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Staphylococcus aureus is associated with significant mortality and increased burden on the healthcare system. Relatively few reliable estimates are available regarding the impact of meticillin-resistant S. aureus (MRSA) infection compared with meticillin-susceptible S. aureus (MSSA) infection.To compare patients with MRSA infection and MSSA infection to identify differences in inpatient mortality, length of stay and costs of hospital services, and identify predictors of MRSA as a cause of S. aureus infection.An analytical, retrospective, longitudinal study using non-identifiable linked data on adults admitted to hospitals of a health district in Australia with a diagnosis of S. aureus infection over a 10-year period. The main outcome measure was 30-day inpatient mortality. Secondary endpoints included total overnight stays, all-cause inpatient mortality, and hospitalization costs within 1 year of index admission.Inpatient mortality at 30, 100 and 365 days was estimated to be significantly greater for patients with MRSA infection. The mean additional cost of MRSA infection when controlling for additional factors was $5988 and 4 nights of additional hospital stay per patient within 1 year of index admission. Key predictors of MRSA infection were: date of index admission; higher comorbidity score; greater socio-economic disadvantage; admission to hospital other than via the emergency department; older age; and prior admission to hospital within 28 days of index admission.MRSA infection is associated with increased inpatient mortality, costs and hospital length of stay compared with MSSA infection. Efforts are required to alleviate the additional burden of MRSA infection on patients and healthcare systems.

An often-overlooked aspect of human missions to Mars is that the optimal path to the Red Planet could include a flyby of Venus. As part of so-called opposition missions, a crewed spacecraft would, after departing Earth, approach Venus en route to Mars. Such Venus flybys would offer unique opportunities to practice deep-space human operations during phases of flight for which a direct return to Earth would be a viable abort option. Indeed, crewed flyby missions to Venus provide a basis for longer-duration human spaceflight activities before committing to longer-duration and lower-launch-cadence missions solely to Mars. During Venus flybys, astronauts bound for Mars could carry out opportunistic “human-in-the-loop” scientific activities, such as controlling an aerial platform or directing in situ sampling by a landed spacecraft for much lower cost than a dedicated crewed mission to Venus. An independent crewed Venus flyby could also serve as a useful systems demonstration mission prior to a first human mission to Mars. With a renewed focus on landing humans on Mars in the 2030s and the formidable challenges still ahead for safe and successful long-duration human spaceflight, the time to consider incorporating Venus on the path to Mars is now.

Mercury's surface preserves a rich history of volcanism, impact cratering, and tectonic deformation. Geological observations show that the earliest evidence of thrust faulting that was induced by the secular cooling and resulting global contraction of the planet coincided with the waning stages of effusive volcanism, but that explosive volcanism continued beyond this point. Stresses from global contraction, however, would have precluded efficient vertical magma ascent. Sites of pyroclastic activity—manifest as irregular depressions surrounded by diffuse, spectrally distinct halos—spatially coincide with lithospheric discontinuities, such as faults or those associated with impact craters. The vast majority of explosive vents are situated on the floors, rims, central peaks, or peak rings of impact structures. A substantial portion of such vents is also proximal to thrust faults: they are most spatially concentrated at or within 20 km of faults, with ever fewer vents progressively farther from tectonic structures. We statistically evaluated the spatial distribution of sites of pyroclastic activity with respect to faults and impact craters by generating sets of random point locations of equal count to those volcanic sites, computing their spatial relationship to the mapped faults and craters, and comparing them to our observations. We find that although the observed proximity of vents to faults is indistinguishable from a random distribution, their spatial association with impact craters is non-random. To examine the interrelatedness of several geospatial relationships of lithospheric weaknesses and pyroclastic activity, we performed a principal component analysis that tested correlations between vent size, the presence of vents within a crater, the diameters and degradation states of those craters, and vent distance from mapped faults, which help tie together interpretations of magma volumes and eruption energies, repeated utilization of magma pathways, and durations of eruptive events in the geological context of global contraction. Results reveal a predominance of small-sized vents indicative of short-lived, low-volume pyroclastic activity that are consistent with suppressed volcanism after the onset of global contraction. Greater size ranges of vents are found in large impact craters and when faults are nearby, which points to denser fracture networks facilitating magma ascent.

