The good clinical practice guideline and its interpretation - perceptions of clinical trial teams in sub-Saharan Africa

To explore the advantages and challenges of working with the Good Clinical Practice (GCP)-International Conference of Harmonization (ICH) E6 guideline and its interpretation from the perspective of clinical trial teams based in sub-Saharan Africa.; We conducted 60 key informant interviews with clinical trial staff at different levels in clinical research centres in Kenya, Ghana, Burkina Faso and Senegal and thematically analysed the responses.; Clinical trial teams perceived working with ICH-GCP as highly advantageous and regarded ICH-GCP as applicable to their setting and efficiently applied. Only for informed consent did some clinical trial staff (one-third) perceive the guideline as insufficiently applicable. Specific challenges included meeting the requirements for written and individual consent, conditions for impartial witnesses for illiterates or legally acceptable representatives for children, guaranteeing voluntary participation and ensuring full understanding of the consent given. It was deemed important to have ICH-GCP compliance monitored by relevant ethics committees and regulatory authorities, without having guidelines applied overcautiously.; Clinical trial teams in sub-Saharan Africa perceived GCP as a helpful guideline, despite having been developed by northern organisations and despite the high administrative burden of implementing it. To mitigate consent challenges, we suggest adapting GCP and making use of the flexibility it offers

Asynchronous division by non-ring FtsZ in the gammaproteobacterial symbiont of <em>Robbea hypermnestra</em>

The reproduction mode of uncultivable microorganisms deserves investigation as it can largely diverge from conventional transverse binary fission. Here, we show that the rod-shaped gammaproteobacterium thriving on the surface of the Robbea hypermnestra nematode divides by FtsZ-based, non-synchronous invagination of its poles-that is, the host-attached and fimbriae-rich pole invaginates earlier than the distal one. We conclude that, in a naturally occurring animal symbiont, binary fission is host-oriented and does not require native FtsZ to polymerize into a ring at any septation stage

Label-Free Analysis with Multiple Parameters Separates G Protein-Coupled Receptor Signaling Pathways

Real-time label-free techniques are used to profile G protein-coupled receptor (GPCR) signaling pathways in living cells. However, interpreting the label-free signal responses is challenging, and previously reported methods do not reliably separate pathways from each other. In this study, a continuous angular-scanning surface plasmon resonance (SPR) technique is utilized for measuring label-free GPCR signal profiles. We show how the continuous angular-scanning ability, measuring up to nine real-time label-free parameters simultaneously, results in more information-rich label-free signal profiles for different GPCR pathways, providing a more accurate pathway separation. For this, we measured real-time full-angular SPR response curves for Gs, Gq, and Gi signaling pathways in living cells. By selecting two of the most prominent label-free parameters: the full SPR curve angular and intensity shifts, we present how this analysis approach can separate each of the three signaling pathways in a straightforward single-step analysis setup, without concurrent use of signal inhibitors or other response modulating compounds

Scattering in the Presence of Electroweak Phase Transition Bubble Walls

We investigate the motion of fermions in the presence of an electro\-weak phase transition bubble wall. We derive and solve the Dirac equation for such fer\-mions, and compute the transmission and reflection coefficients for fermions traveling from the symmetric to the asymmetric phases separated by the domain wall.Comment: TPI--MINN--54, NUC--MINN--93/30--T, UMN--TH--1226/93, LaTex, 29 page

Empathy, engagement, entrainment: the interaction dynamics of aesthetic experience

