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Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies
Research into mechanisms of skin scarring identified transforming growth factor β3 (TGFβ3) as a potential antiscarring therapy. We assessed scar improvement with avotermin (recombinant, active, human TGFβ3).
In three double-blind, placebo-controlled studies, intradermal avotermin (concentrations ranging from 0·25 to 500 ng/100 μL per linear cm wound margin) was administered to both margins of 1 cm, full-thickness skin incisions, before wounding and 24 h later, in healthy men and women. Treatments (avotermin and placebo or standard wound care) were randomly allocated to wound sites by a computer generated randomisation scheme, and within-participant controls compared avotermin versus placebo or standard wound care alone. Primary endpoints were visual assessment of scar formation at 6 months and 12 months after wounding in two studies, and from week 6 to month 7 after wounding in the third. Investigators, participants, and scar assessors were blinded to treatment. Efficacy analyses were intention to treat. These studies are registered with
ClinicalTrials.gov, numbers
NCT00847925,
NCT00847795, and
NCT00629811.
In two studies, avotermin 50 ng/100 μL per linear cm significantly improved median score on a 100 mm visual analogue scale (VAS) by 5 mm (range −2 to 14; p=0·001) at month 6 and 8 mm (−29 to 18; p=0·0230) at month 12. In the third, avotermin significantly improved total scar scores at all concentrations versus placebo (mean improvement: from 14·84 mm [95 % CI 5·5–24·2] at 5 ng/100 μL per linear cm to 64·25 mm [49·4–79·1] at 500 ng/100 μL per linear cm). Nine [60%] scars treated with avotermin 50 ng/100 μL per linear cm showed 25% or less abnormal orientation of collagen fibres in the reticular dermis versus five [33%] placebo scars. After only 6 weeks from wounding, avotermin 500 ng/100 μL per linear cm improved VAS score by 16·12 mm (95% CI 10·61–21·63). Adverse events at wound sites were similar for avotermin and controls. Erythema and oedema were more frequent with avotermin than with placebo, but were transient and deemed to be consistent with normal wound healing.
Avotermin has potential to provide an accelerated and permanent improvement in scarring.
Renovo (UK).
Journal Article
Association for Human Pharmacology in the Pharmaceutical Industry conference 2022: impending change, innovations and future challenges
The Association for Human Pharmacology in the Pharmaceutical Industry’s annual meeting focused on current and impending challenges facing the United Kingdom’s (UK) pharmaceutical industry and how these opportunities can inspire innovation and best practice. The UK pharmaceutical landscape is still evolving following Brexit and learnings from the coronavirus disease 2019 (COVID-19) pandemic. As such, the UK’s clinical community is in a unique position to steer innovation in a meaningful direction. With the continuation of remote forms of working, further opportunities have arisen to support novel practices away from the clinic. The keynote speaker reflected on clinical development over the past 40 years and how the industry must continue to concentrate on patient welfare. The future of drug development was discussed regarding challenges associated with developing translational gene therapies, and the status of investment markets analyzed from a business strategy and consulting perspective. The patient viewpoint was a core theme throughout the conference with patient-centric blood sampling and decentralized clinical trials providing suggestions for how the industry can save costs and increase efficiency. Moreover, the patient perspective was central to a debate over whether ethics requirements should be the same for oncology patients taking part in first-in-human studies as those for healthy subjects. Discussions continued around the changing roles of the Qualified Person and Principal Investigators which underpins how sponsors may want to run future trials in the UK. Lessons learned from conducting challenge trials in healthy volunteers and patients were discussed following a presentation from the serving Chair of the COVID-19 challenge ethics committee. The current state of interactions with the Medicines and Healthcare products Regulatory Agency were also explored. It was considered how the immediate future for the UK clinical trials community is inevitably still linked with Europe; the newly implemented European Medicines Agency Clinical Trials Information System has been met with lukewarm responses, providing a promising opportunity to ensure UK Phase I units continue to play a vital role in global research.
Journal Article
Live cell imaging of Plasmodiophora brassicae—host plant interactions based on a two‐step axenic culture system
Plasmodiophora brassicae, a parasitic protist, induces club‐shaped tumor‐like growth of host Brassicas roots and hypocotyls after infection. Due to its soil‐borne nature and intracellular, biotrophic parasitism the infection biology and early pathogenesis remains in doubt. In this study, we have established a new protocol, based on a two‐step axenic culture of P. brassicae with its host tissues, for easy and in planta observation of cellular interactions between P. brassicae and host plants: first, coculture of P. brassicae with infected canola root tissues, on growth‐medium plates, enables the propagation of P. brassicae that serves as pure inoculum for pathogenicity assays, and second, the pure inoculum is subsequently used for pathogenicity tests on both canola and Arabidopsis seedlings grown on medium plates in Petri dishes. During the first axenic culture, we established a staining protocol by which the pathogen was fluorescently labeled with Nile red and calcofluor white, thus allowing in planta observation of pathogen development. In the pathogenicity assays, our results showed that axenic cultures of P. brassicae, in calli, remains fully virulent and completes its life cycle in both canola and Arabidopsis roots grown in Petri dishes. Combining visualization of fluorescent probe‐labeled P. brassicae structures with fluorescent protein tagging of Arabidopsis cellular components, further revealed dynamic responses of host cells at the early stages of P. brassicae infection. Thus, established protocols for in planta detection of P. brassicae structures and the live cell imaging of P. brassicae—Arabidopsis interactions provide a novel strategy for improving our detailed knowledge of P. brassicae infection in host tissues. Plasmodiophora brassicae, a causal agent of clubroot disease on Brassica crops, displays a complex intracellular, biotrophic life cycle in host tissues. This study established protocols for in planta detection of P. brassicae structures and the live cell imaging of P. brassicae—Arabidopsis interactions, which provide a novel approach for improving our detailed knowledge of P. brassicae infection in host tissues.
