Quality of life impacts from rotavirus gastroenteritis on children and their families in the UK.

AIMS: Rotavirus vaccines (RV) are safe and effective but demand significant investment of healthcare resource. In countries with low mortality due to rotavirus, a key component to assessing cost-effectiveness is quantifying the Health Related Quality of Life (HRQoL) lost due to rotavirus acute gastroenteritis (RVAGE). METHODS: Families with children less than six years old with gastroenteritis were recruited from attendees to Bristol Children's Hospital Emergency Department. Stools were tested for viral causes of gastroenteritis. Children's HRQoL was assessed at presentation using Health Utilities Index 2 (HUI2) with visual analogue scale (VAS). The effect of the child's illness on the HRQoL of up to two adult carers was assessed using EQ-5D-5L. Families completed a daily symptom diary to assess time to recovery and within-family transmission. RESULTS: 127 families consented to take part, 84(65%) had rotavirus as the cause of illness. At the time of attendance, mean paediatric HRQoL with RVAGE was 0.74(HUI2) and 0.42(VAS). Primary/secondary carer's HRQoL was 0.68/0.80 (EQ5D) or 0.70/0.79 (VAS). The mean number of QALYs lost due to RVAGE was 3.1-3.5 per thousand children and 7.7-8.7 per thousand family units. In 52% of RVAGE families at least one other member developed a secondary case of gastroenteritis. For working parents, 69% missed work, for a mean of 2.8 days (95% CI 2.3-3.4). CONCLUSIONS: We have found the HRQoL loss associated with RVAGE in children and their carers to be significantly higher than estimates used for all RV medical attendances in UK cost-effectiveness calculations.The study was supported by the NIHR Health Protection Research Unit in Evaluation of Interventions. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health EnglandThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.vaccine.2015.07.01

Titans of T-Posing : So-Bad-It's-Good in Deadly Premonition

This paper analyses the concept of So-Bad-It’s-Good, the phenomenon of enjoying works precisely because they do not fit into our normative standards of good art, usually for the purposes of being laughed at. Drawing on work from film studies, we outline a cohesive definition of this phenomenon that can be applied across mediums, as well as categorise the most common ways in which it is communicated throughout the texts, highlighting the relationship between the forms and the cultural horizons of the reader. In particular, this thesis applies this definition to digital games, a medium currently lacking in research on this topic. To do so, we have conducted a close-reading of the game Deadly Premonition, a much-noted representative of this concept, attempting to isolate how So-Bad-It’s-Good is expressed through play, rather than through narrative or visuals, and document how the player responds to the text. In doing this, we discovered insight into the differences between digital games and other mediums: the long run time requiring pacing and varied levels of quality to be pleasurable, and the interactive nature necessitating more focus on this badness being benign. Along with this, the ways in which the forms specific to play can be enjoyed for being bad. So-Bad-It’s-Good highlights the importance of how the cultural horizons and expectations we have when entering into a work affect our reception of transgressive qualities, and this paper represents the first step towards exploring that through play

Chronic Recurrent Multifocal Osteomyelitis (CRMO):advancing the diagnosis

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is a little known inflammatory bone disease occurring primarily in children and adolescents. Delays in referral and diagnosis may lead to prolonged courses of antibiotics with in-patient care, unnecessary radiation exposure from multiple plain radiographs or bone scans and repeated surgery including bone biopsies. Children (aged < 18 years) diagnosed with CRMO between January 2005 and December 2012, reviewed at Bristol Royal Hospital for Children were included and all available data collected. Information regarding CRMO was sent to all orthopaedic surgeons in the region in 2009. The aim of the study was to examine the features of the cohort, to examine the length of time to diagnosis and to explore the criteria used for diagnosis with and without biopsy. FINDINGS: Over an 8 year period, 41 patients were diagnosed with CRMO. Symptom onset occurred at a median of 9 years of age and time to diagnosis had a median of 15 months (range 0–92). Correlation coefficient analysis for time to diagnosis by year showed statistical significance with a decreasing trend. From the cohort data, diagnostic criteria were developed; applied retrospectively, 34 (83 %) children may have been diagnosed using the criteria, without a biopsy. CONCLUSIONS: The data suggest that increasing knowledge of this condition may shorten time to diagnosis. Use of the Bristol diagnostic criteria by an experienced clinician may obviate the need for biopsy in some patients

Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages

Abstract Background Interleukin-33 is a member of the IL-1 cytokine family whose functions are mediated and modulated by the ST2 receptor. IL-33-ST2 expression and interactions have been explored in mouse macrophages but little is known about the effect of IL-33 on human macrophages. The expression of ST2 transcript and protein levels, and IL-33-mediated effects on M1 (i.e. classical activation) and M2 (i.e. alternative activation) chemokine marker expression in human bone marrow-derived macrophages were examined. Results Human macrophages constitutively expressed the membrane-associated (i.e. ST2L) and the soluble (i.e. sST2) ST2 receptors. M2 (IL-4 + IL-13) skewing stimuli markedly increased the expression of ST2L, but neither polarizing cytokine treatment promoted the release of sST2 from these cells. When added to na&#239;ve macrophages alone, IL-33 directly enhanced the expression of CCL3. In combination with LPS, IL-33 blocked the expression of the M2 chemokine marker CCL18, but did not alter CCL3 expression in these naive cells. The addition of IL-33 to M1 macrophages markedly increased the expression of CCL18 above that detected in untreated M1 macrophages. Similarly, alternatively activated human macrophages treated with IL-33 exhibited enhanced expression of CCL18 and the M2 marker mannose receptor above that detected in M2 macrophages alone. Conclusions Together, these data suggest that primary responses to IL-33 in bone marrow derived human macrophages favors M1 chemokine generation while its addition to polarized human macrophages promotes or amplifies M2 chemokine expression.http://deepblue.lib.umich.edu/bitstream/2027.42/78250/1/1471-2172-11-52.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78250/2/1471-2172-11-52.pdfPeer Reviewe

Assessing the impacts of the first year of rotavirus vaccination in the United Kingdom

The United Kingdom (UK) added rotavirus (RV) vaccine (Rotarix GlaxoSmithKline) to the national vaccine schedule in July 2013. During the 2012–2014 rotavirus seasons, children presenting to the Bristol Royal Hospital for Children Emergency Department with gastroenteritis symptoms had stool virology analysis (real-time PCR) and clinical outcome recorded. Nosocomial cases were identified as patients with non-gastroenteritis diagnosis testing positive for rotavirus &gt; 48h after admission. In comparison to average pre-vaccine seasons, in the first year after vaccine introduction there were 48% fewer attendances diagnosed with gastroenteritis, 53% reduction in gastroenteritis admissions and a total saving of 330 bed-days occupancy. There was an overall reduction in number of rotavirus-positive stool samples with 94% reduction in children aged under one year and a 65% reduction in those too old to have been vaccinated. In the first year after the introduction of universal vaccination against rotavirus we observed a profound reduction in gastroenteritis presentations and admissions with a substantial possible herd effect seen in older children. Extrapolating these findings to the UK population we estimate secondary healthcare savings in the first year of ca £7.5 (€10.5) million. Ongoing surveillance will be required to determine the long-term impact of the RV immunisation programme

Effects of Sea Level Rise on Water Treatment & Wastewater Treatment Facilities

Sea level rise and its associated effects threaten coastal water utilities in Massachusetts. The Massachusetts Department of Environmental Protection does not know which facilities are at greatest risk of flooding and cannot easily evaluate the impacts of a flood event on particular facilities. Our goal was to identify past research in this field, create a tool to evaluate hazard to coastal water facilities and measure the impact of flooding on these facilities. We have also provided the structure to expand upon these tools and make recommendations to the Massachusetts Department of Environmental Protection for what they can do in the future to focus their mitigation efforts

Case Report: Concomitant Diagnosis of Plasma Cell Leukemia in Patient With JAK2 Positive Myeloproliferative Neoplasm.

Plasma cell dyscrasias and myeloproliferative neoplasms (MPN) are hematologic malignancies arising from two distinct hematopoietic cell lineages. They rarely occur concomitantly. Here, we report a case of a patient with a recent diagnosis of a JAK2 V617F positive MPN who presented with a new diagnosis of plasma cell leukemia. The patient had presented to the hospital with a leukocytosis predominantly comprised of plasma cells, followed by work-up involving peripheral blood flow cytometry, FISH analysis, and bone-marrow biopsy. FISH analysis was suggestive of a common progenitor cell for these distinct hematologic malignancies. To our knowledge, this case represents the second reported instance of a concomitant JAK2 positive MPN with primary plasma cell leukemia