40 research outputs found
Gender differences in hepatitis C seroprevalence and suboptimal vaccination and hepatology services uptake amongst substance misusers
No full textInjecting drug users are the principal at risk group for blood borne viruses. The aim was to assess the feasibility of screening substance misusers for blood borne viruses, and to offer appropriate vaccinations/referral to hepatology services. This was a nurse led prospective 6-month study based at a large Substance Misuse Service in south east England. Of the 196 consecutive individuals assessed, 81 were eligible for HBV immunization of whom only 33.3% completed a vaccination course. Prevalence of positive serological markers were: anti-HBc 14.4%, HBsAg 1.5%, and HCV antibody 37.9%. Compared to men, women were more likely to accept blood borne virus testing (83.3% vs. 62.3%), have ever injected (89.6% vs. 76.3%), overdose (54.2% vs. 23.6%), be anti-HBc positive (27.5% vs. 8.8%), drink alcohol above national recommended guidelines (41.7% vs. 25.7%), and have a positive HCV serology (55% vs. 30.4%) (P?=?0.05 for all). Of the 73 individuals identified with a positive HBsAg and or HCV antibody, only 14 (19.1%) were known to hepatology services and 8 (20%) of those eligible subsequently accepted a specialist referral. In conclusion, serological markers for blood borne viruses remain high in substance misusers (anti-HBc 14.4%, HCV antibody 37.9%), with women more likely to be positive. Overall, only 33.3% and 20%, respectively, complete HBV vaccination and accept a hepatology referral. A multidisciplinary approach is paramount to address both the blood borne viruses and the substance misuse and realignment of hepatitis services to Substance Misuse Services may offer such a strategy
Interferon-α acutely impairs whole-brain functional connectivity network architecture - A preliminary study
No full textInterferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis C infection. Though clinically effective, IFN-α rapidly impairs mood, motivation and cognition, effects that can appear indistinguishable from major depression and provide powerful empirical support for the inflammation theory of depression. Though inflammation has been shown to modulate activity within discrete brain regions, how it affects distributed information processing and the architecture of whole brain functional connectivity networks have not previously been investigated. Here we use a graph theoretic analysis of resting state functional magnetic resonance imaging (rfMRI) to investigate acute effects of systemic interferon-alpha (IFN-α) on whole brain functional connectivity architecture and its relationship to IFN-α-induced mood change. Twenty-two patients with Hepatitis-C infection, initiating IFN-α-based therapy were scanned at baseline and 4h after their first IFN-α dose. The whole brain network was parcellated into 110 cortical and sub-cortical nodes based on the Oxford-Harvard Atlas and effects assessed on higher-level graph metrics, including node degree, betweenness centrality, global and local efficiency. IFN-α was associated with a significant reduction in global network connectivity (node degree) (p=0.033) and efficiency (p=0.013), indicating a global reduction of information transfer among the nodes forming the whole brain network. Effects were similar for highly connected (hub) and non-hub nodes, with no effect on betweenness centrality (p>0.1). At a local level, we identified regions with reduced efficiency of information exchange and a sub-network with decreased functional connectivity after IFN-α. Changes in local and particularly global functional connectivity correlated with associated changes in mood measured on the Profile of Mood States (POMS) questionnaire. IFN-α rapidly induced a profound shift in whole brain network structure, impairing global functional connectivity and the efficiency of parallel information exchange. Correlations with multiple indices of mood change support a role for global changes in brain functional connectivity architecture in coordinated behavioral responses to IFN-α
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A study of John Clare in his historical and political context
No full textAs the title indicates, the basis of the thesis is to set John Clare’s life and work within the context of the social and political history of his time. It is a study that is long overdue. The manner in which topical and political matters were mediated to him and were reflected in his work are analysed. His introduction to the literary and social worlds of Stamford and London is evaluated, and the advantages and disadvantages of patronage assessed. The active and complex political culture of Stamford has been taken into account as this may have affected his later political statements and a growing awareness of his audience. His antagonism to enclosure and the social changes that it engendered are considered. Three major questions that arise from this are addressed. The two local newspapers that Clare is known to have read are used throughout. His correspondence with friends, colleagues and casual correspondents has provided valuable insights as have his poetry and prose writings. Research in the Northamptonshire Record Office has revealed important new information in the form of one book of Enclosure Commissioners’ Minutes dated 1809-14, the first five years of the enclosure of Helpstone, Clare’s native village
Acute effects of interferon-alpha on cellular anabolic and catabolic processes are associated with the development of fatigue during Interferon-alpha-based therapy for Hepatitis-C: A preliminary study
No full textIntroduction
Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis-C virus (HCV) infection. Though clinically effective, IFN-α frequently induces functionally impairing mood and motivation symptoms, particularly fatigue. Unlike mood impairment, which typically emerges after weeks of treatment, fatigue tends to emerge and evolve rapidly, typically within hours of the first IFN-α injection. Despite being a major source of functional impairment during IFN-α and other immune-based therapies, the biological mechanisms underlying fatigue remain poorly understood. Here, we aimed to identify acute immune-response signatures to IFN-α that could predict the later development of fatigue.
