| 411. |
- Schuyler, Alexander J, et al.
(författare)
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Quantitative Binding Assay for Measuring Specific IgG Antibodies to Alpha-Gal Using the Neoglycoprotein Gal-alpha-1,3-Gal-beta-1,4-Glcnac-Human Serum Albumin
- 2015
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 135:2, s. AB188-AB188
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Tick bites are known to induce IgE production to alpha-gal. Elevated alpha-gal IgG1 compared to natural alpha-gal IgG2 production has been reported in alpha-gal IgE+ subjects. We here report further investigation of the relationship between alpha-gal IgG and both reactions to red meat and exposure to ticks. Methods: IgG from serum was absorbed onto recombinant Protein G-Sepharose and incubated with radiolabeled allergen. The radioactivity of bound allergen was measured using a gamma counter. A control curve was generated in parallel to assign unitage. Additional testing of serum immunoglobulins was performed via ImmunoCAP and nephelometry. Results: Alpha-gal IgG was measured in a Northern Sweden cohort and in subjects presenting to allergy clinics in Virginia with delayed reactions to red meat. Alpha-gal IgG was significantly higher in alpha-gal IgE+ subjects versus alpha-gal IgE- subjects, and longitudinal serology in several alpha-gal IgE+ subjects demonstrates parallel alpha-gal IgE and IgG response trends. Among the alpha-gal IgE+ subjects, alpha-gal IgG was higher in those with alpha-gal IgE:total IgE ratios >25%, but was not related to reported severity to red meat. Compared to the alpha-gal IgE- subjects in Virginia, alpha-gal IgG was lower in the group from Northern Sweden, where alpha-gal IgE-mediated hypersensitivity is absent and ticks are rare. Conclusions: Alpha-gal IgG is strongly related to alpha-gal IgE and is significantly lower in prevalence and titer in subjects without tick exposure. The absence of a relationship between alpha-gal IgG and severity of reactions to red meat suggests that the alpha-gal syndrome may not be a suitable candidate for conventional immunotherapy.
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| 412. |
- Scott, Gregory, et al.
(författare)
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Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration.
- 2018
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156 .- 1460-2156. ; 141:2, s. 459-471
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Tidskriftsartikel (refereegranskat)abstract
- Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using 11C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, 11C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater 11C-PBR28 binding. Minocycline reduced 11C-PBR28 binding (mean Δwhite matter binding = -23.30%, 95% confidence interval -40.9 to -5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.
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| 413. |
- Scott, James, et al.
(författare)
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PreHeat : Controlling home heating using occupancy prediction
- 2011
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Ingår i: Proceedings of the 13th international conference on Ubiquitous computing (UbiComp ’11). - New York, NY, USA : ACM. - 9781450306300 ; , s. 281-290
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Konferensbidrag (refereegranskat)abstract
- Home heating is a major factor in worldwide energy use. Our system, PreHeat, aims to more efficiently heat homes by using occupancy sensing and occupancy prediction to automatically control home heating. We deployed PreHeat in five homes, three in the US and two in the UK. In UK homes, we controlled heating on a per-room basis to enable further energy savings. We compared PreHeat’s prediction algorithm with a static program over an average 61 days per house, alternating days between these conditions, and measuring actual gas consumption and occupancy. In UK homes PreHeat both saved gas and reduced MissTime (the time that the house was occupied but not warm). In US homes, PreHeat decreased MissTime by a factor of 6-12, while consuming a similar amount of gas. In summary, PreHeat enables more efficient heating while removing the need for users to program thermostat schedules.
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| 414. |
- Scott, James S., et al.
(författare)
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Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists
- 2014
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society. - 0022-2623 .- 1520-4804. ; 57:21, s. 8984-8998
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Tidskriftsartikel (refereegranskat)abstract
- Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.
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| 415. |
- Scott, James S., et al.
(författare)
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Optimisation of aqueous solubility in a series of G protein coupled receptor 119 (GPR119) agonists
- 2013
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Ingår i: MedChemComm. - : Royal Society of Chemistry (RSC). - 2040-2503 .- 2040-2511. ; 4:1, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- Improving aqueous solubility is a challenge frequently faced within drug discovery programs. Herein we describe increases in solubility in two sub-series of GPR119 agonists through reduction of lipophilicity together with hydrogen bond acceptor modulation. Small molecule X-ray crystallography was utilised to investigate effects on solid state interactions.
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| 416. |
- Scott, Michael James, et al.
(författare)
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Managing Group Projects in Undergraduate Computing
- 2023
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Ingår i: ITiCSE 2023. - : Association for Computing Machinery (ACM). - 9798400701399 ; , s. 597-598
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Konferensbidrag (refereegranskat)abstract
- This panel convenes four educators, each from different institutions and each with experience managing group projects. Their expertise spans topics including: peer assessment and peer evaluation; entrepreneurship; transdisciplinarity; internationalisation; inclusivity; social values; educational technology and tools; feedback and feed-forward; peer rating; free-riders; as well as blended learning; and post-pandemic online discourse. They reflect on the delight of seeing students collaborate to deliver meaningful projects as well as the challenges posed by disengaged students. They also explore a common theme of discordance inherent to teamwork and systems to support student communities.
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| 417. |
- Scott, Whitney, et al.
