Poly(ethyl acrylate) (PEA)/poly(methyl methacrylate) (PMMA) emulsion blends that were combined with unmodified montmorillionite (MMT) to improve the physical properties via nanocomposite formation. ...We prepared a cationic PEA/PMMA latex and used a heterocoagulation process to create a homogeneous dispersion of the clay platelets in the matrix. The cationic PEA/PMMA emulsion blends were prepared using a cationic initiator in the presence of free surfactant, cetyl trimethylammonium bromide (CTABr), followed by mixing with an aqueous slurry of MMT. The PEA/PMMA–MMT nanocomposites could be processed at low temperatures. Low temperature processing prevented the commonly observed discoloration associated with many thermoplastic nanocomposites. DSC, SAXS, TEM and AFM were used to study the dispersion of MMT and morphology of PEA/PMMA–MMT nanocomposites. Tensile stress, elongation at break and Young's modulus demonstrated a significant reinforcing effect of clay.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The mechanisms leading to the development of functional motor symptoms (FMS) are of pathophysiological and clinical relevance, yet are poorly understood.
The aim of the present study was to evaluate ...whether impaired emotional processing at the cognitive level (alexithymia) is present in patients affected by FMS. We conducted a cross-sectional study in a population of patients with FMS and in two control groups (patients with organic movement disorders (OMD) and healthy volunteers).
55 patients with FMS, 33 patients affected by OMD and 34 healthy volunteers were recruited. The assessment included the 20-item Toronto Alexithymia Scale (TAS-20), the Montgomery-Asberg Depression Rating Scale, the Reading the Mind in the Eyes' Test and the Structured Clinical Interview for Personality Disorders.
Alexithymia was present in 34.5% of patients with FMS, 9.1% with OMD and 5.9% of the healthy volunteers, which was significantly higher in the FMS group (χ(2) (2)=14.129, p<0.001), even after controlling for the severity of symptoms of depression. Group differences in mean scores were observed on both the difficulty identifying feelings and difficulty describing feelings dimensions of the TAS-20, whereas the externally orientated thinking subscale score was similar across the three groups. Regarding personality disorder, χ(2) analysis showed a significantly higher prominence of obsessive-compulsive personality disorder (OCPD) in the FMS group (χ(2) (2)=16.217, p<0.001) and 71.4% of those with OCPD also reached threshold criteria for alexithymia.
Because alexithymia is a mental state denoting the inability to identify emotions at a cognitive level, one hypothesis is that some patients misattribute autonomic symptoms of anxiety, for example, tremor, paraesthesiae, paralysis, to that of a physical illness. Further work is required to understand the contribution of OCPD to the development of FMS.
(6‐((R)‐2‐{2‐4‐(4‐Chloro‐phenoxy)‐piperidin‐1‐yl‐ethyl}‐pyrrolidine‐1‐sulphonyl)‐1H‐indole hydrochloride) (SB‐656104‐A), a novel 5‐hydroxytryptamine (5‐HT7) receptor antagonist, potently inhibited ...3H‐SB‐269970 binding to the human cloned 5‐HT7(a) (pKi 8.7±0.1) and 5‐HT7(b) (pKi 8.5±0.2) receptor variants and the rat native receptor (pKi 8.8±0.2). The compound displayed at least 30‐fold selectivity for the human 5‐HT7(a) receptor versus other human cloned 5‐HT receptors apart from the 5‐HT1D receptor (∼10‐fold selective).
SB‐656104‐A antagonised competitively the 5‐carboxamidotryptamine (5‐CT)‐induced accumulation of cyclic AMP in h5‐HT7(a)/HEK293 cells with a pA2 of 8.5.
Following a constant rate iv infusion to steady state in rats, SB‐656104 had a blood clearance (CLb) of 58±6 ml min−1 kg−1 and was CNS penetrant with a steady‐state brain : blood ratio of 0.9 : 1. Following i.p. administration to rats (10 mg kg−1), the compound displayed a t1/2 of 1.4 h with mean brain and blood concentrations (at 1 h after dosing) of 0.80 and 1.0 μM, respectively.