The inhibitory tone that the cerebellum exerts on the primary motor cortex (M1) is known as cerebellar brain inhibition (CBI). Studies show CBI to be relevant to several motor functions, including adaptive motor learning and muscle control. CBI can be assessed noninvasively via transcranial magnetic stimulation (TMS) using a double-coil protocol. Variability in parameter choice and controversy surrounding the protocol's ability to isolate the cerebellothalamocortical pathway casts doubt over its validity in neuroscience research. This justifies a systematic review of both the protocol, and its application. The following review examines studies using the double-coil protocol to assess CBI in healthy adults. Parameters and CBI in relation to task-based studies, other non-invasive protocols, over different muscles, and in clinical samples are reviewed. Of the 1398 studies identified, 24 met selection criteria. It was found that methodological design and selection of parameters in several studies may have reduced the validity of outcomes. Further systematic testing of CBI protocols is warranted, both from a parameter and task-based perspective.

Both endogenic and exogenic formation mechanisms have been proposed for the equatorial ridge on Saturn's moon Iapetus. With photogeological mapping and crater statistics, we find that the morphology of the ridge is best explained by an exogenic origin, principally by the accretion onto the moon's surface of an orbiting ring of material.

The first author acknowledges funding from an Initiative d’Excellence (IDEX) “Attractivité” grant (VOLPERM), funded by the University of Strasbourg. M.H. also acknowledges support from the CNRS (INSU 2016-TelluS-ALEAS). Surface gravitational acceleration (surface gravity) on Mars, the second-smallest planet in the Solar System, is much lower than that on Earth. A direct consequence of this low surface gravity is that lithostatic pressure is lower on Mars than on Earth at any given depth. Collated published data from deformation experiments on basalts suggest that, throughout its geological history (and thus thermal evolution), the Martian brittle lithosphere was much thicker but weaker than that of present-day Earth as a function solely of surface gravity. We also demonstrate, again as a consequence of its lower surface gravity, that the Martian lithosphere is more porous, that fractures on Mars remain open to greater depths and are wider at a given depth, and that the maximum penetration depth for opening-mode fractures (i.e., joints) is much deeper on Mars than on Earth. The result of a weak Martian lithosphere is that dykes—the primary mechanism for magma transport on both planets—can propagate more easily and can be much wider on Mars than on Earth. We suggest that this increased the efficiency of magma delivery to and towards the Martian surface during its volcanically active past, and therefore assisted the exogeneous and endogenous growth of the planet's enormous volcanoes (the heights of which are supported by the thick Martian lithosphere) as well as extensive flood-mode volcanism. The porous and pervasively fractured (and permeable) nature of the Martian lithosphere will have also greatly assisted the subsurface storage of and transport of fluids through the lithosphere throughout its geologically history. And so it is that surface gravity, influenced by the mass of a planetary body, can greatly modify the mechanical and hydraulic behaviour of its lithosphere with manifest differences in surface topography and geomorphology, volcanic character, and hydrology. Postprint

RESUMO - Introdução: Consideradas como um problema crónico de saúde, as perturbações psiquiátricas apresentam uma elevada prevalência em termos de não-adesão ao tratamento. Métodos: Revisão narrativa, não sistemática, da literatura relevante. Resultados: A maioria dos trabalhos de investigação tem incidido sobre os fatores relacionados com o doente que interferem na adesão ao tratamento. No entanto, existem estudos que indicam que a responsabilidade para aumentar a adesão está mais relacionada com o profissional de saúde do que com o doente. Conclusões: Através da identificação de fatores relacionados com os clínicos, pretendemos possibilitar o desenvolvimento de competências que poderão ter um papel importante na adesão ao tratamento dos doentes com perturbações psiquiátricas. ABSTRACT - Introduction: Among the chronic health diseases are psychiatric disorders and it is well established that within this population there is a particularly high prevalence of non-adherence to treatment. Methods: Narrative review, of relevant literature. Results: The majority of the research has focused primarily on the factors related to the patient that interfere with treatment adherence. However, there are studies that seem to indicate that the responsibility for increasing adherence is more related with the health professional than the patient. Conclusions: Through the identification of factors associated with clinicians, we enable the development strategies to increase skills in mental health professionals and that may have an important role in the treatment of patients with psychiatric disorders. info:eu-repo/semantics/publishedVersion

