The relationship between transliminality, hypnotic and imaginative suggestibility, and other personality traits.

To our knowledge, no study has directly examined the link between hypnotic response and the personality trait of transliminality (which is underpinned, for example, by magical ideation, mystical experience, fantasy proneness, absorption, hyperaesthesia). In order to further understand the correlates of suggestibility, the aim of the current project was to investigate whether transliminality is associated with hypnotic and imaginative suggestibility (considering: objective response, subjective response and involuntariness). Another aim was to assess the contribution of transliminality as a predictor of suggestibility when a range of previously studied personality trait measures were considered. Participants completed: the Revised Transliminality Scale, Tellegen Absorption Scale, Creative Experiences Questionnaire, and the Dissociative Experiences Scale II. To avoid context effects, where knowledge or measurement of one trait or ability might influence measurement of another, a separate standalone study was conducted where hypnotic and imaginative (without hypnosis) suggestibility screenings were carried out in-person in small groups using the modified Carleton University Responsiveness to Suggestion Scale. The merging of these two datasets enabled the analyses. Transliminality was weakly correlated with the imaginative suggestibility subjective response measure (r = 0.19). Likewise, weak correlations were found between transliminality and the hypnotic suggestibility response measures (objective, r = 0.21, subjective, r = 0.23, involuntariness, r = 0.24). The multiple regressions (forward selection) reflected the pattern of correlations, with no model for any of the variables, retaining more than a single significant predictor. In summary, this study combination, avoiding context effects, shows transliminality to be a weak predictor of response to suggestion.

Short-term supplement of virgin coconut oil improves endothelial-dependent dilation but not exercise-mediated hyperemia in young adults.

Virgin coconut oil (VCO) is high in antioxidants, which reduce reactive oxygen species-induced conversion of vascular endothelial-derived nitric oxide (NO) to toxic peroxynitrite. As such, flow-mediated dilation (FMD, a surrogate marker of NO bioavailability) and exercise-mediated hyperemia may be enhanced following VCO treatment. Animal research supports these findings, but direct assessments of FMD after short-term VCO use in humans are unknown. We tested the hypotheses that a 4-week VCO supplement (30 mL·d-1) would improve popliteal artery (PA) FMD and the hyperemic response to aerobic exercise. Thirty-four young adults were divided into VCO (n = 19, 9 women, 22 ±â€¯2 years, 24 ±â€¯3 kg·m-2) and control (CON: n = 15, 7 women, 24 ±â€¯2 years, 24 ±â€¯3 kg·m-2) groups. PA-FMD and blood flow were assessed via high-resolution duplex ultrasonography (Vivid i, GE Healthcare, Mississauga, Ontario, Canada). PA blood flow was measured at rest and for 5 minutes following a 10-minute bout of moderate-intensity (60% heart rate reserve) cycling exercise. Total PA blood volume was calculated as the integral of the 5-minute postexercise PA blood flow response. After 4 weeks, PA-FMD increased (P = .04) following VCO supplementation (4.9% ±â€¯0.9% to 5.5% ±â€¯1.2%) with no change (P > .9) in the CON group (5.7% ±â€¯2.1% to 5.8% ±â€¯1.9%). There were no differences (both P > .28) in the postexercise total PA blood volume response in either group (VCO: 495 ±â€¯355 to 598 ±â€¯384 mL; CON: 562 ±â€¯362 to 488 ±â€¯229 mL). Short-term VCO supplementation does not alter aerobic exercise-mediated blood flow responses in young adults. However, the augmented popliteal FMD response observed in the VCO supplement group indicates that short-term VCO supplementation improves vascular endothelial function in young, healthy adults.

A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results.

Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparison of the patient sample included in RCTs reporting on pharmaceutical interventions with patients from everyday clinical practice. The review focused on publications in the fields of cardiology, mental health, and oncology. A range of databases were interrogated (MEDLINE; EMBASE; Science Citation Index; Cochrane Methodology Register). Double-abstract review and data extraction were performed as per protocol specifications. Out of 5,456 de-duplicated abstracts, 52 studies met the inclusion criteria (cardiology, n = 20; mental health, n = 17; oncology, n = 15). Studies either performed an analysis of the baseline characteristics (demographic, socioeconomic, and clinical parameters) of RCT-enrolled patients compared with a real-world population, or assessed the proportion of real-world patients who would have been eligible for RCT inclusion following the application of RCT inclusion/exclusion criteria. Many of the included studies concluded that RCT samples are highly selected and have a lower risk profile than real-world populations, with the frequent exclusion of elderly patients and patients with co-morbidities. Calculation of ineligibility rates in individual studies showed that a high proportion of the general disease population was often excluded from trials. The majority of studies (n = 37 [71.2 %]) explicitly concluded that RCT samples were not broadly representative of real-world patients and that this may limit the external validity of the RCT. Authors made a number of recommendations to improve external validity. Findings from this review indicate that there is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions. This goal could be achieved by trial design modification to include a more representative patient sample and by supplementing RCT evidence with data generated from observational studies. In general, a thoughtful approach to clinical evidence generation is required in which the trade-offs between internal and external validity are considered in a holistic and balanced manner.

