Healthcare professionals' preferences for surgery or primary endocrine therapy to treat older women with operable breast cancer

Introduction : Primary endocrine therapy (PET) is an alternative treatment to surgery for oestrogen receptor (ER) positive operable breast cancer in older women. However, there is variable use of PET in the UK, with up to 40% of patients aged over 70 receiving PET instead of surgery in some regions. Treatment options offered to patients rely heavily on healthcare professional (HCP) assessment and opinion on which treatments are appropriate. Materials and methods : This was a mixed methods study combining semi-structured interviews with HCPs working in high and low PET regions in the UK, followed by a postal questionnaire survey distributed via the Association of Breast Surgery (ABS). Results : Thirty-four HCPs (20 breast surgeons; 13 nurse specialists; 1 geriatrician) were interviewed from 14 sites across the UK and 252/641 questionnaires returned (39%). There was an overriding view that PET is not suitable for patients under the age of 80 unless there are significant comorbidities. Opinion was split regarding the best way to treat patients with dementia. Patient preference was generally stated to be the most important factor when considering treatment, however only around a quarter 65/244 (26.6%) felt that all patients over the age of 70 should be offered PET as an alternative treatment option. Conclusions : Opinions differ on the best way to treat women over 70 with operable breast cancer, especially if they have co-existing dementia, as well as whether they should be offered PET as a treatment option. This may be a significant cause of treatment variation in the UK. Keywords : Breast cancer; Primary endocrine therapy; Surgery; Elderly; Older; Mixed methods.</p

High throughput automated microbial bioreactor system used for clone selection and rapid scale-down process optimization

High throughput automated fermentation systems have become a useful tool in early bioprocess development. In this study, we investigated a 24 x 15 mL single use microbioreactor system, ambr 15f, designed for microbial culture. We compared the fed-batch growth and production capabilities of this system for two Escherichia coli strains, BL21 (DE3) and MC4100, and two industrially relevant molecules, hGH and scFv. In addition, different carbon sources were tested using bolus, linear or exponential feeding strategies, showing the capacity of the ambr 15f system to handle automated feeding. We used power per unit volume (P/V) as a scale criterion to compare the ambr 15f with 1 L stirred bioreactors which were previously scaled-up to 20 L with a different biological system, thus showing a potential 1,300 fold scale comparability in terms of both growth and product yield. By exposing the cells grown in the ambr 15f system to a level of shear expected in an industrial centrifuge, we determined that the cells are as robust as those from a bench scale bioreactor. These results provide evidence that the ambr 15f system is an efficient high throughput microbial system that can be used for strain and molecule selection as well as rapid scale-up. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 2017

Scientific justification for the participation of children and adolescents in HIV-1 vaccine trials in South Africa

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Social creatures: model animal systems for studying the neuroendocrine mechanisms of social behaviour

Work was supported by grants awarded to ML (BBSRC BB/S000224/1), OJB (BO 1958/8-2, GRK 2174), KEB (Wellcome Trust 109614/Z/15/Z, MRC MR/N004574/1), AJ (BBSRC BB/S000801) and GL (Israel Science Foundation #1511/16; United States-Israel Binational Science Foundation #2017325; Nella and Leon Benoziyo Center for Neurological Diseases, Richard F. Goodman Yale/Weizmann Exchange Program and Estate of Emile Mimran).The interaction of animals with conspecifics, termed social behaviour, has a major impact on the survival of many vertebrate species. Neuropeptide hormones modulate the underlying physiology that governs social interactions, and many findings concerning the neuroendocrine mechanisms of social behaviours have been extrapolated from animal models to humans. Neurones expressing neuropeptides show similar distribution patterns within the hypothalamic nucleus, even when evolutionarily distant species are compared. During evolution, hypothalamic neuropeptides and releasing hormones have retained not only their structures, but also their biological functions, including their effects on behaviour. Here, we review the current understanding of the mechanisms of social behaviours in several classes of animals, such as worms, insects and fish, as well as laboratory, wild and domesticated mammals.Publisher PDFPeer reviewe

Developing Next-generation Brain Sensing Technologies - A Review.

Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients

"First pain" in humans: convergent and specific forebrain responses

<p>Abstract</p> <p>Background</p> <p>Brief heat stimuli that excite nociceptors innervated by finely myelinated (Aδ) fibers evoke an initial, sharp, well-localized pain ("first pain") that is distinguishable from the delayed, less intense, more prolonged dull pain attributed to nociceptors innervated by unmyelinated (C) fibers ("second pain"). In the present study, we address the question of whether a brief, noxious heat stimulus that excites cutaneous Aδ fibers activates a distinct set of forebrain structures preferentially in addition to those with similar responses to converging input from C fibers. Heat stimuli at two temperatures were applied to the dorsum of the left hand of healthy volunteers in a functional brain imaging (fMRI) paradigm and responses analyzed in a set of volumes of interest (VOI).</p> <p>Results</p> <p>Brief 41°C stimuli were painless and evoked only C fiber responses, but 51°C stimuli were at pain threshold and preferentially evoked Aδ fiber responses. Most VOI responded to both intensities of stimulation. However, within volumes of interest, a contrast analysis and comparison of BOLD response latencies showed that the bilateral anterior insulae, the contralateral hippocampus, and the ipsilateral posterior insula were preferentially activated by painful heat stimulation that excited Aδ fibers.</p> <p>Conclusions</p> <p>These findings show that two sets of forebrain structures mediate the initial sharp pain evoked by brief cutaneous heat stimulation: those responding preferentially to the brief stimulation of Aδ heat nociceptors and those with similar responses to converging inputs from the painless stimulation of C fibers. Our results suggest a unique and specific physiological basis, at the forebrain level, for the "first pain" sensation that has long been attributed to Aδ fiber stimulation and support the concept that both specific and convergent mechanisms act concurrently to mediate pain.</p

Engaging with community researchers for exposure science: lessons learned from a pesticide biomonitoring study

A major challenge in biomonitoring studies with members of the general public is ensuring their continued involvement throughout the necessary length of the research. The paper presents evidence on the use of community researchers, recruited from local study areas, as a mechanism for ensuring effective recruitment and retention of farmer and resident participants for a pesticides biomonitoring study. The evidence presented suggests that community researchers' abilities to build and sustain trusting relationships with participants enhanced the rigour of the study as a result of their on-the-ground responsiveness and flexibility resulting in data collection beyond targets expected