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Bleeding Data across Baseline FIX Expression Levels in People with Hemophilia B: An Analysis Using the 'Factor Expression Study'
No full textThis article is not available on ChesterRepComplications such as spontaneous and trauma-related bleeding events typically experienced by people with hemophilia B (PWHB) are associated with long-term joint damage and chronic pain, and burdensome treatment with intravenous factor IX administration. Gene therapy, designed to enable the endogenous production of the missing clotting factor, has potential for curative benefit in PWHB (Dolan et al, 2018). Due to its link to risk for bleeding episodes, factor expression level (FEL) is commonly used as an endpoint in hemophilia gene therapy trials. However, little data currently exist linking FEL to bleeding risk in PWHB, most notably within the mild range. As such, the aim of this analysis was to examine the relationship between annual bleed rate (ABR) data across baseline FEL in PWHB.
Methods: Data from adult non-inhibitor PWHB, across Europe and the United States (US) who received clotting factor on-demand (OD), were drawn from the 'Cost of HaEmophilia in adults: a Socioeconomic Survey' (CHESS) studies. The CHESS studies are retrospective, burden-of-illness studies in people with hemophilia A or B, capturing the economic and humanistic burden associated with living with hemophilia. Additional data were collected to supplement the existing CHESS studies, particularly in people with exogenous FEL in the mild and moderate range. ABR was defined as the physician-reported number of bleed events experienced by the patient in the 12 months to study capture. A generalized linear model (GLM) was used to analyze variation in ABR data across FEL, adjusting for covariates age, body mass index (BMI), and blood-borne viruses. Following this, a multivariable restricted cubic spline (RCS) GLM regression was performed to create, model, and test for the potential non-linear relationship between FEL and ABR. The RCS regression employed 3 knots, located at baseline FEL values of 1, 5, and 10, and controlled once again for age, BMI, and blood-borne viruses.
Results: A total of 407 adult non-inhibitor PWHB, receiving an OD therapy regimen and with information on ABR, were profiled. The GLM provided adequate fit for the modeling of bleed data; the average marginal effect at the mean was computed from the GLM regression outputs. After controlling for the effects of all other model covariates, the regression analysis showed a significant association between FEL and ABR; for every 1% increase in FEL, the average ABR decreased by 0.08 units (p<0.001). The results of the RCS regression found a significant non-linear relationship between FEL and ABR, ceteris paribus (p<0.001).
Conclusions: The results of this analysis found baseline FEL to be significantly associated with ABR in PWHB; as baseline FEL increased, ABR reduced. This highlights the clinical importance of new hemophilia gene therapies potentially increasing FEL to that of the mild or non-hemophilic range in terms of reducing patient burden through the better prevention of bleeding events in PWHB
Homelessness Is Socially Created: Cluster Analysis of Social Determinants of Homelessness (SODH) in North West England in 2020
Get PDFAbstract: Poverty creates social conditions that increase the likelihood of homelessness. These include exposure to traumatic life experiences; social disadvantages such as poor educational experiences; being raised in a broken family, care homes or foster care; physical, emotional, and sexual abuse; and neglect at an early age. These conditions reduce people’s ability to negotiate through life challenges. This cross-sectional study documents the clustering and frequency of adverse social conditions among 152 homeless people from four cities in North West England between January and August 2020. Two-step cluster analysis showed that having parents with a criminal record, care history, and child neglect/abuse history was predictive of homelessness. The cluster of indicator
variables among homeless people included sexual abuse (χ2 (N = 152) = 220.684, p < 0.001, Cramer’s V = 0.7), inappropriate sexual behaviour (χ2 (N = 152) = 207.737, p < 0.001, Cramer’s V = 0.7), emotional neglect (χ2 (N = 152) = 181.671, p < 0.001, Cramer’s V = 0.7), physical abuse by step-parent (χ2 (N = 152) = 195.882, p < 0.001, Cramer’s V = 0.8), and physical neglect (χ2 (N = 152) = 205.632, p < 0.001, Cramer’s V = 0.8). Poverty and homelessness are intertwined because of the high prevalence of poverty among the homeless. Poverty sets up a chain of interactions between social conditions that increase the likelihood of unfavourable outcomes: homelessness is at the end of the interaction chain. Interventions supporting families to rise out of poverty may also reduce entry into homelessness
Why practical theology must go public
Get PDFThis is the author's post-print pdf version of an article published in Practical Theology. The article can be found at https://www.tandfonline.com/doi/abs/10.1558/prth.v1i1.11This journal article makes the case for a strong affinity between pastoral studies and practical theology as conceived in the UK and the emerging field of public theology
Transitioning to Organic Rice Farming in Thailand: Drivers and Factors
Get PDFThe Thai government has made it part of the long-term strategy to produce more organic rice, particularly for the Chinese market, to sustain Thai economic growth. However, whilst there has been an increase in organic rice farming, the rate has been relatively slow compared to conventional methods.
