Past-futures in experimental care: breast cancer and HIV medicine

Cambrosio et al. (2018. “Extending Experimentation: Oncology’s Fading Boundary Between Research and Care.” New Genetics and Society 37 (3): 207–226) argue that “experimental care” in contemporary oncology involves the rapid merging of patient research and care, and invite further study into developments across other health conditions. We present a 2018–2019 study of experimental breast cancer care in an urban clinical setting in the light of two other studies in the same hospital group: in the same cancer service (2013–14) and, prompted by these earlier findings, an interview study in HIV services (2014–15). We found that patients and staff anticipated better outcomes by treating sub-types of breast cancer but they also hoped for a better one-size-fits-all approach, akin to the antiretroviral treatments introduced for HIV and explored in our interview study. We conclude that the promise of targeted treatment for sub-types of disease – variously described as experimental care, personalised, precision, stratified and sub-group medicine – is accompanied by hopes for a single, standard, effective approach

Immunological Responses Elicited by Different Infection Regimes with Strongyloides ratti

Nematode infections are a ubiquitous feature of vertebrate life. In nature, such nematode infections are acquired by continued exposure to infective stages over a prolonged period of time. By contrast, experimental laboratory infections are typically induced by the administration of a single (and often large) dose of infective stages. Previous work has shown that the size of an infection dose can have significant effects on anti-nematode immune responses. Here we investigated the effect of different infection regimes of Strongyloides ratti, comparing single and repeated dose infections, on the host immune response that was elicited. We considered and compared infections of the same size, but administered in different ways. We considered infection size in two ways: the maximum dose of worms administered and the cumulative worm exposure time. We found that both infection regimes resulted in Th2-type immune response, characterised by IL4 and IL13 produced by S. ratti stimulated mesenteric lymph node cells, anti-S. ratti IgG1 and intestinal rat mast cell protease II (RMCPII) production. We observed some small quantitative immunological differences between different infection regimes, in which the concentration of IL4, IL13, anti-S. ratti IgG1 and IgG2a and RMCPII were affected. However, these differences were quantitatively relatively modest compared with the temporal dynamics of the anti-S. ratti immune response as a whole

The genome of <i>Strongyloides </i>spp. gives insights into protein families with a putative role in nematode parasitism

SUMMARYParasitic nematodes are important and abundant parasites adapted to live a parasitic lifestyle, with these adaptations all aimed at facilitating their survival and reproduction in their hosts. The recently sequenced genomes of fourStrongyloidesspecies, gastrointestinal parasites of humans and other animals, alongside transcriptomic and proteomic analysis of free-living and parasitic stages of their life cycles have revealed a number of protein families with a putative role in their parasitism. Many of these protein families have also been associated with parasitism in other parasitic nematode species, suggesting that these proteins may play a fundamental role in nematode parasitism more generally. Here, we review key protein families that have a putative role inStrongyloides’ parasitism – acetylcholinesterases, astacins, aspartic proteases, prolyl oligopeptidases, proteinase inhibitors (trypsin inhibitors and cystatins), SCP/TAPS and transthyretin-like proteins – and the evidence for their key, yet diverse, roles in the parasitic lifestyle.</jats:p

Control of Vulval Cell Division Number in the Nematode Oscheius/Dolichorhabditis sp. CEW1