Mare Crisium is composed of a set of volcanic deposits situated in an impact basin on the Moon's near side. The topography of the mare is dominated by an annulus of elevated topography, the inner edge of which is delineated by basin-concentric wrinkle ridges. From a combination of remotely sensed image and topographic data and numerical modeling, we show that the thrust faults that underlie these ridges penetrate up to 20 km in depth, considerably below the base of the mare deposits themselves. Thrust faults of this scale have not heretofore been recognized on the Moon. Mare Crisium sits above a region of uplifted mantle, which contributes to a mass excess beneath the basin, and we demonstrate by comparison with free-air gravity anomaly and derived crustal thickness data for Crisium that the thrust faults structurally bound this elevated mantle material. By means of finite-element models of stresses induced by lithospheric loading within the basin, we argue that the deep-seated thrusts may have been localized by the boundary between the superisostatic mantle material and a sub-isostatic collar of thickened crust that resulted from basin formation and modification shortly after impact. Importantly, numerous other mare-filled mascon basins on the Moon share the same topographic and tectonic characteristics as Crisium, suggesting that they, too, are underlain by deep-seated thrust faults that formed in a similar manner.

We have mapped the major-element composition of Mercury's surface from orbital MESSENGER X-Ray Spectrometer measurements. These maps constitute the first global-scale survey of the surface composition of a Solar System body conducted with the technique of planetary X-ray fluorescence. Full maps of Mg and Al, together with partial maps of S, Ca, and Fe, each relative to Si, reveal highly variable compositions (e.g., Mg/Si and Al/Si range over 0.1–0.8 and 0.1–0.4, respectively). The geochemical variations that we observe are consistent with those inferred from other MESSENGER geochemical remote sensing datasets, but they do not correlate well with units mapped previously from spectral reflectance or morphology. Location-dependent, rather than temporally evolving, partial melt sources were likely the major influence on the compositions of the magmas that produced different geochemical terranes. A large ( > 5 × 10 6 km 2 ) region with the highest Mg/Si, Ca/Si, and S/Si ratios, as well as relatively thin crust, may be the site of an ancient and heavily degraded impact basin. The distinctive geochemical signature of this region could be the consequence of high-degree partial melting of a reservoir in a vertically heterogeneous mantle that was sampled primarily as a result of the impact event.

Mercury's global tectonic history is thought to have been dominated by two major processes: tidal despinning and global contraction. Each process is expected to have produced a distinctive global stress field and resultant fault pattern. Thousands of thrust-fault-related landforms documented on Mercury can be attributed to global contraction, but no global signature of tidal despinning has been conclusively documented. Because global contraction operated throughout an extended portion of Mercury's geologic history, any tidal despinning pattern either would have formed together with global contraction, or would have been modified by global contraction after despinning was complete. Here, we reassess global fracture patterns predicted to result from tidal despinning and from a combination of tidal despinning and global contraction. We specifically make use of rock strength and deformability parameters appropriate for Mercury's fractured lithosphere. Results indicate that a tidal despinning pattern would consist only of a global set of opening-mode fractures (joints) in the upper part of the lithosphere, whereas the combination of tidal despinning and global contraction would have produced a global population of thrust faults, with no preferred orientations in the polar regions but with an increasing preference for north–south orientations toward the equator. If an equatorial bulge from an early state of rapid spin was supported by Mercury's lithosphere, two end-member scenarios for the timing and duration of these two processes may be considered. In one, tidal despinning predated global contraction; in the other, tidal despinning and global contraction overlapped in time. We test the predictions of both scenarios against the distribution and orientations of Mercury's tectonic landforms. The global pattern of thrust faults is generally consistent with predictions for the scenario under which tidal despinning and global contraction temporally overlapped.

Hoarding disorder has a frequent co-occurrence with attention-deficit/hyperactivity disorder (ADHD). An accurate understanding of the comorbidity between hoarding disorder and ADHD remains unclear but is essential to inform appropriate assessment, prevention and treatment approaches. This paper will provide a review of potential comorbidity models and aetiological mechanisms implicated in both disorders in order to inform understanding of the nature of the comorbidity between hoarding disorder and ADHD. A correlated liabilities model is identified that implicates genetic, neurological, and executive functioning factors in the development and maintenance of hoarding symptoms in individuals with ADHD.

