Search

Analysis of circulating tumor DNA (ctDNA) to monitor cancer dynamics and to detect minimal residual disease has been an area of increasing interest. Multiple methods have been proposed but few studies have compared the performance of different approaches. Here we compare detection of ctDNA in serial plasma samples from patients with breast cancer using different tumor-informed and tumor-naïve assays designed to detect structural variants (SVs), single nucleotide variants (SNVs) and/or somatic copy-number aberrations, by multiplex PCR, hybrid capture and different depths of whole genome sequencing. Our results demonstrate that the ctDNA dynamics and allele fractions (AFs) were highly concordant when analyzing the same patient samples using different assays. Tumor-informed assays showed the highest sensitivity for detection of ctDNA at low concentrations. Hybrid capture sequencing targeting between 1,347 and 7,491 tumor-identified mutations at high depth was the most sensitive assay, detecting ctDNA down to an AF of 0.00024% (2.4 parts per million, ppm). Multiplex PCR targeting 21-47 tumor-identified SVs per patient detected ctDNA down to 0.00047% AF (4.7 ppm) and has potential as a clinical assay.

PhD dissertation

Development of a novel method to measure the interaction between the human and their apparel

The aim of the current research was to explore veterans’ experiences of the military to civilian transition, specifically focussing on the role of their sense of self. Twenty military veterans were interviewed through semi-structured interviews and asked about their experiences of transition. In answering the question, what is the role of the self in navigating transition into ‘civvy street’, three themes were generated using reflexive thematic analysis: (1) Destabilising Individualism: People should be standing by their word, and they're not; (2) Re-negotiating the self: Extracting what I needed from the forces to get me forward now; and (3) Forging a self-understanding. This article provided insight into the challenges and complexities that are faced by military veterans as they negotiate their transition. Several implications are discussed including a need for greater recognition of the challenges and a need for greater connectedness through community practices.

Introduction During the COVID-19 pandemic, face to face journal clubs have been curtailed due to Governmental guidance for social distancing. We present an example of a virtual journal club set up for Orthopaedic senior house officers (SHOs) & trainees in the North West Thames (NWT) Deanery from April to August 2020. Methods Our aims were to establish a regular online journal club for orthopaedic trainees in NWT that successfully met the objectives of the more established face to face meetings. Assessment of each session was evaluated using a post attendance survey created using an established online generator. Results 64.4% (16/25 participants) had not attended a virtual journal club before, with 100% (33/33) reporting that they would attend another virtual journal club. 39.4% (13/33) of attendees agreed or strongly agreed that they could participate in sessions over more conventional meetings. 24.2% (8/33) of participants reported experiencing technical issues during the sessions. 90.9% (30/33) of respondents reporting the virtual model to be more convenient than standard journal clubs. Conclusion The potential benefits of significantly increased accessibility, increased visiting expert contribution whilst still adhering to government guidelines; weighed against marginally less effective teaching nonetheless results in an overall benefit

Exploring the effects of alcohol problem framing on problem recognition and stigma

