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Martin Heidegger's Being and Time, published in 1927, is widely regarded as his most important work and it has had a profound influence on twentieth-century philosophy. This Critical Guide draws on recently translated and published primary sources as well as the latest developments in Heidegger scholarship to provide a series of in-depth studies of this influential text. Twelve newly-written essays examine the unity of Being and Time; the nature of human communication; truth as a catalyst of cultural transformation; feminist approaches to Being and Time; the essence of authenticity; curiosity as an epistemic vice; the nature of rationality; realism and idealism; the ontological difference; the origin of time; the possibility of death; and the failure of the Being and Time project. The volume will be particularly valuable to students and scholars interested in phenomenology, existentialism, hermeneutics, metaphysics, epistemology, feminism, and ethics.
Martin Heidegger’s Being and Time was published in 1927, and the text has been intensely discussed and studied ever since. Despite long-standing and unfolding controversies around Heidegger’s affiliation with the Nazis, Heidegger scholarship is ubiquitous. New editions and translations of Heidegger’s work appear regularly. Journals are dedicated exclusively to his philosophy. And countless papers and monographs draw on and address various themes in Heidegger’s writings. Why then another book on Heidegger’s philosophy? Why consider anew Heidegger’s magnum opus, about which so much ink has already been spilled?
This chapter explores the connection between Heidegger’s existentialism and fundamental ontology. Specifically, and contra John Haugeland who argues that existentialism is a key feature of fundamental ontology insofar as taking responsibility for our existence entails getting the being of entities right, this chapter argues that taking responsibility for our existence explicitly exhibits the temporal horizon that is fundamental for all our purpose activities and our understanding of entities, generally.
We present the Evolutionary Map of the Universe (EMU) survey conducted with the Australian Square Kilometre Array Pathfinder (ASKAP). EMU aims to deliver the touchstone radio atlas of the southern hemisphere. We introduce EMU and review its science drivers and key science goals, updated and tailored to the current ASKAP five-year survey plan. The development of the survey strategy and planned sky coverage is presented, along with the operational aspects of the survey and associated data analysis, together with a selection of diagnostics demonstrating the imaging quality and data characteristics. We give a general description of the value-added data pipeline and data products before concluding with a discussion of links to other surveys and projects and an outline of EMU’s legacy value.
Migration played a significant role in shaping the Native populations of the southwest United States and northwest Mexico. Large-scale migrations into and across the region were underlain by small-scale (intraregional) population shifts affected by environmental fluctuations (declines and improvements) and social phenomena such as aggregation and the spread of sociopolitical spheres of influence within the region. We compare projectile point types, mortuary patterns, and biodistance information from Early Agricultural period (2100 BC–AD 50) sites to identify subtle differences in population composition associated with the arrival and spread of maize across the region. Small-scale migrations occurring around the foundation of farming communities in the Sonoran Desert may have established the basis of broad regional connectivity, shared historical ties, and subsequent migration patterns and practices. Rooted in early farming traditions and a shared language family, we argue that farmers expanded north and east from the borderlands, then eventually returned to ancestral homelands when environmental and incursive pressures pushed them back south.
Access to an academic clinical research center (CRC) in health professional shortage areas (HPSA) can help address healthcare disparities and increase research accessibility and enrollment. Here we describe the development of a community-centered CRC in the underserved area of Sunset Park, Brooklyn, New York, centered within a larger academic health network and the evaluation of its outcomes within the first two years. In addition to resources and space, establishment of the CRC required a culturally competent and multilingual team of healthcare professionals and researchers and buy-in from the community. Between 1/2022 and 12/2023, the CRC opened 21 new trials (10 interventional and 11 noninterventional) with greater than 500 participant visits that reflect the racial and ethnic diversity of the community. These participants represent 110 distinct zip codes; 76% of these zip codes are underserved and designated HPSA. 60% self-identified as non-White and 20% identified as Hispanic, with 12 other distinct ethnicities represented. 28% of participants speak 11 languages other than English. Community-based CRCs can be created with sustainable growth to align with the mission of the National Institutes of Health and U.S. Food and Drug Administration to meet the ever-growing clinical, social, and research needs of the communities they serve.
This study analyses the current literature to evaluate the effectiveness of dabrafenib and trametinib in the multi-modal treatment of anaplastic thyroid cancer (ATC).
Method
A systematic review and meta-analysis of the literature were undertaken. The primary endpoint measured was overall response rate (ORR) defined by the RECIST v1.1 guidelines. Secondary endpoints were 12-month overall survival (OS), median OS and progression-free survival (PFS).
Results
Of 656 identified reports, 8 studies were included which featured 95 patients (median age 68.5 years, 46 per cent male). Median follow-up period was 11.8 months with a 12-month OS of 51 per cent. Median OS was 10.4 months. Progression-free survival (PFS) was 6.5 months. The ORR was 71 per cent. A total of 65 patients exhibited a partial or complete response in radiological tumour size. Side effects compared favourably to other kinase inhibitors.