Individuals reporting high levels of schizotypal personality traits appear to experience low subjective wellbeing, yet little is known about the underlying mechanisms. The aim of the present study was to examine relationships between schizotypal traits and life satisfaction, and the possible role of negative affect. Two hundred and thirty-five healthy individuals completed the Schizotypal Personality Questionnaire, the Personal Wellbeing Index, and the Depression Anxiety Stress Scales-21. Schizotypal traits were associated with lower overall life satisfaction and satisfaction with specific life domains, and greater negative affect. After controlling for negative affect, global schizotypy and the negative and disorganised schizotypal factors were associated with lower overall life satisfaction. Diminished subjective wellbeing appears to be characteristic along the continuum of psychosis, even in individuals reporting subclinical manifestations of schizophrenic-like personality features. The fact that higher schizotypal traits correspond to low life satisfaction above what is explained by negative affective states indicates that there are other factors contributing to this relationship. Neurocognition and social cognition are the most obvious candidates for further exploration.

Background Tranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30-day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1-year clinical outcomes. Methods Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery. Results The rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85; 95% confidence interval, 0.64-1.13; P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87; 95% CI, 0.76-1.00; P = .053). Conclusions In this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events.

The Kerguelen Archipelago is part of an oceanic plateau with a complex history. Little work has been done on the tectonics of the onshore areas, even though the extensive outcrop renders the islands especially good for structural work. We present the results of three field campaigns and remote sensing analysis carried out in the main Kerguelen Island, around Val Travers valley and Mt Ross volcano (Central Plateau) and in the Rallier du Baty peninsula (SW part of the archipelago). We have mapped faults, fracture sets, and the location and geometry of intrusive bodies. We found that the plateau basalt lavas that make up most of the area are densely fractured, crossed by many veins, dykes and some small faults. This work provides a general framework for the structure of Kerguelen Archipelago that is dominated by 110°-striking faults and veins, dyke swarms and an alignment of recent central volcanoes, which have formed in N-S to NNW-SSE directed extensional stress field. The other structures are fractures, veins and dykes which strike 130–150°, 000° and 030–050°. They are likely related to transform faults of the Indian oceanic crust and to faults of the north Kerguelen Plateau (offshore basement of the archipelago). These buried structures were likely re-activated by a low magnitude stress field.

Shock is defined as a complex clinical syndrome caused by an acute failure of circulatory function, with depleted tissue and organ perfusion, where delivery of oxygen and substrates to body tissues as well as removal of metabolic waste products are inadequate. The role of the nurse is to be immediately involved in the assessment of patients at risk for developing sepsis and in their treatment. Nurses’ knowledge of evidence-based guidelines can help ensure patients with sepsis can receive therapies, which are based on the latest scientific evidence. The purpose of this article will be to present an overview of the evidence-based recommendations for the treatment of pediatric patients with sepsis, highlighting the role of nursing management.

Ascraeus Mons was one of the first of the Martian volcanoes to be imaged by the High Resolution Stereo Camera (HRSC) experiment onboard the ESA Mars Express spacecraft. These images show much of the volcano at a higher resolution than previously, and details of its lava flows, sinuous rilles, flank vents and tectonic features indicate an unexpected origin for some of these features. We establish the time-stratigraphic sequence for these features, and use a numerical model on HRSC stereo DTMs of the sinuous rilles, and conclude that they were formed by water erosion. Terrestrial analogues for such features are found at Reunion Island and other volcanoes. We then examine the overall structure of the volcano, which is dissimilar to that of large terrestrial volcanoes in important respects, and perform laboratory analogue experiments of its deformation, concluding that the tectonic features were formed by sinking of the volcano into a substratum that was much weaker than the volcanic edifice. An ice-rich substratum melted by a combination of pressure melting and magmatic heating seems the most likely mechanism. Analogous water-escape structures in a similar volcanic situation have been identified at Mt Haddington in the Antarctic. The possible role of a hydrological cycle and a hydrothermal system within the volcano are discussed. Based on field evidence, we propose that much of the broad aprons of lobate flows issuing from the NE and SSW foot of Ascraeus Mons are composed of mudflows rather than lava flows. These different approaches are linked into a coherent history of this volcano. The similarity of Ascraeus Mons to Pavonis Mons and Arsia Mons (though Ascraeus is younger) suggests that some of our conclusions may apply to these volcanoes too.

Attention-Deficit/Hyperactivity Disorder (AD/HD) is the most common psychiatric disorder of childhood, but it is becoming increasingly apparent that more than half the childhood sufferers will continue to manifest symptoms of the disorder as adults. While the EEG of children with AD/HD has been extensively examined, comparatively little research has been conducted into the EEG of adults with the disorder. This study thus investigated the EEG of 20 adult males with AD/HD, and an age- and gender-matched control group, during an eyes-closed resting condition. The EEG was Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. The AD/HD group had significantly less absolute delta and more relative theta, across the entire scalp, than the control group. In absolute beta, the AD/HD group had less power at the midline, and an enhancement in power in the right posterior region. These results are similar to those found in children with AD/HD, and may suggest the presence of a processing deficit. A right posterior elevation in beta activity was also found, which could be related to the ongoing presence of reading disabilities in these subjects.

