To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Bayesian analysis of radiocarbon (14C) dates in North American archaeology is increasing, especially among archaeologists working in deeper time. However, historical archaeologists have been slow to embrace these new techniques, and there have been only a few examples of the incorporation of calendar dates as informative priors in Bayesian models in such work in the United States. To illustrate the value of Bayesian approaches to sites with both substantial earlier Native American occupations as well as a historic era European presence, we present the results of our Bayesian analysis of 14C dates from the earlier Guale village and the Mission period contexts from the Sapelo Shell Ring Complex (9MC23) in southern Georgia. Jefferies and Moore have explored the Spanish Mission period deposits at this site to better understand the Native American interactions with the Spanish during the 16th and 17th centuries along the Georgia Coast. Given the results of our Bayesian modeling, we can say with some degree of confidence that the deposits thus far excavated and sampled contain important information dating to the 17th-century mission on Sapelo Island. In addition, our modeling of new dates suggests the range of the pre-Mission era Guale village. Based on these new dates, we can now say with some degree of certainty which of the deposits sampled likely contain information that dates to one of the critical periods of Mission period research, the AD 1660–1684 period that ushered in the close of mission efforts on the Georgia Coast.
Hernando de Soto's expedition through the southeastern United States between 1539 and 1543 is often regarded as a watershed moment for the collapse of Indigenous societies across the region. Historical narratives have proposed that extreme depopulation as a result of early contact destabilized Indigenous economies, politics, networks, and traditions. Although processes of depopulation and transformation were certainly set in motion by this and earlier colonial encounters, the timing, temporality, and heterogeneous rhythms of postcontact Indigenous histories remain unclear. Through the integration of radiocarbon and archaeological data from the Mississippian earthen platform mound at Dyar (9GE5) in central Georgia, we present a case of Indigenous endurance and resilience in the Oconee Valley that has long been obfuscated by materially based chronologies and typologies. Bayesian chronological modeling suggests that Indigenous Mississippian traditions persisted for up to 130 years beyond contact with European colonizers. We argue that advances in modeling radiocarbon dates, along with meaningful consultation/collaboration with descendant communities, can contribute to efforts that move us beyond a reliance on materially based chronologies that can distort and erase Indigenous histories.
Over the years, the practice of medicine has evolved from authority-based to experience-based to evidence-based with the introduction of the scientific process, clinical trials, and outcomes-based data analysis (Tebala GD. Int J Med Sci. 2018;15(12):1397-1405). The time required to perform the necessary randomized controlled trials, a systematic literature review, and meta-analysis of these trials to then create, accept, promulgate, and educate the practicing clinicians to use the evidence-based clinical guidelines is typically measured in years. When the severe acute respiratory syndrome novel coronavirus-2 (SARS-nCoV-2) pandemic commenced in Wuhan, China at the end of 2019, there were few available clinical guidelines to deploy, let alone adapt and adopt to treat the surge of coronavirus disease 2019 (COVID-19) patients. The aim of this study is to first explain how clinical guidelines, on which bedside clinicians have grown accustomed, can be created in the midst of a pandemic, with an evolving scientific understanding of the pathophysiology of the hypercoagulable state. The second is to adapt and adopt current venous thromboembolism diagnostic and treatment guidelines, while relying on the limited available observational reporting of COVID-19 patients to create a comprehensive clinical guideline to treat COVID-19 patients.
Design & Manufacture Knowledge Mapping is a critical activity in medium-to-large organisations supporting many organisational activities. However, techniques for effective mapping of knowledge often employ interviews, consultations and appraisals. Although invaluable in providing expert insight, the application of such methods is inherently intrusive and resource intensive. This paper presents word co-occurrence graphs as a means to automatically generate knowledge maps from technical documents and validates against expert generated knowledge maps.
OBJECTIVES/GOALS: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatologic disease childhood and a cause of pain and potential disability. JIA has a strong genetic component and no known cure. The goal of this study is to evaluate allele-dependent effects of a novel JIA risk variant at 1q24.3. METHODS/STUDY POPULATION: JIA patients meeting criteria for the two most common disease subtypes (oligoarticular and RF neg polyarthritis) were genotyped using the Immunochip, an Illumina array with dense coverage of the HLA region and 186 other loci previously reported in autoimmune diseases. Phase I association findings (Hinks, 2013) and Phase II analysis (unpublished) of an expanded cohort (4,271 JIA and 14,390 controls) identified new risk loci, including rs78037977 at 1q24.3. We prioritized rs78037977 and predicted possible impacted mechanisms based on Bayesian predictions of attributable risk, the surrounding chromatin landscape, and transcription factor binding data. A luciferase reporter assay was used to assess allele-dependent enhancer activity. RESULTS/ANTICIPATED RESULTS: rs78037977 is located between FASLG and TNFSF18 at chromosome 1q24.3 is associated with JIA (p = 6.3x10−09), and explains 94% of the posterior probability at this locus; no other SNPs in linkage disequilibrium (r2>0.6). The chromatin landscape around rs78037977 contains H3K4Me1 and H3K27Ac marks, which are indicative of enhancer activity. Further, >160 transcription factors have chromatin immunoprecipitation followed by sequencing (ChIP-seq) peaks overlapping rs78037977 in various cellular contexts. In luciferase reporter assays, the region around rs78037977 containing the reference A allele had ~2-fold increased enhancer activity compared to the non-reference allele. DISCUSSION/SIGNIFICANCE OF IMPACT: This work provides in vitro evidence to support allele-dependent enhancer activity of a novel JIA-risk variant at 1q24.3. Our ongoing work investigates the effect of the DNA-containing region of rs78037977 on gene expression and differential transcription factor binding at rs78037977.
