The process of conducting herbal medicine research through the clinical trials exemption scheme

The primary aims of this study were to develop research methodology in order to investigate the efficacy of herbal medicine in alleviating menopausal symptoms, and to prepare an application for submission to the Medicines Control Agency (MCA) to gain approval to run a randomised, double blind, placebo controlled clinical trial. A research protocol was developed which outlined the key stages of the study for subsequent review and approval by an ethics committee. An operations manual was developed to guide and instruct clinicians on how the study should be implemented. This required the development of case history notes, screening procedures, timetable flow charts and adverse event reporting cards specifically for this study. An original herbal formula was developed for this study based on a literature review of medicinal plants. A 54-page exemption from licences MLA-164 application was completed, which set out in detail the design of the study. The pharmacological properties of the medicinal plants were reviewed from the literature and listed in detail to satisfy the MCA's requirements for scientific evidence of efficacy and safety. Heavy metal analysis was performed for quality control purposes to examine the feasibility of being able to meet specification limits for metal contamination in medicinal herbs. This was conducted using Inductively Coupled Plasma-Atomic Emission Spectroscopy on a total of 16 herb samples, eight samples of Hypericum perforatum L. and eight samples of Salvia officinalis L. from cultivation sites in the UK and Europe. Mean metal ion concentrations of lead, cadmium, mercury, copper, zinc, nickel and chromium were found to be below statutory limits and guidelines, and would therefore satisfy the requirements of an MLA- 164 application for metal contamination. High Performance Liquid Chromatography was performed using UV detector and Diode-Array detector systems to determine the suitability of each method to provide a `fingerprint' analysis of the medicinal herbs for the purposes of establishing plant authenticity. The diode-array analysis was superior to simple UV detector methodology because it was able to provide greater accuracy to determine the chemical group for some unknown constituents. However, neither system provided adequate phytochemical profiles to authenticate the medicinal plants. The research study provided a novel insight into the processes required for the design and implementation of a herbal medicine clinical trial, and has expanded the current knowledge of the requirements for completing a clinical trials application (MLA-164) to the MCA

Melt-extruded polyethylene oxide (PEO) rods as drug delivery vehicles: Formulation, performance as controlled release devices and the influence of co-extruded excipients on drug release profiles

The utility of controlled release medication formulations lies in their ability to keep drugs at steady levels in the blood plasma of recipients and within the termini of the maximum and minimum effective therapeutic levels. This avoids the “ups” and “downs” of medication levels within the body which would have been the result had conventional immediate release tablets been administered instead. In the veterinary field, controlled release medications are essential¹ because of the logistical difficulties of administering drugs on a regular (e.g., daily) basis to animals. The chief advantages of controlled release veterinary medications lie in the ease with which they can be administered; decrease in stress for animals, owing to less need for rounding up and frequent dosing; and, most importantly for farmers, the reduced cost of treatment relative to that for a multiple dosage regime

Vibrational branching ratios in photoionization of CO and N2

We report results of experimental and theoretical studies of the vibrational branching ratios for CO 4sigma(-1) photoionization from 20 to 185 eV. Comparison with results for the 2sigma(u)(-1) channel of the isoelectronic N-2 molecule shows the branching ratios for these two systems to be qualitatively different due to the underlying scattering dynamics: CO has a shape resonance at low energy but lacks a Cooper minimum at higher energies whereas the situation is reversed for N-2

Discrimination and social identity processes predict impairment and dysfunction among heavy drinkers

Background: Previous research has linked discrimination to poorer health. Yet health risk behaviours such as heavy alcohol consumption are often targeted with stigmatising public health campaigns. The current study sought to establish the link between experiencing discrimination and health outcomes among heavy drinkers, with a focus on exploring the multiple social identity processes that might underpin this relationship. Method: A survey was conducted with 282 people who self-reported consuming alcohol above recommended guidelines. We measured discrimination experienced as a drinker, components of social identification as a drinker (centrality, satisfaction, solidarity, homogeneity, and self-stereotyping), and two health outcomes: psychological distress and severity of alcohol use disorder symptomatology. Results: Discrimination was a moderate-large predictor of psychological distress and alcohol use disorder symptoms. Three social identity constructs were implicated in the link between discrimination and ill-health: identity centrality and homogeneity positively mediated this relationship, while identity satisfaction was a negative mediator. The model explained a large proportion of the variance (39-47%) in health outcomes. Discussion: Results are interpreted with an emphasis on the need to avoid stigmatising messaging and to prioritise social identity processes to prevent and treat substance use disorders. We further highlight the need for social identity researchers to consider the multidimensional nature of social identities, especially in the context of stigmatised groups

The Commercial Fishery of Virginia 1955-77 with emphasis on the James, York and Rappahannock Rivers

The commercial fishery of Virginia is one of the most diverse in the United States. Three principal zones exist: the Atlantic Ocean, Chesapeake Bay, and the major rivers. Finfish, shellfish, and crabs are harvested in each zone. Within the finfishes, several distinct groups are taken.: industrial fish, food fish, and fish for bait. For each group there are migratory, anadromous, and resident species. Within these there are freshwater, brackish, and marine species. The shellfish and crab group make up another category of high value and diverse life forms. The purpose of this report is to summarize a part of the diversity. The James, York, and Rappahannock rivers (Fig. 1) are treated in detail to determine population trends and fluctuations of the principal commercial species

