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Suppressor of cytokine signalling 3 (SOCS3) turnover and regulation of human saphenous vein smooth muscle cell signalling and function
No full textNeointimal hyperplasia (NIH) is a cardiovascular disease characterised by increased smooth muscle cell (SMC) inflammation and proliferation. Suppressor of cytokine signalling 3 (SOCS3) limits Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in vascular remodelling but is limited by its short biological half-life. Therefore, mutation of all 9 Lys residues that are potential sites of ubiquitylation to Arg should produce a mutated SOCS3 resistant to ubiquitin-mediated proteasomal degradation (“Lys-less” SOCS3). This study hypothesise that enhancing SOCS3 stability and limiting JAK/STAT signalling may provide sustained inhibition of the vascular remodelling in NIH.
Lentiviral transduction of WT and Lys-less SOCS3 in human saphenous vein (HSVSMCs) was highly efficient after 48 hours (>97%) and was sustained over 2 weeks. Lys-less SOCS3 was resistant to ubiquitylation contrary to WT-transduced HSVECs, and Lys-less SOCS3 was more stable (t1/2=4h) than WT (t1/2<4h) (n=6, P<0.001) in HSVSMCs. In HSVSMCs, both Lys-less SOCS3 and WT inhibited sIL-6Rα/IL-6 mediated STAT3 activation but not extracellular signal regulated protein kinase 1/2 (ERK1/2) by 80±7% (Lys-lessSOCS3/pSTAT3) and 74±6% (WT/pSTAT3) (n=3, P<0.05) and similarly inhibited PDGF-mediated STAT3 activation but not ERK1/2 by 67±17% (Lys-less SOCS3/pSTAT3) and 72±18% (WT/pSTAT3) (n=3, P<0.05). Functionally, Lys-less SOCS3 and WT were equivalent in inhibiting sIL-6Rα/IL-6 and PDGF-induced proliferation, whilst having no effects on PDGF-induced migration in HSVSMCs.
Lys-less SOCS3 can be successfully transduced into primary HSVSMCs. It is more stable than WT yet retains its functional ability to ameliorate pro-inflammatory signalling and SMC proliferation, making it an attractive option for developing treatment of NIH.University of Botswan
Noria and its derivatives as hosts for chemically and thermally robust Type II porous liquids
No full textYesPorous Liquids (PLs) are a new class of material that possess both fluidity and permanent porosity. As such they can act as enhanced, selective solvents and may ultimately find applications which are not possible for porous solids, such as continuous flow separation processes. Type II PLs consist of empty molecular hosts dissolved in size-excluded solvents and to date have mainly been based on hosts that have limited chemical and thermal stability. Here we identify Noria, a rigid cyclic oligomer as a new host for the synthesis of more robust Type II PLs. Although the structure of Noria is well-documented, we find that literature has overlooked the true composition of bulk Noria samples. We find that bulk samples typically consist of Noria (ca. 40%), a Noria isomer, specifically a resorcinarene trimer, “R3” (ca. 30%) and other unidentified oligomers (ca. 30%). Noria has been characterised crystallographically as a diethyl ether solvate and its 1H NMR spectrum fully assigned for the first time. The previously postulated but unreported R3 has also been characterised crystallographically as a dimethyl sulfoxide solvate, which confirms its alternative connectivity to Noria. Noria and R3 have low solubility which precludes their use in Type II PLs, however, the partially ethylated derivative Noria-OEt dissolves in the size-excluded solvent 15-crown-5 to give a new Type II PL. This PL exhibits enhanced uptake of methane (CH4) gas supporting the presence of empty pores in the liquid. Detailed molecular dynamics simulations support the existence of pores in the liquid and show that occupation of the pores by CH4 is favoured. Overall, this work revises the general accepted composition of bulk Noria samples and shows that Noria derivatives are appropriate for the synthesis of more robust Type II PLs.Agencia Nacional de Promoción Científica y TecnológicaPICT-2015-1835. Universidad Nacional de CuyoUnassigned. Engineering and Physical Sciences Research CouncilEP/R005540/
Adaptive and Robust Multi-Gigabit Techniques Based MmWave Massive MU-MIMO Beamforming For 5G Wireless and Mobile Communications Systems. A Road Map for Simple and Robust Beamforming Scheme and Algorithms Based Wideband MmWave Massive MU-MIMO for 5G Wireless and Mobile Communications Systems
No full textOver recent years, the research and studies have focused on innovative solutions in various aspects
and phases related to the high demands on data rate and energy for fifth-generation and beyond
(B5G). This thesis aims to improve the energy efficiency, error rates, low-resolution
ADCs/DACs, antenna array structures and sum-rate performances of a single cell downlink
broadband millimetre-wave (mmWave) systems with orthogonal frequency division multiplexing
(OFDM) modulation and deploying multi-user massive multiple inputs multiple outputs (MU mMIMO) by applying robust beamforming techniques and detection algorithms that support
multiple streams per user (UE) in various environments and scenarios to achieve low complexity
system design with reliable performance and significant improvement in users perceived quality
of service (QoS).
