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Aim Accounting for sampling bias is the greatest challenge facing presence‐only and presence‐background species distribution models; no matter what type of model is chosen, using biased data will mask the true relationship between occurrences and environmental predictors. To address this issue, we review four established bias correction techniques, using empirical occurrences with known sampling effort, and virtual species with known distributions. Innovation Occurrence data come from a national recording scheme of hoverflies (Syrphidae) in Great Britain, spanning 1983–2002. Target‐group backgrounds, distance‐restricted backgrounds, travel time to cities and human population density were used to account for sampling bias in 58 species of hoverfly. Distributions generated by bias correction techniques were compared in geographical space to the distribution produced accounting for known sampling effort, using Schoener's distance, centroid shifts and range size changes. To validate our results, we performed the same comparisons using 50 randomly generated virtual species. We used sampling effort from the hoverfly recording scheme to structure our biased sampling regime, emulating complex real‐life sampling bias. Main conclusions Models made without any correction typically produced distributions that mapped sampling effort rather than the underlying habitat suitability. Target‐group backgrounds performed the best at emulating sampling effort and unbiased virtual occurrences, but also showed signs of overcompensation in places. Other methods performed better than no‐correction, but often differences were difficult to visually detect. In line with previous studies, when sampling effort is unknown, target‐group backgrounds provide a useful tool for reducing the effect of sampling bias. Models should be visually inspected for biological realism to identify any areas of potential overcompensation. Given the disparity between corrected and un‐corrected models, sampling bias constitutes a major source of error in species distribution modelling, and more research is needed to confidently address the issue.

Aim To develop a causal understanding of the drivers of Species distribution model (SDM) performance. Location United Kingdom (UK). Methods We measured the accuracy and variance of SDMs fitted for 518 species of invertebrate and plant in the UK. Our measure of variance reflects variation among replicate model fits, and taxon experts assessed model accuracy. Using directed acyclic graphs, we developed a causal model depicting plausible effects of explanatory variables (e.g. species' prevalence, sample size) on SDM accuracy and variance and quantified those effects using a multilevel piecewise path model. Results According to our model, sample size and niche completeness (proportion of a species' niche covered by sampling) directly affect SDM accuracy and variance. Prevalence and range completeness have indirect effects mediated by sample size. Challenging conventional wisdom, we found that the effect of prevalence on SDM accuracy is positive. This reflects the facts that sample size has a positive effect on accuracy and larger sample sizes are possible for widespread species. It is possible, however, that the omission of an unobserved confounder biased this effect. Previous studies, which reported negative correlations between prevalence and SDM accuracy, conditioned on sample size. Main conclusions Our model explicates the causal basis of previously reported correlations between SDM performance and species/data characteristics. It also suggests that niche completeness has similarly large effects on SDM accuracy and variance as sample size. Analysts should consider niche completeness, or proxies thereof, in addition to sample size when deciding whether modelling is worthwhile.

1. Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2. We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3. We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4. People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5. Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes.

Hydraulic traits were studied in temperate, woody evergreens in a high-elevation heath community to test for trade-offs between the delivery of water to canopies at rates sufficient to sustain photosynthesis and protection against disruption to vascular transport caused by freeze—thaw-induced embolism. Freeze—thaw-induced loss in hydraulic conductivity was studied in relation to xylem anatomy, leaf- and sapwood-specific hydraulic conductivity and gas exchange characteristics of leaves. We found evidence that a trade-off between xylem transport capacity and safety from freeze—thaw-induced embolism affects photosynthetic activity in over-wintering evergreens. The mean hydraulically weighted xylem vessel diameter and sapwood-specific conductivity correlated with susceptibility to freeze—thaw-induced embolism. There was also a strong correlation of hydraulic supply and demand across species; interspecific differences in stomatal conductance and CO₂ assimilation rates were correlated linearly with sapwood- and leaf-specific hydraulic conductivity. Xylem vessel anatomy mediated an apparent trade-off between resistance to freeze—thaw-induced embolism and hydraulic and photosynthetic capacity during the winter. These results point to a new role for xylem functional traits in determining the degree to which species can maintain photosynthetic carbon gain despite freezing events and cold winter temperatures.