Methods
In this exploratory study, we analyzed whole blood transcriptomics in a longitudinal sample of 27 HCV patients initiating IFN-α and Ribavirin therapy. Blood samples were obtained at baseline and 4½ hours after the first IFN-α dose and transcriptomic data was obtained using Affymetrix Human Gene 1.1 ST Array Strips. Gene expression data visualization and quality control were assessed using Partek Genomics Suite V6.6 and protein–protein interaction networks using STRING and Ingenuity Pathway Analysis (IPA). A Fatigue Visual Analogue Scale (fVAS) was utilized to record fatigue symptoms at baseline, 4½ hours and 4 weeks after initiation of treatment.
Results
IFN-α was associated with an upregulation of 526 transcripts and a downregulation of 228 genes, indicating a rapid transcriptomic response in whole blood within 4½ hours of injection. 93 genes were significantly positively correlated with changes in fatigue, with gene expression changes measured from baseline to 4.5 h and increases in fatigue assessed from baseline to week 4 on the fVAS. We identified a novel network of predominantly cytosolic ribosomal units and ubiquitin proteins implicated in modulating mTOR signaling that was associated with the development of fatigue 4 weeks after initiation of IFN-α treatment (p = 0.0078).
Conclusion
Our findings suggest that acute activation of this anabolic/catabolic network by IFN-α may predispose to the experience of fatigue similar to evidence found in cancer-related fatigue. Further investigation is warranted to confirm the exploratory nature of these observations
Epidemiology and differential diagnosis of NSAID-induced injury to the mucosa of the small intestine
No full textNon-steroidal anti-inflammatory drugs cause small-bowel inflammation in about 60% of patients receiving these drugs long-term. The inflammation is associated with small intestinal bleeding, protein loss, ulcers and occasionally strictures. Treatment options for NSAID enteropathy include metronidazole, sulphasalazine and misoprostol, and some patients may require surgery. The diagnosis of NSAID enteropathy is not always straightforward. It is especially difficult to differentiate it from the ileitis associated with spondylarthropathy and, at times, that of Crohn's disease. An investigational algorithm is suggested for this purpose. In the last decade a number of small-bowel diseases have been identified, where none were thought to exist, because of the increasing use of enteroscopy and new sensitive tests for intestinal inflammation. Optimal treatments of these conditions are still to be studied
Nicolaus Mameranus: poetry and politics at the court of Mary Tudor
No full textThis thesis is the first full length study of the Luxembourgian poet Nicolaus
Mameranus (1500-c.1567) in the past century, and the first in the English language.
It contains select translation and analysis of previously unknown works, new
information about his life, and a modern, expanded bibliographical overview of his
extant writing. The thesis focuses primarily on the poet’s association with the culture
and politics of Marian England, particularly on the spring of 1557 when he
accompanied Philip II on the sovereign’s second voyage to see his wife, Mary I. In
London Mameranus published three collections of his Latin poetry, later presenting
to the Queen seven of his own books and a petition proffering his counsel. After her
death, Mameranus wrote a report on her funeral service in Brussels.
Taking these texts, situating them alongside other rarely heard voices, and
contextualising them within a substantial collection of historical evidence, I provide
a reassessment of the latter stages of Mary’s reign. Where most studies of the period,
including even the latest revisionist ones, see 1557 as the year in which the country
began its decline into warfare and famine, marked by the Queen’s second false
pregnancy, her problems with the papacy, and her eventual death in the subsequent
year, I argue instead that, for many in and around the court, this period was
characterised by an atmosphere of hope and progression, spurred on by the King’s
visit. I argue that the royal couple successfully re-forged their image at the apex of a
political union that many considered the foundation of a new Anglo-Habsburg
dynasty, and, equally successfully, represented their dual monarchy as a bastion in
the fight to reform Catholic Christianity in the wake of the Protestant Reformation.
Rather than being satisfied with the idea that Mary was able successfully to negotiate
and represent her own political role within the marriage to her supporters in England,
I also propose that foreign observers such as Mameranus widely understood and
endorsed her role as Queen regnant, even on an international stage.