The objective of this study was to determine the glycemic index (GI) and insulin index (II) of raisins and evaluate if these values are similar in different populations. The study subjects consisted of 10 healthy sedentary individuals (S; age, 25.7 +/- 1.3 years; body mass index [BMI] = 23.3 +/- 1.7 kg/m(2)), 11 aerobically trained adults (A; age, 23.1 +/- 1.0 years; BMI = 24.1 +/- 0.3 kg/m(2)), and 10 prediabetic adults (P; age, 50.0 +/- 2.6 years; BMI = 32.6 +/- 1.9 kg/m(2)). Subjects consumed 50 g of available carbohydrate from raisins and from a glucose solution (reference food) on 2 separate occasions. Serum glucose and insulin concentrations were measured from capillary fingerstick blood samples at baseline and at 15, 30, 45, 60, 90, and 120 minutes (and 150 and 180 minutes for P group) postprandially. The GI of raisins was low (GI, < or = 55) in the S (49.4 +/- 7.4) and P (49.6 +/- 4.8) groups and was moderate (GI, 55-69) in the A group (62.3 +/- 10.5), but there were no differences among the subject groups (P = .437). The II of raisins was 47.3 +/- 9.4, 51.9 +/- 6.5, and 54.4 +/- 8.9 for the S, A, and P groups, respectively. On average, the A group secreted 2- to 2.5-fold less insulin per gram of carbohydrate compared with the S and P groups (P < .05). Thus, raisins are a low to moderate GI food, with a correspondingly low II. The lower insulin response in the A group compared with the other groups suggests enhanced insulin sensitivity.

Bonamia ostreae is an intracellular haplosporidian parasite in European flat oysters Ostrea edulis that occurs on both coasts of the United States and causes significant mortality in Europe. Canada was considered free of B. ostreae until 2004, when it was first detected in O. edulis obtained for laboratory study from a western Canadian oyster farm. Bonamia ostreae was confirmed in O. edulis at the index farm in November 2004 using histopathology, conventional polymerase chain reaction (PCR) assays, restriction fragment length polymorphism (RFLP) analysis, and sequencing of the PCR product. Archived samples of European flat oysters obtained from the index farm between 1999 and 2004 (n = 343) were re-examined and all samples collected before 2003 (n = 306) were confirmed negative for B. ostreae by histopathology (n = 306) and PCR (n = 62). In archived samples from 2003, B. ostreae was detected in 3 of 37 O. edulis by histopathology (n = 2) and/or PCR (n = 2). Also, records indicate that B. ostreae was not detected in O. edulis (n = 348) from five other locations in western Canada between 1986 and 2000. To better understand the distribution and prevalence of B. ostreae in western Canada, 607 oysters from the index farm and 2 additional farms were sampled in the summer of 2005. All 3 farms had been stocked with O. edulis spat from the State of Washington, USA, where B. ostreae is endemic. Samples were analyzed by histopathology and a new real-time PCR that amplifies a 68-bp target DNA fragment. B. ostreae was detected in all three locations, with prevalence ranging from 0.5 to 11.1%. Diagnostic sensitivity of the real-time PCR method was consistently greater than histopathology. Also, preliminary evidence supports the conclusion that real-time PCR on paraffin sections is more sensitive than histopathology; B. ostreae DNA was confirmed in 4 oysters by real-time PCR on paraffin-embedded tissues (and independently confirmed on unfixed tissues) that was not detected by histopathology. As a result of these findings, O. edulis spat are no longer allowed to be imported from endemic areas into Canada.

Establishing project status for large, complex projects is a key concern; particularly so in the aerospace industry where projects are about as complex as they get in modern industry. In practice, project “visibility” lies at the intersection of two disciplines, that of Project Management (PM) and Configuration Management (CM). While project visibility has received a fair amount of attention from the standpoint of PM, its CM counterpart, configuration status accounting (CSA), is not so well explored. The research reported here examines how CSA is carried out in the European aerospace industry where the application of CM is crucial given the safety-critical nature of the products. Through questionnaire survey and case study the research shows limited use of CSA data until the product gets close to release to the customer thus restricting the effectiveness of CM support to project management activities.

