria óptima. La infección postoperatoria y la infección del sitio quirúrgico (surgical site infection, SSI) no solo son inconvenientes para los pacientes y costosas, sino que también pueden estar asociadas con malos resultados oncológicos. Este estudio realizó un metaanálisis para evaluar los efectos oncológicos de la SSI en pacientes con cáncer colorrectal. MÉTODOS: Se realizó un metaanálisis registrado en PROSPERO, aprobado por el comité ético, siguiendo las pautas de PRISMA y utilizando las bases de datos PubMed y Scopus para estudios entre 2007-2017 que describían los efectos de las complicaciones infecciosas postoperatorias en la supervivencia oncológica en el cáncer colorrectal. Los resultados se separaron para el grupo de infección del sitio quirúrgico (SSI) y de fuga anastomótica. Se incluyeron los artículos con una puntuación ≥ 18 según el índice MINORS. Para los factores de riesgo se calcularon los cocientes de riesgos instantáneos (hazard ratios, HR) mediante un modelo de efectos aleatorios y el método de Mantel-Haenszel con los i.c. del 95% utilizando el programe RevMan5. RESULTADOS: Se revisaron 5.027 artículos de los cuales 43 cumplieron con los criterios de inclusión. En total fueron 154.981 pacientes en los cuales las complicaciones infecciosas tuvieron efectos negativos significativos en la supervivencia global (HR: 1,37 i.c. del 95%: 1,28-1,46) y la supervivencia específica relacionada con el cáncer (HR: 2,58 i.c. del 95%: 2,15-3,10). La fuga anastomótica ocurrió en un 7,4% de los casos e impactó negativa y significativamente en la supervivencia libre de enfermedad (HR: 1,14 i.c. del 95%: 1,09-1,20), en la supervivencia global (HR: 1,34 i.c. del 95%: 1,28-1,39), en la supervivencia específica relacionada con el cáncer (HR: 1,43 i.c. del 95% 1.31-1.55), en la recidiva local (HR: 1,18 i.c. del 95%: 1,06-1,32) y en la recidiva global (HR: 1,46 i.c. del 95%: 1,27-1,68). CONCLUSIÓN: Este metaanálisis identificó un impacto negativo significativo en la supervivencia global y en la supervivencia específica relacionada con el cáncer en pacientes con complicaciones postoperatorias infecciosas sometidos a cirugía colorrectal.

Distance to treatment as a factor for loss to follow up of hepatitis C patients in North East England.

BACKGROUND: A large proportion of the 200 000 HCV-infected individuals in the UK are undiagnosed or lost to follow-up. Engaging known infected individuals in treatment is essential for elimination. METHODS: Using PHE surveillance data and HCV treatment registers from North East of England (NE) treatment centres for 1997-2016, we estimated the number of HCV cases not linked to treatment and the proportion with active infection. We compared distances of treated and untreated cases to treatment services, and assessed the effect of expanding HCV treatment into existing drug and alcohol treatment centres in the NEE on treatment accessibility. RESULTS: The odds of being treated was associated with distance to treatment services. Confirmatory results for ~50% were not reported to PHE NE. Overall, 3385 patients reported to PHE NE had no record of treatment; we estimated 1621 of these may have been lost to follow-up after confirmation of active infection. CONCLUSIONS: Poor access to healthcare services may contribute to under-diagnosis or loss to follow-up. Expanding HCV treatment delivery into NEE drug and alcohol treatment centres would improve the accessibility of treatment services to people infected with/at risk of HCV. This may increase the proportion receiving treatment and support progress towards elimination.

Large outbreak of multiple gastrointestinal pathogens associated with fresh curry leaves in North East England, 2013.

A total of 592 people reported gastrointestinal illness following attendance at Street Spice, a food festival held in Newcastle-upon-Tyne, North East England in February/March 2013. Epidemiological, microbiological and environmental investigations were undertaken to identify the source and prevent further cases. Several epidemiological analyses were conducted; a cohort study; a follow-up survey of cases and capture re-capture to estimate the true burden of cases. Indistinguishable isolates of Salmonella Agona phage type 40 were identified in cases and on fresh curry leaves used in one of the accompaniments served at the event. Molecular testing indicated entero-aggregative Escherichia coli and Shigella also contributed to the burden of illness. Analytical studies found strong associations between illness and eating food from a particular stall and with food items including coconut chutney which contained fresh curry leaves. Further investigation of the food supply chain and food preparation techniques identified a lack of clear instruction on the use of fresh uncooked curry leaves in finished dishes and uncertainty about their status as a ready-to-eat product. We describe the investigation of one of the largest outbreaks of food poisoning in England, involving several gastrointestinal pathogens including a strain of Salmonella Agona not previously seen in the UK.

