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We present stable isotope and osteological data from human remains at Paloma, Chilca I, La Yerba III, and Morro I that offer new evidence for diet, lifestyle, and habitual mobility in the first villages that proliferated along the arid Pacific coast of South America (ca. 6000 cal BP). The data not only reaffirm the dietary primacy of marine protein for this period but also show evidence at Paloma of direct access interactions between the coast and highlands, as well as habitual mobility in some parts of society. By locating themselves at the confluence of diverse coastal and terrestrial habitats, the inhabitants of these early villages were able to broaden their use of resources through rounds of seasonal mobility, while simultaneously increasing residential sedentism. Yet they paid little substantial health penalty for their settled lifestyles, as reflected in their osteological markers of stature and stress, compared with their agriculturalist successors even up to five millennia later. Contrasting data for the north coast of Chile indicate locally contingent differences. Considering these data in a wider chronological context contributes to understanding how increasing sedentism and population density laid the foundations here for the emergence of Late Preceramic social complexity.
In rapidly growing and high-burden urban centres, identifying tuberculosis (TB) transmission hotspots and understanding the potential impact of interventions can inform future control and prevention strategies. Using data on local demography, TB reports and patient reporting patterns in Dhaka South City Corporation (DSCC) and Dhaka North City Corporation (DNCC), Bangladesh, between 2010 and 2017, we developed maps of TB reporting rates across wards in DSCC and DNCC and identified wards with high rates of reported TB (i.e. ‘hotspots’) in DSCC and DNCC. We developed ward-level transmission models and estimated the potential epidemiological impact of three TB interventions: active case finding (ACF), mass preventive therapy (PT) and a combination of ACF and PT, implemented either citywide or targeted to high-incidence hotspots. There was substantial geographic heterogeneity in the estimated TB incidence in both DSCC and DNCC: incidence in the highest-incidence wards was over ten times higher than in the lowest-incidence wards in each city corporation. ACF, PT and combined ACF plus PT delivered to 10% of the population reduced TB incidence by a projected 7%–9%, 13%–15% and 19%–23% over five years, respectively. Targeting TB hotspots increased the projected reduction in TB incidence achieved by each intervention 1.4- to 1.8-fold. The geographical pattern of TB notifications suggests high levels of ongoing TB transmission in DSCC and DNCC, with substantial heterogeneity at the ward level. Interventions that reduce transmission are likely to be highly effective and incorporating notification data at the local level can further improve intervention efficiency.
The approach to vascular access in children with CHD is a complex decision-making process that may have long-term implications. To date, evidence-based recommendations have not been established to inform this process.
The RAND/UCLA Appropriateness Method was used to develop miniMAGIC, including sequential phases: definition of scope and key terms; information synthesis and literature review; expert multidisciplinary panel selection and engagement; case scenario development; and appropriateness ratings by expert panel via two rounds. Specific recommendations were made for children with CHD.
Recommendations were established for the appropriateness of the selection, characteristics, and insertion technique of intravenous catheters in children with CHD with both univentricular and biventricular physiology.
miniMAGIC-CHD provides evidence-based criteria for intravenous catheter selection for children with CHD.
ABSTRACT IMPACT: This is the first study to use QUINT analyses to examine heterogeneity of treatment effect for group medical visits among individuals with type 2 diabetes. QUINT is a data driven method that assumes no a priori assumptions regarding effect moderators - an important step in the path towards personalized medicine. OBJECTIVES/GOALS: To examine heterogeneity of treatment effect (HTE) in Jump Start, a trial that compared the effectiveness of group medical visits (GMVs) focused on medication management only versus the addition of intensive weight management (WM) on glycemic control for patients with type 2 diabetes and body mass index >=27kg/m^2. METHODS/STUDY POPULATION: Jump Start patients (n=263) were randomized to a GMV-based medication management plus low carbohydrate diet-focused WM program (WM/GMV; n = 127) or GMV-based medication management only (GMV; n = 136) for diabetes control. We used QUalitative INteraction Trees (QUINT), a tree-based clustering method, to determine if there were subgroups of patients who derived greater benefit from either WM/GMV or GMV. Subgroup predictors included 32 baseline demographic, clinical, and psychosocial factors. Outcome was hemoglobin A1c (HbA1c). We conducted internal validation via bootstrap resampling to estimate bias in the range of mean outcome differences among arms. RESULTS/ANTICIPATED RESULTS: QUINT analyses indicated that for patients who had not previously attempted weight loss, WM/GMV resulted in better glycemic control than GMV alone (mean difference in HbA1c improvement = 1.48%). For patients who had previously attempted weight loss and had lower cholesterol and blood urea nitrogen levels, GMV alone was better than WM/GMV (mean difference in HbA1c improvement = 1.51%). Internal validation resulted in moderate corrections in the mean HbA1c differences between arms; however, differences remained in the clinically significant range. DISCUSSION/SIGNIFICANCE OF FINDINGS: Among patients with diabetes and BMI>=27kg/m^2, a low-carbohydrate, weight loss focus may better improve HbA1c in those who have never attempted weight loss. A medication management focus may be better in those who have attempted weight loss and have lower cholesterol and blood urea nitrogen.