SB‐656104‐A produced a significant reversal of the 5‐CT‐induced hypothermic effect in guinea pigs, a pharmacodynamic model of 5‐HT7 receptor interaction in vivo (ED50 2 mg kg−1).
SB‐656104‐A, administered to rats at the beginning of the sleep period (CT 0), significantly increased the latency to onset of rapid eye movement (REM) sleep at 30 mg kg−1 i.p. (+93%) and reduced the total amount of REM sleep at 10 and 30 mg kg−1 i.p. with no significant effect on the latency to, or amount of, non‐REM sleep. SB‐269970‐A produced qualitatively similar effects in the same study.
In summary, SB‐656104‐A is a novel 5‐HT7 receptor antagonist which has been utilised in the present study to provide further evidence for a role for 5‐HT7 receptors in the modulation of REM sleep.
British Journal of Pharmacology (2003) 139, 705–714. doi:10.1038/sj.bjp.0705290
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More ...recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.
Full text
Available for:
FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
AbstractThe SPIRIT 2013 (The Standard Protocol Items: Recommendations for Interventional Trials) statement aims to improve the completeness of clinical trial protocol reporting, by providing ...evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there is a growing recognition that interventions involving artificial intelligence need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes.The SPIRIT-AI extension is a new reporting guideline for clinical trials protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI. Both guidelines were developed using a staged consensus process, involving a literature review and expert consultation to generate 26 candidate items, which were consulted on by an international multi-stakeholder group in a 2-stage Delphi survey (103 stakeholders), agreed on in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The SPIRIT-AI extension includes 15 new items, which were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations around the handling of input and output data, the human-AI interaction and analysis of error cases.SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.
Background/aims
Functional visual symptoms are relatively common symptoms seen by ophthalmologists. However, there are no consensus guidelines on ophthalmological management of this condition, and ...there is a paucity of knowledge about the collective challenges experienced in treating patients with functional visual symptoms. In order to establish an ophthalmological perspective on this condition, we undertook the first national survey of experience, knowledge and management of functional visual symptoms amongst ophthalmologists.
Methods
An online survey was disseminated to ophthalmologists in the UK via all Royal College of Ophthalmology college tutors.
Results
One hundred nineteen ophthalmologists completed the survey. Functional visual symptoms accounted for 3% of all new referrals. Forty per cent of respondents felt they had a good understanding of functional visual symptoms. Two-thirds reported a need for further training in this area. Respondents estimated two-thirds of patients’ symptoms improved, but a third experienced severe or extreme disability. Following diagnosis, a minority of patients were referred to mental health or neurology services. The majority of respondents described difficulty discussing psychological factors, with a lack of time or space in a clinic preventing a holistic approach. Free text comments highlighted a lack of access to dedicated psychological support for patients.
Conclusion
Functional visual symptoms are disabling and are seen relatively frequently by ophthalmologists. This preliminary survey suggests that care pathways for patients with functional visual symptoms could be optimised. Fostering links between ophthalmology and existing services with expertise in functional disorders could improve patient care and clinician education and ultimately encourage research in this area.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance ...has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.
