Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.

SUMMARY: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

Changes in Presentation of Celiac Disease in Ireland From the 1960s to 2015.

BACKGROUND & AIMS: Celiac disease is an immune-mediated enteropathy characterized with high heterogeneity in presentation among genetically predisposed individuals. In recent years, a change in the phenotypic presentation of celiac disease has been reported. We studied clinical presentation, from 1960 through 2015, in Ireland, which has a high incidence of celiac disease. METHODS: We performed a retrospective analysis of medical charts from patients diagnosed with celiac disease at 5 secondary referral centers in Ireland from 1960 through 2015 (n = 749; median age, 56 years; age range, 18-91 years). The cohort was divided into 5 groups based on year of diagnosis (≤1985, 1986-1995, 1996-2005, 2006-2010, or 2011 and later). We collected findings from clinical presentation at diagnosis; serology tests; small intestinal biopsy analyses; and patients' demographic, clinical, and family data. Presentations at diagnosis were classified according to the Oslo criteria as follows: classical (patients presenting with malabsorption), nonclassical (no signs or symptoms of malabsorption at presentation), or subclinical (below the threshold of clinical detection). The primary outcome was change in clinical presentation of celiac disease over time. RESULTS: Of the 749 patients studied, 512 were female and 237 were male (ratio of 2.2:1). Female patients were diagnosed at younger ages than male patients (42 vs 47 years, respectively; P = .004), and had more immune-mediated conditions than male patients (35.7% for female patients vs 21.5% for male patients; P < .001). For patients diagnosed as adults (after the age of 18 years), the median age of diagnosis increased from 34.0 years during the period ≤1985 to median ages of 44-46 years after 1985 (P < .002). A smaller proportion of patients presented with classical features of celiac disease after 2010 (48.4%) than ≤1985 (85.2%); the proportion of patients with nonclassical or subclinical celiac disease increased from 14.8% ≤1985 to 51.6% after 2010 (P = .006 for each). Biopsies categorized as Marsh 3c decreased, from 52.2% in the period 1996-2005 to 22.5% in the period after 2010 (P = .003). The prevalence of associated thyroid disease has decreased during the study period, from 36.6% ≤1985 to 17.1% after 2010 (P = .039), whereas body mass index at diagnosis increased from 21.5 kg/m2 ≤1985 to 24.8 kg/m2 after 2010 (P < .001). CONCLUSIONS: We found the clinical presentation of celiac disease changed significantly in Ireland from 1960 through 2015. The age of presentation in adulthood increased over this time period, as did the proportions of patients with nonclassical or subclinical disease.

Characterizing Zinc Speciation in Soils from a Smelter-Affected Boreal Forest Ecosystem.

HudBay Minerals, Inc., has mined and/or processed Zn and Cu ore in Flin Flon, MB, Canada, since the 1930s. The boreal forest ecosystem and soil surrounding these facilities have been severely impacted by mixed metal contamination and HSO deposition. Zinc is one of the most prevalent smelter-derived contaminants and has been identified as a key factor that may be limiting revegetation. Metal toxicity is related to both total concentrations and speciation; therefore, X-ray absorption spectroscopy and X-ray fluorescence mapping were used to characterize Zn speciation in soils throughout the most heavily contaminated areas of the landscape. Zinc speciation was linked to two distinct soil types. Group I soils consist of exposed soils in weathered positions of bedrock outcrops with Zn present primarily as franklinite, a (ZnFeO) spinel mineral. Group II soils are stabilized by an invasive metal-tolerant grass species, with Zn found as a mixture of octahedral (Fe oxides) and tetrahedral Mn oxides) adsorption complexes with a franklinite component. Soil erosion influences Zn speciation through the redistribution of Zn and soil particulates from Group I landscape positions to Group II soils. Despite Group II soils having the highest concentrations of CaCl-extractable Zn, they support metal-tolerant plant growth. The metal-tolerant plants are probably preferentially colonizing these areas due to better soil and nutrient conditions as a result of soil deposition from upslope Group I areas. Zinc concentration and speciation appears to not influence the colonization by metal-tolerant grasses, but the overall soil properties and erosion effects prevent the revegetation by native boreal forest species.