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2 -mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1 -methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1- methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy. Around 10% of high-grade serous ovarian carcinomas (HGSOC) harbor BRCA1 promoter methylation, but it is uncertain how it predicts response to PARP inhibition. Here, the authors show that homozygous BRCA1 methylation predicts response to rucaparib while heterozygous methylation of BRCA1 predicts resistance in HGSOC.

Background Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. Methods This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. Results Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P  < 0.001), dCCA (26.4%, P   =  0.020), and finally PDAC (12.9%, P  < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. Conclusions Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for “periampullary cancers” or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.

IntroductionDespite use of operative and non-operative interventions to reduce blood loss during liver resection, 20%–40% of patients receive a perioperative blood transfusion. Extensive intraoperative blood loss is a major risk factor for postoperative morbidity and mortality and receipt of blood transfusion is associated with serious risks including an association with long-term cancer recurrence and overall survival. In addition, blood products are scarce and associated with appreciable expense; decreasing blood transfusion requirements would therefore have health system benefits. Tranexamic acid (TXA), an antifibrinolytic, has been shown to reduce the probability of receiving a blood transfusion by one-third for patients undergoing cardiac or orthopaedic surgery. However, its applicability in liver resection has not been widely researched.Methods and analysisThis protocol describes a prospective, blinded, randomised controlled trial being conducted at 10 sites in Canada and 1 in the USA. 1230 eligible and consenting participants will be randomised to one of two parallel groups: experimental (2 g of intravenous TXA) or placebo (saline) administered intraoperatively. The primary endpoint is receipt of blood transfusion within 7 days of surgery. Secondary outcomes include blood loss, postoperative complications, quality of life and 5-year disease-free and overall survival.Ethics and disseminationThis trial has been approved by the research ethics boards at participating centres and Health Canada (parent control number 177992) and is currently enrolling participants. All participants will provide written informed consent. Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov.Trial registration numberNCT02261415.

Famed author Jack Ganssle has selected the very best embedded systems design material from the Newnes portfolio and compiled into this volume. The result is a book covering the gamut of embedded design-from hardware to software to integrated embedded systems-with a strong pragmatic emphasis. In addition to specific design techniques and practices, this book also discusses various approaches to solving embedded design problems and how to successfully apply theory to actual design tasks. The material has been selected for its timelessness as well as for its relevance to contemporary embedded design issues. This book will be an essential working reference for anyone involved in embedded system design! Table of Contents:Chapter 1. Motors - Stuart BallChapter 2. Testing - Arnold S. BergerChapter 3. System-Level Design - Keith E. CurtisChapter 4. Some Example Sensor, Actuator and Control Applications and Circuits (Hard Tasks) - Lewin ARW EdwardsChapter 5. Installing and Using a Version Control System - Chris Keydel and Olaf MedingChapter 6. Embedded State Machine Implementation - Martin GomezChapter 7. Firmware Musings - Jack GanssleChapter 8. Hardware Musings - Jack GanssleChapter 9. Closed Loop Controls, Rabbits, and Hounds - John M. HollandChapter 10. Application Examples David J. Katz and Rick GentileChapter 11. Analog I/Os - Jean LaBrosseChapter 12. Optimizing DSP Software - Robert OshanaChapter 13. Embedded Processors - Peter Wilson *Hand-picked content selected by embedded systems luminary Jack Ganssle*Real-world best design practices including chapters on FPGAs, DSPs, and microcontrollers*Covers both hardware and software aspects of embedded systems

[...]stress perfusion CMR alone has already been compared with FFR and shown to have an even better diagnostic accuracy than that reported by Greenwood and colleagues (positive predictive value 90.9%, negative predictive value 93.9%).2 Similar findings were reported by Rieber and colleagues,5 again using CMR perfusion imaging alone. The state-of-theart technology is applied only for CMR imaging. [...]SPECT shows incon clusive results, mainly because of patient motion or attenuation artefacts secondary to long acquisition times and lack of attenuation correction, which are in great part solved by use of modern SPECT instrumentation.3,4 Additionally, by contrast with CMR assess ment, criteria for a positive SPECT are not detailed, which might explain the low diagnostic accuracy reported for SPECT (eg, how is ischaemia assessed?).