Spatial patterning of vulval precursor cell fates is achieved through a different two-stage induction mechanism in the nematode Oscheius/Dolichorhabditis sp. CEW1 compared with Caenorhabditis elegans. We therefore performed a genetic screen for vulva mutants in Oscheius sp. CEW1. Most mutants display phenotypes unknown in C. elegans. Here we present the largest mutant category, which affects division number of the vulva precursors P(4-8).p without changing their fate. Among these mutations, some reduce the number of divisions of P4.p and P8.p specifically. Two mutants omit the second cell cycle of all vulval lineages. A large subset of mutants undergo additional rounds of vulval divisions. We also found precocious and retarded heterochronic mutants. Whereas the C. elegans vulval lineage mutants can be interpreted as overall (homeotic) changes in precursor cell fates with concomitant cell cycle changes, the mutants described in Oscheius sp. CEW1 do not affect overall precursor fate and thereby dissociate the genetic mechanisms controlling vulval cell cycle and fate. Laser ablation experiments in these mutants reveal that the two first vulval divisions in Oscheius sp. CEW1 appear to be redundantly controlled by a gonad-independent mechanism and by a gonadal signal that operates partially independently of vulval fate induction

A microarray analysis of gene expression in the free-living stages of the parasitic nematode Strongyloides ratti

BACKGROUND: The nematode Strongyloides ratti has two adult phases in its lifecycle: one obligate, female and parasitic and one facultative, dioecious and free-living. The molecular control of the development of this free-living generation remains to be elucidated. RESULTS: We have constructed an S. ratti cDNA microarray and used it to interrogate changes in gene expression during the free-living phase of the S. ratti life-cycle. We have found very extensive differences in gene expression between first-stage larvae (L1) passed in faeces and infective L3s preparing to infect hosts. In L1 stages there was comparatively greater expression of genes involved in growth. We have also compared gene expression in L2 stages destined to develop directly into infective L3s with those destined to develop indirectly into free-living adults. This revealed relatively small differences in gene expression. We find little evidence for the conservation of transcription profiles between S. ratti and S. stercoralis or C. elegans. CONCLUSION: This is the first multi-gene study of gene expression in S. ratti. This has shown that robust data can be generated, with consistent measures of expression within computationally determined clusters and contigs. We find inconsistencies between EST representation data and microarray hybridization data in the identification of genes with stage-specific expression and highly expressed genes. Many of the genes whose expression is significantly different between L1 and iL3s stages are unknown beyond alignments to predicted genes. This highlights the forthcoming challenge in actually determining the role of these genes in the life of S. ratti

Language in tuberculosis services: can we change to patient-centred terminology and stop the paradigm of blaming the patients?

The words 'defaulter', 'suspect' and 'control' have been part of the language of tuberculosis (TB) services for many decades, and they continue to be used in international guidelines and in published literature. From a patient perspective, it is our opinion that these terms are at best inappropriate, coercive and disempowering, and at worst they could be perceived as judgmental and criminalising, tending to place the blame of the disease or responsibility for adverse treatment outcomes on one side-that of the patients. In this article, which brings together a wide range of authors and institutions from Africa, Asia, Latin America, Europe and the Pacific, we discuss the use of the words 'defaulter', 'suspect' and 'control' and argue why it is detrimental to continue using them in the context of TB. We propose that 'defaulter' be replaced with 'person lost to follow-up'; that 'TB suspect' be replaced by 'person with presumptive TB' or 'person to be evaluated for TB'; and that the term 'control' be replaced with 'prevention and care' or simply deleted. These terms are non-judgmental and patient-centred. We appeal to the global Stop TB Partnership to lead discussions on this issue and to make concrete steps towards changing the current paradigm

Consideration Sets and Their Role in Modelling Doctor Recommendations About Contraceptives

Copyright © 2015 John Wiley & Sons, Ltd. Decisions about prescribed contraception are typically the result of a consultation between a woman and her doctor. In order to better understand contraceptive choice within this environment, stated preference methods are utilized to ask doctors about what contraceptive options they would discuss with different types of women. The role of doctors is to confine their discussion to a subset of products that best match their patient. This subset of options forms the consideration set from which the ultimate recommendation is made. Given the existence of consideration sets we address the issue of how to model appropriately the ultimate recommendations. The estimated models enable us to characterize doctor recommendations and how they vary with patient attributes and to highlight where recommendations are clear and when they are uncertain. The results also indicate systematic variation in recommendations across different types of doctors, and in particular we observe that some doctors are reluctant to embrace new products and instead recommend those that are more familiar. Such effects are one possible explanation for the relatively low uptake of more cost effective longer acting reversible contraceptives and indicate that further education and training of doctors may be warranted. Copyright © 2015 John Wiley & Sons, Ltd