Serpentine soils are formed from weathering of serpentinite, the ultramafic parent material that provides serpentine soils with their unique identity. Weathering of serpentinite results in a plethora of edaphic factors that impose strong selection pressures on plant life, with high magnesium (Mg) to calcium (Ca) ratio, low fertility, and high levels of geologically derived metals such as cobalt (Co), chromium (Cr), and nickel (Ni). Appropriately, plant life on serpentine soils is often specialized, sparse, and endemic which in turn affects the ecosystems that develop on serpentine soils from the landscape scale down to the physiology of their inhabitants. At the landscape scale, selection by serpentine edaphic factors may result in sharply delineated changes in plant community structure, resulting in abrupt changes in ground cover and habitat. At the physiological scale, plant adaptation to ultramafic soils is thought to have resulted in the emergence of heavy metal hyperaccumulation. Interestingly, plant species closely related to hyperaccumulators may be found living adjacent to them on serpentine soils, but the opposite strategy for coping with elevated levels of heavy metals whereby heavy metals are excluded from the vascular system. Studying the development and differentiation of the rhizosphere of serpentine adapted plants may lead to a better understanding of how plants have evolved to cope with the varied abiotic stresses posed by, but not exclusive to, serpentine soils. This research seeks to contribute to the understanding of hyperaccumulation by asking, what are the fundamental differences between the rhizospheres of hyperaccumulating and non-accumulating serpentine adapted plants, and could those differences be related to these contrasting strategies for inhabiting serpentine soils? In the research reported here, rhizospheres of Ni hyperaccumulating and non-hyperaccumulating plants growing in two serpentine soils, Neshaminy silt loam and Chrome silt loam, were interrogated using a multidisciplinary approach including x-ray absorption spectroscopy for in-situ Ni speciation, ratiometric fluorescent imaging for in-situ spatially resolved O2 concentrations and pH, and bacterial community structure via 16S rRNA gene amplicon sequencing and phospholipid fatty acid analysis. Overall, the results of this research suggest that Ni speciation in the rhizosphere of some Ni hyperaccumulators may contain a greater abundance of mineral sored species compared to a non-accumulator, hypertolerant plant. Oxygen content and pH did not differ among plant types and does not appear to explain differences in Ni speciation among rhizospheres. In Neshaminy silt loam soils, a clear differentiation in rhizosphere microbial community structure was observed, while in Chrome silt loams the differences were more subtle. Due to the lack of evidence for differing pH and redox environments across the rhizosphere of Ni hyperaccumulating and non-accumulating plants presented in this study and others, along with support for the differentiation of these environments along biological lines, it appears more likely that differences in Ni speciation and availability are driven by differences in root and microbial biochemistry., Copyright © James W. Morris 2020, Funding Information: This research was supported by the National Science Foundation Graduate Research Fellowship Program from August 2015 - August 2018.

This manuscript is in preparation for a Special Issue on Environmental and Human Dynamics of the Yangtze River and Mississippi River Deltas: Temporal and Geographical Perspectives to be published in Geomorphology. The expected publication date is after May, 2021. An updated version of this manuscript will be added to this repository soon after it is accepted for publication.

Supplemental material, Supplement_-_Prediction_of_Social_Behavior_060719 for Prediction of social behavior in autism spectrum disorders: Explicit versus implicit social cognition by Cara M Keifer, Amori Yee Mikami, James P Morris, Erin J Libsack and Matthew D Lerner in Autism

Additional file 1. Criterion latent variable quartile plots for all significant effects for each model.

Colorectal cancer (CRC) screening has been shown to decrease CRC mortality, yet significant disparities persist among those living in rural areas, from minority backgrounds, and those having low income. The purpose of this two-arm randomized controlled trial is to test the effectiveness and fidelity of a stepped care (increasing intensity as needed) approach to promoting 3-year adherence to CRC screening via fecal immunochemical testing (FIT) or colonoscopy in rural community clinics serving high rates of low-income and minority patients. We hypothesize that, compared to enhanced usual care (EUC), patients receiving the multifaceted CRC screening intervention will demonstrate higher rates of CRC screening completion over 3 years. Participants from six federally qualified health centers (FQHCs; N = 1200 patients) serving predominately low-income populations in rural Louisiana will be randomized to the intervention or EUC arm. All participants will receive health literacy-directed CRC counseling, simplified materials about both the FIT and colonoscopy procedures, and motivational interviewing to aid in the determination of test preference. Participants in the intervention arm will also receive motivational reminder messages from their primary care provider (via audio recording or tailored text) for either a scheduled colonoscopy or return of a completed FIT. Participants in the EUC arm will receive the standard follow-up provided by their clinic or colonoscopy facility. The primary outcome will be completion of either colonoscopy or annual FIT over 3 years. Results will provide evidence on the effectiveness of the intervention to decrease disparities in CRC screening completion related to health literacy, race, and gender. Trial registration:Clinicaltrials.gov Identifier NCT04313114.

Schuerch et al. (2018) [1] deserve credit for compiling a wide range of disparate, global datasets that will be instrumental in predicting future coastal wetland change. However, we challenge their projections that range from modest losses to substantial gains worldwide by the end of this century. Their modeling does not adequately capture the role of sediment supply which must be treated volumetrically, with profound implications for their projections. We anticipate that an appropriate modification will result in substantially different projections, with rates of coastal wetland loss that generally increase as a function of relative sea-level rise (RSLR), regardless of the human adaptation scenario. This is also in line with the findings from a precursor study [2] by a subset of the Schuerch et al. group.