The performance of the four 5G candidate mmWave frequencies, 28 GHz, 39 GHz, 60 GHz, and
73 GHz, are investigated for indoor/outdoor propagation scenarios, including path loss models
and multipath delay spread values. Results are compared to confirm that the received power and
delay spread is decreased with increasing frequency. The results were also validated with the
measurement findings for 60 GHz.
Then several proposed design models of beamforming are studied and implemented modified
algorithms of Hybrid Beamforming (HBF) approaches in indoor/outdoor scenarios over large
scale fading wideband mmWave /Raleigh channels. Firstly, three beamforming based diagonalize
the Equivalent Virtual Channel Matrix (EVCM) schemes with the optimal linear combining
methods are presented to overcoming the self-interference problems in Quasi-Orthogonal-Space
Time Block Code (QO-STBC) systems over narrowband mmWave Single-User mMIMO (SU mMIMO). The evaluated results show that the proposed beamforming based- Single Value
Decomposition (SVD) outperforms the conventional beamforming and standard QO-STBC
techniques in terms of BER and spectrum efficiency.
Next, the proposed HBF algorithm approaches with the fully/ partially connected structures are
developed and applied for sum-rate and symbol error rate (SER) performance maximization MU mMIMO-OFDM system, including HBF based on block diagonalization (BD) method Constraint/Unconstraint RF Power, Codebook, Kalman schemes. In addition, the modified near optimal linear HBF-Zero Forcing (HBF-ZF) and HBF-Minimum Mean Square Error (HBF MMSE) schemes, considering both fully-connected and partially-connected structures.
Finally, Simulation results using MATLAB platform, demonstrate that the proposed HBF based codebook and most likely HBF based-unconstraint RF power algorithms achieve significant
performance gains in terms SER and sum-rate efficiency as well as show high immunity against
the deformities and disturbances in the system compared with other HBF algorithm schemes.Ministry of Higher Education and Scientific Research, the Republic of Ira
Artificial Intelligence-based Public Healthcare Systems: G2G Knowledge-based Exchange to Enhance the Decision-making Process
Get PDFYesWith the rapid evolution of data over the last few years, many new technologies have arisen with artificial intelligent (AI) technologies at the top. Artificial intelligence (AI), with its infinite power, holds the potential to transform patient healthcare. Given the gaps revealed by the 2020 COVID-19 pandemic in healthcare systems, this research investigates the effects of using an artificial intelligence-driven public healthcare framework to enhance the decision-making process using an extended model of Shaft and Vessey (2006) cognitive fit model in healthcare organizations in Saudi Arabia. The model was validated based on empirical data collected using an online questionnaire distributed to healthcare organizations in Saudi Arabia. The main sample participants were healthcare CEOs, senior managers/managers, doctors, nurses, and other relevant healthcare practitioners under the MoH involved in the decision-making process relating to COVID-19. The measurement model was validated using SEM analyses. Empirical results largely supported the conceptual model proposed as all research hypotheses are significantly approved. This study makes several theoretical contributions. For example, it expands the theoretical horizon of Shaft and Vessey's (2006) CFT by considering new mechanisms, such as the inclusion of G2G Knowledge-based Exchange in addition to the moderation effect of Experience-based decision-making (EDBM) for enhancing the decision-making process related to the COVID-19 pandemic. More discussion regarding research limitations and future research directions are provided as well at the end of this study
Diagnostic radiographer advanced clinical practice in the United Kingdom - A national cross-sectional survey
Get PDFYesTo survey the diagnostic radiography workforce in the United Kingdom (UK) at an organisational level to ascertain the scope of advanced practice and compliance with Health Education England standards for multiprofessional advanced clinical practice (ACP).