One hundred and thirty-nine university students completed measures of schizotypy and subjective well-being (SWB). Inverse associations were found between schizotypy and SWB scores. These results provide evidence that diminished SWB is characteristic along the schizophrenia continuum. Further research is required to determine the mechanisms by which schizotypal individuals experience reduced life satisfaction.

Anger can contribute to offending behaviour and to behavioural difficulties in prison environments. As such, training in self-management of anger has been a common strategy in an attempt to reduce such behaviours. However, the vast majority of research into anger in offenders has been conducted using male participants. This has led to a lack of knowledge specific to the treatment needs of angry female prisoners. This paper investigates the extent to which a sample of Australian female offenders differs from Australian male offenders in their expression and experience of anger. Fifty women and 121 men were given the State-Trait Anger Expression Inventory [Spielberger, C.D. (1991). State-Trait Anger Expression Inventory: STAXI Professional Manual. Florida: Psychological Assessment Resources] and the Novaco Anger Scale [Novaco, R. W. (1994). Anger as a risk factor for violence among the mentally disordered. In J. Monohan, & H. J. Steadman (Eds.), Violence and mental disorder. Chicago: University of Chicago Press]. The data collected from female participants was then contrasted with identical data collected from male inmates in the separate study [Howells, K., Day, A., Bubner, S., Jauncey, S. (2000). Anger needs and treatment responsivity in male prisoners. Unpublished manuscript: University of South Australia.]. Results indicated significant main effects for gender in a majority of the subscales of the two measures, with significant differences found in both the experience and expression of anger for male and female prisoners. The results are discussed in terms of the implications for correctional service providers with respect to the specific psychological needs of female offenders.

Background & Aims Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect. Methods We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods. Results There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began ( P = .003) and the accelerated dosing regimen ( P = .03). Conclusions In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.

DOSE ESCALATION STUDY USING 4D CT PLANNING IN LOCALLY ADVANCED PANCREATIC CANCER G. Radhakrishna1, M. collins1, S. Wilson1, D. Sebag-Montefiore1, B. Carey1, S. Swift1, K. Franks1, J. Lilley2, D. Smith1, S. Kirwin1, R. Lindsay1, H. Summers1, A. Woolley1, P. Byrne1, N. Roberts1, J. Sykes1, A. Needham1, A. M. Crellin1 1 ST JAMES INSTITUTE OF ONCOLOGY THE LEEDS TEACHING HOSPITALS NHS TRUST, Leeds, United Kingdom 2 ST JAMES’S INSTITUTE OF ONCOLOGY, Leeds, United Kingdom

Introduction: Approximately 30% of patients diagnosed with pancreatic cancer will present with locally advanced unresectable disease (LAPC). Improved planning techniques provide the opportunity for dose escalation. Methods: From February 2010 to September 2010, patients with LAPC suitable for CRT were planned using contrast enhanced 4D CT scanning. We compared 4D CT treatment planned according to local protocol using 50.4 Gy (4D50.4) and 55.8 Gy (4D55.8) compared with the NCRN/SCALOP protocol (50.4 Gy SCALOP50.4). Our local protocol defines gross tumour volume (GTV) outlined on all respiratory phases of image sets generated by 4D CT with a radiologist (using the SCALOP study protocol). An internal target volume (ITV) was generated as a composite of all GTVs. This ITV was grown with 1 cm circumferential margin and 1.2 cm superior–inferiorly to define a PTV. Dose constraints and PTV coverage were defined by the SCALOP protocol. Results: We identified nine patients who had 4D CT scans from April to October 2010. We found that the mean reduction in small bowel doses for V15small bowel was 17% and the mean V45small bowel was reduced by 28% when 4D50.4 was compared with SCALOP50.4. With dose escalation to 55.8 Gy, 4D55.8 remained compliant with the organs at risk constraints and these values, including the mean small bowel doses (V15small bowel and V45small bowel) remained comparable to the SCALOP50.4. Patients set-up errors were reviewed during treatment and found to be acceptable for our PTV margins. No acute grade 3 or 4 toxicity was observed of the eight patients treated with 4D50.4 plans. Conclusion: In this study, 4D CT planning using our protocol would allow dose escalation without a significant increase in the small bowel dose.

data between the three groups except in the predictive IQ measured by the Japanese Adult Reading Test (F(2, 42)=10.64, p