Effects of Dolomitic Limestone Application on Zinc Speciation in Boreal Forest Smelter-Contaminated Soils.

Anthropogenic activities at the HudBay Minerals, Inc., Flin Flon (Manitoba, Canada) mining and processing facility have severely affected the surrounding boreal forest ecosystem. Soil contamination occurred via a combination of metal and sulfuric acid deposition and has resulted in forest dieback and ineffective natural recovery. A community-led effort to revegetate areas of the landscape through the application of a dolomitic limestone has been met with varied success. Zinc (Zn) speciation has shown to be closely linked to the presence or absence of an invasive metal-tolerant grass species, with soils being broadly classed into two revegetation response groups. Group I, characterized by the absence of metal-tolerant grasses, and group II, characterized by the presence of metal-tolerant grasses. The systematic approach used to lime areas of the landscape produced a liming chronosequence for each group. This study used a combination of X-ray absorption spectroscopy, X-ray fluorescence mapping, and X-ray diffraction techniques to determine the effect of liming on Zn speciation in these chronosequences. Liming group I soils resulted in the formation of a neo-phase Zn-Al-hydroxy interlayer coprecipitate and subsequent rapid boreal forest revegetation. The effect of liming on Zn speciation on the group II soils resulted in a gradual transition of increasingly stable adsorption species, culminating with a stable Zn-Al-layered double hydroxide precipitate. Boreal forest vegetation has failed to recolonize group II soils during the study. However, the formation of the layered double hydroxide species resulted in a significant reduction in CaCl-extractable Zn. Further research is required to determine how to promote the revegetation of these soils.

The second Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of Helicobacter pylori infection in adult patients in Ireland.

BACKGROUND: There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori ( H. pylori ) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies. OBJECTIVE: The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting. METHODS: The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12). CONCLUSION: These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Thiol-ene click reaction as a general route to functional trialkoxysilanes for surface coating applications.

Functionalized trialkoxysilanes are widely used to modify the surface properties of materials and devices. It will be shown that the photoinitiated radical-based thiol-ene "click" reaction provides a simple and efficient route to diverse trialkoxysilanes. A total of 15 trialkoxysilanes were synthesized by reacting either alkenes with 3-mercaptopropyltrialkoxysilane or thiols with allyltrialkoxysilanes in the presence of a photoinitiator. The functionalized trialkoxysilanes were obtained in quantitative to near-quantitative yields with high purity. The photochemical reactions can be run neat in standard borosilicate glassware using a low power 15-W blacklight. A wide range of functional groups is tolerated in this approach, and even complex alkenes click with the silane precursors. To demonstrate that these silanes can be used as surface coating agents, several were reacted with iron oxide superparamagnetic nanoparticles and the loadings quantified. The photoinitiated thiol-ene reaction thus offers a facile and efficient method for preparing surface-active functional trialkoxysilanes.

Contribution of crop residue, soil, and fertilizer nitrogen to nitrous oxide emissions varies with long-term crop rotation and tillage.