Star and Stellar Cluster Formation: ALMA-SKA Synergies

© 2015 The Author(s). This work is made available under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license https://creativecommons.org/licenses/by-nc-sa/3.0/.Over the next decade, observations conducted with ALMA and the SKA will reveal the process of mass assembly and accretion onto young stars and will be revolutionary for studies of star formation. Here we summarise the capabilities of ALMA and discuss recent results from its early science observations. We then review infrared and radio variability observations of both young low-mass and high-mass stars. A time domain SKA radio continuum survey of star forming regions is then outlined. This survey will produce radio light-curves for hundreds of young sources, providing for the first time a systematic survey of radio variability across the full range of stellar masses. These light-curves will probe the magnetospheric interactions of young binary systems, the origins of outflows, trace episodic accretion on the central sources and potentially constrain the rotation rates of embedded sources

Design, Stability and Efficacy of a New Targeting Peptide for Nanoparticulate Drug Delivery to SH-SY5Y Neuroblastoma Cells

In recent years, rabies virus-derived peptide (RDP) has shown promise as a specific neural cell targeting ligand, however stability of the peptide in human serum was unknown. Herein, we report the molecular modelling and design of an optimised peptide sequence based on interactions of RDP with the α7 subunit of the nicotinic acetylcholine receptor (nAChR). The new sequence, named DAS, designed around a 5-mer sequence which demonstrated optimal nAChR binding in silico, showed greatly improved stability for up to 8 hours in human serum in comparison to RDP, which degraded within 2 hours at 37 °C. In vitro analysis using SH-SY5Y neuroblastoma cells showed that DAS-conjugated nanoparticles containing the cytotoxic drug doxorubicin (DAS-Dox-NP) displayed significantly enhanced cytotoxicity compared with untargeted doxorubicin-loaded nanoparticles (Dox-NP). DAS-Dox-NP had no significant effect on non-neural cell types, confirming its neural-specific targeting properties. In this manuscript, we report the design and testing of an optimised peptide ligand, conjugated to a nanoparticulate delivery vehicle and specifically targeted to neural cells. Future impact of an innovative targeting peptide ligand combining the ability to selectively identify the target and facilitate cellular internalisation could enable the successful treatment of many neural cell disorders

Stakeholder involvement in systematic reviews: a protocol for a systematic review of methods, outcomes and effects

Background There is an expectation for stakeholders (including patients, the public, health professionals, and others) to be involved in research. Researchers are increasingly recognising that it is good practice to involve stakeholders in systematic reviews. There is currently a lack of evidence about (A) how to do this and (B) the effects, or impact, of such involvement. We aim to create a map of the evidence relating to stakeholder involvement in systematic reviews, and use this evidence to address the two points above. Methods We will complete a mixed-method synthesis of the evidence, first completing a scoping review to create a broad map of evidence relating to stakeholder involvement in systematic reviews, and secondly completing two contingent syntheses. We will use a stepwise approach to searching; the initial step will include comprehensive searches of electronic databases, including CENTRAL, AMED, Embase, Medline, Cinahl and other databases, supplemented with pre-defined hand-searching and contacting authors. Two reviewers will undertake each review task (i.e., screening, data extraction) using standard systematic review processes. For the scoping review, we will include any paper, regardless of publication status or study design, which investigates, reports or discusses involvement in a systematic review. Included papers will be summarised within structured tables. Criteria for judging the focus and comprehensiveness of the description of methods of involvement will be applied, informing which papers are included within the two contingent syntheses. Synthesis A will detail the methods that have been used to involve stakeholders in systematic reviews. Papers from the scoping review that are judged to provide an adequate description of methods or approaches will be included. Details of the methods of involvement will be extracted from included papers using pre-defined headings, presented in tables and described narratively. Synthesis B will include studies that explore the effect of stakeholder involvement on the quality, relevance or impact of a systematic review, as identified from the scoping review. Study quality will be appraised, data extracted and synthesised within tables. Discussion This review should help researchers select, improve and evaluate methods of involving stakeholders in systematic reviews. Review findings will contribute to Cochrane training resources

Teacher leadership, power, and the gendered space of teaching: intersections and discourses

Relying on critical feminist understandings of power, this study explores how the gendered expectations and intersectional identity of women teachers impacts their negotiation of power in the practice of teacher leadership and social justice advocacy. This study takes a critical stance towards the existing body of literature and challenges the current feminized and patriarchal understanding of teacher leadership. Using a collaborative autoethnographic approach, a group of practicing teacher leaders examined their lived experiences as teacher leaders. The participants reported experiencing gendered expectations in their teaching contexts of support/nurturing, passivity, collaboration, normative gender expression, and all-encompassing teacher identity. Practicing teacher leadership in this gendered environment was a balancing act that required the ability to be a “chameleon.” The complexity of teaching and intricate nature of connections and networks allowed teachers to pick and choose a variety of strategies and resources with which to negotiate power. The study finds that much of the work of teacher leadership involved negotiating the interpersonal and cultural domains of power in order to develop coalitions of diverse stakeholders to resist the oppressive forces found in the structural and disciplinary domains. The teachers reported often having to “play against” negative assumptions of their ability to be leaders based on race and gender. The study concludes that the scholarly understanding of the practice of teacher leadership must be redefined to include the social justice focus of much of its practice, the intricacy of teachers’ networks, an understanding of power as multidirectional and multidimensional, the nuance of gendered norms found in teaching, and the unresolved paradoxes that teacher leaders face every day