Longitudinal thermal heterogeneity in rivers and refugia for coldwater species: effects of scale and climate change.

Climate-change driven increases in water temperature pose challenges for aquatic organisms. Predictions of impacts typically do not account for fine-grained spatiotemporal thermal patterns in rivers. Patches of cooler water could serve as refuges for anadromous species like salmon that migrate during summer. We used high-resolution remotely sensed water temperature data to characterize summer thermal heterogeneity patterns for 11,308 km of 2nd- to 7th-order rivers throughout the Pacific Northwest and northern California (USA). We evaluated (1) water temperature patterns at different spatial resolutions, (2) the frequency, size, and spacing of cool thermal patches suitable for Pacific salmon (i.e., contiguous stretches ≥0.25 km, ≤15°C and ≥2°C cooler than adjacent water), and (3) potential influences of climate change on availability of cool patches. Thermal heterogeneity was nonlinearly related to the spatial resolution of water temperature data, and heterogeneity at fine resolution (<1 km) would have been difficult to quantify without spatially continuous data. Cool patches were generally >2.7 and <13.0 km long, and spacing among patches was generally >5.7 and <49.4 km. Thermal heterogeneity varied among rivers, some of which had long uninterrupted stretches of warm water ≥20°C, and others had many smaller cool patches. Our models predicted little change in future thermal heterogeneity among rivers, but within-river patterns sometimes changed markedly compared to contemporary patterns. These results can inform long-term monitoring programs as well as near-term climate-adaptation strategies.

Transition Probabilities of Co ii Weak Lines to the Ground and Low Metastable Levels.

New branching fraction (BF) measurements based primarily on data from a cross-dispersed echelle spectrometer are reported for 84 lines of Co ii. The BFs for 82 lines are converted to absolute atomic transition probabilities using radiative lifetimes from laser-induced fluorescence (LIF) measurements on 19 upper levels of the lines. A lifetime of 3.3(2) ns for the z5D0 level is used based on LIF measurements for lifetimes of the four other levels in the z5D term. Twelve of the eighty-four lines are weak transitions connecting to the ground and low metastable levels of Co+. Another 46 lines are strong transitions connecting to the ground and low metastable levels of Co+. For these lines, log(gf) values were measured in earlier studies and, with a few exceptions, are confirmed in this study. Such lines, if unblended in stellar spectra, have the potential to yield Co abundance values unaffected by any breakdown of the local thermodynamic equilibrium approximation in stellar photospheres because the ground and low metastable levels of Co+ are the primary population reservoirs of Co in the photospheres of interest. Weak lines, if unblended, are useful in photospheres with high Co abundance, and strong lines are useful in metal-poor photospheres. New hyperfine structure A constants for 28 levels of ionized Co from least-squares fits to Fourier transform spectra line profiles are reported. These laboratory data are applied to re-determine the Co abundance in the metal-poor halo star HD 84937. BFs and transition probabilities for 19 lines are reported for the first time.

IMPROVED Cr II log(gf ) VALUES AND ABUNDANCE DETERMINATIONS IN THE PHOTOSPHERES OF THE SUN AND METAL-POOR STAR HD 84937.

New emission branching fraction (BF) measurements for 183 lines of the second spectrum of chromium (Cr II) and new radiative lifetime measurements from laser-induced fluorescence for 8 levels of Cr+ are reported. The goals of this study are to improve transition probability measurements in Cr II and reconcile solar and stellar Cr abundance values based on Cr I and Cr II lines. Eighteen spectra from three Fourier Transform Spectrometers supplemented with ultraviolet spectra from a high-resolution echelle spectrometer are used in the BF measurements. Radiative lifetimes from this study and earlier publications are used to convert the BFs into absolute transition probabilities. These new laboratory data are applied to determine the Cr abundance log ε in the Sun and metal-poor star HD 84937. The mean result in the Sun is 〈logε (Cr II)〉 = 5.624±0.009 compared to 〈logε(Cr I)〉 = 5.644 ± 0.006 on a scale with the hydrogen abundance log ε(H) = 12 and with the uncertainty representing only line-to-line scatter. A Saha (ionization balance) test on the photosphere of HD 84937 is also performed, yielding 〈logε(Cr II)〉 = 3.417 ± 0.006 and 〈log ε(Cr I, lower level excitation potential E. P. >30 eV)〉 = 3.3743±30.011 for this dwarf star. We find a correlation of Cr with the iron-peak element Ti, suggesting an associated nucleosynthetic production. Four iron-peak elements (Cr along with Ti, V, and Sc) appear to have a similar (or correlated) production history-other iron-peak elements appear not to be associated with Cr.