This research focuses on determining the drivers and factors that influences conversion to organic rice farming in order to better inform local and national policies. It provides an insight into the processes in the decision-making process of famers and the practices they use. Questionnaire and interview data from farmers from the leading rice production region, Surin was analyzed using logistic regression to understand the driver for of organic rice farming and well as the barrier and challenges of adopting to this practice. The findings highlight the critical role of extension farm officers in promoting, educating and motivating farmers to take on organic farming. The ability to access (affordable) loans through local cooperative and land-ownership were also key motivational factors. Young people (under 25) are not engaging with farming generally and this is a major barrier to long-term growth in the organic rice industry in Thailand
Effect of a single serving of pecan nuts on blood lipids and weight: a single blind randomised control trial
Get PDFThis article has been accepted for publication and will appear in a revised form, subsequent to peer review and/or editorial input by Cambridge University Press, in Proceedings of the Nutrition Society published by Cambridge University Press. Copyright The Authors 2018.Nuts are a common component of many traditional cardioprotective diets primarily due to their ability to lower blood lipids and reduce cardiovascular risk(1, 2). Studies consistently show nut intake is associated with favourable changes in energy balance(3). However there is a paucity of data examining the acute changes following nut consumption. We sought to examine the effect of a single serving of pecan nuts on plasma lipids and bodyweight.
Participants were sampled from the University of Chester, UK. Individuals (n = 54) were screened for eligibility to participate. Those meeting entry criteria (n = 25) of being either male or female aged 30 years or more and with no previous history of CVD were randomised to either a control (CON) or pecan nut group (PECAN). Participants in the PECAN group received a single 50 g serving of pecan nuts. Capillary blood was taken for analysis of triacylglycerol, total-cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein-cholesterol and non-high density lipoprotein cholesterol (TAG, TC, LDL-C, HDL-C and non-HDL-C, respectively), and anthropometric measurements were performed. All measurements were repeated after 3 days. Participants were instructed to record all food and drink consumed, and not to change their habitual eating habits. Procedures were approved by the Faculty of Medicine, Dentistry and Clinical Sciences Research Ethics Committee, University of Chester.
No significant effect on TC, HDL-C or TAG was observed during the study (Fig. 1A–C). LDL-C decreased by 0.09 ± 0.37 mmol/L and increased by 0.16 ± 0.40 mmol/L in CON and PECAN groups, respectively. Non-HDL-C showed a similar pattern with the CON group showing a decrease and PECAN group displaying an increase (−0.18 ± 0.36 mmol/L vs. 0.16 ± 0.40 mmol/L, respectively). Bodyweight significantly (P = 0.025) decreased in the PECAN group when compared to the CON group (−0.58 ± 0.56 kg vs. −0.05 ± 0.55 kg, respectively).