OBJECTIVES/GOALS: The purpose of this work is to investigate natural buffering capacity of liver tissue and tumors, to understand and exploit differences for therapy. Using this work, we will determine the concentrations of reagents (acids or bases) used in ablation treatment to optimize treatment by increasing tumor toxicity and minimizing healthy tissue toxicity. METHODS/STUDY POPULATION: For this preliminary study, two methods will be used: benchtop pH experiments ex vivo and non-invasive imaging using acidoCEST MRI in vivo. For ex vivo, two types of tissues will be tested: non-cancerous liver and tumor tissue from HepG2 inoculated mice (n = 10). After mice are euthanized, pH will be measured in tissue homogenates at baseline and then the homogenates will be placed in either acidic (acetic acid) or basic (sodium hydroxide) solutions with varied concentrations (0.5–10M) and time recorded until pH returns to baseline. For in vivo imaging, Mia PaCA-2 flank model mice (n = 10) will be imaged with acidoCEST MRI to quantify pH at baseline. Mice will then be injected intratumorally with (up to 100 μL of) acid or base at increasing concentrations and imaged to quantify pH changes in the tumor. RESULTS/ANTICIPATED RESULTS: For this study, buffering capacity is defined as the concentration threshold for which tissue can buffer pH back to within normal range. Non-cancerous tissue is likely to buffer a wider range of concentrations compared to tumor tissue. From the benchtop experiment, comparison of time-to-buffer will be made for each concentration of acid/base for the two tissue types. AcidoCEST MRI will provide in vivo buffering capacity and potentially demonstrate tumor heterogeneity of buffering capacity. For both experiments, a pH vs. concentration curve for the two tissue types will allow for comparison of ex vivo to in vivo experiments, which will differentiate contributions of local tissue buffering capacity from the full body’s natural bicarbonate buffer system that depends on respiration and blood flow. DISCUSSION/SIGNIFICANCE OF IMPACT: The pH of the body must be maintained within a narrow range. With cancer, impairment in regulation of tumor metabolism causes acidosis, lowering extracellular pH in tumors. It remains unclear if pH plays a role in local recurrence or tumor toxicity. This work will determine if acidoCEST MRI can measure deliberate alteration of pH and how this change affects biology.
Introduction: Affecting roughly 1 in 5 pregnancies, early pregnancy loss is a common experience for reproductive-aged women. In Canada, most women do not establish care with an obstetrical provider until the second trimester of pregnancy. Consequently, pregnant patients experiencing symptoms of early pregnancy loss frequently access care in the emergency department (ED). The objective of this study was to describe the resource utilization and outcomes of women presenting to two Ontario EDs for early pregnancy loss or threatened early pregnancy loss. Methods: This was a retrospective cohort study of pregnant (≤20 weeks), adult (≥18 years) women in two EDs (one community hospital with 110,000 annual ED visits; one academic hospital with 65,000 annual ED visits) between January 2010 and December 2017. Patients were identified by diagnostic codes indicating early pregnancy loss or threatened early pregnancy loss. Results: A total of 16,091 patients were included, with a mean (SD) age of 32.8 (5.6) years. Patients had a total of 22,410 ED visits for early pregnancy complications, accounting for 1.6% of the EDs’ combined visits during the study period. Threatened abortion (n = 11,265, 50.3%) was the most common ED diagnosis, followed by spontaneous abortion (n = 5,652, 25.2%), ectopic pregnancy (n = 3,242, 14.5%), missed abortion (n = 1,541, 6.9%), and other diagnoses (n = 710, 3.2%). 8,000 (44.8%) patients had a radiologist-interpreted ultrasound performed during the initial ED visit. Median (IQR) ED length of stay was 3.4 (2.3 to 5.1) hours. There were 4,561 (25.6%) return ED visits within 30 days, of which 2,317 (50.8%) occurred less than 24 hours of index visit, and 481 (10.6%) were for scheduled, next day ultrasound. The total number of hospital admissions was 1,793 (8.0%), and the majority were for ectopic pregnancy (n = 1,052, 58.7%). Of admitted patients, 1,320 (73.6%) underwent surgical interventions related to early pregnancy. There were 474 (10.4%) patients admitted to hospital during return ED visits. Conclusion: Pregnant patients experiencing symptoms of early pregnancy loss in the ED frequently had radiologist-interpreted US and low rates of hospital admission, yet had high rates of return ED visits. This study highlights the heavy reliance on Ontario EDs to care for patients experiencing complications of early pregnancy.
Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.
The utility of questionnaire based self-report measures for non-clinical psychotic symptoms is unclear and there are few reliable data about the nature and prevalence of these phenomena in children. The study aimed to investigate psychosis-like symptoms (PLIKS) in children utilizing both self-report measures and semi-structured observer rated assessments.
The study was cross-sectional; the setting being an assessment clinic for members of the ALSPAC birth cohort in Bristol, UK. 6455 respondents were assessed over 21 months, mean age 12.9 years. The main outcome measure was: 12 self-report screening questions for psychotic symptoms followed by semi-structured observer rated assessments by trained psychology graduates. The assessment instrument utilised stem questions, glossary definitions, and rating rules adapted from DISC-IV and SCAN items.
The 6-month period prevalence for one or more PLIKS rated by self-report questions was 38.9 % (95% CI = 37.7-40.1). Prevalence using observer rated assessments was 13.7% (95% CI = 12.8-14.5). Positive Predictive Values for the screen questions versus observer rated scores were low, except for auditory hallucinations (PPV=70%; 95% CI = 67.1-74.2). The most frequent observer rated symptom was auditory hallucinations (7.3%); in 18.8% of these cases symptoms occurred weekly or more. The prevalence of DSM-IV ‘core’ schizophrenia symptoms was 3.62%. Rates were significantly higher in children with low socio-economic status.
With the exception of auditory hallucinations, self-rated questionnaires are likely to substantially over-estimate the frequency of PLIKS in 12-year-old children. However, more reliable observer rated assessments reveal that PLIKS occur in a significant proportion of children.
Psychosis and adult Attention Deficit Hyperactivity Disorder (ADHD) have shared attributes, but evidence that they are associated is sparse and inconsistent.
We tested hypotheses that 1] adult ADHD symptoms are associated with psychosis and individual psychotic symptoms 2] links between ADHD symptoms and psychosis are mediated by prescribed ADHD medications, use of illicit drugs, and dysphoric mood (depression and anxiety).
The Adult Psychiatric Morbidity Survey 2007 (N=7403) provided data for regression and multiple mediation analyses. ADHD symptoms were coded from the ADHD Self-Report Scale (ASRS). Dependent variables comprised auditory hallucinations, paranoid ideation, and identified psychosis.
Higher ASRS total score was significantly associated with psychosis (O.R: 1.11; 95% CI 1.02-1.20; p = 0.013), paranoid ideation (O.R:1.12; CI 1.09-1.14; p<0.001) and auditory hallucinations (O.R 1.11; CI 1.08-1.15; p<0.001) even after controlling for socio-demographic variables, verbal IQ, autism spectrum disorder traits, childhood conduct problems, hypomanic mood and dysphoric mood. The link between higher ADHD symptoms and psychosis variables was significantly mediated by dysphoric mood (psychosis, 21%; paranoid ideation, 23%; auditory hallucination, 11%), but not by prescribed ADHD medication or use of amphetamine, cocaine or cannabis.
Higher levels of adult ADHD symptoms and psychosis are linked, and dysphoric mood may form part of the mechanism. Those with greater levels of ADHD symptoms in adulthood may be at higher risk of psychosis. Our analyses contradict the clinical view that the main explanation for people with ADHD symptoms developing psychosis is abuse of illicit drugs or ADHD medications.
Dietary patterns describe the combination of foods and beverages in a diet and the frequency of habitual consumption. Better understanding of childhood dietary patterns and antenatal influences could inform intervention strategies to prevent childhood obesity. We derived empirical dietary patterns in 1142 children (average age 6·0 (sd 0·2) years) in New Zealand, whose mothers had participated in the Screening for Pregnancy Endpoints (SCOPE) cohort study and explored associations with measures of body composition. Participants (Children of SCOPE) had their diet assessed by FFQ, and dietary patterns were extracted using factor analysis. Three distinct dietary patterns were identified: ‘Healthy’, ‘Traditional’ and ‘Junk’. Associations between dietary patterns and measures of childhood body composition (waist, hip, arm circumferences, BMI, bioelectrical impedance analysis-derived body fat % and sum of skinfold thicknesses (SST)) were assessed by linear regression, with adjustment for maternal influences. Children who had higher ‘Junk’ dietary pattern scores had 0·24 (sd 0·08; 95 % CI 0·04, 0·13) cm greater arm and 0·44 (sd 0·05; 95 % CI 0·01, 0·10) cm greater hip circumferences and 1·13 (sd 0·07; 95 % CI 0·03, 0·12) cm greater SST and were more likely to be obese (OR 1·74; 95 % CI 1·07, 2·82); those with higher ‘Healthy’ pattern scores were less likely to be obese (OR 0·62; 95 % CI 0·39, 1·00). In a large mother–child cohort, a dietary pattern characterised by high-sugar and -fat foods was associated with greater adiposity and obesity risk in children aged 6 years, while a ‘Healthy’ dietary pattern offered some protection against obesity. Targeting unhealthy dietary patterns could inform public health strategies to reduce the prevalence of childhood obesity.