Anemia management: development of a rapidaccess anemia and intravenous iron service.

This article describes the initiation and evolution of the Rapid-Access Anemia Clinic (RAAC) at Guy's and St Thomas' Hospitals, London, UK. This clinic was set up to provide diagnosis and treatment, and to coordinate investigative procedures, where necessary, into the underlying causes of anemia. Initially piloted with anemic preoperative orthopedic patients, the clinic now treats a wide range of conditions, deriving from both internal and external referrals. Treatment includes dietary advice, supplementation with iron, vitamin B12 and folate, and blood transfusion. Most patients at the RAAC need iron replacement, the majority of which require intravenous (IV) iron. Therefore the first-line IV iron-administration protocol is carefully considered to ensure viability of the service and patient satisfaction. Four IV irons available in the UK are discussed, with explanation of the benefits and drawbacks of each product and the reasoning behind the IV iron choice at different stages of the RAAC's development. Costs to the service, affected by IV iron price and administration regimen, are considered, as well as the product's contraindications. Finally, the authors reflect on the success of the RAAC and how it has improved patients' quality-of-treatment experience, in addition to benefiting the hospital and National Health Service in achieving specific health-care mandates and directives. Drawing from the authors' experiences, recommendations are given to assist others in setting up and providing a successful rapid-access anemia service or similar facility.

Correlation of screening and confirmatory results in tiered immunogenicity testing by solution-phase bridging assays.

Biotherapeutic proteins induce undesired immune responses that can affect drug efficacy and safety. For this reason, immunogenicity assessment is an integral part of drug development and is mandated by the regulatory authorities. Immunogenicity is typically evaluated by a tiered approach consisting of a screening assay followed by a competitive inhibition with unlabeled drug serving as confirmatory assay and additional characterization of the immune response. The confirmatory assay is intended to reduce the number of false positive responses generated in the screening tier and ensure that all samples are correctly classified as positive or negative. The positive-negative sample decisions are based on screening and confirmatory assay cut points that are statistically derived through evaluation of drug-naive samples. In this paper, we describe the analysis of cut point data for the presence of statistical correlation between the screening and confirmatory results. Data were obtained from validations of solution-phase bridging assays for detection of anti-drug antibodies against monoclonal antibody therapeutics. All data sets showed moderate to strong positive correlation, indicating that the screening and confirmatory assays were not independent and were likely to generate similar information. We present theoretical evidence that correlated results may be a general feature of the tiered approach when the same test platform is used for both screening and confirmatory assays. The competitive inhibition test, therefore, may be of limited value beyond reduction of the overall false positive rate. Our results indicate that similar sample results could be obtained by using just the screening assay with the false positive rate set to 1%.

UK guidelines on the management of iron deficiency in pregnancy.

Iron deficiency is the most common deficiency state in the world, affecting more than 2 billion people globally. Although it is particularly prevalent in less-developed countries, it remains a significant problem in the developed world, even where other forms of malnutrition have already been almost eliminated. Effective management is needed to prevent adverse maternal and pregnancy outcomes, including the need for red cell transfusion. The objective of this guideline is to provide healthcare professionals with clear and simple recommendations for the diagnosis, treatment and prevention of iron deficiency in pregnancy and the postpartum period. This is the first such guideline in the UK and may be applicable to other developed countries. Public health measures, such as helminth control and iron fortification of foods, which can be important to developing countries, are not considered here. The guidance may not be appropriate to all patients and individual patient circumstances may dictate an alternative approach.

Primary-care based participatory rehabilitation: users' views of a horticultural and arts project.