In conclusion, a single serving of pecan nuts had no significant impact on lipid markers of cardiovascular risk. Bodyweight was significantly reduced consistent with recent literature showing a favourable relationship with nut intake and energy balance(3)
Benefits of musical training on implicit memory and learning in healthy older adults and individuals with dementia
Get PDFAgeing is linked to a variety of health issues, but perhaps the most well documented feature of growing older is that it is associated with memory decline (Ward, Berry & Shanks, 2013). It is well established that explicit memory declines with age, with the rate of decline being an important predictor of the diagnosis of dementia (Ward et al., 2013). Implicit memory is involved in everyday tasks that, with practice, become largely automatic. The process of implicit learning is generally defined as the ability to acquire knowledge unconsciously. An effective way of improving health in older adults is through music. Making music is one of the essential skills that requires the use of implicit knowledge. Procedural learning is one type of implicit knowledge that focuses on the learning of a skill through repeated performance and practise. To become a professional musician takes years of skill training, for example, practising
scales improves finger patterns in pianists, which over time becomes an implicit motor skill that helps with musical performance. Previous research that has looked at implicit memory in musicians, has focused on young adults and found that both musicians and
non-musicians performed equally on implicit knowledge tasks (Bigand et al. 2001). This thesis aimed to look at whether musical training is associated with better performance in implicit memory in healthy older adults and individual with dementia. To do this
implicit memory tasks including an adaptation of the Phoneme Monitoring Task (Bigand et al., 2001), Serial Reaction Time Task (Nissen & Bullemer, 1987) and The Word Completion tasks (Tulving, Schacter & Stark, 1982), were completed by healthy older
adults and individuals with dementia both musicians and non-musicians.
Overall, results showed that musicians, both older adults and individuals with dementia, performed better than non-musicians on procedural learning tasks (Serial Reaction Time Task) but there was no difference on implicit tasks such as priming. Although both musicians and non-musicians with dementia showed reaction times that would suggest procedural learning for repeated sequences, only musicians showed a significant difference between repeated and novel sequences, suggesting that musical training benefits procedural learning. Overall, both health older adult musicians and musicians with dementia performed faster than non-musicians on both the Serial Reaction Time Task and the Adapted Phoneme Monitoring task. However, results did not reach significance on the Adapted Phoneme Monitoring Task. The results suggest that musical training benefits procedural learning in musicians, which could have positive implications for future learning in older adults and individuals with dementia
Kurt Schwitters in Isolation - An Aesthetics of Resistance
Get PDFThis research forms part of an integrated practice and writing, and ongoing photographic artworks made in relation to the context of isolation, internment and exile. These images are photographed using small and medium format cameras, which in their use oscillate between the instantaneous moment encountered, and a pre-conceived image, which activate the spaces, which they index. A portfolio of photographs responds to the site of Hutchinson ‘P’ Camp and its environs as it exists today. Other images and object based works respond specifically to small paintings of glimpsed views, which carry the viewer over the rooftops of Douglas to the horizon.Following his escape from Norway and arrival in Britain - via Edinburgh - Kurt Schwitters was interned in the Isle of Man from July 1940 to November 1941. The essay investigates Kurt Schwitters isolation and marginalised position during the internment period and the different modalities of exile which Schwitters trajectory reveals. Upon his arrival in Douglas Schwitters use of the discarded and worthless in his finding, collecting and transformation of materials was already established. In the context of exile this process finds its denouement in a series of collages, assemblages, sculpture and paintings, which form part of an archive of over 200 works made during this time. In these works, the febrile and sensitive nature of their handling and making embodies the conditions of habitation, isolation and exile within which they were crafted. The artworks which Schwitters made embody a very specific material presence in the rarefied use of objects, materials and things, which take on a different significance in this context.