Full text
Available for:
FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
GABA
B
receptors are G-protein-coupled receptors that mediate slow synaptic inhibition in the brain and spinal cord. These receptors are heterodimers assembled from GABA
B1
and GABA
B2
subunits, ...neither of which is capable of producing functional GABA
B
receptors on homomeric expression. GABA
B1,
although able to bind GABA, is retained within the endoplasmic reticulum (ER) when expressed alone. In contrast, GABA
B2
is able to access the cell surface when expressed alone but does not couple efficiently to the appropriate effector systems or produce any detectable GABA-binding sites. In the present study, we have constructed chimeric and truncated GABA
B1
and GABA
B2
subunits to explore further GABA
B
receptor signaling and assembly. Removal of the entire C-terminal intracellular domain of GABA
B1
results in plasma membrane expression without the production of a functional GABA
B
receptor. However, coexpression of this truncated GABA
B1
subunit with either GABA
B2
or a truncated GABA
B2
subunit in which the C terminal has also been removed is capable of functional signaling via G-proteins. In contrast, transferring the entire C-terminal tail of GABA
B1
to GABA
B2
leads to the ER retention of the GABA
B2
subunit when expressed alone. These results indicate that the C terminal of GABA
B1
mediates the ER retention of this protein and that neither of the C-terminal tails of GABA
B1
or GABA
B2
is an absolute requirement for functional coupling of heteromeric receptors. Furthermore although GABA
B1
is capable of producing GABA-binding sites, GABA
B2
is of central importance in the functional coupling of heteromeric GABA
B
receptors to G-proteins and the subsequent activation of effector systems.
AbstractObjectiveTo describe the development and validation of a novel patient reported outcome measure for symptom burden from long covid, the symptom burden questionnaire for long covid ...(SBQ-LC).DesignMultiphase, prospective mixed methods study.SettingRemote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021.Participants13 adults (aged ≥18 years) with self-reported long covid and 10 clinicians evaluated content validity. 274 adults with long covid field tested the draft questionnaire.Main outcome measuresPublished systematic reviews informed development of SBQ-LC’s conceptual framework and initial item pool. Thematic analysis of transcripts from cognitive debriefing interviews and online clinician surveys established content validity. Consensus discussions with the patient and public involvement group of the Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient reported outcomes and immunology to targeted therapies (TLC Study) confirmed face validity. Rasch analysis of field test data guided item and scale refinement and provided initial evidence of the SBQ-LC’s measurement properties.ResultsSBQ-LC (version 1.0) is a modular instrument measuring patient reported outcomes and is composed of 17 independent scales with promising psychometric properties. Respondents rate their symptom burden during the past seven days using a dichotomous response or 4 point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that can be transformed to a linear (0-100) score. Higher scores represent higher symptom burden. After rating scale refinement and item reduction, all scales satisfied the Rasch model requirements for unidimensionality (principal component analysis of residuals: first residual contrast values <2.00 eigenvalue units) and item fit (outfit mean square values within 0.5 -1.5 logits). Rating scale categories were ordered with acceptable category fit statistics (outfit mean square values <2.0 logits). 14 item pairs had evidence of local dependency (residual correlation values >0.4). Across the 17 scales, person reliability ranged from 0.34 to 0.87, person separation ranged from 0.71 to 2.56, item separation ranged from 1.34 to 13.86, and internal consistency reliability (Cronbach’s alpha) ranged from 0.56 to 0.91.ConclusionsSBQ-LC (version 1.0) is a comprehensive patient reported outcome instrument developed using modern psychometric methods. It measures symptoms of long covid important to people with lived experience of the condition and may be used to evaluate the impact of interventions and inform best practice in clinical management.
IMPORTANCE: Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, ...the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. OBJECTIVE: To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension). DESIGN, SETTING, AND PARTICIPANTS: The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network’s methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols. RESULTS: The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n = 21) reduced this to 56 items, which were considered by 138 international stakeholder survey participants and 99 Delphi panelists. The final wording of the SPIRIT-PRO Extension was agreed on at a consensus meeting (n = 29 participants) and reviewed by external group of experts during a consultation period. Eleven extensions and 5 elaborations to the SPIRIT 2013 checklist were recommended for inclusion in clinical trial protocols in which PROs are a primary or key secondary outcome. Extension items focused on PRO-specific issues relating to the trial rationale, objectives, eligibility criteria, concepts used to evaluate the intervention, time points for assessment, PRO instrument selection and measurement properties, data collection plan, translation to other languages, proxy completion, strategies to minimize missing data, and whether PRO data will be monitored during the study to inform clinical care. CONCLUSIONS AND RELEVANCE: The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome. Improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.
PDF