Finally, this thesis is also a study in the culture of counsel in the early modern
period, examining the rhetoric and genre that a Catholic author deployed in his
efforts to effect political and religious change in the mid-century. Countering
traditional histories of political thought, which look predominantly at Protestant
reformers and the development of republicanism and civil government, this thesis
proposes that Mameranus’ writing is evidence of a vibrant Catholic tradition that
relied for its efficacy on a distinctly Erasmian strand of princely humanism, that
successfully adapted its predecessor’s call for the reform of Christianity to a post-
Reformation, confessionalised political sphere, and that held as its ideal a polity that
was Catholic and Imperial
Diagnostic accuracy and clinical application of faecal calprotectin in adult patients presenting with gastrointestinal symptoms in primary care
No full textOBJECTIVE: Assessment of faecal calprotectin (fCal) test performance in primary care within an irritable bowel syndrome (IBS) diagnostic pathway.METHODS: Study based on consecutively collected fCal data from 962 patients, aged 18-45, presenting to their general practitioner (GP) with persistent gastrointestinal symptoms.RESULTS: Six hundred and eighty six (71%) patients had a negative (<50 μg/g) and 276 (29%) had a positive fCal. 28% (77/276) of the patients testing positive and 3% (17/686) of those testing negative had an organic diagnosis. At 50 μg/g the sensitivity of the test for organic disease was 82%, (95% confidence interval [CI] 73-89) and the specificity was 77% (95% CI 74-80), with negative predictive value (NPV) and positive predictive value (PPV) of 98% and 28%, respectively. A cut-off increase to 150 μg/g reduces the NPV by 1% whilst increasing the PPV to 71%. This would reduce colonoscopy and flexible sigmoidoscopy bookings by 10% at the cost of four missed cases of inflammatory bowel disease.CONCLUSIONS: This study provides the first evidence on the use of fCal testing in primary care. The low prevalence of organic disease in this setting has a significant impact on test performance. This suggests a need for change in cut-off value, to improve PPV whilst accepting a reduction in test sensitivity, if it is to be used as part of the pathway for management of patients with suspected IBS.</p
M600 Servo Test Stand Makani Power
No full textTempest has designed and built a test stand to validate the servo selection for Makani Power’s M600 prototype. The test stand tests the servo at a specified frequency and torque. It also includes an environmental housing that can later be used to incorporate a heater, cooler, and humidifier. The applied frequency, torque, and servo position is controlled by the operator. The stand also measures and provides a readout for temperatures throughout the chamber, humidity within the chamber, frequency felt by the servo, and load applied to the servo. The table has two tiers: the first tier supports all torque application components and the second tier supports the servo, vibration motor, and the chamber. The chamber table has the vibration motor attached underneath. The torque system is comprised of a linear pneumatic cylinder attached to rope which wraps around two pulleys (one attached to the servo shaft and one free spinning). The environmental chamber is constructed from rigid insulation walls and is a 9 cubic feet box. All of the sensors connect to a microcontroller and readout to an external computer. We are confident that our design satisfies the customer’s needs and will assist them in choosing the appropriate servo for the M600
Interferon and anti-TNF therapies differentially modulate amygdala reactivity which predicts associated bidirectional changes in depressive symptoms
No full textA third of patients receiving Interferon-α (IFN-α) treatment for Hepatitis-C develop major depressive disorder (MDD). Conversely, anti-Tumor Necrosis Factor (TNF) therapies improve depression providing key empirical support for the “inflammatory theory” of depression. Heightened amygdala reactivity (particularly to negatively valanced stimuli) is a consistent finding within MDD; can predict treatment efficacy and reverses following successful treatment. However, whether IFN-α and anti-TNF enhance/attenuate depressive symptoms through modulation of amygdala emotional reactivity is unknown. Utilizing a prospective study design, we recruited 30 patients (mean 48.0 ± 10.5 years, 21 male) initiating IFN-α treatment for Hepatitis-C and 30 (mean 50.4 ± 15.7 years, 10 male) anti-TNF therapy for inflammatory arthritis. All completed an emotional face-processing task during fMRI and blood sampling before and after their first IFN-α (4-h) or anti-TNF (24-h) injection and follow-up psychiatric assessments for 3 months of treatment. IFN-α significantly increased depression symptoms (Hamilton Depression Rating Scale HAM-D) at 4 weeks (p 0.1). Conversely, anti-TNF significantly improved depressive symptoms (Hospital Anxiety and Depression Rating Scale HADS) at both 24-h (P = 0.015) and 12 weeks (p = 0.018). In support of our a-priori hypothesis, both IFN-α and anti-TNF significantly modulated amygdala reactivity with IFN-α acutely enhancing right amygdala responses to sad (compared with neutral) faces (p = 0.032) and anti-TNF conversely decreasing right amygdala reactivity (across emotional valence) (p = 0.033). Furthermore, these changes predicted IFN-induced increases in HAM-D 4 weeks later (R2 = 0.17, p = 0.022) and anti-TNF-associated decreases in HADS at 24-h (R2 = 0.23, p = 0.01) suggesting that actions of systemic inflammation on amygdala emotional reactivity play a mechanistic role in inflammation-associated depressive symptoms
