Application of liquid chromatography-mass spectrometry-based metabolic profiling in inflammatory bowel disease

The inflammatory bowel diseases (IBD), Crohn’s Disease (CD) and Ulcerative colitis (UC), are chronic inflammatory diseases of the gastrointestinal tract, whose aetiology has yet to be determined, but is widely thought to be the result of genetic, immune, microbial, metabolic and environmental influences. IBD has been the subject of microbial and metabolomic research for many years due to associations between UC, CD and alterations in the gut microbiome, as well as measurable changes in systemic metabolism. In this thesis, the breadth of metabolomic research in IBD across multiple human biosamples has been documented in a systematic review. The majority of studies have used untargeted ‘global profiling’ techniques and the review highlights potential advantages that a targeted metabolomic and lipidomic approach to IBD research may bring. The first IBD-specific and targeted liquid-chromatography mass-spectrometry method was developed and validated. The method also employed a novel application of a derivatizing agent to stool samples, as well as previously studied urine and blood components. The application of this method in multiple biosamples showed alterations in concentrations of key microbial and mammalian molecules, comparing IBD patients to healthy controls. The utility of this method when compared to untargeted approaches was also explored, demonstrating the potential advantages of targeted metabolomic methods in IBD research. Results from a lipidomic analysis of IBD stool samples showed significant differences in bioactive lipid species in the stool samples of both UC and CD patients compared to healthy controls. This analysis was integrated with 16S ribosomal RNA (16S rRNA) gene-based sequencing data, identifying correlations between IBD associated bacterial groups and significantly altered stool lipids. This study was also the first to attempt to measure oxylipins in human stool samples. The studies undertaken in this thesis demonstrate the potential of targeted metabolomic analyses in IBD, through novel mass spectrometry approaches.Open Acces

Caregiving and allostatic load predict future illness and disability: A population-based study

BACKGROUND: Caring for sick or disabled relatives is a key model for understanding the effects of chronic stress on immunity/inflammation; biomarkers which are part of an index of allostatic load. Here, we examine whether caring and allostatic load are predictive of future illness/disability and if the association between caring and illness/disability is mediated by allostatic load. METHOD: Using data from the Understanding Society Wave 2 (2011) and Wave 9 (2017–2019) datasets in the UK, a sample of 471 of caregivers and 2,151 non-caregivers (all initially healthy) were compared on allostatic load and future illness/disability. RESULTS: Caregivers had higher allostatic risk scores, for total as well as immune and non-immune biomarkers, and were more likely (23.3% vs 17.4%) to have an illness/disability in the future compared to non-caregivers. Moreover, caregiving was responsible for a 33% future illness/disability risk. Further, allostatic load was also predictive of excess risk (OR ​= ​1.18, 95% CI ​= ​1.08 – 1.26; p ​< ​.001); higher allostatic load was associated with increased risk of illness/disability in the future. In an unadjusted mediation model, allostatic load mediated the association between caregiving and future illness/disability. However, after controlling for confounding, the mediation became non-significant. CONCLUSIONS: These results confirm that caregiving and allostatic load are damaging for future health. Results are also discussed in relation to public health aspects of caregiving

The Tellus geochemical surveys, results and applications

Ambitions to complete geochemical mapping across the island of Ireland were developed in the 1980s and the first phases began in western Northern Ireland in the early 1990s. Subsequent phases in Northern Ireland and the Republic of Ireland were begun from 2004. The Tellus and Tellus Border geochemical sampling programmes of 2004–12 resulted in the most comprehensive maps of their kind for the northern region of Ireland. These programmes covered 30% of the island of Ireland, albeit at different sampling densities, with detailed soil and stream sampling. Soils were sampled at 10,335 sites and streams at a further 9501 sites. 1269 urban sites were sampled in Belfast and Derry–Londonderry. The survey methodologies followed the established sampling protocols of the GB Geochemical Baseline Survey of the Environment (G‑BASE). Applying these systematic approaches of sampling and quality control was the foundation for developing coherent and comparable cross-border data sets. The samples were analysed by internationally accredited laboratories. In all media, typically around 55 inorganic chemical elements and ions, and physico-chemical properties were analysed and measured. The maps of these elements reveal wide variations across the area, reflecting the influence of the underlying geology, mineralisation, and anthropogenic and environmental factors. The data, which are open and freely available, have prompted an increase in mineral exploration and research into a range of environmental questions

