Virtual patient educational programme to teach counselling to clinical pharmacists: development and proof of concept

Pharmacist–patient counselling can benefit patients and optimise care, but appropriate training is required. A virtual patient (VP) tool to teach pharmacists non-vitamin K oral anticoagulant counselling was developed; the VP may be used for continuing professional development. The objective was to develop and show proof of concept of the VP. A cyclic development approach was adopted whereby the client, developers and a steering group informed VP design, content and aesthetic. This included formal and informal evaluation; ethical approval was not required. The VP received varied feedback. Positive feedback concerned the technology and the high-standard of animations. Negative elements concerned international VP use and differences in practice, also technological comments, regarding VP delivery and usability on various electronic devices. The VP was reported to be ‘valuable’ and realistic with high-quality animations. The steering group commented on VP’s clinical appropriateness, cultural relevance and usability. Areas highlighted for improvement were rectified during development, including the incorporation of printable feedback. European considerations concerned differences in culture and practice. The development process successfully developed the VP and the proof of the concept was demonstrated. This will inform future VP development; a large-scale VP evaluation is underway

Poiseuille geometry shear flow apparatus for small-angle scattering experiments

Published versio

Evaluating Active U: an Internet-mediated physical activity program.

Background: Engaging in regular physical activity can be challenging, particularly during the winter months. To promote physical activity at the University of Michigan during the winter months, an eight-week Internet-mediated program (Active U) was developed providing participants with an online physical activity log, goal setting, motivational emails, and optional team participation and competition. Methods: This study is a program evaluation of Active U. Approximately 47,000 faculty, staff, and graduate students were invited to participate in the online Active U intervention in the winter of 2007. Participants were assigned a physical activity goal and were asked to record each physical activity episode into the activity log for eight weeks. Statistics for program reach, effectiveness, adoption, and implementation were calculated using the Re-Aim framework. Multilevel regression analyses were used to assess the decline in rates of data entry and goal attainment during the program, to assess the likelihood of joining a team by demographic characteristics, to test the association between various predictors and the number of weeks an individual met his or her goal, and to analyze server load. Results: Overall, 7,483 individuals registered with the Active U website (≈16% of eligible), and 79% participated in the program by logging valid data at least once. Staff members, older participants, and those with a BMI < 25 were more likely to meet their weekly physical activity goals, and average rate of meeting goals was higher among participants who joined a competitive team compared to those who participated individually (IRR = 1.28, P < .001). Conclusion: Internet-mediated physical activity interventions that focus on physical activity logging and goal setting while incorporating team competition may help a significant percentage of the target population maintain their physical activity during the winter months

Redox linked flavin sites in extracellular decaheme proteins involved in microbe-mineral electron transfer

Extracellular microbe-mineral electron transfer is a major driving force for the oxidation of organic carbon in many subsurface environments. Extracellular multi-heme cytochromes of the Shewenella genus play a major role in this process but the mechanism of electron exchange at the interface between cytochrome and acceptor is widely debated. The 1.8 Å x-ray crystal structure of the decaheme MtrC revealed a highly conserved CX8C disulfide that, when substituted for AX8A, severely compromised the ability of S. oneidensis to grow under aerobic conditions. Reductive cleavage of the disulfide in the presence of flavin mononucleotide (FMN) resulted in the reversible formation of a stable flavocytochrome. Similar results were also observed with other decaheme cytochromes, OmcA, MtrF and UndA. The data suggest that these decaheme cytochromes can transition between highly reactive flavocytochromes or less reactive cytochromes, and that this transition is controlled by a redox active disulfide that responds to the presence of oxygen

Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc.

The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell-based therapeutics

A Comparative Study of Vertebral Pathologies and Anomalies in Two Medieval British Populations