Agriculture is an important contributor to N2O emissions - a potent greenhouse gas - with high peaks occurring when soil mineral nitrogen (N) is high (e.g., after mineralization of organic N and N fertilizer application). Nitrogen dynamics in soil and consequently N2O emissions are affected by crop and soil management practices (e.g., crop rotation and tillage), an effect mostly assessed in the literature through comparisons of total N2O emission. Hence, information is scarce on the effect of these management practices on specific N sources affecting N2O emissions (i.e., N fertilizer, soil, above and belowground crop residues) - a knowledge gap explored in this study with the use of 15N tracers. The isotope approach enabled refinement on global N2O budget by directly determining the emission factors (EF) of above and belowground crop residues that vary in chemical composition and comparison with default EF values (e.g., IPCC EFs). Our experiment was conducted over the full-cycle of long-term crop rotations to (i) compare N2O totals and intensity, under no-tillage and conventional tillage, simple and diverse rotation; (ii) partition total N2O emissions into soil, N fertilizer, above and belowground crop residue N sources; (iii) compare the 12-month EF of crop residue against the default values proposed by IPCC (2019). For the tillage effect, annual N2O emissions were from 1.2- to 2.0-times higher on CT than NT soil due to 40% increased soil N derived N2O emission in CT. The diversified crop rotation emitted 1.3-times higher N2O than the simple rotation over the full-cycle of the rotations, but the effect was due to differences in N fertilizer rate between the rotations since emissions were equivalent when scaled by N rate. Finally, our results suggested that default IPCC EF are overestimated for crop residues under CT and NT, simple and diverse rotations as measured EFs never surpassed 0.1%.

Sociodemographic variables as predictors of adverse outcome in SARS-CoV-2 infection: an Irish hospital experience.

INTRODUCTION: Our hospital found itself at the epicentre of the Irish COVID-19 pandemic. We describe the organisational challenges faced in managing the surge and identified risk factors for mortality and ICU admission among hospitalised SARS-CoV-2-infected patients. METHODS: All hospitalised SARS-CoV-2 patients diagnosed between March 13 and May 1, 2020, were included. Demographic, referral, deprivation, ethnicity and clinical data were recorded. Multivariable regression, including age-adjusted hazard ratios (HR (95% CI), was used to explore risk factors associated with adverse outcomes. RESULTS: Of 257 inpatients, 174 were discharged (68%) and 39 died (15%) in hospital. Two hundred three (79%) patients presented from the community, 34 (13%) from care homes and 20 (8%) were existing inpatients. Forty-five percent of community patients were of a non-Irish White or Black, Asian or minority ethnic (BAME) population, including 34 Roma (13%) compared to 3% of care home and 5% of existing inpatients, (p < 0.001). Twenty-two patients were healthcare workers (9%). Of 31 patients (12%) requiring ICU admission, 18 were discharged (58%) and 7 died (23%). Being overweight/obese HR (95% CI) 3.09 (1.32, 7.23), p = 0.009; a care home resident 2.68 (1.24, 5.6), p = 0.012; socioeconomically deprived 1.05 (1.01, 1.09), p = 0.012; and older 1.04 (1.01, 1.06), p = 0.002 were significantly associated with death. Non-Irish White or BAME were not significantly associated with death 1.31 (0.28, 6.22), p = 0.63 but were significantly associated with ICU admission 4.38 (1.38, 14.2), p = 0.014 as was being overweight/obese 2.37 (1.37, 6.83), p = 0.01. CONCLUSION: The COVID-19 pandemic posed unprecedented organisational issues for our hospital resulting in the greatest surge in ICU capacity above baseline of any Irish hospital. Being overweight/obese, a care home resident, socioeconomically deprived and older were significantly associated with death, while ethnicity and being overweight/obese were significantly associated with ICU admission.

Repeat-pulse 13CO2 labeling of canola and field pea: implications for soil organic matter studies.