In 2014, a DNA-based phylogenetic study confirming the paraphyly of the grass subtribe Sporobolinae proposed the creation of a large monophyletic genus Sporobolus, including (among others) species previously included in the genera Spartina, Calamovilfa, and Sporobolus. Spartina species have contributed substantially (and continue contributing) to our knowledge in multiple disciplines, including ecology, evolutionary biology, molecular biology, biogeography, experimental ecology, biological invasions, environmental management, restoration ecology, history, economics, and sociology. There is no rationale so compelling to subsume the name Spartina as a subgenus that could rival the striking, global iconic history and use of the name Spartina for over 200 yr. We do not agree with the subjective arguments underlying the proposal to change Spartina to Sporobolus. We understand the importance of both the objective phylogenetic insights and of the subjective formalized nomenclature and hope that by opening this debate we will encourage positive feedback that will strengthen taxonomic decisions with an interdisciplinary perspective. We consider that the strongly distinct, monophyletic clade Spartina should simply and efficiently be treated as the genus Spartina. Fil: Bortolus, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina Fil: Adam, Paul. University Of New South Wales (unsw) Australia; Australia Fil: Adams, Janine B.. Nelson Mandela University; Sudáfrica Fil: Ainouche, Malika L.. University of Rennes 1; Francia Fil: Ayres, Debra. University of California; Estados Unidos Fil: Bertness, Mark D.. Brown University; Estados Unidos Fil: Bouma, Tjeerd J.. University of Utrecht; Países Bajos. Utrecht University; Países Bajos Fil: Bruno, John F.. University of North Carolina; Estados Unidos Fil: Caçador, Isabel. Universidade de Lisboa; Portugal Fil: Carlton, James T.. Williams College. Maritime Studies Program. Mystic Seaport; Estados Unidos Fil: Castillo, Jesus M.. Universidad de Sevilla; España Fil: Costa, Cesar S. B.. Universidade Federal Do Rio Grande; Brasil Fil: Davy, Anthony J.. University of East Anglia; Reino Unido Fil: Deegan, Linda. Woods Hole Research Center; Estados Unidos Fil: Duarte, Bernardo. Universidade de Lisboa; Portugal Fil: Figueroa, Enrique. Universidad de Sevilla; España Fil: Gerwein, Joel. California State Coastal Conservancy; Estados Unidos Fil: Gray, Alan J.. Centre for Ecology and Hydrology; Reino Unido Fil: Grosholz, Edwin D.. University of California at Davis; Estados Unidos Fil: Hacker, Sally D.. State University of Oregon; Estados Unidos Fil: Hughes, A. Randall. University Northeastern; Estados Unidos. Northeastern University; Estados Unidos Fil: Mateos Naranjo, Enrique. Universidad de Sevilla; España Fil: Mendelssohn, Irving A.. Louisiana State University; Estados Unidos Fil: Morris, James T.. University of South Carolina; Estados Unidos Fil: Muñoz-Rodríguez, Adolfo F.. Universidad de Huelva; España Fil: Nieva, Francisco J. J.. Scripps Institution of Oceanography; Estados Unidos Fil: Levin, Lisa A.. Scripps Institution of Oceanography; Estados Unidos Fil: Li, Bo. School Of Life Sciences Fudan University; China Fil: Liu, Wenwen. Xiamen University; China Fil: Pennings, Steven C.. University Of Houston; Estados Unidos Fil: Schwindt, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentina

NOAA Technical Memorandum NOS NCCOS ; 263

Circulating tumor DNA (ctDNA) offers new opportunities for noninvasive cancer management. Detecting ctDNA in plasma is challenging because it constitutes only a minor fraction of the total cell-free DNA (cfDNA). Pre-analytical factors affect cfDNA levels contributed from leukocyte lysis, hence the ability to detect low-frequency mutant alleles. This study investigates the effects of the delay in processing, storage temperatures, different blood collection tubes, centrifugation protocols, and sample shipment on cfDNA levels. Peripheral blood (n = 231) from cancer patients (n = 62) were collected into K3EDTA or Cell-free DNA BCT tubes and analyzed by digital PCR, targeted amplicon, or shallow whole-genome sequencing. To assess pre-analytic effects, plasma was processed under different conditions after 0, 6, 24, 48, 96 hours, and 1 week at room temperature or 4°C, or using different centrifugation protocols. Digital PCR showed that cfDNA levels increased gradually with time in K3EDTA tubes, but were stable in BCT tubes. K3EDTA samples stored at 4°C showed less variation than room temperature storage, but levels were elevated compared with BCT. A second centrifugation at 3000 × g gave similar cfDNA yields compared with higher-speed centrifugation. Next-generation sequencing showed negligible differences in background error or copy number changes between K3EDTA and BCT, or following shipment in BCT. This study provides insights into the effects of sample processing on ctDNA analysis.

Tumour heterogeneity leads to the development of multiple resistance mechanisms during targeted therapies. Identifying the dominant driver(s) is critical for treatment decision. We studied the relative dynamics of multiple oncogenic drivers in longitudinal plasma of 50 EGFR‐mutant non‐small‐cell lung cancer patients receiving gefitinib and hydroxychloroquine. We performed digital PCR and targeted sequencing on samples from all patients and shallow whole‐genome sequencing on samples from three patients who underwent histological transformation to small‐cell lung cancer. In 43 patients with known EGFR mutations from tumour, we identified them accurately in plasma of 41 patients (95%, 41/43). We also found additional mutations, including EGFR T790M (31/50, 62%), TP53 (23/50, 46%), PIK3CA (7/50, 14%) and PTEN (4/50, 8%). Patients with both TP53 and EGFR mutations before treatment had worse overall survival than those with only EGFR. Patients who progressed without T790M had worse PFS during TKI continuation and developed alternative alterations, including small‐cell lung cancer‐associated copy number changes and TP53 mutations, that tracked subsequent treatment responses. Longitudinal plasma analysis can help identify dominant resistance mechanisms, including non‐druggable genetic information that may guide clinical management., EMBO Molecular Medicine, 10 (6), ISSN:1757-4676, ISSN:1757-4684

Search strategy. Details the search strategy applied for the systematic review. (PDF 1100 kb)

Quality assessment. Shows the quality assessment of RCTs and observational studies included in the analysis. (PDF 1103 kb)

Numerical example. Shows a numerical example illustrating the calculation of the distance measure between single armed studies. (PDF 1101 kb)

Reason for exclusion. Details the reason for excluding studies in the quantitative analysis. (PDF 1102 kb)

WinBUGs code. Contains WinBUGs code and input data for the analysis. (PDF 1103 kb)

Rankogram. Shows the rankograms for the white and the black network of the RCT only analysis. (PDF 1103 kb)

All pairwise comparisons. Table containing hazard ratios and 95% credible intervals of all pairwise comparisons in the combined analysis. (PDF 1100 kb)

SUCRA all scenarios. SUCRA ranking score of all licensed treatments of individual matches connecting both networks as well as the base case scenario containing all matches. (PDF 1100 kb)

This thesis is not available on this repository until the author agrees to make it public. If you are the author of this thesis and would like to make your work openly available, please contact us: thesis@repository.cam.ac.uk., The Library can supply a digital copy for private research purposes; interested parties should submit the request form here: http://www.lib.cam.ac.uk/collections/departments/digital-content-unit/ordering-images, Please note that print copies of theses may be available for consultation in the Cambridge University Library's Manuscript reading room. Admission details are at http://www.lib.cam.ac.uk/collections/departments/manuscripts-university-archives

Figure S2. Exploration of prioritised variant genes within co-expression modules from the case study. Exploration of prioritised variant genes within co-expression module 3 (leukocyte activation involved in immune response) for the 5 Gene Significance measures. Module membership is defined as the correlation between the gene profile and the eigengene of module 3. Dots are weighted according to effect size. A p-value cutoff of

The debate on gun control dates back to the ratification of Second Amendment in 1791. The history of gun control in the United States has issues such as slavery, criminalization of giving the Catholics guns and the regulation of storage of gun powders in houses. The ratification of the Second Amendment was part of the enactment of Bill of Rights – the first ten amendments to the original Constitution of 1787. Recent cultural debates that revolve around gun control and ownership lack substantive consideration of the American history up to and after the ratification of the Second Amendment in 1791. This thesis calls for consideration of upholding the contents and intents of the Bill of Rights on the right to bear arms. This research study employs qualitative research design and has elements such as questionnaires, interviews, observations, focus group discussions and case study in collecting data. It is anchored on the Theory of Individual Rights to give a hypothesis that gun ownership is not to blame for recent happenings in United States regarding regular killings in the country. A total of 300 participants are employed for this research drawn from five States of the United States namely, Massachusetts, Georgia, Oregon, California and Alaska. In each of the five states, 50 persons were asked to fill out questionnaires and ten were interviewed. The participants who filled out questionnaires were selected randomly while only senior political officials in the States were interviewed.

Figure S1. Consensus clustering of dbNSFP rankscores for 1084 protein-changing variants revealed in the case study. Consensus clustering of dbNSFP rankscores for 1084 protein-changing variants identified in the case study. To determine the most meaningful number of clusters of prediction scores, we first assess the consensus CDFs (Figure S1A) and the relative change in the area under the CDF curve (Î (k), Fig. S1B). Here, Î (k) did not increase markedly at more than 5 clusters. Next, using the heatmap of the hierarchical clustering of consensus indexes for the different cluster numbers (Figure S1C), we can question the plausibility of clusters in light of the different prediction score categories. This approach revealed that a fifth cluster created another subcluster in the conservation scores only, indicating that 4 clusters could be a more systematic choice. (A) Plot of cumulative distribution functions (CDFs) corresponding to the consensus matrices in the range between 2 and 6 clusters. (B) Relative change in the area under the CDF curve (Î k). (C) Heatmap illustrating the hierarchical clustering of consensus index for 4 clusters of prediction algorithms based on 100 permutations and resampling of 80% of the algorithms and 80% of the variants. Functions provided by the ConsensusClusterPlus R package were used to perform the analysis [41]. (PDF 325 kb)

Westminster College's first-year composition courses have generally been taught in person, with two accompanying information literacy instruction sessions. However, several composition courses have recently been taught online, and the librarians wanted to make sure that the corresponding online information course stayed engaging and interactive. The college's instructional designer and a librarian teamed up to implement the three pillars of the Community of Inquiry theory for online education as well as activities that addressed the new ACRL Information Literacy Framework. The online IL course will now consist of a combination of interactive tutorials, moderated discussion forums, and activities that help merge the ACRL standards and the framework's threshold concepts. Objectives for the session will include offering examples of how the framework can work for in-person and online information literacy instruction; presenting the Community of Inquiry model as a theoretical basis for online learning; and providing resources for Instructional Design best practices.

Going beyond Orientalism in its examination of novels dealing with British colonisation in the West, as well as the East Indies, the postcolonial frame of my thesis develops recent theorisations of the Romantic ‘stranger’. Analysing a range of novels from the much anthologised Mansfield Park (1814), to less well-known narratives such as John Thelwall’s The Daughter of Adoption (1801) and Sir Walter Scott’s Saint Ronan’s Well (1823), my thesis seeks to account for a model of ‘colonial cosmopolitanism’ within fiction of the period. Considering the cosmopolitan dimensions of the transferential rhetoric of slavery, my thesis explores the ways in which, Jane Austen, Amelia Opie and Maria Edgeworth consider the position of women in domestic society through a West Indian frame. Demonstrating the need for reform both at home and abroad, such novels are representative of a fledgling cosmopolitanism that is often overlooked in current criticism. In seeking to account for ‘colonial cosmopolitanism’ as a new model for reading fiction composed during the Romantic period, my thesis attempts to add further nuance to current understandings of sympathetic exchange during the process of British colonisation. In chapters four and five I will develop my analysis of novels dealing with colonial expansion in the Caribbean to consider novels which deal with the Indian subcontinent. Although stopping short of questioning colonial expansion, discourses of ‘colonial cosmopolitanism’, as my thesis demonstrates, provided a foundation for humanitarian and cultural engagement which was mutually transformative for both the coloniser and the colonised.

Nuclear spins are known to experience spontaneous long-range correlations only below 2.5 mili-Kelvin in superfluid $^3$He. Here we present the first evidence of nuclear spin coupling in molecular hydrogen (H$_2$) at 74-92 Kelvin using neutron scattering, showing a fundamental change in nature from the incoherent scattering universally expected from hydrogen, which reflects single particle properties of uncorrelated nuclear spins, to coherent, with a peak materializing on the elastic line, indicating H$_2$-H$_2$ nuclear spin correlations. In this novel phase, the dynamic response of the system also changes nature, and collective excitations with an effective mass of nine H$_2$ are observed with inelastic scattering at momentum transfers up to 37 \AA$^{-1}$, corresponding to length scales smaller than the H-H bond, where previous experiments have always found single atom excitations. This novel behavior has only been observed from H$_2$ within the subnanometer sized graphitic pores of a carbon material, marking the first demonstration that a confined materials environment can be used to control nuclear spin correlations., Comment: Submitted 12-21-2015

Social network analysis (SNA) is used by the DoD to describe and analyze social networks, leading to recommendations for operational decisions. However, social network models are constructed from various information sources of indeterminate reliability. Inclusion of unreliable information can lead to incorrect models resulting in flawed analysis and decisions. This research develops a methodology to assist the analyst by quantitatively identifying and categorizing information sources so that determinations on including or excluding provided data can be made. This research pursued three main thrusts. It consolidated binary similarity measures to determine social network information sources' concordance and developed a methodology to select suitable measures dependent upon application considerations. A methodology was developed to assess the validity of individual sources of social network data. This methodology utilized source pairwise comparisons to measure information sources? concordance and a weighting schema to account for sources' unique perspectives of the underlying social network. Finally, the developed methodology was tested over a variety of generated networks with varying parameters in a design of experiments paradigm (DOE). Various factors relevant to conditions faced by SNA analysts potentially employing this methodology were examined. The DOE was comprised of a 2(exp 4) full factorial design augmented with a nearly orthogonal Latin hypercube. A linear model was constructed using quantile regression to mitigate the non-normality of the error terms.

As humans, we interact with our environment and the other species inhabiting it in a variety of ways. Animals not only provide a source of sustenance, but a means for humans to express their social concepts through interaction. The range of human interactions with other species can still be seen in our modern world; such as the use of animal characteristics as metaphors and the humanisation of certain species. Douglas (1990, 33) suggests we think about how animals relate to one another, on the basis of our own relationships. Therefore, human social categories are extended into the animal world. Classical literature can offer examples of this. Aristotle (Politics, 1254b) discussed the similarity between working animals and slaves, which in Roman law were treated together, noting ‘the usefulness of slaves diverges little from that of animals; bodily service for the necessities of life is forthcoming from both’. This entwining of the human and animal worlds was also present in the form of animal sacrifices and Gilhus (2006) has discussed the inventions and developments of such a tradition in depth. Evidence of animal sacrifice is not just limited to the classical world, for example we also have evidence from iconographic depictions from Mesoamerica (Emery 2005), as well as ethnographic observations (Morris 2000, 138). \ud \ud The challenge we face is to use archaeologically recovered faunal data to investigate such social zooarchaeological issues. As the majority of animal remains are of a fragmentary nature, most investigations into social concepts have utilised articulated animal remains. A number of terms have been used when discussing such concepts including animal burials and special animal deposits. However, for this paper the term associated bone group (ABG) has been adopted. Although at first it may appear unimportant, the terminology and language used by archaeologists describing a deposit can greatly influence its interpretation, and importantly, the concepts of other archaeologists. Terms such as ‘special’, to many archaeologists, automatically implies a ritual connotation, similarly ‘burial’, a term utilised mainly for human remains, may conjure images of a ceremonial/ritual event. This is important because within British archaeology the interpretation of these deposits has been stuck in a dichotomy between the ritual and the mundane (Morris 2008a; 2010c). Hill (1995) was also critical of the use of ‘special deposit’ and suggested the term associated/articulated bone group, to remove any connotations.\ud \ud This paper draws on the results of a project that investigated the nature of ABGs in Britain from the Neolithic (c.4000BC) to the end of the late medieval period (c.AD1550). Due to the large time-span it was not possible to investigate every deposit in Britain, therefore just published data from southern England (Dorset, Hampshire and Wiltshire) and Yorkshire was utilised. The results of the project are discussed in detail elsewhere, along with a complete list of the sites recorded (Morris 2008b; 2010c), therefore a brief overview of the major trends will be discussed here. Further consideration will then be given to the interpretation of these deposits and a biographical method based on the actions used to create the ABG will be considered. Finally the paper will use this approach to discuss the presence of ritual animal killings in the British archaeological record.