Schwitters status as an artist in exile is that of a ‘double-bind’ having fled a home to which he and fellow refugee artists could likely never return. The situation was one defined, confined and reconfigured by circumstances both within and beyond his control in terms of the choice and or availability of materials, which he and fellow artists had access to. These conditions were ultimately defined by the isolation, uncertainty and fear, which the internees endured in their separation from family and friends. At the same time the fabric of the environment and significantly here the lived-in-space, which Schwitters inhabited came to signify the hermetic nature of specific works and performances. The separation from home, family and friends and the depression and anxiety, which Schwitters and other internees suffered was compounded in their not knowing from one week to the next when they might be released. This was exasperated as a result of the restrictions which their correspondence was subject to in its censorship
“If ever there was someone to keep me at home”: Theorizing screen representations of siblinghood through a case study of Into the Wild (2007)
Get PDFThis is an Accepted Manuscript of an article published by Taylor & Francis in Quarterly Review of Film and Video on 04/03/2021, available online: https://doi.org/10.1080/10509208.2021.1886823Images of siblings pervade the screen, yet their representation remains under-explored. Though sibling relationships are common, these lateral bonds are often overlooked in favor of the vertical bonds privileged by Freudian psychoanalysis. Into the Wild (dir. Sean Penn 2007), though ostensibly focused on the solitary journey of its protagonist, Chris McCandless, can be read as a narrative of siblinghood and here serves as a case study for exploring ways of theorizing the sibling relationship on screen. Often, there is an inherent anxiety embedded within representations of close adult bonds between brothers and sisters, resulting in frequent on-screen separation. Though Chris and his sister Carine are similarly separated for the majority of the film, their relationship is foregrounded by framing Chris’s story through Carine’s re-telling. Here, the sibling pair may be better understood through the prism of modern discourses of the soulmate, emphasizing the value of knowledge to the sibling relationship and looking beyond the vertical to consider how lateral bonds might be excavated from the edges of the screen
Setting an International Research Agenda for Fear of Cancer Recurrence: an online delphi consensus study
Get PDFThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permissionBackground: Fear of cancer recurrence (FCR) is common amongst cancer survivors. There is rapidly growing research interest in FCR but a need to prioritise research to address the most pressing clinical issues and reduce duplication and fragmentation of effort. This study aimed to establish international consensus among clinical and academic FCR experts regarding priorities for FCR research.
Methods: Members of the International Psycho-oncology Society (IPOS) Fear of Cancer Recurrence Special Interest Group (FORwards) were invited to participate in an online Delphi study. Research domains identified in Round 1 were presented and discussed at a focus group (Round 2) to consolidate the domains and items prior to presentation in further survey rounds (Round 3) aimed at gaining consensus on research priorities of international significance.
Results: Thirty four research items were identified in Round 1 and 33 of the items were consolidated into 6 overarching themes through a focus group discussion with FCR experts. The 33 research items were presented in subsequent rounds of the delphi technique. Twenty one participants contributed to delphi round 1, 16 in round 2 and 25 and 29 participants for subsequent delphi rounds. Consensus was reached for 27 items in round 3.1. A further 4 research items were identified by panellists and included in round 3.2. After round 3.2, 35 individual research items were ratified by the panellists. Given the high levels of consensus and stability between rounds no further rounds were conducted. Overall intervention research was considered the most important focus for FCR research. Panellists identified models of care that facilitate greater access to FCR treatment and evaluation of the effectiveness of FCR interventions in real world settings as the two research items of highest priority. Defining the mechanisms of action and active components across FCR/P interventions, was the third highest priority identified.
Conclusions: The findings of this study outline a research agenda for international FCR research. Intervention research to identify models of care that increase access to treatment, are based on a flexible approach based on symptom severity and can be delivered within routine clinical care, were identified as research areas to prioritise. Greater understanding of the active components and mechanisms of action of existing FCR interventions will facilitate increased tailoring of interventions to meet patient need
Evidence of a disability paradox in patient-reported outcomes in haemophilia.
Get PDFPeople with inherited and long-term conditions such as haemophilia have been shown to adapt to their levels of disability, often reporting better quality of life (QoL) than expected from the general population (the disability paradox). To investigate the disability paradox in people with haemophilia in the United States by examining preference differences in health state valuations versus the general population. We conducted a discrete choice experiment including duration to capture valuations of health states based on patient-reported preferences. Participants indicated their preferences for hypothetical health states using the EQ-5D-5L, where each participant completed 15 of the 120 choice tasks. Response inconsistencies were evaluated with dominated and repeated scenarios. Conditional-logit regressions with random sampling of the general population responses were used to match the sample of patients with haemophilia. We compared model estimates and derived preferences associated with EQ-5D-5L health states. After removing respondents with response inconsistencies, 1327/2138 (62%) participants remained (177/283 haemophilia; 1150/1900 general population). Patients with haemophilia indicated higher preference value for 99% of EQ-5D-5L health states compared to the general population (when matched on age and gender). The mean health state valuation difference of 0.17 indicated a meaningful difference compared to a minimal clinically important difference threshold of 0.07. Results were consistent by haemophilia type and severity. Our findings indicated the presence of a disability paradox among patients with haemophilia, who reported higher health states than the general population, suggesting the impact of haemophilia may be underestimated if general population value sets are used. [Abstract copyright: © 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd.]Funder: uniQure Inc
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