Improving long-term disaster recovery research in Australia through boosting dataset comparability

Emergencies and disasters are increasing in frequency and complexity in Australia and around the world.1 It is well established that the effects of these events take a long time to recover from. There is strong and growing evidence to show that different segments of society are exposed to disasters in different ways, with people and communities affected in interconnected and compounding ways

IT Workforce Trends: Implications For IS Programs

Findings in an IT workforce study support the emphasis of business content espoused by IS curriculum guidelines. Business domain and project management skills are critical to keep in house while technical skills were cited as the top skills sourced. Paradoxically, technical skills are those cited for entry-level positions. We discuss the issues raised by these findings and recommend several approaches for IS programs to consider. IS programs must offer a functionally integrated curriculum and deliver it in an experiential business context. We provide several examples of innovative pedagogical approaches and industry alliances which demonstrate mechanisms to provide students with a stronger business orientation in applying IT. We recommend a more proactive approach to enrollment including better promotion of IS programs

HII Region Oxygen Abundances in Starbursting Transition Dwarf Galaxies

We present empirical HII region oxygen abundances for a sample of low-luminosity starburst galaxies which are in a short lived evolutionary state. All five galaxies are characterized by centrally concentrated star formation, which is embedded in smooth stellar envelopes resembling dE-like systems. The galaxies also have small gas contents with typical M_{HI}/L_{B} ~ 0.1 resulting in gas exhaustion timescales less than 1 Gyr, even when molecular gas is considered. We find, compared to other morphologically similar systems, the galaxies of this sample have surprisingly high oxygen abundances with 12 + log(O/H) ~ 9.0. We propose that these objects are a subclass of evolved blue compact dwarfs, which have exhausted most of their gas supply while retaining their metals. We further propose that we are seeing these objects during a short phase in which they are nearing the end of their starburst activity, and could become early-type dwarfs.Comment: 13 pages, 3 figures, accepted by ApJ Letter

The unified protocol for transdiagnostic treatment of emotional disorders compared with diagnosis-specific protocols for anxiety disorders a randomized clinical trial

IMPORTANCE: Transdiagnostic interventions have been developed to address barriers to the dissemination of evidence-based psychological treatments, but only a few preliminary studies have compared these approaches with existing evidence-based psychological treatments. OBJECTIVE: To determine whether the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is at least as efficacious as single-disorder protocols (SDPs) in the treatment of anxiety disorders. DESIGN, SETTING, AND PARTICIPANTS: From June 23, 2011, to March 5, 2015, a total of 223 patients at an outpatient treatment center with a principal diagnosis of panic disorder with or without agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, or social anxiety disorder were randomly assigned by principal diagnosis to the UP, an SDP, or a waitlist control condition. Patients received up to 16 sessions of the UP or an SDP for 16 to 21 weeks. Outcomes were assessed at baseline, after treatment, and at 6-month follow-up. Analysis in this equivalence trial was based on intention to treat. INTERVENTIONS: The UP or SDPs. MAIN OUTCOMES AND MEASURES: Blinded evaluations of principal diagnosis clinical severity rating were used to evaluate an a priori hypothesis of equivalence between the UP and SDPs. RESULTS: Among the 223 patients (124 women and 99 men; mean [SD] age, 31.1 [11.0] years), 88 were randomized to receive the UP, 91 to receive an SDP, and 44 to the waitlist control condition. Patients were more likely to complete treatment with the UP than with SDPs (odds ratio, 3.11; 95% CI, 1.44-6.74). Both the UP (Cohen d, −0.93; 95% CI, −1.29 to −0.57) and SDPs (Cohen d, −1.08; 95% CI, −1.43 to −0.73) were superior to the waitlist control condition at acute outcome. Reductions in clinical severity rating from baseline to the end of treatment (β, 0.25; 95% CI, −0.26 to 0.75) and from baseline to the 6-month follow-up (β, 0.16; 95% CI, −0.39 to 0.70) indicated statistical equivalence between the UP and SDPs. CONCLUSIONS AND RELEVANCE: The UP produces symptom reduction equivalent to criterion standard evidence-based psychological treatments for anxiety disorders with less attrition. Thus, it may be possible to use 1 protocol instead of multiple SDPs to more efficiently treat the most commonly occurring anxiety and depressive disorders.This study was funded by grant R01 MH090053 from the National Institute of Mental Health. (R01 MH090053 - National Institute of Mental Health)First author draf

