Mathematical applications of inductive logic programming

Accepted versio

Site-Specific Immunomodulator: A Novel Treatment for Crohn\u27s Disease

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously every second day, for a minimum of 2.5 months and a maximum of 11 months. All 10 patients reported improvement of symptoms while on the SSI QBECO treatment. Seven patients reported full resolution of clinical symptoms during a course of SSI QBECO of at least three months. Three patients have experienced ongoing sustained clinical remission after discontinuing all medications, including SSI treatment. The longest case of clinical remission is still ongoing (\u3e4 years). No serious severe adverse clinical events were reported. Collectively, we conclude that treatment with the immunoactive SSI QBECO was well tolerated and effective for treatment of Crohn’s disease in this case series

TOOLympics 2019: An Overview of Competitions in Formal Methods

Evaluation of scientific contributions can be done in many different ways. For the various research communities working on the verification of systems (software, hardware, or the underlying involved mechanisms), it is important to bring together the community and to compare the state of the art, in order to identify progress of and new challenges in the research area. Competitions are a suitable way to do that. The first verification competition was created in 1992 (SAT competition), shortly followed by the CASC competition in 1996. Since the year 2000, the number of dedicated verification competitions is steadily increasing. Many of these events now happen regularly, gathering researchers that would like to understand how well their research prototypes work in practice. Scientific results have to be reproducible, and powerful computers are becoming cheaper and cheaper, thus, these competitions are becoming an important means for advancing research in verification technology. TOOLympics 2019 is an event to celebrate the achievements of the various competitions, and to understand their commonalities and differences. This volume is dedicated to the presentation of the 16 competitions that joined TOOLympics as part of the celebration of the 25th anniversary of the TACAS conference

Recalculation of dose for each fraction of treatment on TomoTherapy.

OBJECTIVE: The VoxTox study, linking delivered dose to toxicity requires recalculation of typically 20-37 fractions per patient, for nearly 2000 patients. This requires a non-interactive interface permitting batch calculation with multiple computers. METHODS: Data are extracted from the TomoTherapy(®) archive and processed using the computational task-management system GANGA. Doses are calculated for each fraction of radiotherapy using the daily megavoltage (MV) CT images. The calculated dose cube is saved as a digital imaging and communications in medicine RTDOSE object, which can then be read by utilities that calculate dose-volume histograms or dose surface maps. The rectum is delineated on daily MV images using an implementation of the Chan-Vese algorithm. RESULTS: On a cluster of up to 117 central processing units, dose cubes for all fractions of 151 patients took 12 days to calculate. Outlining the rectum on all slices and fractions on 151 patients took 7 h. We also present results of the Hounsfield unit (HU) calibration of TomoTherapy MV images, measured over an 8-year period, showing that the HU calibration has become less variable over time, with no large changes observed after 2011. CONCLUSION: We have developed a system for automatic dose recalculation of TomoTherapy dose distributions. This does not tie up the clinically needed planning system but can be run on a cluster of independent machines, enabling recalculation of delivered dose without user intervention. ADVANCES IN KNOWLEDGE: The use of a task management system for automation of dose calculation and outlining enables work to be scaled up to the level required for large studies.JES is supported by Cancer Research UK through the Cambridge Cancer Centre. MR, AB and KH are supported by Cancer Research UK through the VoxTox Research Programme. NGB is supported by the NIHR Cambridge Biomedical Research Centre.This is the author accepted manuscript. The final version is available from British Institute of Radiology via http://dx.doi.org/10.1259/bjr.2015077