Both the quantity and quality of plant residues can impact soil properties and processes. Isotopic tracers can be used to trace plant residue decomposition if the tracer is homogeneously distributed throughout the plant. Continuous labeling will homogeneously label plants but is not widely accessible because elaborate equipment is needed. In order to determine if the more accessible repeat-pulse labeling method could be used to trace plant residue decomposition, this labeling procedure was employed using (13)CO(2) to enrich field pea and canola plants in a controlled environment. Plants were exposed weekly to pulses of 33 atom% (13)CO(2) and grown to maturity. The distribution of the label throughout the plant parts (roots, stem, leaves, and pod) and biochemical fractions (ADF and ADL) was determined. The label was not homogeneously distributed throughout the plant; in particular, the pod fractions were less enriched than other fractions indicating the importance of continuing labeling well into plant maturity for pod-producing plants. The ADL fraction was also less enriched than the ADF fraction. Because of the heterogeneity of the label throughout the plant, caution should be applied when using the repeat-pulse method to trace the fate of (13)C-labeled residues in the soil. However, root contributions to below-ground C were successfully determined from the repeat-pulse labeled root material, as was (13)C enrichment of soil within the top 15 cm. Canola contributed more above- and below-ground residue C than field pea; however, canola was also higher in ADF and ADL fractions indicating a more recalcitrant residue.

Graphoepitaxial assembly of asymmetric ternary blends of block copolymers and homopolymers.

Ternary blends of cylinder-forming polystyrene-block-poly(methyl methacrylate) block copolymers and polystyrene and poly(methyl methacrylate) homopolymers were assembled in trench features of constant width. Increasing the fraction of homopolymer in the blend increased the spacing and size of block copolymer domains, which were oriented perpendicular to the substrate to form a hexagonal lattice within the trench. The number of rows of cylinders within the trench was controlled by the blend composition. Depending on the domain size and spacing, the hexagonal lattice was stretched or compressed perpendicular to the trench walls but not perturbed parallel to the walls, indicating a decoupling of the perturbation in the perpendicular and parallel directions. The row spacing was uniform across the trench as a function of position from the trench wall. The results are compared with an analytical model and with Monte Carlo simulations.

Prevalence of coexisting autoimmune thyroidal diseases in coeliac disease is decreasing.

BACKGROUND: Coeliac disease (CD) is associated with an increased risk of other immune-mediated conditions. Aim: To investigate the prevalence of coexistent immune-mediated diseases in CD patients, and changes in the prevalence of autoimmune thyroidal diseases over the last 50 years. METHODS: Medical record data were collected retrospectively from 749 CD patients in Ireland. Prevalence of autoimmune diseases was compared with previously published results from general populations. Patients were divided into four groups based on the year of diagnosis to analyse changes in the prevalence of autoimmune thyroidal disease over time. RESULTS: Median age at the time of CD diagnosis was 56 years (range 18-91 years). A total of 233 (31.1%) patients had a coexistent immune-mediated condition (IMC). Autoimmune thyroidal diseases were seen in 149 (19.9%) patients, hypothyroidism in 110 (14.7%), type 1 diabetes in 27 (3.6%), psoriasis in 20 (2.7%), inflammatory bowel disease in 14 (1.9%) and rheumatoid arthritis in 12 (1.6%). All conditions were more common in CD patients than in the general population. Type 1 diabetes was diagnosed mainly before CD, whereas there was no such trend in other conditions. Autoimmune thyroidal diseases became less common in female CD patients over time. CONCLUSIONS: Prevalence of autoimmune diseases is increased in adult CD patients compared with the general population. However, concomitant autoimmune thyroidal diseases became less common over time in women.

Integration of racial, cultural, ethnic, and socioeconomic factors into a gastrointestinal pathophysiology course.

BACKGROUND & AIMS: Our study describes a faculty development program to encourage the integration of racial, cultural, ethnic, and socioeconomic factors such as obesity, inability to pay for essential medications, the use of alternative medicine, dietary preferences, and alcoholism in a gastrointestinal pathophysiology course. METHODS: We designed a 1-hour faculty development session with longitudinal reinforcement of concepts. The session focused on showing the relevance of racial, ethnic, cultural, and socioeconomic factors to gastrointestinal diseases, and encouraged tutors to take an active and pivotal role in discussion of these factors. The study outcome was student responses to course evaluation questions concerning the teaching of cultural and ethnic issues in the course as a whole and by individual tutorials in 2004 (pre-faculty development) and in 2006 to 2008 (post-faculty development). RESULTS: Between 2004 and 2008, the proportion of students reporting that "Issues of culture and ethnicity as they affect topics in this course were addressed" increased significantly (P = .000). From 2006 to 2008, compared with 2004, there was a significant increase in the number of tutors who "frequently" taught culturally competent care according to 60% or greater of their tutorial students (P = .003). The tutor's age, gender, prior tutor experience, rank, and specialty did not significantly impact results. CONCLUSIONS: An innovative faculty development session that encourages tutors to discuss racial, cultural, ethnic, and socioeconomic issues relevant to both care of the whole patient and to the pathophysiology of illness is both effective and applicable to other preclinical and clinical courses.