Journal Article
The Association for Human Pharmacology in the Pharmaceutical Industry London Meeting October 2019: Impending Change, Innovation, and Future Challenges
The Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI) annual meeting focused on impending change, innovation, and future challenges facing early phase drug development as we move into the second decade of the 21th century. The meeting opened with discussion around the technical revolution in pharmaceutical medicine over the 4 decades since the AHPPI was founded and how transformative technologies have accompanied the introduction of processes such as physiologically based pharmacokinetic modeling. During the meeting examples were presented of how in terms of the development of new therapies, the classic phases of clinical drug development are becoming a thing of the past and the lines between the phases have begun to blur, particularly in the field of oncology. The contribution that monoclonal antibodies have made to medicine and the next chapter in their design and use was also discussed. A representative of the UK’s Medicine and Healthcare Products Regulatory Agency discussed the increasing numbers of requests to approve complex innovative design trials, how novel trial designs are impacting on the traditional linear “phase” approach to drug development and the common pitfalls associated with them. Guidance was provided from a regulator’s viewpoint on what was meant by the term “novel design” and how to submit successful trial applications for such complex trials. In an Oxford-style debate, the audience discussed the motion that “there is no longer a need to include placebo subjects in early clinical trials.” The keynote speaker focused on delivering change in complex environments such as the field of drug development. The afternoon session included presentations on the challenges associated with drug product design, the complexities within non-oral dosage forms and proposed new methods of formulations for drug delivery. Presentations were also given on advances in mechanistic and computational pharmacokinetic modeling and how they have proved to be valuable tools to rationalize and facilitate the process of drug development.
Journal Article
The Association for Human Pharmacology in the Pharmaceutical Industry London Meeting 2018: Brexit and Other Challenges in Early Phase Drug Development
The Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI) annual meeting focused on the changing face of early phase drug development and opened with a keynote speech concerning the revolution in pharmaceutical medicine over the last 30 years and the impact this has had on the way patients are treated. Examples were presented of how translational pharmaceutics is being used to tackle the high drug candidate failure rate and is improving productivity when moving drug candidates from the laboratory through to clinical proof of concept. The European Medicines Agency revised 2007 Risk Mitigation guideline on first in human (FIH) clinical trials was discussed. The focus of the revised guideline, which came into force in February 2018, is on risk mitigation and promotion of safety and will assist drug sponsors with the design and performance of early clinical studies. The use of integrated adaptive protocol designs in early clinical development was discussed in relation to the challenges involved when running early phase clinical trials in patients. The Health Regulatory Authority presented its strategies to ensure that following Brexit, the United Kingdom remains an attractive place to conduct Phase I clinical trials. The Medicines and Healthcare products Regulatory Agency confirmed that in the event of a \"no deal\" Brexit, it is well placed to implement and influence many provisions of the new EU CTR. The meeting provided an opportunity to discuss the changing regulatory environment and the opportunities and challenges facing the United Kingdom following Brexit with invited speakers from a range of disciplines including drug development, clinical trials and research organizations, government science policy and regulatory agencies.
Journal Article
Christian Change Agents: Analyzing the Effectiveness of a Christian Leadership Program among Students in a Central Kentucky Restoration Church
This dissertation examines the effectiveness of a Christian leadership program in producing Christian change agents. It evaluates the effectiveness of the Christian leadership program based on its strengths and weaknesses. In addition, the dissertation considers improvements for future adaptations of the Christian leadership program. Participants in the project were all from the central Kentucky Restoration Church, primarily white and middle class. The participants consisted of five change agents (program participants) and four program mentors. The research explored the biblical and theological framework with respect to discipleship and mentoring. It also investigated adolescence and emerging adulthood as well as practices that contributed to the formation of Christian change agents. The research further reviewed mentoring and experiential learning. The project was a post-intervention that utilized the qualitative instruments of interviews and a focus group to gather data for analysis. The findings revealed that time management was a weakness, and that field trips and personality inventories were effective in producing Christian change agents.
Dissertation
Barriers to African Americans in Healthcare Leadership Attainment and the Need for Sponsorship
In 2018, African Americans made up 8% of executive leaders in healthcare organizations despite national diversity inclusion initiatives. Even with initiatives in place, there remains a scarcity in African American representation at the C-level and on the Boards of Healthcare organizations. This qualitative phenomenological study was an effort to illustrate how mentorship can reduce barriers in African Americans' who desire executive positions in healthcare. The critical race and career development theories formed the lens used to assess this phenomenon in this study. Purposeful and snowball sampling methods were useful for identifying participants for this qualitative study. Twenty-four participants met the criteria for the study. Anonymous online questionnaires and recorded interviews were the two methods of data collection. Data analysis included open coding, line-by-line data review, and the use of Nvivo to identify frequencies of themes. Emergent themes were identified and provided a comprehensive interpretation of the participant's lived experiences. This study found that African Americans experience numerous microaggressions that they perceive as barriers to their healthcare career progression. Additionally, the study discovered that having a mentor was not only beneficial to the career progressions of African Americans in healthcare but more explicitly, having a sponsor was far more vital for executive career attainment. The findings of this study may inspire social modifications by providing African Americans who aspire to attain healthcare executive leadership roles, insight on challenge management mechanisms, and thus build genuine trust among the African American community that leads to a better health outcome.
Dissertation