174 diagnostic imaging departments were invited to participate in a cross-sectional electronic survey focused upon advanced level practice and their educational and accreditation expectations (October-December 2019). Breast imaging, computed tomography, fluoroscopy, interventional radiology, lithotripsy, magnetic resonance imaging and projectional radiography were included.
A total of 97 responses were received, of which 79 were eligible for inclusion (45%). Respondents reported advanced-level practice roles across all imaging modalities, which included clinical reporting, procedural-based and combined roles. Radiograph and mammogram reporting were most prevalent (95 and 67% of Trusts), with fluoroscopy the most frequent procedure-only role (25%). Only 39% of trusts required adherence to the four pillars of ACP within job descriptions, and only 12% requiring a full Masters qualification.
Diagnostic radiographer reporting and procedure-based roles in the NHS are varied and widespread. However, inconsistencies in fulfilment against the expected standards for advanced practice exist. Realignment of advanced-level roles to delineate enhanced and advanced clinical practice may ensure consistency between roles and professions. A requirement for accreditation as an advanced (clinical) practitioner with adherence to advanced practice requirements could therefore provide value to accreditation for both individual practitioners and Trusts.
Within the UK, diagnostic radiographer roles previously self-identified as advanced-level practice may be termed enhanced practice when not adhering to expected ACP standards
What Are the Barriers and Enablers to the Implementation of Pharmacogenetic Testing in Mental Health Care Settings?
Get PDFYesIn psychiatry, the selection of antipsychotics and antidepressants is generally led by a trial-and-error approach. The prescribing of these medications is complicated by sub-optimal efficacy and high rates of adverse drug reactions (ADRs). These both contribute to poor levels of adherence. Pharmacogenetics (PGx) considers how genetic variation can influence an individual’s response to a drug. Pharmacogenetic testing is a tool that could aid clinicians when selecting psychotropic medications, as part of a more personalized approach to prescribing. This may improve the use of and adherence to these medications. Yet to date, the implementation of PGx in mental health environments in the United Kingdom has been slow. This review aims to identify the current barriers and enablers to the implementation of PGx in psychiatry and determine how this can be applied to the uptake of PGx by NHS mental health providers. A systematic searching strategy was developed, and searches were carried out on the PsychInfo, EmBase, and PubMed databases, yielding 11 appropriate papers. Common barriers to the implementation of PGx included cost, concerns over incorporation into current workflow and a lack of knowledge about PGx; whilst frequent enablers included optimism that PGx could lead to precision medicine, reduce ADRs and become a more routine part of psychiatric clinical care. The uptake of PGx in psychiatric care settings in the NHS should consider and overcome these barriers, while looking to capitalize on the enablers identified in this review.Bradford District Care NHS Foundation Trust in partnership with the University of Bradford; National Institute for Health Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR Yorkshire and Humber PSTRC); National Institute for Health Research Leeds in vitro Diagnostics Co-operative
Paired Evaluation: Preliminary Report from the Pilot Evaluation of the Paired App
Get PDFYesRomantic relationships are extremely important to people’s happiness and well-being, yet many
people do not seek advice with relationship issues or may do so only once serious problems arise.
Paired is a commercially available relationships app. Launched in October 2020, it currently has over
12,000 daily active users, predominantly in the US and UK.