A holistic approach to palaeopathological studies using historical documentation and clinical, archaeological and epidemiological literature can provide important information as to the health, lifestyles, socioeconomic and occupational status of individuals from the past. Applying this approach, the study provides an overview and comparative analysis of the spinal health of two contemporaneous British skeletal samples from the medieval period; St Owen’s Cemetery, an urban based population from Gloucester (n=68) and Poulton a rural, agrarian community from Cheshire (n=70). Sex and age at death were estimated using a variety of osteological techniques and descriptive statistics and Chi-square statistical tests were computed to identify and assess inter- and intra-population differences. Although some significant differences were observed, both skeletal samples had similar types and anatomical locations of the pathological conditions observed. St Owen’s Cemetery exhibits higher frequencies of degenerative conditions and vertebral fractures, whereas Poulton displays higher frequencies of congenital conditions such as lumbosacral anomalies and cervical vertebral synostosis (possible Klippel-Feil Syndrome). Age of onset of degenerative conditions is markedly earlier in Poulton indicating occupational status from a younger age than their contemporaries in St Owen’s. Females are more affected by degenerative conditions and vertebral fractures than the males in both samples. The frequency of the aforementioned conditions increases dramatically with age suggesting the fractures could be related to osteoporosis. Significant differences were observed between population samples in the frequency of osteoarthritis in the thoracic segment of middle adult males and females in which St Owen’s exhibit double the amount. This indicates that biomechanical stresses were more likely to have been placed on the thoracic segment such as carrying heavier loads and repetitive bending and twisting in a singular occupational role in an urban setting such as a craft (cordwainer) or working for a merchant guild. Frequency of infectious lesions is comparable in both samples, indicating similar exposure to pathogens albeit there may be differences in the type of infections present. Males are more affected than the females in the rural sample suggesting that pathogens in the soil and livestock may be the cause of the lesions observed. The findings of this study are generally consistent with other published data, although frequency of vertebral trauma in the urban sample far exceeds other contemporary sites. The study presented here provides a glimpse into medieval life in both the large town and the rural farming community in the British Isles. Further studies include comparing data from more contemporary urban and rural populations to produce a more holistic study on medieval health and lifestyle in the British Isles including further analysis of larger skeletal samples from Poulton and St Owen’s. Additional observation of complete skeletons including body mass and stature and radiographic analyses will give further supportive evidence for some diagnoses

Vortex detection and quantum transport in mesoscopic graphene Josephson-junction arrays

We investigate mesoscopic Josephson junction arrays created by patterning superconducting disks on monolayer graphene, concentrating on the high-$T/T_c$ regime of these devices and the phenomena which contribute to the superconducting glass state in diffusive arrays. We observe features in the magnetoconductance at rational fractions of flux quanta per array unit cell, which we attribute to the formation of flux-quantized vortices. The applied fields at which the features occur are well described by Ginzburg-Landau simulations that take into account the number of unit cells in the array. We find that the mean conductance and universal conductance fluctuations are both enhanced below the critical temperature and field of the superconductor, with greater enhancement away from the graphene Dirac point.This work was financially supported by the Engineering and Physical Sciences Research Council, and an NPL/EPSRC Joint Postdoctoral Partnership (RG61493).This is the accepted manuscript. The final version is available at http://journals.aps.org/prb/abstract/10.1103/PhysRevB.91.245418

A prospective cohort study assessing clinical referral management & workforce allocation within a UK regional medical genetics service

Abstract Ensuring patient access to genomic information in the face of increasing demand requires clinicians to develop innovative ways of working. This paper presents the first empirical prospective observational cohort study of UK multi-disciplinary genetic service delivery. It describes and explores collaborative working practices including the utilisation and role of clinical geneticists and non-medical genetic counsellors. Six hundred and fifty new patients referred to a regional genetics service were tracked through 850 clinical contacts until discharge. Referral decisions regarding allocation of lead health professional assigned to the case were monitored, including the use of initial clinical contact guidelines. Significant differences were found in the cases led by genetic counsellors and those led by clinical geneticists. Around a sixth, 16.8% (109/650) of referrals were dealt with by a letter back to the referrer or re-directed to another service provider and 14.8% (80/541) of the remaining patients chose not to schedule an appointment. Of the remaining 461 patients, genetic counsellors were allocated as lead health professional for 46.2% (213/461). A further 61 patients did not attend. Of those who did, 86% (345/400) were discharged after one or two appointments. Genetic counsellors contributed to 95% (784/825) of total patient contacts. They provided 93.7% (395/432) of initial contacts and 26.8% (106/395) of patients were discharged at that point. The information from this study informed a planned service re-design. More research is needed to assess the effectiveness and efficiency of different models of collaborative multi-disciplinary working within genetics services. Keywords (MeSH terms) Genetic Services, Genetic Counseling, Interdisciplinary Communication, Cohort Studies, Delivery of Healthcare, Referral and Consultation

Does physical activity counselling enhance the effects of a pedometer-based intervention over the long-term : 12-month findings from the Walking for Wellbeing in the West study

Peer reviewedPublisher PD

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe