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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

ROSE provides professional development and networking opportunities for CC and HBCU faculty.

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

The 2022 High Level Workshop on the European Research Area focused on ethics and integrity when science engages with the public, such as when advising decision makers, communicating to citizens, or having the public participate in the research process. In the current situation, with many different challenges facing us, decision makers and the public expect researchers to speak with a clear voice and offer direction and solutions. At the same time, the relevance, reliability, and accountability of expert knowledge is sometimes contested. Engagement with the public becomes an ever more important priority. It can better align the expectations and needs from society with what science can do, and enables science to better respond to societal concerns. The High Level Workshop looked at how such engagement can take place with the highest ethics and integrity standards.

Hypothesis: SARS-CoV-2 amplifies pre-existing dysbiosis induced mucosal inflammation and this can cause a severe systemic inflammatory disease. The microbial flora perturbation can persist long after the virus has been eliminated leading to a wide range of long Covid symptoms. Evidence: Dysbiosis induced mucosal inflammation increases with age and is strongly associated with the metabolic syndrome (obesity, type 2 diabetes mellitus, ischaemic heart disease, hypertension, and depression). These are risk factors for the conversion of mild to severe Covid-19. Certain common strains of Staphylococcus aureus, which is commonly carried in pharyngeal mucosa, can trigger a cytokine cascade as seen in severe Covid-19. Blood group A and vitamin D deficiency, which are risk factors for hospitalisation in Covid-19 are also associated with increased S. aureus pharyngeal carriage rates. Multi-inflammatory syndrome in children is a post Covid condition which resembles toxic shock syndrome and Kawasaki disease (the former is known to be caused by staphylococcal pyrogenic toxins). A number of studies have shown dysbiosis of the oral mucosa and rectal mucosa in patients who progress to severe Covid-19. The wide range of pathology seen during and following SARS-CoV-2 infection is more in keeping with dysbiosis induced inflammation (multiple pathogenic bacteria at multiple sites) than with an otherwise simple viral induced respiratory tract infection. Implication: Optimization of the microbial flora, prior to encountering the virus, could have reduced the severity of the pandemic. The consumption of fermented foods, especially yoghurt, holds the most promise for reducing dysbiosis induced mucosal inflammation and preventing a wide range of complications. Reduced mucosal inflammation brings not only health but also happiness in which oxytocin has a key role.

Texts and artworks composed in the context of Japan's measles epidemic in 1862 provided the public with recommendations about foods that were beneficial or detrimental for the prevention and treatment of measles. These texts and artworks constitute important historical sources essential for understanding how diets changed during the epidemic and for identifying foodstuffs that were commonly eaten by ordinary Japanese people prior to the epidemic.

Aim Restarting elective services presents a challenge to restore and improve many of the planned patient care pathways which have been suspended during the response to the COVID-19 pandemic. A significant backlog of planned elective work has built up representing a considerable volume of patient need. We aimed to investigate the health status, quality of life, and the impact of delay for patients whose referrals and treatment for symptomatic joint arthritis had been delayed as a result of the response to COVID-19. Methods We interviewed 111 patients referred to our elective outpatient service and whose first appointments had been cancelled as a result of the response to the COVID-19 pandemic. Results Patients reported significant impacts on their health status and quality of life. Overall, 79 (71.2%) patients reported a further deterioration in their condition while waiting, with seven (6.3%) evaluating their health status as ‘worse than death’. Conclusions Waiting lists are clearly not benign and how to prioritize patients, their level of need, and access to assessment and treatment must be more sophisticated than simply relying on the length of time a patient has been waiting. This paper supports the contention that patients awaiting elective joint arthroplasty report significant impacts on their quality of life and health status. This should be given appropriate weight when patients are prioritized for surgery as part of the recovery of services following the COVID-19 pandemic. Elective surgery should not be seen as optional surgery—patients do not see it in this way.

In a demonstration (DEMO) reactor, mitigation of the large heat load on the divertor target to the below material and engineering limits is a key requirement for operation. Systems modeling is used to design entire fusion power plants and, therefore, has to be able to appropriately capture the divertor challenge. Therefore, it is important to validate these models against comprehensive SOL-divertor simulation codes and experiments. A 1-D divertor model in PROCESS was investigated, compared to the results of 2-D SONIC simulation under the detachment condition. The comparison shows how the 1-D divertor model handles the power loss mechanisms from the outboard mid-plane to the outer divertor target for a DEMO-like condition. The results show good agreement on the calculated value of the total power crossing the separatrix (

This research note describes the biographies of D?r?y and Ri Mitsuei, two Persians whose visits to Japan in the 7th and 8th Centuries are recorded in the Nihon Shoki and Shoku Nihongi. The research note outlines and critically engages with contemporary research, and seeks to suggest that much of the current knowledge regarding the biographies of the two figures is unsubstantiated. Furthermore, the research note seeks to provide new starting points for the analysis of the two figures. Whilst it argues that little can be known about the figure of D?r?y, the research note seeks to interact and add to debates regarding his name, nationality, rank, and the roles of other people who are often mentioned alongside him in scholarly works. Turning to Ri Mitsuei, the research note adds to previous research undertaken by the author revising some of the conclusions that he drew elsewhere.

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

Objectives: To determine the associations between comorbidities, health-related quality of life (HRQoL) and functional impairment in people with mild-to-moderate chronic kidney disease (CKD) in primary care.Design: Cross-sectional analysis at 5-year follow-up in a prospective cohort study.Setting: Thirty-two general practitioner surgeries in England.Participants: 1008 participants with CKD stage 3 (of 1741 people recruited at baseline in the Renal Risk in Derby study) who survived to 5?years and had complete follow-up data for HRQoL and functional status (FS).Primary and secondary outcome measures HRQoL assessed using the 5-level EQ-5D version (EQ-5D-5L, with domains of mobility, self-care, usual activities, pain/discomfort and anxiety/depression and index value using utility scores calculated from the English general population), and FS using the Karnofsky Performance Status scale (functional impairment defined as Karnofksy score ?70). Comorbidity was defined by self-reported or doctor-diagnosed condition, disease-specific medication or blood result.Results: Mean age was 75.8 years. The numbers reporting some problems in EQ-5D-5L domains were: 582 (57.7%) for mobility, 166 (16.5%) for self-care, 466 (46.2%) for usual activities, 712 (70.6%) for pain/discomfort and 319 (31.6%) for anxiety/depression. Only 191 (18.9%) reported no problems in any domain. HRQoL index values showed greater variation among those with lower FS (eg, for those with Karnofsky score of 60, the median (IQR) EQ-5D index value was 0.45 (0.24 to 0.68) compared with 0.94 (0.86 to 1) for those with Karnofsky score of 90). Overall, 234 (23.2%) had functional impairment.In multivariable logistic regression models, functional impairment was independently associated with experiencing problems for all EQ-5D-5L domains (mobility: OR 16.87 (95% CI 8.70 to 32.79, p < 0.001, self-care: OR 13.08 (95% CI 8.46 to 20.22), p< 0.001, usual activities: OR 8.27 (95% CI 5.43 to 12.58), p< 0.001, pain/discomfort: OR 2.94 (95% CI 1.86 to 4.67), p< 0.001, anxiety/depression: 3.08 (95% CI 2.23 to 4.27), p< 0.001). Higher comorbidity count and obesity were independently associated with problems in mobility, self-care, usual activities and pain/discomfort: for three or more comorbidities versus none: (mobility: OR 2.10 (95% CI 1.08 to 4.10, p for trend 0.002), self-care: OR 2.64 (95% CI 0.72 to 9.67, p for trend 0.05), usual activities: OR 4.20 (95% CI 2.02 to 8.74, p for trend < 0.001), pain/discomfort: OR 3.06 (95% CI 1.63 to 5.73, p for trend < 0.001)), and for obese (body mass index (BMI) ?30?kg/m2) versus BMI < 25?kg/m2: (mobility: OR 2.44 (95% CI 1.61 to 3.69, p for trend < 0.001), self-care: OR 1.98 (95% CI 1.06 to 3.71, p for trend 0.003), usual activities: OR 1.82 (95% CI 1.19 to 2.76, p for trend 0.019), pain/discomfort: OR 2.37 (95% CI 1.58 to 3.55, p for trend < 0.001)). Female sex, lower FS and lower educational attainment were independently associated with anxiety/depression (ORs 1.60 (95% CI 1.18 to 2.16, p 0.002), 3.08 (95% CI 2.23 to 4.27, p< 0.001) and 1.67 (95% CI 1.10 to 2.52, p 0.009), respectively). Older age, higher comorbidity count, albuminuria (?30?mg/mmol vs < 3?mg/mmol), lower educational attainment (no formal qualifications vs degree level) and obesity were independently associated with functional impairment (ORs 1.07 (95% CI 1.04 to 1.09, p< 0.001), 2.18 (95% CI 0.80 to 5.96, p for trend < 0.001), 1.74 (95% CI 0.82 to 3.68, p for trend 0.005), 2.08 (95% CI 1.26 to 3.41, p for trend < 0.001) and 4.23 (95% CI 2.48 to 7.20), respectively).Conclusions: The majority of persons with mild-to-moderate CKD reported reductions in at least one HRQoL domain, which were independently associated with comorbidities, obesity and functional impairment.