Study on the combined effects of solvent evaporation and polymer flow upon block copolymer self-assembly and alignment on topographic patterns.

Microphase separation of a polystyrene-block-polyisoprene-block-polystyrene triblock copolymer thin film under confined conditions (i.e., graphoepitaxy) results in ordered periodic arrays of polystyrene cylinders aligned parallel to the channel side-wall and base in a polyisoprene matrix. Polymer orientation and translational ordering with respect to the topographic substrate were elucidated by atomic force microscopy (AFM) while film thickness and polymer profile within the channel were monitored by cross-sectional transmission electron microscopy (TEM) as a function of time over a 6 h annealing period at 120 degrees C. Upon thermal annealing, the polymer film simultaneously undergoes three processes: microphase separation, evaporation of trapped solvent, and mass transport of polymer from the mesas into the channels. A significant volume of solvent is trapped within the polymer film upon spin coating arising from the increased polymer/substrate interfacial area due to the topographic pattern. Mass transport of polymer during this process results in nonuniform films, where subtle changes in the film thickness within the channel have profound effects on the microphase separation process. The initially disordered structure within the film underwent an orientation transition via an intermediate formation of perpendicular cylinders (nonequilibrium) to a parallel (equilibrium) orientation with respect to the channel base. Herein, we present a time-resolved study of the cylinder reorientation process detailing how changing film thickness during the annealing process dramatically affects both the local and lateral orientation of the observed structure. Finally, a brief mathematical model is provided to evaluate spin coating over a complex topography following a classical asymptotic approximation of the Navier-Stokes equations for the as-deposited films.

Depth of interaction calibration for PET detectors with dual-ended readout by PSAPDs.

Many laboratories develop depth-encoding detectors to improve the trade-off between spatial resolution and sensitivity in positron emission tomography (PET) scanners. One challenge in implementing these detectors is the need to calibrate the depth of interaction (DOI) response for the large numbers of detector elements in a scanner. In this work, we evaluate two different methods, a linear detector calibration and a linear crystal calibration, for determining DOI calibration parameters. Both methods can use measurements from any source distribution and location, or even the intrinsic lutetium oxyorthosilicate (LSO) background activity, and are therefore well suited for use in a depth-encoding PET scanner. The methods were evaluated by measuring detector and crystal DOI responses for all eight detectors in a prototype depth-encoding PET scanner. The detectors utilize dual-ended readout of LSO scintillator arrays with position-sensitive avalanche photodiodes (PSAPDs). The LSO arrays have 7 x 7 elements, with a crystal size of 0.92 x 0.92 x 20 mm(3) and pitch of 1.0 mm. The arrays are read out by two 8 x 8 mm(2) area PSAPDs placed at opposite ends of the arrays. DOI is measured by the ratio of the amplitude of the total energy signals measured by the two PSAPDs. Small variations were observed in the DOI responses of different crystals within an array as well as DOI responses for different arrays. A slightly nonlinear dependence of the DOI ratio on depth was observed and the nonlinearity was larger for the corner and edge crystals. The DOI calibration parameters were obtained from the DOI responses measured in a singles mode. The average error between the calibrated DOI and the known DOI was 0.8 mm if a linear detector DOI calibration was used and 0.5 mm if a linear crystal DOI calibration was used. A line source phantom and a hot rod phantom were scanned on the prototype PET scanner. DOI measurement significantly improved the image spatial resolution no matter which DOI calibration method was used. A linear crystal DOI calibration provided slightly better image spatial resolution compared with a linear detector DOI calibration.