An epidemiological review of gastrointestinal outbreaks associated with Clostridium perfringens, North East of England, 2012-2014.

An anecdotal increase in C. perfringens outbreaks was observed in the North East of England during 2012-2014. We describe findings of investigations in order to further understanding of the epidemiology of these outbreaks and inform control measures. All culture-positive (>105 c.f.u./g) outbreaks reported to the North East Health Protection Team from 1 January 2012 to 31 December 2014 were included. Epidemiological (attack rate, symptom profile and positive associations with a suspected vehicle of infection), environmental (deficiencies in food preparation or hygiene practices and suspected vehicle of infection) and microbiological investigations are described. Forty-six outbreaks were included (83% reported from care homes). Enterotoxin (cpe) gene-bearer C. perfringens were detected by PCR in 20/46 (43%) and enterotoxin (by ELISA) and/or enterotoxigenic faecal/food isolates with indistinguishable molecular profiles in 12/46 (26%) outbreaks. Concerns about temperature control of foods were documented in 20/46 (43%) outbreaks. A suspected vehicle of infection was documented in 21/46 (46%) of outbreaks (meat-containing vehicle in 20/21). In 15/21 (71%) identification of the suspected vehicle was based on descriptive evidence alone, in 5/21 (24%) with supporting evidence from an epidemiological study and in 2/21 (10%) with supporting microbiological evidence. C. perfringens-associated illness is preventable and although identification of foodborne outbreaks is challenging, a risk mitigation approach should be taken, particularly in vulnerable populations such as care homes for the elderly.

Cicada Wing Surface Topography: An Investigation into the Bactericidal Properties of Nanostructural Features.

Recently, the surface of the wings of the Psaltoda claripennis cicada species has been shown to possess bactericidal properties and it has been suggested that the nanostructure present on the wings was responsible for the bacterial death. We have studied the surface-based nanostructure and bactericidal activity of the wings of three different cicadas (Megapomponia intermedia, Ayuthia spectabile and Cryptotympana aguila) in order to correlate the relationship between the observed surface topographical features and their bactericidal properties. Atomic force microscopy and scanning electron microscopy performed in this study revealed that the tested wing species contained a highly uniform, nanopillar structure on the surface. The bactericidal properties of the cicada wings were investigated by assessing the viability of autofluorescent Pseudomonas fluorescens cells following static adhesion assays and targeted dead/live fluorescence staining through direct microscopic counting methods. These experiments revealed a 20-25% bacterial surface coverage on all tested wing species; however, significant bactericidal properties were observed in the M. intermedia and C. aguila species as revealed by the high dead:live cell ratio on their surfaces. The combined results suggest a strong correlation between the bactericidal properties of the wings and the scale of the nanotopography present on the different wing surfaces.

Case studies of conservation plans that incorporate geodiversity.

Geodiversity has been used as a surrogate for biodiversity when species locations are unknown, and this utility can be extended to situations where species locations are in flux. Recently, scientists have designed conservation networks that aim to explicitly represent the range of geophysical environments, identifying a network of physical stages that could sustain biodiversity while allowing for change in species composition in response to climate change. Because there is no standard approach to designing such networks, we compiled 8 case studies illustrating a variety of ways scientists have approached the challenge. These studies show how geodiversity has been partitioned and used to develop site portfolios and connectivity designs; how geodiversity-based portfolios compare with those derived from species and communities; and how the selection and combination of variables influences the results. Collectively, they suggest 4 key steps when using geodiversity to augment traditional biodiversity-based conservation planning: create land units from species-relevant variables combined in an ecologically meaningful way; represent land units in a logical spatial configuration and integrate with species locations when possible; apply selection criteria to individual sites to ensure they are appropriate for conservation; and develop connectivity among sites to maintain movements and processes. With these considerations, conservationists can design more effective site portfolios to ensure the lasting conservation of biodiversity under a changing climate.

Projected climate-driven faunal movement routes.