BACKGROUND: Participation in horticulture and arts may improve wellbeing in those with mental and physical illness. AIM: To conduct an in-depth exploration of the views and experience of participants of a primary-care-based horticultural and participatory arts rehabilitation project (Sydenham Garden). DESIGN AND SETTING: Qualitative interview study of a primary-care-based horticultural and participatory arts rehabilitation project in South London. METHOD: Semi-structured interviews were conducted with 16 participants (referred to as 'coworkers') of Sydenham Garden. Seven were female. Participants were aged between 38 and 91 years and had a range of severe mental and physical health problems; most had depression. The interviews were analysed using constant comparison and thematic analysis. RESULTS: Data were overwhelmingly positive concerning participation. Coworkers considered participation in the project to promote wellbeing by providing purposeful and enjoyable activity and interest, improving mood and self-perceptions, and providing an escape from life's pressures. Being outdoors was considered therapeutic. The most-valued aspect of participation was the social contact derived as a result of it. Many of the coworkers who were interviewed developed transferable skills, including nationally recognised qualifications, which they valued highly. CONCLUSION: Delivery of horticultural therapy and participatory arts is a feasible model for improving wellbeing in patients in primary care who have serious illness. Longer-term studies are needed to address what happens to people after leaving such projects.

Does integrated emergency care reduce mortality and non-elective admissions? A retrospective analysis.

OBJECTIVES: The authors reconfigured the emergency care system of Addenbrookes Hospital, Cambridge. The medical admissions unit and the emergency department (ED) have been combined into one emergency assessment unit. This paper aims to determine if reconfiguration has reduced non-elective hospital admissions and reduced mortality for non-elective admissions. DESIGN: A retrospective 'before and after' study in a teaching hospital. Routinely collected data were used to evaluate the effectiveness of this approach. Setting One acute trust in the UK. Main outcome measures Inhospital mortality rates and standardised admission ratios (SAR) between 2003 and 2009. RESULTS: There was a significant trend towards improved survival, both for non-elective admissions and deaths in the ED (z=-3.92; p>0.001), despite the age and acuity of patients increasing. There was a marked decrease in the SAR. Formal complaints, incident reports and the proportion of patients leaving before treatment declined, whereas the proportion of patients re-admitted as an emergency within 28 days did not change. CONCLUSIONS: Integrating emergency care within a hospital reduces hospital admissions, is associated with reduced inhospital mortality and a better quality of care.

The sound of silence: ionic mechanisms encoding sound termination.

Offset responses upon termination of a stimulus are crucial for perceptual grouping and gap detection. These gaps are key features of vocal communication, but an ionic mechanism capable of generating fast offsets from auditory stimuli has proven elusive. Offset firing arises in the brainstem superior paraolivary nucleus (SPN), which receives powerful inhibition during sound and converts this into precise action potential (AP) firing upon sound termination. Whole-cell patch recording in vitro showed that offset firing was triggered by IPSPs rather than EPSPs. We show that AP firing can emerge from inhibition through integration of large IPSPs, driven by an extremely negative chloride reversal potential (E(Cl)), combined with a large hyperpolarization-activated nonspecific cationic current (I(H)), with a secondary contribution from a T-type calcium conductance (I(TCa)). On activation by the IPSP, I(H) potently accelerates the membrane time constant, so when the sound ceases, a rapid repolarization triggers multiple offset APs that match onset timing accuracy.

Effects of Na(+)/Ca(2+)-exchanger overexpression on excitation-contraction coupling in adult rabbit ventricular myocytes.

The Na(+)/Ca(2+)-exchanger (NCX) is the main mechanism by which Ca(2+) is transported out of the ventricular myocyte. NCX levels are raised in failing human heart, and the consequences of this for excitation-contraction coupling are still debated. We have increased NCX levels in adult rabbit myocytes by adenovirally-mediated gene transfer and examined the effects on excitation-contraction coupling after 24 and 48 h. Infected myocytes were identified through expression of green fluorescent protein (GFP), transfected under a separate promoter on the same viral construct. Control experiments were done with both non-infected myocytes and those infected with adenovirus expressing GFP only. Contraction amplitude was markedly reduced in NCX-overexpressing myocytes at either time point, and neither increasing frequency nor raising extracellular Ca(2+) could reverse this depression. Resting membrane potential and action potential duration were largely unaffected by NCX overexpression, as was peak Ca(2+) entry via the L-type Ca(2+) channel. Systolic and diastolic Ca(2+) levels were significantly reduced, with peak systolic Ca(2+) in NCX-overexpressing myocytes lower than diastolic levels in control cells at 2 m m extracellular Ca(2+). Both cell relengthening and the decay of the Ca(2+) transient were significantly slowed. Sarcoplasmic reticulum (SR) Ca(2+) stores were completely depleted in a majority of myocytes, and remained so despite increasingly vigorous loading protocols. Depressed contractility following NCX overexpression is therefore related to decreased SR Ca(2+) stores and low diastolic Ca(2+) levels rather than reduced Ca(2+) entry.