Animal disease events can lead to international trade restrictions which can vary in duration, products included, and geographical extent. Accounting for multilateral resistance between trading partners, a general gravity model of trade is estimated with a Hausman-Taylor and a Hausman-Taylor seemingly unrelated estimator to evaluate the trade quantity impact by commodity resulting from highly pathogenic poultry disease events in 24 exporting markets. Commodity specific results show that quantity traded and products demanded during a disease event differ by commodities. Understanding these impacts can better prepare exporters for potential changes in trade quantity given a disease event.
Conditions and evidence continue to evolve related to the prediction of the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus (iVDPV) excreters, which affect assumptions related to forecasting risks and evaluating potential risk management options. Multiple recent reviews provided information about individual iVDPV excreters, but inconsistencies among the reviews raise some challenges. This analysis revisits the available evidence related to iVDPV excreters and provides updated model estimates that can support future risk management decisions. The results suggest that the prevalence of iVDPV excreters remains highly uncertain and variable, but generally confirms the importance of managing the risks associated with iVDPV excreters throughout the polio endgame in the context of successful cessation of all oral poliovirus vaccine use.
We sampled individual growth rings from three ancient remnant bald cypress (Taxodium distichum) trees from a massive buried deposit at the mouth of the Altamaha River on the Georgia Coast to determine the best technique for radiocarbon (14C) dating pretreatment. The results of our comparison of traditional ABA pretreatment and holocellulose and α-cellulose fractions show no significant differences among the pretreatments (<1 sigma) thereby suggesting that ABA pretreatment will prove sufficient for the development of a high-resolution 14C tree-ring chronology based on these ancient bald cypresses which will indicate whether the U.S. Southeast is subject to a regional radiocarbon offset.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350
m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200
m images will also have a factor
30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
Folic acid (FA) supplementation is recommended in the periconceptional period, for the prevention of neural tube defects. Limited data are available on the folate status of New Zealand (NZ) pregnant women and its association with FA supplementation intake. Objectives were to examine the relationship between plasma folate (PF) and reported FA supplement use at 15 weeks’ gestation and to explore socio-demographic and lifestyle factors associated with PF. We used data and blood samples from NZ participants of the Screening for Pregnancy Endpoints cohort study. Healthy nulliparous women with singleton pregnancy (n 1921) were interviewed and blood samples collected. PF was analysed via microbiological assay. Of the participants, 73 % reported taking an FA supplement at 15 weeks’ gestation – of these, 79 % were taking FA as part of/alongside a multivitamin supplement. Of FA supplement users, 56 % reported consuming a daily dose of ≥800 μg; 39 % reported taking less than 400 µg/d. Mean PF was significantly higher in women reporting FA supplementation (54·6 (se 1·5) nmol/l) v. no FA supplementation (35·1 (se 1·6) nmol/l) (P<0·0001). Reported daily FA supplement dose and PF were significantly positively correlated (r 0·41; P<0·05). Younger maternal age, Pacific and Maori ethnicity and obesity were negatively associated with PF levels; vegetarianism was positively associated with PF. Reported FA supplement dose was significantly associated with PF after adjustment for socio-demographic, lifestyle confounders and multivitamin intake. The relationship observed between FA supplementation and PF demonstrates that self-reported intake is a reliable proxy for FA supplement use in this study population.
Formally established in the fall of 1947, the Laboratory of Archaeology at the University of Georgia is an archaeological research and collection repository. It is considered one of the premier institutions for curation of archaeological collections from the American Southeast. For over 70 years, the Laboratory has served as a repository for objects and associated records generated from archaeological projects and research undertaken by faculty, students, CRM professionals, and state and federal agencies. The Laboratory curates over 20,000 cubic feet of artifacts as well as paper and digital archives. In addition, the Laboratory houses the Georgia Archaeological Site File and manages data from more than 59,000 archaeological sites, including over 11,500 archaeological reports. In this paper, we explore implementation procedures for bringing legacy collections up to modern curation standards. We also outline how we migrate the data on paper records into the digital realm, articulating them within a comprehensive framework.