Experimental characterization and system simulations of depth of interaction PET detectors using 0.5 mm and 0.7 mm LSO arrays.

Small animal PET scanners may be improved by increasing the sensitivity, improving the spatial resolution and improving the uniformity of the spatial resolution across the field of view. This may be achieved by using PET detectors based on crystal elements that are thin in the axial and transaxial directions and long in the radial direction, and by employing depth of interaction (DOI) encoding to minimize the parallax error. With DOI detectors, the diameter of the ring of the PET scanner may also be decreased. This minimizes the number of detectors required to achieve the same solid angle coverage as a scanner with a larger ring diameter and minimizes errors due to non-collinearity of the annihilation photons. In this study, we characterize prototype PET detectors that are finely pixelated with individual LSO crystal element sizes of 0.5 mm x 0.5 mm x 20 mm and 0.7 mm x 0.7 mm x 20 mm, read out at both ends by position sensitive avalanche photodiodes (PSAPDs). Both a specular reflector and a diffuse reflector were evaluated. The detectors were characterized based on the ability to clearly resolve the individual crystal elements, the DOI resolution and the energy resolution. Our results indicate that a scanner based on any of the four detector designs would offer improved spatial resolution and more uniform spatial resolution compared to present day small animal PET scanners. The greatest improvements to spatial resolution will be achieved when the detectors employing the 0.5 mm x 0.5 mm x 20 mm crystals are used. Monte Carlo simulations were performed to demonstrate that 2 mm DOI resolution is adequate to ensure uniform spatial resolution for a small animal PET scanner geometry using these detectors. The sensitivity of such a scanner was also simulated using Monte Carlo simulations and was shown to be greater than 10% for a four ring scanner with an inner diameter of 6 cm, employing 20 detectors per scanner ring.

A study of the timing properties of position-sensitive avalanche photodiodes.

In this paper, we study position-dependent timing shifts and timing resolution in position sensitive avalanche photodiodes (PSAPDs) and their effects on the coincidence window used in positron emission tomography (PET) systems using these devices. There is a delay in PSAPD signals that increases as the excitation position moves from the corner to the center of the device and the timing resolution concurrently worsens. The difference in timing between the center and the corner can be up to 30.7 ns for a 14 x 14 mm(2) area PSAPD. This means that a PSAPD-based PET system could require a very wide coincidence timing window (>60 ns) if this effect is not corrected, although the individual crystal pairs still have full-width half-maximum (FWHM) timing resolutions better than 7.4 ns. In addition to characterizing the timing properties of PSAPDs, two correction methods were developed and applied to data from a pair of PSAPD detectors. These two timing offset corrections reduced the timing shift of a crystal pair from 52.4 ns to 9.7 ns or 1.3 ns, improved the FWHM timing resolution of the detector pair from 24.6 ns to 9.5 ns or 6.0 ns and reduced the timing window (sufficient to cover at least twice the FWHM for all crystal pairs) from 65.1 ns to 22.0 ns or 15.2 ns, respectively. A two-step timing alignment method is proposed for a PET system consisting of multiple PSAPDs. Lastly, the effect of PSAPD size on the timing performance was also evaluated.

PET Performance Evaluation of an MR-Compatible PET Insert.