This thesis uses the Wallachian Revolution of 1848 as a window through which to see and study questions about time, revolution, national and European identity, personal and popular sovereignty, and the relationship between central and local interests in mid- nineteenth-century Europe. It argues that liberal intellectuals in the two Danubian Principalities thought about their national pasts and futures in European terms during the 1840s and re-imagined the idea of Europe from the periphery. It was only with the outbreak of revolution across Europe in 1848 that they began to think of changing the present. Popular sovereignty lay at the heart of the revolutionary programme. Opportunities to participate in national politics were opened to rural and urban populations alike, and these changes mirrored those across the continent during the revolutionary year. The history of Southeastern Europe should not be viewed as divorced from that of the rest of Europe. Debates on peasant emancipation and land mirrored those about the right to work in France, and both were connected to ideas of political sovereignty. To be sovereign as a whole, the people needed to be sovereign as individuals, which meant they needed the means to sustain themselves. In a city like Paris this meant they needed the right to work. In the agrarian context of rural Wallachia it meant they needed land. But while the general European revolution spurred the Wallachians to act, it also hindered their chance of success. The grand unified revolution broke apart, and counterrevolutionary forces picked them off one by one. A joint Ottoman-Russian occupation followed for Wallachia. The revolutionaries had attempted to Europeanise the principality. They took local concerns and transformed them into national debates. The counterrevolutionaries reversed these trends. They provincialised the principality, imposed new state apparatuses of control, and divided local grievances from national politics. It was not a return to the pre-revolutionary order. It was the creation of a new order that could preserve something of the character of the pre-revolutionary era while responding to the changing needs and circumstances of Wallachia., Pigott Doctoral Studentship

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

Using the ultrafast laser inscription technique, buried channel waveguides have been fabricated in gallium lanthanum sulfide and gallium lanthanum sulfide selenide glasses to demonstrate the suitability of the materials for supercontinuum generation in the mid-IR. Supercontinuum generation was performed using 100 femtosecond pump pulses with micro-Joule pulse energies and a center wavelength of 4.6 µm, which is in the anomalous dispersion regime for these waveguides. Under such pump conditions, supercontinuum was obtained covering a 25-dB-bandwidth of up to 6.1 μm with a long-wavelength edge of 8 µm. To our knowledge, this represents the broadest and the longest-wavelength IR supercontinuum generated from an ultrafast laser inscribed waveguide to date.

Using the ultrafast laser inscription technique, buried channel waveguides have been fabricated in gallium lanthanum sulfide and gallium lanthanum sulfide selenide glasses to demonstrate the suitability of the materials for supercontinuum generation in the mid-IR. Supercontinuum generation was performed using 100 femtosecond pump pulses with microJoule pulse energies and a center wavelength of 4.6 µm, which is in the anomalous dispersion regime for these waveguides. Under such pump conditions, supercontinuum was obtained covering a 25-dB-bandwidth of up to 6.1 um with a long-wavelength edge of 8 µm. To our knowledge, this represents the broadest and the longest-wavelength IR supercontinuum generated from an ultrafast laser inscribed waveguide to date.

NOAA Technical Memorandum NOS NCCOS ; 263

Glioma is difficult to detect or characterize using current liquid biopsy approaches. Detection of cell‐free tumor DNA (cftDNA) in cerebrospinal fluid (CSF) has been proposed as an alternative to detection in plasma. We used shallow whole‐genome sequencing (sWGS, at a coverage of < 0.4×) of cell‐free DNA from the CSF of 13 patients with primary glioma to determine somatic copy number alterations and DNA fragmentation patterns. This allowed us to determine the presence of cftDNA in CSF without any prior knowledge of point mutations present in the tumor. We also showed that the fragmentation pattern of cell‐free DNA in CSF is different from that in plasma. This low‐cost screening method provides information on the tumor genome and can be used to target those patients with high levels of cftDNA for further larger‐scale sequencing, such as by whole‐exome and whole‐genome sequencing., EMBO Molecular Medicine, 10 (12), ISSN:1757-4676, ISSN:1757-4684

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.

In this talk, we describe our recent work on selenium modified Ga:La:S glasses. The addition of Se improves the infrared transmission sufficiently to capture enough of the 8-12 micron window to allow thermal imaging, while at the same time, allowing sufficient visible transmission for object recognition using conventional image capturing. The addition of Se has other implications, increasing the optical nonlinearity, providing longer fluorescent lifetimes when doped with rare earth ions and expanding the transmission window in the important 3-5 micron region. Ga:La:S glasses are superior to commercially available chalcogenides based on alloys of Ga and/or As with S, Se and/or Te. They offer significantly higher alkaline resistance, greater mechanical strength and over 300ºC higher working temperature (Tg > 500ºC). All of these new features suggest Ga:La:S-Se may be a material suitable for the next generation of mid-IR sources through supercontinuum or rare earth doping.

