High-resolution computed tomography reconstructions of invertebrate burrow systems

The architecture of biogenic structures can be highly influential in determining species contributions to major soil and sediment processes, but detailed 3-D characterisations are rare and descriptors of form and complexity are lacking. Here we provide replicate high-resolution micro-focus computed tomography (μ-CT) data for the complete burrow systems of three co-occurring, but functionally contrasting, sediment-dwelling inter-tidal invertebrates assembled alone, and in combination, in representative model aquaria. These data (≤2,000 raw image slices aquarium−1, isotropic voxel resolution, 81 μm) provide reference models that can be used for the development of novel structural analysis routines that will be of value within the fields of ecology, pedology, geomorphology, palaeobiology, ichnology and mechanical engineering. We also envisage opportunity for those investigating transport networks, vascular systems, plant rooting systems, neuron connectivity patterns, or those developing image analysis or statistics related to pattern or shape recognition. The dataset will allow investigators to develop or test novel methodology and ideas without the need to generate a complete three-dimensional computation of exemplar architecture

Systematic evaluation of patient-reported outcome (PRO) protocol content and reporting in UK cancer clinical trials: the EPiC study protocol.

Emerging evidence suggests that patient-reported outcome (PRO)-specific information may be omitted in trial protocols and that PRO results are poorly reported, limiting the use of PRO data to inform cancer care. This study aims to evaluate the standards of PRO-specific content in UK cancer trial protocols and their arising publications and to highlight examples of best-practice PRO protocol content and reporting where they occur. The objective of this study is to determine if these early findings are generalisable to UK cancer trials, and if so, how best we can bring about future improvements in clinical trials methodology to enhance the way PROs are assessed, managed and reported.Trials in which the primary end point is based on a PRO will have more complete PRO protocol and publication components than trials in which PROs are secondary end points.Completed National Institute for Health Research (NIHR) Portfolio Cancer clinical trials (all cancer specialities/age-groups) will be included if they contain a primary/secondary PRO end point. The NIHR portfolio includes cancer trials, supported by a range of funders, adjudged as high-quality clinical research studies. The sample will be drawn from studies completed between 31 December 2000 and 1 March 2014 (n=1141) to allow sufficient time for completion of the final trial report and publication. Two reviewers will then review the protocols and arising publications of included trials to: (1) determine the completeness of their PRO-specific protocol content; (2) determine the proportion and completeness of PRO reporting in UK Cancer trials and (3) model factors associated with PRO protocol and reporting completeness and with PRO reporting proportion.The study was approved by the ethics committee at University of Birmingham (ERN_15-0311). Trial findings will be disseminated via presentations at local, national and international conferences, peer-reviewed journals and social media including the CPROR twitter account and UOB departmental website (http://www.birmingham.ac.uk/cpro0r)

Miniaturization optimized weapon killing power during the social stress of late pre-contact North America (AD 600-1600)

Before Europeans arrived to Eastern North America, prehistoric, indigenous peoples experienced a number of changes that culminated in the development of sedentary, maize agricultural lifeways of varying complexity. Inherent to these lifeways were several triggers of social stress including population nucleation and increase, intergroup conflict (warfare), and increased territoriality. Here, we examine whether this period of social stress co-varied with deadlier weaponry, specifically, the design of the most commonly found prehistoric archery component in late pre-contact North America: triangular stone arrow tips (TSAT). The examination of modern metal or carbon projectiles, arrows, and arrowheads has demonstrated that smaller arrow tips penetrate deeper into a target than do larger ones. We first experimentally confirm that this relationship applies to arrow tips made from stone hafted onto shafts made from wood. We then statistically assess a large sample (n = 742) of late pre-contact TSAT and show that these specimens are extraordinarily small. Thus, by miniaturizing their arrow tips, prehistoric people in Eastern North America optimized their projectile weaponry for maximum penetration and killing power in warfare and hunting. Finally, we verify that these functional advantages were selected across environmental and cultural boundaries. Thus, while we cannot and should not rule out stochastic, production economizing, or non-adaptive cultural processes as an explanation for TSAT, overall our results are consistent with the hypothesis that broad, socially stressful demographic changes in late pre-contact Eastern North America resulted in the miniaturization–and augmented lethality–of stone tools across the region

International perspectives on suboptimal patient-reported outcome trial design and reporting in cancer clinical trials: a qualitative study

Purpose: Evidence suggests that the patient-reported outcome (PRO) content of cancer trial protocols is frequently inadequate and non-reporting of PRO findings is widespread. This qualitative study examined the factors influencing suboptimal PRO protocol content, implementation, and reporting, and use of PRO data during clinical interactions. Methods: Semi-structured interviews were conducted with four stakeholder groups: (1) trialists and chief investigators; (2) people with lived experience of cancer; (3) international experts in PRO cancer trial design; (4) journal editors, funding panelists, and regulatory agencies. Data were analyzed using directed thematic analysis with an iterative coding frame. Results: Forty-four interviews were undertaken. Several factors were identified that could influenced effective integration of PROs into trials and subsequent findings. Participants described (1) late inclusion of PROs in trial design; (2) PROs being considered a lower priority outcome compared to survival; (3) trialists’ reluctance to collect or report PROs due to participant burden, missing data, and perceived reticence of journals to publish; (4) lack of staff training. Strategies to address these included training research personnel and improved communication with site staff and patients regarding the value of PROs. Examples of good practice were identified. Conclusion: Misconceptions relating to PRO methodology and its use may undermine their planning, collection, and reporting. There is a role for funding, regulatory, methodological, and journalistic institutions to address perceptions around the value of PROs, their position within the trial outcomes hierarchy, that PRO training and guidance is available, signposted, and readily accessible, with accompanying measures to ensure compliance with international best practice guidelines

Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.http://deepblue.lib.umich.edu/bitstream/2027.42/78314/1/1750-1326-5-45.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/2/1750-1326-5-45.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/3/1750-1326-5-45-S1.PDFPeer Reviewe

Heat treatment significantly increases the sharpness of silcrete stone tools

Humans were regularly heat-treating stone tool raw materials as early as 130,000 years ago. The late Middle Stone Age (MSA) and Late Stone Age (LSA) of South Africa's Western Cape region provides some of the earliest and most pervasive archaeological evidence for this behaviour. While archaeologists are beginning to understand the flaking implications of raw material heat treatment, its potential functional benefits remain unanswered. Using silcrete from the Western Cape region, we investigate the impact of heat treatment on stone tool cutting performance. We quantify the sharpness of silcrete in its natural, unheated form, before comparing it with silcrete heated in three different conditions. Results show that heat-treated silcrete can be significantly sharper than unheated alternatives, with cutting forces halving and energy requirements reducing by approximately two-thirds. The data suggest that silcrete may have been heat treated during the South African MSA and LSA to increase the sharpness and performance of stone cutting edges. This early example of material engineering has implications for understanding Stone Age populations’ technological capabilities, inventiveness and raw material choices. We predict that heat-treatment behaviours in other prehistoric and ethnographic contexts may also be linked to increases in edge sharpness and concerns about functional performance

Electronic Patient Reporting of Adverse Events and Quality of Life: A Prospective Feasibility Study in General Oncology

PURPOSE: Adverse event (AE) reporting is essential in clinical trials. Clinician interpretation can result in under-reporting; therefore, the value of patient self-reporting has been recognized. The National Cancer Institute has developed a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) for direct patient AE reporting. A nonrandomized prospective cohort feasibility study aimed to explore the compliance and acceptability of an electronic (Internet or telephone) system for collecting patient self-reported AEs and quality of life (QOL). METHODS: Oncology patients undergoing treatment (chemotherapy, targeted agents, hormone therapy, radiotherapy, and/or surgery) at 2 hospitals were sent automated weekly reminders to complete PRO-CTCAE once a week and QOL (for a maximum of 12 weeks). Patients had to speak/understand English and have access to the Internet or a touch-tone telephone. Primary outcome was compliance (proportion of expected questionnaires), and recruitment rate, attrition, and patient/staff feedback were also explored. RESULTS: Of 520 patients, 249 consented (47.9%)—mean age was 62 years, 51% were male, and 70% were married—and 230 remained on the study at week 12. PRO-CTCAE was completed at 2,301 (74.9%) of 3,074 timepoints and QOL at 749 (79.1%) of 947 timepoints. Individual weekly/once every 4 weeks compliance reduced over time but was more than 60% throughout. Of 230 patients, 106 (46.1%) completed 13 or more PRO-CTCAE, and 136 (59.1%) of 230 patients completed 4 QOL questionnaires. Most were completed on the Internet (82.3%; mean age, 60.8 years), which was quicker, but older patients preferred the telephone option (mean age, 70.0 years). Positive feedback was received from patients and staff. CONCLUSION: Self-reporting of AEs and QOL using an electronic home-based system is feasible and acceptable. Implementation of this approach in cancer clinical trials may improve the precision and accuracy of AE reporting

How Many Species Are There on Earth and in the Ocean?

The diversity of life is one of the most striking aspects of our planet; hence knowing how many species inhabit Earth is among the most fundamental questions in science. Yet the answer to this question remains enigmatic, as efforts to sample the world's biodiversity to date have been limited and thus have precluded direct quantification of global species richness, and because indirect estimates rely on assumptions that have proven highly controversial. Here we show that the higher taxonomic classification of species (i.e., the assignment of species to phylum, class, order, family, and genus) follows a consistent and predictable pattern from which the total number of species in a taxonomic group can be estimated. This approach was validated against well-known taxa, and when applied to all domains of life, it predicts ∼8.7 million (±1.3 million SE) eukaryotic species globally, of which ∼2.2 million (±0.18 million SE) are marine. In spite of 250 years of taxonomic classification and over 1.2 million species already catalogued in a central database, our results suggest that some 86% of existing species on Earth and 91% of species in the ocean still await description. Renewed interest in further exploration and taxonomy is required if this significant gap in our knowledge of life on Earth is to be closed

Potential for re-emergence of wheat stem rust in the United Kingdom

This is the final version. Available on open access from Springer Nature via the DOI in this recordWheat stem rust, a devastating disease of wheat and barley caused by the fungal pathogen Puccinia graminis f. sp. tritici, was largely eradicated in Western Europe during the mid-to-late twentieth century. However, isolated outbreaks have occurred in recent years. Here we investigate whether a lack of resistance in modern European varieties, increased presence of its alternate host barberry and changes in climatic conditions could be facilitating its resurgence. We report the first wheat stem rust occurrence in the United Kingdom in nearly 60 years, with only 20% of UK wheat varieties resistant to this strain. Climate changes over the past 25 years also suggest increasingly conducive conditions for infection. Furthermore, we document the first occurrence in decades of P. graminis on barberry in the UK . Our data illustrate that wheat stem rust does occur in the UK and, when climatic conditions are conducive, could severely harm wheat and barley production.This project was funded by an institute development grant from the EI (Norwich, UK), an Industrial Partnership Award (BB/M025519/1) from the BBSRC, a European Research Council Starting Grant awarded to D.G.O.S. (number 715638), H2020 project EMPHASIS (number 634179), by the BBSRC Institute Strategic Programmes BB/J004553/1 and BB/P012574/1, the John Innes Foundation, and an African Women in Agricultural Research and Development (AWARD) fellowship to R.N.K