A recent version of the view that aesthetic experience is based in empathy as inner imitation explains aesthetic experience as the automatic simulation of actions, emotions, and bodily sensations depicted in an artwork by motor neurons in the brain. Criticizing the simulation theory for committing to an erroneous concept of empathy and failing to distinguish regular from aesthetic experiences of art, I advance an alternative, dynamic approach and claim that aesthetic experience is enacted and skillful, based in the recognition of others’ experiences as distinct from one’s own. In combining insights from mainly psychology, phenomenology, and cognitive science, the dynamic approach aims to explain the emergence of aesthetic experience in terms of the reciprocal interaction between viewer and artwork. I argue that aesthetic experience emerges by participatory sense-making and revolves around movement as a means for creating meaning. While entrainment merely plays a preparatory part in this, aesthetic engagement constitutes the phenomenological side of coupling to an artwork and provides the context for exploration, and eventually for moving, seeing, and feeling with art. I submit that aesthetic experience emerges from bodily and emotional engagement with works of art via the complementary processes of the perception–action and motion–emotion loops. The former involves the embodied visual exploration of an artwork in physical space, and progressively structures and organizes visual experience by way of perceptual feedback from body movements made in response to the artwork. The latter concerns the movement qualities and shapes of implicit and explicit bodily responses to an artwork that cue emotion and thereby modulate over-all affect and attitude. The two processes cause the viewer to bodily and emotionally move with and be moved by individual works of art, and consequently to recognize another psychological orientation than her own, which explains how art can cause feelings of insight or awe and disclose aspects of life that are unfamiliar or novel to the viewer

The excess mortality risk of diabetes associated with functional decline in older adults: Results from a 7-year follow-up of a nationwide cohort in Taiwan

<p>Abstract</p> <p>Background</p> <p>Diabetes is associated with an increased risk of functional decline in older adults. Few studies have investigated the contribution of functional decline to excess mortality risk in older people with diabetes. The aim of this study was to examine how diabetes in combination with different levels of functional decline affects 7-year mortality in older adults.</p> <p>Methods</p> <p>We analyzed data from a nationally representative sample of people aged 65 years and over, participating in the 2001 National Health Interview Survey in Taiwan. A total of 1873 participants were followed through 2002-2008, of whom 286 (15.3%) had a history of diabetes confirmed by a medical professional. Participants were divided into three functional status groups: (1) high functioning-no limitations involving activities of daily living (ADLs), instrumental activities of daily living (IADLs), or physical functioning; (2) low functioning-limitations in one or more ADLs; (3) middle functioning-all participants in between groups 1 and 2.</p> <p>Results</p> <p>The crude mortality rate was 52.7 per 1,000 person-years in those with diabetes and 34.1 per 1,000 person-years in those without diabetes. After adjustment for other factors, diabetes alone was not associated with an increased mortality risk in those with high functioning. However, diabetes alone had a hazard ratio (HR) for mortality of 1.90 (95%CI = [1.02-3.53]) in those with middle functioning and 3.67 (95%CI = [1.55-8.69]) in those with low functioning. The presence of diabetes and one or more other chronic conditions was associated with a HR for mortality of 2.46 (95%CI = [1.61-3.77]) in those with middle functioning and 4.03 (95%CI = [2.31-7.03]) in those with low functioning.</p> <p>Conclusions</p> <p>Our results indicate that diabetes is not associated with increased mortality in those with high functioning. There was a gradient effect of functional decline on mortality in individuals with diabetes. Additionally, among participants with other chronic conditions, functional decline was associated with a greater burden of mortality in older adults with diabetes. These findings highlight the critical importance of the prevention of cardiovascular disease morbidity and the maintenance of functional abilities in order to reduce mortality risk in older adults with diabetes.</p

Dynamics of Two Higgs Doublet CP Violation and Baryogenesis at the Electroweak Phase Transition

We quantitatively study the charge transport mechanism of electroweak baryogenesis in a realistic two-Higgs-doublet model, comparing the contributions from quarks and leptons reflecting from electroweak domain walls, and comparing the exact profile of the CP-violating phase with a commonly used ansatz. We note that the phenomenon of spontaneous CP violation at high temperature can occur in this model, even when there is no CP violation at zero temperature. We include all known effects which are likely to influence the baryon production rate, including strong sphalerons, the nontrivial dispersion relations of the quasiparticles in the plasma, and Debye screening of gauged charges. We confirm the claim of Joyce, Prokopec and Turok that the reflection of tau leptons from the wall gives the dominant effect. We conclude that this mechanism is marginally strong enough to produce the observed baryon asymmetry of the universe.Comment: 49 pp. latex, 6 figures; section on diffusion expanded and corrected, published versio