Evaluation of the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population

Background Bowel cancer is common and is a major cause of death. Meta-analysis of randomised controlled trials estimates that screening for colorectal cancer using faecal occult blood (FOB) test reduces mortality from colorectal cancer by 16%. However, FOB testing has a low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. Serum MMP-9 is potentially an accurate, low risk and cost-effective population screening tool. This study aims to evaluate the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population. Methods/Design People aged 50 to 69 years, who registered in participating general practices in the West Midlands Region, will be asked to complete a questionnaire that asks about symptoms. Respondents who describe any colorectal symptoms (except only abdominal bloating and/or anal symptoms) and are prepared to provide a blood sample for MMP9 estimation and undergo a colonoscopy (current gold standard investigation) will be recruited at GP based clinics by a research nurse. Those unfit for colonoscopy will be excluded. Colonoscopies will be undertaken in dedicated research clinics. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the colonoscopy findings, and the combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined. Discussion Colorectal cancer is a major cause of morbidity and mortality. Most colorectal cancers arise from adenomas and there is a period for early detection by screening, but available tests have risks, are unacceptable to many, have high false positive rates or are expensive. This study will establish the potential of serum MMP-9 as a screening test for colorectal cancer. If it is confirmed as accurate and acceptable, this serum marker has the potential to assist with reducing the morbidity and mortality from colorectal cancer

The evolution of stable silicon isotopes in a coastal carbonate aquifer on Rottnest Island, Western Australia

Dissolved silicon (dSi) is a key nutrient in the oceans, but data regarding Si isotopes in coastal aquifers are not widely available. Here we investigate the Si isotopic composition of 12 fresh and 16 saline groundwater samples from Rottnest Island, Western Australia, which forms part of the world's most extensive aeolianite deposit (the Tamala Limestone formation). In total, two bedrock samples were also collected from Rottnest Island for Si isotope analysis. The δ30Si values of groundwater samples ranged from −0.4 ‰ to +3.6 ‰ with an average +1.6 ‰, and the rock samples were −0.8 ‰ and −0.1 ‰. The increase in δ30Si values in fresh groundwater is attributed to the removal of the lighter Si isotopes into secondary minerals and potentially also adsorption onto Fe (oxy)hydroxides. The positive correlations between δ30Si values and dSi concentrations (ρ = 0.59; p = 0.02) and δ30Si values and Cl, but not dSi and Cl concentrations, are consistent with vertical mixing between the younger fresh groundwater and the deeper groundwater, which have undergone a greater degree of water–rock interactions. This has produced a spatial pattern in δ30Si across the aquifer due to the local hydrogeology, resulting in a correlation between δ30Si and tritium activities when considering all groundwater types (ρ = −0.68; p = 0.0002). In the deeper aquifer, the inverse correlation between dSi and Cl concentrations (ρ = −0.79; p = 0.04) for the more saline groundwater is attributed to groundwater mixing with local seawater that is depleted in dSi (< 3.6 µM). Our results from this well-constrained island aquifer system demonstrate that stable Si isotopes usefully reflect the degree of water–aquifer interactions, which is related to groundwater residence time and local hydrogeology. Our finding that lithogenic Si dissolution occurs in the freshwater lens and the freshwater–seawater transition zone on Rottnest Island appears to supports the recent inclusion of a marine–submarine groundwater discharge term in the global dSi mass balance. Geologically young carbonate aquifers, such as Rottnest Island, may be an important source of dSi in coastal regions with low riverine input and low oceanic dSi concentrations

Viral time capsule:a global photo-elicitation study of child and adolescent mental health professionals during COVID-19

Objective To examine, through photo-elicitation, the personal and professional impact of the COVID-19 pandemic on mental health professionals working with children and adolescents around the globe. Methods We invited the submission of images collected about the pandemic between May and August 2020. We encouraged participants to yoke personal reflections or voice memos to their images. Using snowball sampling, we began with two invitations, including one to the graduates of a mentorship program continuously hosted since 2004 by the International Association of Child and Adolescent Psychiatry and Allied Professions (IACAPAP). We analyzed de-identified images and anonymized transcripts through iterative coding using thematic analysis informed by rich picture analysis and aided by NVivo software. Results We collected submissions from child and adolescent mental health professionals (n = 134) working in 54 countries spread across the five continents. We identified four overarching domains with component themes that revealed both the commonality and the uniqueness of the pandemic experience around the globe: (1) Place (adjusting to emptiness and stillness; shifting timeframes; blending of spaces); (2) Person (disruption to life rhythms; emotional toll; positives of the pandemic); (3) Profession (changing practices; outreach efforts; guild pride-and guilt); and (4) Purpose (from pandemic to syndemic; from lamenting to embracing; planning toward a better tomorrow). Conclusions Photo-elicitation provided a disarming and efficient means to learn about individual, regional, and global similarities and differences regarding the professionals charged with addressing the mental health needs of children and adolescents around the globe. These findings may help inform practice changes in post-pandemic times

In-vehicle nitrogen dioxide concentrations in road tunnels

There is a lack of knowledge regarding in-vehicle concentrations of nitrogen dioxide (NO) during transit through road tunnels in urban environments. Furthermore, previous studies have tended to involve a single vehicle and the range of in-vehicle NO concentrations that vehicle occupants may be exposed to is not well defined. This study describes simultaneous measurements of in-vehicle and outside-vehicle NO concentrations on a route through Sydney, Australia that included several major tunnels, minor tunnels and busy surface roads. Tests were conducted on nine passenger vehicles to assess how vehicle characteristics and ventilation settings affected in-vehicle NO concentrations and the in-vehicle-to-outside vehicle (I/O) concentration ratio. NO was measured directly using a cavity attenuated phase shift (CAPS) technique that gave a high temporal and spatial resolution. In the major tunnels, transit-average in-vehicle NO concentrations were lower than outside-vehicle concentrations for all vehicles with cabin air recirculation either on or off. However, markedly lower I/O ratios were obtained with recirculation on (0.08–0.36), suggesting that vehicle occupants can significantly lower their exposure to NO in tunnels by switching recirculation on. The highest mean I/O ratios for NO were measured in older vehicles (0.35–0.36), which is attributed to older vehicles having higher air exchange rates. The results from this study can be used to inform the design and operation of future road tunnels and modelling of personal exposure to NO