Public self-management of care (i.e. self-help) is target for technological investment, as digital health
and well-being apps gain popularity. There are currently over 318,000 health apps available
worldwide, with a further 200+ new health apps coming onto the market each day. Research has
shown that mobile health (mHealth, i.e. health and well-being apps) can be effective in supporting
behaviour change: helping us to adopt and maintain healthy behaviours. However, many health and
well-being apps are not based on reliable research evidence, the only indication of an app’s quality
deriving from ‘user reviews’. Paired is evidence-based. Focusing on the area of romantic
relationships, it seeks to support and enhance couple relationships, before the point when
professional help may be needed.
Researchers at The Open University (OU) and the University of Brighton evaluated the effectiveness
of Paired, using a mixed methods approach...
We created the Quality of Relationship Index (QRI), a rigorously-developed measure of overall
relationship quality. We found that quality of communication – the underpinning dimension of all
relationship maintenance behaviour – was most strongly related to overall relationship quality...
In developing the QRI, we explored change in different aspects of relationship quality, whilst using
Paired...
Integration of the findings from our analyses of different data sources, and the ‘dose-response’
effect that we consistently observed, together give us confidence that Paired is responsible for the
improvements to relationship quality that its users enjoy.The Open Universit
Energy Efficient RF for UDNs
No full textMulti-standard RF front-end is a critical part of legacy and future emerging mobile architectures, where the size, the efficiency, and the integration of the elements in the RF front-end will affect the network key performance indicators (KPIs). This chapter discusses power amplifier design for both handset and base station applications for 5G and beyond. Also, this chapter deals with filter-antenna design for 5G applications that include a synthesis-based approach, differentially driven reconfigurable planar filter-antenna, and an insensitive phased array antenna with air-filled slot-loop resonators
Status of primary and secondary mental healthcare of people with severe mental illness: an epidemiological study from the UK PARTNERS2 programme
Get PDFYesThere is global interest in the reconfiguration of community mental health services, including primary care, to improve clinical and cost effectiveness.
This study seeks to describe patterns of service use, continuity of care, health risks, physical healthcare monitoring and the balance between primary and secondary mental healthcare for people with severe mental illness in receipt of secondary mental healthcare in the UK.
We conducted an epidemiological medical records review in three UK sites. We identified 297 cases randomly selected from the three participating mental health services. Data were manually extracted from electronic patient medical records from both secondary and primary care, for a 2-year period (2012-2014). Continuous data were summarised by mean and s.d. or median and interquartile range (IQR). Categorical data were summarised as percentages.
The majority of care was from secondary care practitioners: of the 18 210 direct contacts recorded, 76% were from secondary care (median, 36.5; IQR, 14-68) and 24% were from primary care (median, 10; IQR, 5-20). There was evidence of poor longitudinal continuity: in primary care, 31% of people had poor longitudinal continuity (Modified Modified Continuity Index ≤0.5), and 43% had a single named care coordinator in secondary care services over the 2 years.
The study indicates scope for improvement in supporting mental health service delivery in primary care. Greater knowledge of how care is organised presents an opportunity to ensure some rebalancing of the care that all people with severe mental illness receive, when they need it. A future publication will examine differences between the three sites that participated in this study.This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research programme (grant reference no. RP-PG-0611-20004). Professors Siobhan Reilly, Richard Byng and Max Birchwood are partially supported by the NIHR Applied Research Collaboration (ARC) for North West Coast, Care South West Peninsula and West Midlands, respectively
Isostructurality of quinoxaline crystal phases: The interplay of weak hydrogen bonds and halogen bonding
Get PDFYesTailoring the physical properties of molecular crystals though the construction of solid solutions requires the existence of isostructural crystals. Simple substitutions of a given molecular framework can give a range of different crystal structures. A set of quinoxaline derivatives, C8H4N2(C6H4X)2,Q3,3′X2, has been investigated (X = F, Cl, Br, I and Me) where kinetic factors generated a set of isostructural crystals for the lighter halogens (F, Cl, Br) alone. Computational analysis shows that the stabilising interactions are maximal for Cl, while DSC studies demonstrate the existence of more stable polymorphs for both F and Br containing systems. Steric factors appear to have a lower contribution than the balance of weaker hydrogen and halogen bonding shown by the Me and I containing systems displaying different packing driven by CH⋯N/CH⋯π bonds and I⋯I bonds respectively