A magnetic resonance (MR) compatible positron emission tomography (PET) insert has been developed in our laboratory for simultaneous small animal PET/MR imaging. This system is based on lutetium oxyorthosilicate (LSO) scintillator arrays with position-sensitive avalanche photodiode (PSAPD) photodetectors. The PET performance of this insert has been measured. The average reconstructed image spatial resolution was 1.51 mm. The sensitivity at the center of the field of view (CFOV) was 0.35%, which is comparable to the simulation predictions of 0.40%. The average photopeak energy resolution was 25%. The scatter fraction inside the MRI scanner with a line source was 12% (with a mouse-sized phantom and standard 35 mm Bruker 1H RF coil), 7% (with RF coil only) and 5% (without phantom or RF coil) for an energy window of 350-650 keV. The front-end electronics had a dead time of 390 ns, and a trigger extension dead time of 7.32 µs that degraded counting rate performance for injected doses above ~0.75 mCi (28 MBq). The peak noise-equivalent count rate (NECR) of 1.27 kcps was achieved at 290 µCi (10.7 MBq). The system showed good imaging performance inside a 7-T animal MRI system; however improvements in data acquisition electronics and reduction of the coincidence timing window are needed to realize improved NECR performance.

Chemical interactions and their role in the microphase separation of block copolymer thin films.

The thermodynamics of self-assembling systems are discussed in terms of the chemical interactions and the intermolecular forces between species. It is clear that there are both theoretical and practical limitations on the dimensions and the structural regularity of these systems. These considerations are made with reference to the microphase separation that occurs in block copolymer (BCP) systems. BCP systems self-assemble via a thermodynamic driven process where chemical dis-affinity between the blocks driving them part is balanced by a restorative force deriving from the chemical bond between the blocks. These systems are attracting much interest because of their possible role in nanoelectronic fabrication. This form of self-assembly can obtain highly regular nanopatterns in certain circumstances where the orientation and alignment of chemically distinct blocks can be guided through molecular interactions between the polymer and the surrounding interfaces. However, for this to be possible, great care must be taken to properly engineer the interactions between the surfaces and the polymer blocks. The optimum methods of structure directing are chemical pre-patterning (defining regions on the substrate of different chemistry) and graphoepitaxy (topographical alignment) but both centre on generating alignment through favourable chemical interactions. As in all self-assembling systems, the problems of defect formation must be considered and the origin of defects in these systems is explored. It is argued that in these nanostructures equilibrium defects are relatively few and largely originate from kinetic effects arising during film growth. Many defects also arise from the confinement of the systems when they are 'directed' by topography. The potential applications of these materials in electronics are discussed.

Measurement of the IgM and IgG Autoantibody Immune Responses in Human Serum has High Predictive Value for the Presence of Colorectal Cancer.

INTRODUCTION: Colorectal cancer is a major public health issue, with incidences continuing to rise owing to the growing and aging world population. Current screening strategies for colorectal cancer diagnosis suffer from various limitations, including invasiveness and poor uptake. Consequently, there is an unmet clinical need for a minimally invasive, sensitive, and specific method for detecting the presence of colorectal cancer and pre-malignant lesions. PATIENTS AND METHODS: An indirect enzyme-linked immunosorbent assay was used to measure the primary (IgM) and secondary (IgG) adaptive humoral immune responses to a panel of previously identified cancer antigens in the sera of normal and adenoma samples, and sera from patients with colorectal cancer. RESULTS: An optimal panel of 7 biomarkers capable of identifying patients with colorectal cancer as distinct from both normal and adenoma samples is identified. The cumulative sensitivity and specificity of the assay are 70.8% and 86.5%, respectively. The positive and negative predictive values of the cohort are 77.3% and 82.1%. This assay was not able to accurately discriminate between normal and adenoma samples. Patients whose serum was positive for the presence of anti-ICLN IgM autoantibodies had a significantly poorer 5-year survival than patients whose serum was negative (P = .004). CONCLUSION: This study describes a novel minimally invasive enzyme-linked immunosorbent assay-based method, capable of identifying patients with colorectal cancer as distinct from both normal and adenoma samples. Patients are likely to be far more amenable to a blood-based test such as the one described herein, rather than a fecal-based test, likely leading to increased patient uptake.