How severe is diabetes after total pancreatectomy?:A case-matched analysis

OBJECTIVES: Total pancreatectomy (TP) is associated with significant morbidity and mortality. The severity of postoperative diabetes and existence of ‘brittle diabetes’ are unclear. This study sought to identify quality of life (QoL) and diabetes-specific outcomes after TP. METHODS: Patients who underwent TP were matched for age, sex and duration of diabetes with patients with type 1 diabetes. General QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire QLQ-C30 and the PAN26 tool. Diabetes-specific outcomes were assessed using the Problem Areas in Diabetes (PAID) tool and an assessment of diabetes-specific complications and outcomes. RESULTS: A total of 123 patients underwent TP; 88 died (none of diabetic complications) and two were lost to follow-up. Of the remaining 33 patients, 28 returned questionnaires. Fourteen general and pancreas-specific QoL measurements were all significantly worse amongst the TP cohort (QLQ-C30 + PAN26). However, when diabetes-specific outcomes were compared using the PAID tool, only one of 20 was significantly worse. HbA1c values were comparable (P = 0.299), as were diabetes-related complications such as hypoglycaemic attacks and organ dysfunction. CONCLUSIONS: Total pancreatectomy is associated with impaired QoL on general measures compared with that in type 1 diabetes patients. Importantly, however, there was almost no significant difference in diabetes-specific outcomes as assessed by a diabetes-specific questionnaire, or in diabetes control. This study does not support the existence of ‘brittle diabetes’ after TP

Design: One, but in different forms

This overview paper defends an augmented cognitively oriented generic-design hypothesis: there are both significant similarities between the design activities implemented in different situations and crucial differences between these and other cognitive activities; yet, characteristics of a design situation (related to the design process, the designers, and the artefact) introduce specificities in the corresponding cognitive activities and structures that are used, and in the resulting designs. We thus augment the classical generic-design hypothesis with that of different forms of designing. We review the data available in the cognitive design research literature and propose a series of candidates underlying such forms of design, outlining a number of directions requiring further elaboration

Accumulated dose to the rectum, measured using dose-volume histograms and dose-surface maps, is different from planned dose in all patients treated with radiotherapy for prostate cancer.

OBJECTIVE: We sought to calculate accumulated dose (DA) to the rectum in patients treated with radiotherapy for prostate cancer. We were particularly interested in whether dose-surface maps (DSMs) provide additional information to dose-volume histograms (DVHs). METHODS: Manual rectal contours were obtained for kilovoltage and daily megavoltage CT scans for 10 participants from the VoxTox study (380 scans). Daily delivered dose recalculation was performed using a ray-tracing algorithm. Delivered DVHs were summated to create accumulated DVHs. The rectum was considered as a cylinder, cut and unfolded to produce daily delivered DSMs; these were summated to produce accumulated DSMs. RESULTS: Accumulated dose-volumes were different from planned in all participants. For one participant, all DA levels were higher and all volumes were larger than planned. For four participants, all DA levels were lower and all volumes were smaller than planned. For each of these four participants, ≥1% of pixels on the accumulated DSM received ≥5 Gy more than had been planned. CONCLUSION: Differences between accumulated and planned dose-volumes were seen in all participants. DSMs were able to identify differences between DA and planned dose that could not be appreciated from the DVHs. Further work is needed to extract the dose data embedded in the DSMs. These will be correlated with toxicity as part of the VoxTox Programme. ADVANCES IN KNOWLEDGE: DSMs are able to identify differences between DA and planned dose that cannot be appreciated from DVHs alone and should be incorporated into future studies investigating links between DA and toxicity.JES is supported by Cancer Research UK through the Cambridge Cancer Centre. NGB is supported by the NIHR Cambridge Biomedical Research Centre. KH, MR and AMB are supported by the VoxTox Research Programme, which is funded by Cancer Research UK.This is the final version of the article. It first appeared from the British Institute of Radiology via http://dx.doi.org/10.1259/bjr.2015024

Outsourcing and financial performance: A negative curvilinear effect

This study asks how a firm's degree of outsourcing across all activities influences financial performance. We argue there is an optimal degree of outsourcing, where firms outsource some activities yet integrate others, and that deviations lower performance in a negatively curvilinear fashion. We find empirical support, using 1995 and 1998 data on a sample of manufacturing businesses in the Netherlands, and show that the steepness of the curve increases under conditions of high uncertainty. We show the magnitude of the uncertainty effect on performance outcomes through a post hoc scenario analysis. Thus we provide a specific, theoretically and empirically grounded prediction of how outsourcing affects performance with implications for theory and practice

Photochemical Fingerprinting Is a Sensitive Probe for the Detection of Synthetic Cannabinoid Receptor Agonists; Toward Robust Point-of-Care Detection

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid "photochemical fingerprinting"approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device.</p