Historically, many species moved great distances as climates changed. However, modern movements will be limited by the patterns of human-dominated landscapes. Here, we use a combination of projected climate-driven shifts in the distributions of 2903 vertebrate species, estimated current human impacts on the landscape, and movement models, to determine through which areas in the western hemisphere species will likely need to move to track suitable climates. Our results reveal areas with projected high densities of climate-driven movements - including, the Amazon Basin, the southeastern United States and southeastern Brazil. Some of these regions, such as southern Bolivia and northern Paraguay, contain relatively intact landscapes, whereas others such as the southeastern United States and Brazil are heavily impacted by human activities. Thus, these results highlight both critical areas for protecting lands that will foster movement, and barriers where human land-use activities will likely impede climate-driven shifts in species distributions.

Economic-based projections of future land use in the conterminous United States under alternative policy scenarios.

Land-use change significantly contributes to biodiversity loss, invasive species spread, changes in biogeochemical cycles, and the loss of ecosystem services. Planning for a sustainable future requires a thorough understanding of expected land use at the fine spatial scales relevant for modeling many ecological processes and at dimensions appropriate for regional or national-level policy making. Our goal was to construct and parameterize an econometric model of land-use change to project future land use to the year 2051 at a fine spatial scale across the conterminous United States under several alternative land-use policy scenarios. We parameterized the econometric model of land-use change with the National Resource Inventory (NRI) 1992 and 1997 land-use data for 844 000 sample points. Land-use transitions were estimated for five land-use classes (cropland, pasture, range, forest, and urban). We predicted land-use change under four scenarios: business-as-usual, afforestation, removal of agricultural subsidies, and increased urban rents. Our results for the business-as-usual scenario showed widespread changes in land use, affecting 36% of the land area of the conterminous United States, with large increases in urban land (79%) and forest (7%), and declines in cropland (-16%) and pasture (-13%). Areas with particularly high rates of land-use change included the larger Chicago area, parts of the Pacific Northwest, and the Central Valley of California. However, while land-use change was substantial, differences in results among the four scenarios were relatively minor. The only scenario that was markedly different was the afforestation scenario, which resulted in an increase of forest area that was twice as high as the business-as-usual scenario. Land-use policies can affect trends, but only so much. The basic economic and demographic factors shaping land-use changes in the United States are powerful, and even fairly dramatic policy changes, showed only moderate deviations from the business-as-usual scenario. Given the magnitude of predicted land-use change, any attempts to identify a sustainable future or to predict the effects of climate change will have to take likely land-use changes into account. Econometric models that can simulate land-use change for broad areas with fine resolution are necessary to predict trends in ecosystem service provision and biodiversity persistence.

A cryogenic circulating advective multi-pass absorption cell.

A novel absorption cell has been developed to enable a spectroscopic survey of a broad range of polycyclic aromatic hydrocarbons (PAH) under astrophysically relevant conditions and utilizing a synchrotron radiation continuum to test the still controversial hypothesis that these molecules or their ions could be carriers of the diffuse interstellar bands. The cryogenic circulating advective multi-pass absorption cell resembles a wind tunnel; molecules evaporated from a crucible or injected using a custom gas feedthrough are entrained in a laminar flow of cryogenically cooled buffer gas and advected into the path of the synchrotron beam. This system includes a multi-pass optical White cell enabling absorption path lengths of hundreds of meters and a detection sensitivity to molecular densities on the order of 10(7) cm(-3). A capacitively coupled radio frequency dielectric barrier discharge provides ionized and metastable buffer gas atoms for ionizing the candidate molecules via charge exchange and the Penning effect. Stronger than expected clustering of PAH molecules has slowed efforts to record gas phase PAH spectra at cryogenic temperatures, though such clusters may play a role in other interstellar phenomena.

Thrombospondins in cancer.

The thrombospondins (TSPs) are a family of five proteins that are involved in the tissue remodeling that is associated with embryonic development, wound healing, synaptogenesis, and neoplasia. These proteins mediate the interaction of normal and neoplastic cells with the extracellular matrix and surrounding tissue. In the tumor microenvironment, TSP-1 has been shown to suppress tumor growth by inhibiting angiogenesis and by activating transforming growth factor beta. TSP-1 inhibits angiogenesis through direct effects on endothelial cell migration and survival, and through effects on vascular endothelial cell growth factor bioavailability. In addition, TSP-1 may affect tumor cell function through interaction with cell surface receptors and regulation of extracellular proteases. Whereas the role of TSP-1 in the tumor microenvironment is the best characterized, the other TSPs may have similar functions. (Part of a Multi-author Review).

Structures of thrombospondins.