Reducing in-stent restenosis therapeutic manipulation of miRNA in vascular remodeling and inflammation

Background: Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro–ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury.&lt;p&gt;&lt;/p&gt; Objectives: This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents.&lt;p&gt;&lt;/p&gt; Methods: Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis.&lt;p&gt;&lt;/p&gt; Results: We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation.&lt;p&gt;&lt;/p&gt; Conclusions: MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting

The silence of self-knowledge

Gareth Evans famously affirmed an explanatory connection between answering the question whether p and knowing whether one believes that p. This is commonly interpreted in terms of the idea that judging that p constitutes an adequate basis for the belief that one believes that p. This paper formulates and defends an alternative, more modest interpretation, which develops from the suggestion that one can know that one believes that p in judging that p

An Electrochemical Study of Frustrated Lewis Pairs: A Metal-free Route to Hydrogen Oxidation

[Image: see text] Frustrated Lewis pairs have found many applications in the heterolytic activation of H(2) and subsequent hydrogenation of small molecules through delivery of the resulting proton and hydride equivalents. Herein, we describe how H(2) can be preactivated using classical frustrated Lewis pair chemistry and combined with in situ nonaqueous electrochemical oxidation of the resulting borohydride. Our approach allows hydrogen to be cleanly converted into two protons and two electrons in situ, and reduces the potential (the required energetic driving force) for nonaqueous H(2) oxidation by 610 mV (117.7 kJ mol(–1)). This significant energy reduction opens routes to the development of nonaqueous hydrogen energy technology

Racial Differences in Cortical Bone Mass, Size and Estimated Strength at the Tibial Diaphysis in Early Pubertal Children

poster abstractOsteoporotic fracture rates differ according to race, with blacks having up to half the rate of whites. The reduced fracture rate in blacks has been suggested to be due to their superior bone mass; however, mass is not the sole determinant of bone strength. Bone strength, and consequent fracture risk, is also influenced by how bone material is distributed or structured. It is likely bone structure also contributes to the lower incidence of fractures in blacks and that racial differences in bone structure have roots in childhood. The aim of this study was to assess the influence of race on pQCT-derived cortical bone mass, size and estimated strength at the tibial diaphysis in early pubertal children. 160 children were recruited, with equal subjects according to race (black, n=80; white, n=80) and sex (female, n=80; male, n=80). Subjects were at sexual maturation stages 2 or 3. Tomographic slices of the tibial diaphysis at 66% proximal from the medial malleolus were acquired using pQCT. Slices were assessed for cortical volumetric BMD (Ct.vBMD), cortical BMC (Ct.BMC), total (Tt.Ar) and cortical (Ct.Ar) area, density weighted maximum (IMAX) and minimum (IMIN) second moments of area, density-weighted polar strength-strain index (SSIP), and muscle cross-sectional area (mCSA). Group differences were assessed by two-way analysis of covariance, with race (black vs. white) and sex (female vs. male) as independent variables. Covariates included predicted years from peak height velocity (maturity offset), tibial length and mCSA. There were no interactions between race and sex (all P=0.50-0.98) or main effect for sex (all P=0.08-0.45). Blacks had 15.7% more Ct.BMC, and 10.8-11.8% larger Tt.Ar and Ct.Ar than whites (all P<0.001). The greater enhancement of Ct.BMC relative to Ct.Ar resulted in blacks having 3.6% greater Ct.vBMD than whites (P<0.001). The combination of increased cortical bone mass, size and density in blacks contributed to enhanced estimated bone strength, with IMAX, IMIN and SSIP being 20.0%, 34.5% and 25.2% greater in blacks than whites, respectively (all P<0.001). These data indicate that early pubertal black children have enhanced bone mass, size and estimated bone strength at the tibial diaphysis versus whites, independent of tibial length and mCSA. They suggest bone structural differences may contribute to observed racial differences in fracture rates and that structural divergence between races develops during childhood

The Gattini South Pole UV Experiment

The Gattini South Pole UV experiment (Gattini SPUV) was deployed to the South Pole dark sector in February 2010 and has recently completed a highly successful first season of winter time observations. The experiment has, for the first time ever, measured and categorized the optical night sky brightness at the very blue wavelengths. The experiment consists of a remotely operated 6” aperture custom designed telescope. The telescope feeds a blue sensitive imager with 4 degree field of view that contains a bank of 3 filters: SDSS g’, Bessel U and a custom “super U” filter specifically designed to probe the sky emission at wavelengths approaching the atmospheric cut-off. The filters are continually cycled with exposure times ranging from 30 to 300 seconds throughout the winter period. The telescope, in addition, feeds a 2 degree long slit VPH grating spectrograph with R~1000. The bandwidth is 350-450nm. The spectra are recorded simultaneously with the imager exposures. The experiment is designed for low temperature Antarctic operation and resides on the roof of the MAPO building in the South Pole Antarctic sector. The primary science goals are to categorize the Antarctic winter-time sky background at the very bluest of wavelengths as a pathfinder for the Antarctic Cosmic Web Imager. We present a technical overview of the experiment and results from the first winter season