(författare)
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Acceptability of psychologically-based pain management and online delivery for people living with HIV and chronic neuropathic pain : a qualitative study
- 2021
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Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 21:2, s. 296-307
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Chronic neuropathic pain is common in people living with HIV. Psychological treatments can improve quality of life for people with chronic pain in general, and online delivery can increase access to these treatments. However, the acceptability of psychological treatment and online delivery have not been investigated in-depth in people living with HIV and chronic neuropathic pain. Therefore, a qualitative study was undertaken to explore views about a psychological treatment for pain management in this population and to investigate the acceptability of online treatment delivery.Methods: Qualitative interviews were conducted and analysed using inductive thematic analysis, adopting a critical realist perspective. Twenty-six people living with HIV and chronic neuropathic pain completed semi-structured interviews. Their views about a psychological treatment for pain management and online delivery were explored in-depth.Results: Three themes and 12 subthemes were identified. Theme one represents a desire for a broader approach to pain management, including not wanting to take more pills and having multidimensional goals that were not just focussed on pain relief. Theme two includes barriers to online psychologically-based pain management, including concerns about using the Internet and confidentiality. Theme three describes treatment facilitators, including accessibility, therapist support, social connection, and experiencing success.Conclusions: A psychological treatment for chronic neuropathic pain management appears acceptable for people living with HIV. Therapist-supported online delivery of cognitive-behavioural pain management may be acceptable for people living with HIV given appropriate development of the treatment to address identified barriers to engagement. These data can inform developments to enhance engagement in online psychologically-informed pain management in people living with HIV and more broadly in remote delivery of psychological treatments.
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| 418. |
- Scott, Whitney, et al.
(författare)
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Feasibility randomized-controlled trial of online acceptance and commitment therapy for painful peripheral neuropathy in people living with HIV : The OPEN study
- 2021
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Ingår i: European Journal of Pain. - : John Wiley & Sons. - 1090-3801 .- 1532-2149. ; 25:7, s. 1493-1507
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Tidskriftsartikel (refereegranskat)abstract
- Background Neuropathic pain negatively affects quality of life among people living with HIV (PLWH). This study examined the feasibility of conducting a full-scale randomized-controlled trial of online acceptance and commitment therapy ("ACT OPEN") for neuropathic pain in PLWH. Methods Using a parallel-groups design, thirty-eight participants were randomized to ACT OPEN or a waitlist control (2:1). Participants completed standard self-report outcome measures at baseline, and two- and five-months post-randomization. Participants were aware of their allocation, but assessment was blinded. Results Twenty-five participants were randomized to ACT OPEN and 13 to the control (of 133 referrals). ACT OPEN completion was 69% and two-month trial retention was 82%. Treatment credibility and satisfaction scores for ACT OPEN were comparable to scores reported in previous trials of cognitive-behavioural treatments for pain. Four adverse events were reported during the study, including one serious adverse event; all of these were unrelated to the research procedures. Small to moderate effects and 95% confidence intervals suggest that the true effect may favour ACT OPEN for improvements in pain intensity/interference and depression. Conclusions A full-scale RCT of online ACT for pain management in PLWH may be feasible with refinements to trial design to facilitate recruitment. Significance Research on pain management in people living with HIV has primarily focused on pharmacological treatments with limited success. This is the first study to show the potential feasibility of a psychological treatment based on acceptance and commitment therapy delivered online and tailored for pain management in people with HIV ("ACT OPEN"). ACT OPEN may be a promising treatment in this population and further evaluation in a full-scale randomized-controlled trial appears warranted.
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| 419. |
- Seiler, Roland, et al.
(författare)
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Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 72:4, s. 544-554
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Tidskriftsartikel (refereegranskat)abstract
- Background: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. Objective: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Design, setting, and participants: Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Intervention: Gene expression analysis was used to assign subtypes. Outcome measurements and statistical analysis: Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. Results and limitations: The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Conclusions: Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Patient summary: Different molecular subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation. Molecular subtypes in muscle-invasive bladder cancer appear have an impact on patient response to neoadjuvant chemotherapy (NAC); namely, patients with basal tumors showed the most benefit from NAC and should be prioritized for NAC. Moreover, these subtypes can be identified in a single sample by our discovered classifier.
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| 420. |
- Sharma, Sapna, et al.
(författare)
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A global database of lake surface temperatures collected by in situ and satellite methods from 1985–2009
- 2015
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Ingår i: Scientific Data. - : Macmillan Publishers Limited. - 2052-4463. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Global environmental change has influenced lake surface temperatures, a key driver of ecosystem structure and function. Recent studies have suggested significant warming of water temperatures in individual lakes across many different regions around the world. However, the spatial and temporal coherence associated with the magnitude of these trends remains unclear. Thus, a global data set of water temperature is required to understand and synthesize global, long-term trends in surface water temperatures of inland bodies of water. We assembled a database of summer lake surface temperatures for 291 lakes collected in situ and/or by satellites for the period 1985–2009. In addition, corresponding climatic drivers (air temperatures, solar radiation, and cloud cover) and geomorphometric characteristics (latitude, longitude, elevation, lake surface area, maximum depth, mean depth, and volume) that influence lake surface temperatures were compiled for each lake. This unique dataset offers an invaluable baseline perspective on global-scale lake thermal conditions as environmental change continues.
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