Calculus students are taught that an indefinite integral is defined only up to an additive constant, and as a consequence generations of students have assiduously added ‘+C’ to their calculus homework. Although ubiquitous, these constants rarely garner much attention, and typically loiter without intent around the ends of equations, feeling neglected. There is, however, useful work they can do, work which is particularly relevant in the contexts of integral tables and computer algebra systems. We begin, therefore, with a discussion of the context, before returning to coax the constants out of the shadows and assign them their tasks.
Background: Delayed or in vitro inactive empiric antibiotic therapy may be detrimental to survival in patients with bloodstream infections (BSIs). Understanding the landscape of delayed or discordant empiric antibiotic therapy (DDEAT) across different patient, pathogen, and hospital types, as well as by their baseline resistance milieu, may enable providers, antimicrobial stewardship programs, and policy makers to optimize empiric prescribing. Methods: Inpatients with clinically suspected serious infection (based on sampling of blood cultures and receiving systemic antibiotic therapy on the same or next day) found to have BSI were identified in the Cerner Healthfacts EHR database. Patients were considered to have received DDEAT when, on culture sampling day, they received either no antibiotic(s) or none that displayed in vitro activity against the pathogenic bloodstream isolate. Antibiotic-resistant phenotypes were defined by in vitro resistance to taxon-specific prototype antibiotics (eg, methicillin/oxacillin resistance in S. aureus) and were used to estimate baseline resistance prevalence encountered by the hospital. The probability of DDEAT was examined by bacterial taxon, by time of BSI onset, and by presence versus absence of antibiotic-resistance phenotypes, sepsis or septic shock, hospital type, and baseline resistance. Results: Of 26,036 assessable patients with a BSI at 131 US hospitals between 2005 and 2014, 14,658 (56%) had sepsis, 3,623 (14%) had septic shock, 5,084 (20%) had antibiotic-resistant phenotypes, and 8,593 (33%) received DDEAT. Also, 4,428 (52%) recipients of DDEAT received no antibiotics on culture sampling day, whereas the remaining 4,165 (48%) received in vitro discordant therapy. DDEAT occurred most often in S. maltophilia (87%) and E. faecium (80%) BSIs; however, 75% of DDEAT cases and 76% of deaths among recipients of DDEAT collectively occurred among patients with S. aureus and Enterobacteriales BSIs. For every 8 bacteremic patients presenting with septic shock, 1 patient did not receive any antibiotics on culture day (Fig. 1A). Patients with BSIs of hospital (vs community) onset were twice as likely to receive no antibiotics on culture day, whereas those with bloodstream pathogens displaying antibiotic-resistant (vs susceptible) phenotypes were 3 times as likely to receive in vitro discordant therapy (Fig. 1B). The median proportion of DDEAT ranged between 25% (14, 37%) in eight <300-bed teaching hospitals in the lowest baseline resistance quartile and 40% (31, 50%) at five ≥300-bed teaching hospitals in the third baseline resistance quartile (Fig. 2). Conclusions: Delayed or in vitro discordant empiric antibiotic therapy is common among patients with BSI in US hospitals regardless of hospital size, teaching status, or local resistance patterns. Prompt empiric antibiotic therapy in septic shock and hospital-onset BSI needs more support. Reliable detection of S. aureus and Enterobacteriales bloodstream pathogens and their resistance patterns earlier with rapid point-of-care diagnostics may mitigate the population-level impact of DDEAT in BSI.
Funding: This study was funded in part by the National Institutes of Health Clinical Center, National Institutes of Allergy and Infectious Diseases, National Cancer Institute (NCI contract no. HHSN261200800001E) and the Agency for Healthcare Research and Quality.
The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.
We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8–18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.
Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.
Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.
During the COVID-19 pandemic, the antimicrobial stewardship module in our electronic medical record was reconfigured for the management of COVID-19 patients. This change allowed our subspecialist providers to review charts quickly to optimize potential therapy and management during the patient surge.
Assessment of unique and potentially significant fossils may be considerably compromised by surrounding matrix. This paper assesses a fossil barnacle group from the mid to late Eocene of Seymour Island, off the Antarctic Peninsula, that potentially has very significant phylogenetic importance. It discusses why the specimen could be significant, and describes and applies as a proof of concept an advanced imaging technique, using X-ray Computed Tomography (CT), that was effectively employed to confirm systematic taxonomy with virtual 3-D sections through the specimen. In this case, the Antarctic barnacle's complex internal plate morphologies were resolved by advanced 3-D imaging, such that a taxonomic attribution could be made to either the Archaeobalanidae or Austrobalanidae, excluding the initial assessment of Coronulidae, which would have otherwise been allusive.