High risk prescribing in older adults: Prevalence, clinical and economic implications and potential for intervention at the population level

Background: High risk prescribing can compromise independent wellbeing and quality of life in older adults. The aims of this project are to determine the prevalence, risk factors, clinical consequences, and costs of high risk prescribing, and to assess the impact of interventions on high risk prescribing in older people. Methods. The proposed project will utilise data from the 45 and Up Study, a large scale cohort of 267,153 men and women aged 45 and over recruited during 2006-2009 from the state of New South Wales, Australia linked to a range of administrative health datasets. High risk prescribing will be assessed using three indicators: polypharmacy (use of five or more medicines); Beers Criteria (an explicit measure of potentially inappropriate medication use); and Drug Burden Index (a pharmacologic dose-dependent measure of cumulative exposure to anticholinergic and sedative medicines). Individual risk factors from the 45 and Up Study questionnaire, and health system characteristics from health datasets that are associated with the likelihood of high risk prescribing will be identified. The main outcome measures will include hospitalisation (first admission to hospital, total days in hospital, cause-specific hospitalisation); admission to institutionalised care; all-cause mortality, and, where possible, cause-specific mortality. Economic costs to the health care system and implications of high risk prescribing will be also investigated. In addition, changes in high risk prescribing will be evaluated in relation to certain routine medicines-related interventions. The statistical analysis will be conducted using standard pharmaco-epidemiological methods including descriptive analysis, univariate and multivariate regression analysis, controlling for relevant confounding factors, using a number of different approaches. Discussion. The availability of large-scale data is useful to identify opportunities for improving prescribing, and health in older adults. The size of the 45 and Up Study, along with linkage to health databases provides an important opportunity to investigate the relationship between high risk prescribing and adverse outcomes in a real-world population of older adults. © 2013 Gnjidic et al.; licensee BioMed Central Ltd

A world of cobenefits : solving the global nitrogen challenge

Houlton, Benjamin Z. University of California. John Muir Institute of the Environment. Davis, CA, USA.Houlton, Benjamin Z. University of California. Department of Land, Air and Water Resources. Davis, CA, USA.Almaraz, Maya. University of California. Department of Land, Air and Water Resources. Davis, CA, USA.Aneja, Viney. North Carolina State University at Raleigh. Department of Marine, Earth, and Atmospheric Sciences. Raleigh, NC, USA.Austin, Amy T. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA). Buenos Aires, Argentina.Austin, Amy T. CONICET – Universidad de Buenos Aires. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA). Buenos Aires, Argentina.Bai, Edith. Chinese Academy of Sciences. Institute of Applied Ecology. CAS Key Laboratory of Forest Ecology and Management. Shenyang, China.Bai, Edith. Northeast Normal University. School of Geographical Sciences. Changchun, China.Cassman, Kenneth. University of Nebraska – Lincoln. Department of Agronomy and Horticulture. Lincoln. NE, USA.Compton, Jana E. Environmental Protection Agency. Western Ecology Division. Washington, DC, USA.Davidson, Eric A. University of Maryland Center for Environmental Science. Appalachian Laboratory. Cambridge, MD, USA.865-872Nitrogen is a critical component of the economy, food security, and planetary health. Many of the world's sustainability targets hinge on global nitrogen solutions, which, in turn, contribute lasting benefits for (i) world hunger; (ii) soil, air, and water quality; (iii) climate change mitigation; and (iv) biodiversity conservation. Balancing the projected rise in agricultural nitrogen demands while achieving these 21st century ideals will require policies to coordinate solutions among technologies, consumer choice, and socioeconomic transformation