An explication of the neural substrates for social perception is an important component in the emerging field of social cognitive neuroscience and is relevant to the field of cognitive neuroscience as a whole. Prior studies from our laboratory have demonstrated that passive viewing of biological motion (Pelphrey, Mitchell, et al., 2003; Puce et al., 1998) activates the posterior superior temporal sulcus (STS ) region. Furthermore, recent evidence has shown that the perceived context of observed gaze shifts (Pelphrey, Singerman, et al., 2003; Pelphrey et al., 2004) modulates STS activity. Here, using event-related functional magnetic resonance imaging at 4 T, we investigated brain activity in response to passive viewing of goal- and nongoal-directed reaching-to-grasp movements. Participants viewed an animated character making reaching-to-grasp movements either toward (correct) or away (incorrect) from a blinking dial. Both conditions evoked significant posterior STS activity that was strongly right lateralized. By examining the time course of the blood oxygenation level-dependent response from areas of activation, we observed a functional dissociation. Incorrect trials evoked significantly greater activity in the STS than did correct trials, while an area posterior and inferior to the STS (likely corresponding to the MT/ V5 complex) responded equally to correct and incorrect movements. Parietal cortical regions, including the superior parietal lobule and the anterior intraparietal sulcus, also responded equally to correct and incorrect movements, but showed evidence for differential responding based on the hand and arm (left or right) of the animated character used to make the reaching-to-grasp movement. The results of this study further suggest that a region of the right posterior STS is involved in analyzing the intentions of other people's actions and that activity in this region is sensitive to the context of observed biological motions.

Balancing the needs of information distributors and their audiences has grown harder in the age of the Internet. While the demand for attention continues to increase rapidly with the volume of information and communication, the supply of human attention is relatively fixed. Markets are a social institution for efficiently balancing supply and demand of scarce resources. Charging a price for sending messages may help discipline senders from demanding more attention than they are willing to pay for. Price may also help recipients estimate the value of a message before reading it. We report the results of two laboratory experiments to explore the consequences of a pricing system for electronic mail. Charging postage for email causes senders to be more selective and send fewer messages. However, recipients did not use the postage paid by senders as a signal of importance. These studies suggest markets for attention have potential, but their design needs more work.

This article outlines a method originated by the author during World War II for evaluating short range weather forecasts. An interesting feature is the use of “deviational penalty scores” to adjust for the relative ease or difficulty of forecasting for varying weather situations. A number of other studies on weather forecast evaluation by other authors lead to different methods of analysis (see references at end of article). The author has encountered situations in other fields where variations of the method proved useful. As an instance, some elements of this method were used in designing a scoring procedure for rating bombing proficiency of air crews during the Korean War. * The author is particularly indebted to Lewis T. Reinwald of the Corporation for Economic & Industrial Research for suggestions made for this article.

This article illustrates an original method of adjusting defective data when gross errors can be detected. The method entails an assumption concerning the distribution of total errors in order to estimate the effect of undetectable errors. While this type of situation may not be common, it could occur in almost any data-gathering activity and could therefore have application in a wide variety of organizations.

Approximately 46 million acres or 88 per cent of the land area of the state of Utah has been classified by Reuss and Blanch (1951) as "range land open for grazing." Although some of this area cannot be grazed because of inaccessibility, lack of water, poison plants, and similar factors, it is estimated that some 40 million acres or 78 per cent of the total land area is available for grazing. Most of this grazing land is federally owned (73 per cent), while only 22 per cent is privately held, and 5 per cent is state owned.

Background: Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established. Methods: Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine. Results: Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings. Conclusions: These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.

BACKGROUND: Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established. METHODS: Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine. RESULTS: Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings. CONCLUSIONS: These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

Table S2. Showing the input variant format of CVE. (PDF 69 kb)

Table S2. Showing the input variant format of CVE. (PDF 69 kb)

Background: Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established. Methods: Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine. Results: Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings. Conclusions: These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.