OBJECTIVES/GOALS: The impact of baseline BMI on glycemic response to group medical visits (GMV) and weight management (WM)-based interventions is unclear. Our objective is to determine how baseline BMI class impacts patient responses to GMV and interventions that combine WM/GMV. METHODS/STUDY POPULATION: We will perform a secondary analysis of Jump Start, a randomized, controlled trial that compared the effectiveness of a GMV-based low carbohydrate diet-focused WM program (WM/GMV) to traditional GMV-based medication management (GMV) on diabetes control. The primary and secondary outcomes will be change in hemoglobin A1c (HbA1c) and weight at 48 months, respectively. Study participants will be stratified into BMI categories defined by BMI 27-29.9kg/m2, 30.0-34.9kg/m2, 35.0-39.9kg/m2, and ≥40.0kg/m2. Hierarchical mixed models will be used to examine the differential impact of the WM/GMV intervention compared to GMV on changes in outcomes by BMI class category. RESULTS/ANTICIPATED RESULTS: Jump Start enrolled 263 overweight Veterans (BMI ≥ 27kg/m2) with type 2 diabetes. At baseline, mean BMI was 35.3 and mean HbA1c was 9.1. 14.5% were overweight (BMI 27–29.9) and 84.5% were obese (BMI ≥ 30). The proposed analyses are ongoing. We anticipate that patients in the higher BMI obesity classes will demonstrate greater reductions in HbA1c and weight with the WM/GMV intervention relative to traditional GMV. DISCUSSION/SIGNIFICANCE OF IMPACT: This work will advance the understanding of the relationship between BMI and glycemic response to targeted interventions, and may ultimately provide guidance for interventions for type 2 diabetes.
We shall begin the chapter by explaining what PageRank is and how it is computed efficiently. Yet the war between those who want to make the Web useful and those who would exploit it for their own purposes is never over. When PageRank was established as an essential technique for a search engine, spammers invented ways to manipulate the PageRank of a Web page, often called link spam. That development led to the response of TrustRank and other techniques for preventing spammers from attacking PageRank. We shall discuss TrustRank and other approaches to detecting link spam. Finally, this chapter also covers some variations on PageRank. These techniques include topic-sensitive PageRank (which can also be adapted for combating link spam) and the HITS, or “hubs and authorities” approach to evaluating pages on the Web.
We include in this chapter a discussion of generalizations of MapReduce, first to systems that support acyclic workflows and then to systems that implement recursive algorithms. Our last topic for this chapter is the design of good MapReduce algorithms, a subject that often differs significantly from the matter of designing good parallel algorithms to be run on a supercomputer. When designing MapReduce algorithms, we often find that the greatest cost is in the communication. We thus investigate communication cost and what it tells us about the most efficient MapReduce algorithms. For several common applications of MapReduce we are able to give families of algorithms that optimally trade the communication cost against the degree of parallelism.
We begin our discussion of locality-sensitive hashing (LSH) with an examination of the problem of finding similar documents – those that share a lot of common text. We first show how to convert documents into sets in a way that lets us view textual similarity of documents as sets having a large overlap. A second key trick we need is minhashing, which is a way to convert large sets into much smaller representations, called signatures, that still enable us to estimate closely the Jaccard similarity of the represented sets. Finally, we see how to apply the bucketing idea inherent in LSH to the signatures. In Section 3.5 we begin our study of how to apply LSH to items other than sets. We consider the general notion of a distance measure that tells to what degree items are similar. Then, we consider the general idea of locality-sensitive hashing, and we see how to do LSH for some data types other than sets. We examine in detail several applications of the LSH idea. Finally, we consider some techniques for finding similar sets that can be more efficient than LSH when the degree of similarity we want is very high.
Scholars and policy makers need systematic assessments of the validity of the measures produced by V-Dem. In Chapter 6, we present our approach to comparative data validation – the set of steps we take to evaluate the precision, accuracy, and reliability of our measures, both in isolation and compared to extant measures of the same concepts. Our approach assesses the degree to which measures align with shared concepts (content validation), shared rules of translation (data generation assessment), and shared realities (convergent validation). Within convergent validity, we execute two convergent validity tests. First, we examine convergent validity as it is typically conceived – examining convergence between V-Dem measures and extant measures. Second, we evaluate the level of convergence across coders, considering the individual coder and country traits that predict coder convergence. Throughout the chapter, we focus on three indices included in the V-Dem data set: polyarchy, corruption, and core civil society. These three concepts collectively provide a “hard test” for the validity of our data, representing a range of existing measurement approaches, challenges, and solutions.