This thesis explores the history of Christianity and conversion to it in 16th and 17th Century Japan. It argues that conversion is a complex phenomenon which happened for a variety of reasons. Furthermore, it argues that due to the political context and limitations acting upon the mission, the majority of conversions in 16th and 17th Century Japan lacked an element of epistemological change (classically understood). The first chapter explores theories of conversion suggesting that conversion in 16th and 17th Century Japan included sorts of religious change not usually encapsulated in the term conversion including adhesion, communal and forced conversion. Moreover, it argues that contextual factors are the most important factors in religious change. The second chapter explores political context contending that it was the political environment of Japan that ultimately decided whether conversion was possible. This chapter charts the evolution of the Japanese context as it became more hostile toward Christianity. In the third chapter, the context of the mission is explored. It is argued that limitations acting upon the mission shaped post-conversion faith, so that changes to practice and ritual rather than belief became the mark of a successful conversion. The fourth chapter explores methods of conversion, the factors influencing it, and post-conversion faith more directly. It argues that Christianity spread primarily through social networks, but that conversion was also influenced by economic incentive, other realworld benefits, and Christianity’s perceived efficacy. Building on Chapter Three, the final chapter also seeks to illustrate that the missionaries were not successful in their attempts to spur epistemological change or instil a detailed knowledge of theology or doctrine amongst their converts.

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

Ultrafast laser inscription has been used to produce channel waveguides in Ge22As20Se58 glass (GASIR-1, Umicore N.V). The mode field diameter and waveguide losses at 2.94 mu m were measured along with the waveguide dispersion in the 1 to 4.5 mu m range, which is used to estimate the zero-dispersion wavelength. Z-scan measurements of bulk samples have also been performed to determine the nonlinear refractive index. Finally, midIR supercontinuum generation has been shown when pumping the waveguides with femtosecond pulses centered at 4.6 mu m. Supercontinuum spanning approximately 4 mu m from 2.5 to 6.5 mu m was measured which, to the best of the authors' knowledge, represents the broadest and the deepest IR supercontinuum from an ultrafast laser inscribed waveguide to date. This work, combined with the long wavelength transmission of GASIR-1 up to 15 mu m, paves the way for realizing further ultrafast laser inscribed waveguide devices in GASIR-1 for mid-IR integrated optics applications. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License.

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)

During the 3rd to the 1st century BC on a small settlement consisting of a handful of roundhouses set in an area of open-country close to arable land, a six-year-old male horse was killed. Following its death the horse was partially dismembered; its lower jaw was removed, its tail and parts of its skin where cut from it, as were its hind legs and left forelimb, all below the knee. The now bloodied horse carcass was dragged, pulled and handled until it lay centrally within a pit on the outskirts of the settlement. The horse carcass was placed on its right-hand side, the remains of its head resting on its chest, its one remaining complete leg extended out away from the body. Once in position, soil was thrown into the pit, until the horse carcass was no longer visible. There the horse lay, the remaining soft tissue being slowly consumed by bacteria from the horses’ own gut and the soil which now enclosed it, until only the bones survived. What remains of the horse was next seen over two millennia later in 1977, when a team of archaeologists led by Peter Fasham excavated the site of Winnall Down, Winchester, ahead of the construction of the M3 motorway. The pit in which the articulated horse remains were discovered was labeled as pit 10161 and the horse bones, excavated from layer 10164, were duly bagged, cleaned, boxed and sent to the Ancient Monuments Laboratory at the University of Southampton. There they were subsequently examined and reported on by Mark Maltby, before finally being archived with Hampshire Museum service, where they remain to this day.

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as describedw previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.

Summary form only given. Ultrafast laser inscription (ULI) allows the fabrication of compact, highly-efficient and robust laser sources over a broad range of crystalline, ceramic and glass gain media. For instance, subsurface waveguides can be formed by the stress induced refractive index modification effect which takes place between two parallel modified regions referred to as “Type II” guiding [1]. Previously, a family of laser hosts known as sesquioxides, namely Lu2O3, Sc2O3 and LuScO3, have been shown to demonstrate efficient, high-power and tunable laser operation around the 2 μm region in both continuous-wave and pulsed regimes when doped with Tm3+ [2, 3]. Combining the Tm3+-doped sesquioxide material properties with the ULI waveguide laser geometry provides a means to produce compact, low-threshold and efficient laser sources near 2 μm with the potential for high pulse repetition rate ultrafast operation. Here we report, to the best of our knowledge, the first demonstration of a ceramic Tm:Lu2O3 waveguide laser source fabricated by ULI. Postprint

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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