Thrombospondins are large secreted, multimodular, calcium-binding glycoproteins that have complex roles in mediating cellular processes. Determination of high-resolution structures of thrombospondins has revealed unique and interesting protein motifs. Here, we review this progress and discuss implications for function. By combining structures of modules from thrombospondins and related extracellular proteins it is now possible to prepare an overall model of the structure of thrombospondin-1 and thrombospondin-2 and discern features of other thrombospondins. (Part of a multi-author Review).

Characteristics of homeless HIV-positive outreach responders in urban US and their success in primary care treatment.

Homeless HIV+ persons with persistent mental illness and substance use disorders need services, but are hard to reach and enrol into treatment. Connecting them to services is a major challenge of the AIDS epidemic. This report describes characteristics of homeless HIV+ substance abusers who responded to outreach and enrolled in integrated treatment services. The target population was urban, homeless, HIV+ individuals with substance dependence and/or mental illness diagnoses. Health and physical functioning were measured using a refinement of the Medical Outcomes Study Health Survey. Questions based on the PRIME-MD measured subjects' mental health status. Outreach occurred at shelters, soup kitchens, and on the streets. The outreach team consisted of a nurse, substance abuse counsellor, and a formerly homeless person. Outreach contacted 3,059 individuals; 1,446 entered the clinic, 110 of 206 eligible candidates enrolled in the study, and 82.7% of study participants completed 12-month follow-up interviews. Enrollees exhibited 5th percentile composite health scores. They reported heavy street drug use and unmet service needs particularly for housing and financial assistance. Outreach successfully recruited targeted individuals into treatment. They stayed in treatment and demonstrated improvements on measures of physical and mental health 12-months later.

Characterization of integrin beta6 and thrombospondin-1 double-null mice.

To identify overlapping and non-overlapping functions for TSP-1 and alphavbeta6, we crossed TSP-1-null and beta6-null mice and compared the phenotype of the double-null mice with those of wild-type and single-null mice. The double-null mice exhibited focal acute and organizing pneumonia that was more severe than the wild-type and single-null mice as well as a significantly higher incidence of inflammation in tissues other than the lung. The TSP-1-null and beta6-null mice exhibited a five to eight-fold increase in granulocyte recruitment to the lung three days after exposure to lipopolysaccharide. They also had abnormalities that were infrequently observed in the wild-type and single-null mice, including heart degeneration (8.35% in wild-type and 28.1% in double-null mice), hyperplasia of the glandular of the stomach (2.8% in wild-type and 21.1% in double-null mice) and endometrial hyperplasia (0% in wild-type and 38.5% in double-null females). Furthermore, the beta6-null and double-null mice displayed a significant elevation in benign and malignant cancers. Stomach papillomas, squamous cell carcinomas of the ear and stomach, and adenocarcinomas of the lungs, vagina/cervix and colon were observed with the highest frequency. These data demonstrate that TSP-1 and alphavbeta6 are involved in regulation of the immune system and epithelial homeostasis. They also indicate that alphavbeta6 functions as a tumor suppressor gene and that activation of TGFbeta by TSP-1 and alphavbeta6 contributes to normal tissue architecture and function.

Effect of cartilage oligomeric matrix protein on mesenchymal chondrogenesis in vitro.

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) mutations have been identified as responsible for two arthritic disorders, multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). However, the function of COMP in chondrogenic differentiation is largely unknown. Our investigation focuses on analyzing the function of normal COMP protein in cartilage biology. METHODS AND RESULTS: To explore the function of COMP we make use of an in vitro model system for chondrogenesis, consisting of murine C3H10T1/2 mesenchymal cells maintained as a high-density micromass culture and stimulated with bone morphogenetic protein 2 (BMP-2). Under these culture conditions, C3H10T1/2 cells undergo active chondrogenesis in a manner analogous to that of embryonic limb mesenchymal cells, and have been shown to serve as a valid model system to investigate the mechanisms regulating mesenchymal chondrogenesis. Our results indicate that ectopic COMP expression enhances several early aspects of chondrogenesis induced by BMP-2 in this system, indicating that COMP functions in part to positively regulate chondrogenesis. Additionally, COMP has inhibitory effects on proliferation of cells in monolayer. However, at later times in micromass culture, ectopic COMP expression in the presence of BMP-2 causes an increase in apoptosis, with an accompanying reduction in cell numbers in the micromass culture. However, the remaining cells retain their chondrogenic phenotype. CONCLUSIONS: These data suggest that COMP and BMP-2 signaling converge to regulate the fate of these cells in vitro by affecting both early and late stages of chondrogenesis.