Conclusion
Dabrafenib and trametinib exhibit a promising tumour response with a tolerable side profile. BRAF/MEK inhibitors continue to provide robust responses in BRAF-mutated ATC. The heterogeneity and lack of controls in included studies limits the confidence in the conclusions drawn.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
One of the goals of open science is to promote the transparency and accessibility of research. Sharing data and materials used in network research is critical to these goals. In this paper, we present recommendations for whether, what, when, and where network data and materials should be shared. We recommend that network data and materials should be shared, but access to or use of shared data and materials may be restricted if necessary to avoid harm or comply with regulations. Researchers should share the network data and materials necessary to reproduce reported results via a publicly accessible repository when an associated manuscript is published. To ensure the adoption of these recommendations, network journals should require sharing, and network associations and academic institutions should reward sharing.
Staphylococcus aureus nasal carriers were randomized (1:1) to XF-73 or placebo nasal gel, administered 5x over ∼24hrs pre-cardiac surgery. S. aureus burden rapidly decreased after 2 doses (–2.2log10 CFU/mL; placebo –0.01log10 CFU/mL) and was maintained to 6 days post-surgery. Among XF-73 patients, 46.5% received post-operative anti-staphylococcal antibiotics versus 70% in placebo (P = 0.045).
This essay characterizes one way people are organized by their ideas about the ideas of others, namely, “ideational structure.” I clarify its role in social explanation, compare it to some standard social ontologies, and propose that it is an important element in an ideology.
OBJECTIVES/GOALS: The overall goals of this project are: (1) to demonstrate the utility of staff with cross-disciplinary skills in biostatistics and epidemiology as program managers for CTSA BERD Cores, and (2) examine streamlined processes in project triaging, consultations, and data extractions for CTSA service requests when individuals are in this role. METHODS/STUDY POPULATION: Biostatistics and epidemiology are partnered disciplines incorporated in a variety of research areas, especially in human health sciences and health care. For interdisciplinary teams, including individuals trained in both specialties results in efficient research collaborations. When these individuals are program managers for research navigation, processes become more effective and expedited for project timelines and workflows across the CTSA. Examples of this integration are described in vignettes from project triaging, statistical consultations, and data extractions from CTSA service requests. Process comparisons of previous and current workflows are presented to show the advantages of utilizing this type of program manager within these areas of BERD. RESULTS/ANTICIPATED RESULTS: This project defines three areas of integration for a program manager with cross-disciplinary training in biostatistics and epidemiology: (1) project triaging to statistical teams, (2) study design and analysis consultations, and (3) data extractions. Each of these areas demonstrates prior processes that once would require multiple steps in CTSA service requests (including time, resources, and personnel) and identified common issues (slow response to requests, data re-extractions, and challenges providing statistical support) that are now avoided with a manager with cross-training in biostatistics and epidemiology methods. The advantages and disadvantages of integrating these individuals are also described. DISCUSSION/SIGNIFICANCE: BERD Cores seeking improvements to research navigation processes can gain efficiency by incorporating program managers with cross-disciplinary training in biostatistics and epidemiology. BERD Cores may also use this as a case study for translational science with innovation to longstanding challenges in CTSA research workflows.
The aim of this study was to assess whether adding Ca2+ to aggregate or native forms of β-lactoglobulin alters gut hormone secretion, gastric emptying rates and energy intake in healthy men and women. Fifteen healthy adults (mean ± sd: 9M/6F, age: 24 ± 5 years) completed four trials in a randomised, double-blind, crossover design. Participants consumed test drinks consisting of 30 g of β-lactoglobulin in a native form with (NATIVE + MINERALS) and without (NATIVE) a Ca2+-rich mineral supplement and in an aggregated form both with (AGGREG + MINERALS) and without the mineral supplement (AGGREG). Arterialised blood was sampled for 120 min postprandially to determine gut hormone concentrations. Gastric emptying was determined using 13C-acetate and 13C-octanoate, and energy intake was assessed with an ad libitum meal at 120 min. A protein × mineral interaction effect was observed for total glucagon-like peptide-1 (GLP-1TOTAL) incremental AUC (iAUC; P < 0·01), whereby MINERALS + AGGREG increased GLP-1TOTAL iAUC to a greater extent than AGGREG (1882 ± 603 v. 1550 ± 456 pmol·l−1·120 min, P < 0·01), but MINERALS + NATIVE did not meaningfully alter the GLP-1 iAUC compared with NATIVE (1669 ± 547 v. 1844 ± 550 pmol·l−1·120 min, P = 0·09). A protein × minerals interaction effect was also observed for gastric emptying half-life (P < 0·01) whereby MINERALS + NATIVE increased gastric emptying half-life compared with NATIVE (83 ± 14 v. 71 ± 8 min, P < 0·01), whereas no meaningful differences were observed between MINERALS + AGGREG v. AGGREG (P = 0·70). These did not result in any meaningful changes in energy intake (protein × minerals interaction, P = 0·06). These data suggest that the potential for Ca2+ to stimulate GLP-1 secretion at moderate protein doses may depend on protein form. This study was registered at clinicaltrials.gov (NCT04659902).