Flow heterogeneity in the fractured Chalk aquifer of southern England

The aim of the current work is to investigate the heterogeneity of flow in the Chalk aquifer of southern England. The rock mass properties and hydraulic characteristics of the aquifer have been characterised using a suite of geological and geophysical surveys and hydraulic tests. Fracture logs have been produced based on core logging and using optical images of boreholes. Flow has been characterised using borehole flow logs and dilution tests and hydraulic conductivity measured using packer tests. Fractures have been recorded with apertures in the range <1mm to about 30cm (sub-karstic enlargement) in diameter, however, hydrogeologically significant flow is not restricted to the enlarged fractures and is affected by the local groundwater head distribution. The work is being undertaken as part of the LOCAR Programme. LOCAR is a multi-project programme with the aim of measuring and modelling processes controlling water and material fluxes within lowland permeable catchments in the UK

The Grizzly, February 1, 2001

Fight to Save Collegeville dam Reaches Critical Point • UC to Honor Black History • Duryea, Maples in Need of Repairs, Students Say • Biology Majors Spend Break in Costa Rica • Opinions: Absolut Pathetic: Student Alcohol Abuse on Campus a Sobering, Serious Problem; Election Critical to Israel\u27s Future; Hail to the Chief or Hail to the Thief? • Get Weekly Dose of S&M, Double S on Ursinus TV • Berman Exhibit Looks \u27Beyond the Wall\u27 • As Winter Roars, How to Keep the Flu Virus From Getting to You • Bears Basketball Downs Mules, Improves to 12-6 • Snell Symposium Meets with Success • Swim Team Succeeds Poolside in Spite of Loss • Gymnastics in Midst of Terrific Seasonhttps://digitalcommons.ursinus.edu/grizzlynews/1482/thumbnail.jp

The 100 patient stories project: Patient and family member views on how clinicians (should) enact Open Disclosure - a qualitative study

Objectives To investigate patients’ and family members’ perceptions and experiences of disclosure of healthcare incidents and to derive principles of effective disclosure. Design Retrospective qualitative study based on 100 semi-structured, in depth interviews with patients and family members. Setting Nationwide multisite survey across Australia. Participants 39 patients and 80 family members who were involved in high severity healthcare incidents (leading to death, permanent disability, or long term harm) and incident disclosure. Recruitment was via national newspapers (43%), health services where the incidents occurred (28%), two internet marketing companies (27%), and consumer organisations (2%). Main outcome measures Participants’ recurrent experiences and concerns expressed in interviews. Results Most patients and family members felt that the health service incident disclosure rarely met their needs and expectations. They expected better preparation for incident disclosure, more shared dialogue about what went wrong, more follow-up support, input into when the time was ripe for closure, and more information about subsequent improvement in process. This analysis provided the basis for the formulation of a set of principles of effective incident disclosure. Conclusions Despite growing prominence of open disclosure, discussion about healthcare incidents still falls short of patient and family member expectations. Healthcare organisations and providers should strengthen their efforts to meet patients’ (and family members’) needs and expectations