Geological mapping of an area along the Frisco Railroad between Cuba and Saint James

The chief object of the work has been the location of the Roubidoux-Jefferson City contact, if it occurred within a mile of the railroad. Distances and positions along the track were obtained by the use of a map and by counting telephone poles. Other locations were made by obtaining their bearing and distance from these points by the use of a compass and by pacing. Elevations were carried by aneroid barometers, using the railroad elevations at mile points as bench marks. An attempt has been made to locate all important outcrops; but these are shown only on the field map. Extreme accuracy has not been attempted; however, the chief drainage courses have been fairly accurately located, and the contours give a fair idea of the topography and elevations --Introduction, Methods of Field Work, page 1

Towards a person-centered medical education: challenges and imperatives (I)

It is increasingly claimed that modern medicine has entered into crisis —a crisis of knowledge (uncertainty over what counts as “evidence” for decision-making and what does not), care (a deficit in sympathy, empathy, compassion, dignity, autonomy), patient safety (neglect, iatrogenic injury, malpractice, excess deaths), economic costs (which threaten to bankrupt health systems worldwide) and clinical and institutional governance (a failure of basic and advanced management, inspirational and transformational leadership). We believe such a contention to be essentially correct. In the current article, we ask how the delineated components of the crisis can be individually understood in order to allow them to be collectively addressed. We ask how a transition can be effected away from impersonal, decontextualized and fragmented services in the direction of newer models of service provision that are personalized, contextualized and integrated. How, we ask, can we improve healthcare outcomes while simultaneously containing or lowering their costs? In initial answer to such questions —which are of considerable political as well as clinical significance— we assert that a new approach has become necessary, particularly in the context of the current epidemic of multi-morbid and socially complex long term illness. This new approach, we argue, is represented by the development and application of the concepts and methods of person-centered healthcare (PCH), a philosophy and technique in the care of the sick that enables clinicians and health systems to re-introduce humanistic ideals into clinical practice alongside continuing scientific advance, thereby restoring to medicine the humanism it has lost in over a century of empiricism. But the delivery of a person-centered healthcare within health systems requires a person-centered education and training. In this article we consider, then, why person-centered teaching innovations in the undergraduate medical curriculum are necessary, as a first step, to achieving real progress in the integrity of modern undergraduate medical education. Without such innovations, we do not believe that suitable foundations for subsequent innovations in postgraduate training can be laid and, with them, a continuing professional education in PCH that spans entire medical careers. We first review the historical perspectives of relevance to our arguments and then advocate a radical re-think of what we believe to be the urgent imperatives for a modern medical undergraduate and postgraduate training.post-print300 K

What it’s like to be a _____: Why it’s (often) unethical to use VR as an empathy nudging tool

In this article, we apply the literature on the ethics of choice-architecture (nudges) to the realm of virtual reality (VR) to point out ethical problems with using VR for empathy-based nudging. Specifically, we argue that VR simulations aiming to enhance empathic understanding of others via perspective-taking will almost always be unethical to develop or deploy. We argue that VR-based empathy enhancement not only faces traditional ethical concerns about nudge (autonomy, welfare, transparency), but also a variant of the semantic variance problem that arises for intersectional perspective-taking. VR empathy simulations deceive and manipulate their users about their experiences. Despite their often laudable goals, such simulations confront significant ethical challenges. In light of these goals and challenges, we conclude by proposing that VR designers shift from designing simulations aimed at producing empathic perspective-taking to designing simulations aimed at generating sympathy. These simulations, we claim, can avoid the most serious ethical issues associated with VR nudges, semantic variance, and intersectionalit

SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex

DISC1 is a multifunctional, intracellular scaffold protein. At the cellular level, DISC1 plays a pivotal role in neural progenitor proliferation, migration, and synaptic maturation. Perturbation of the biological pathways involving DISC1 is known to lead to behavioral changes in rodents, which supports a clinical report of a Scottish pedigree in which the majority of family members with disruption of the DISC1 gene manifest depression, schizophrenia, and related mental conditions. The discrepancy between modest evidence in genetics and strong biological support for the role of DISC1 in mental conditions suggests a working hypothesis that regulation of DISC1 at the protein level, such as posttranslational modification, may play a role in the pathology of mental conditions. In this study, we report on the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where the small ubiquitin-related modifier (SUMO) and its homologs are conjugated to a large number of cellular proteins, which in turn regulates their subcellular distribution and protein stability. By using in silico, biochemical, and cell-biological approaches, we now demonstrate that human DISC1 is SUMOylated at one specific lysine 643 (K643). We also show that this residue is crucial for proper neural progenitor proliferation in the developing cortex

Molecular basis of cobalamin-dependent RNA modification

Queuosine (Q) was discovered in the wobble position of a transfer RNA (tRNA) 47 years ago, yet the final biosynthetic enzyme responsible for Q-maturation, epoxyqueuosine (oQ) reductase (QueG), was only recently identified. QueG is a cobalamin (Cbl)-dependent, [4Fe-4S] cluster-containing protein that produces the hypermodified nucleoside Q in situ on four tRNAs. To understand how QueG is able to perform epoxide reduction, an unprecedented reaction for a Cbl-dependent enzyme, we have determined a series of high resolution structures of QueG from Bacillus subtilis. Our structure of QueG bound to a tRNA[superscript Tyr] anticodon stem loop shows how this enzyme uses a HEAT-like domain to recognize the appropriate anticodons and position the hypermodified nucleoside into the enzyme active site. We find Q bound directly above the Cbl, consistent with a reaction mechanism that involves the formation of a covalent Cbl-tRNA intermediate. Using protein film electrochemistry, we show that two [4Fe-4S] clusters adjacent to the Cbl have redox potentials in the range expected for Cbl reduction, suggesting how Cbl can be activated for nucleophilic attack on oQ. Together, these structural and electrochemical data inform our understanding of Cbl dependent nucleic acid modification.National Science Foundation (U.S.) (MCB 1122977)National Institutes of Health (U.S.) (GM72623 S01, GM120283, and GM17151

An ethical code for commercial VR/AR applications

The commercial VR/AR marketplace is gaining ground and is becoming an ever larger and more significant component of the global economy. While much attention has been paid to the commercial promise of VR/AR, comparatively little attention has been given to the ethical issues that VR/AR technologies introduce. We here examine existing codes of ethics proposed by the ACM and IEEE and apply them to the unique ethical facets that VR/AR introduces. We propose a VR/AR code of ethics for developers and apply this code to several commercial applications

The impact of HIV exposure and maternal Mycobacterium tuberculosis infection on infant immune responses to bacille Calmette-Guérin vaccination.

OBJECTIVE: The objective of this study is to assess the effect of maternal HIV and Mycobacterium tuberculosis (Mtb) infection on cellular responses to bacille Calmette-Guérin (BCG) immunization. DESIGN: A mother-infant cohort study. METHODS: Samples were collected from mother-infant pairs at delivery. Infants were BCG-vaccinated at 6 weeks of age and a repeat blood sample was collected from infants at 16 weeks of age. BCG-specific T-cell proliferation and intracellular cytokine expression were measured by flow cytometry. Secreted cytokines and chemokines in cell culture supernatants were analysed using a Multiplex assay. RESULTS: One hundred and nine (47 HIV-exposed and 62 HIV-unexposed) mother-infants pairs were recruited after delivery and followed longitudinally. At birth, proportions of mycobacteria-specific proliferating T cells were not associated with either in-utero HIV exposure or maternal Mtb sensitization. However, in-utero HIV exposure affected infant-specific T-cell subsets [tumour necrosis factor-alpha (TNF-α) single positive proliferating CD4⁺ T cells and interferon-gamma (IFN-γ), TNF-α dual-positive CD4⁺ T cells]. Levels of TNF-α protein in cell culture supernatants were also significantly higher in HIV-exposed infants born to Mtb-sensitized mothers. In the presence of maternal Mtb sensitization, frequencies of maternal and newborn BCG-specific proliferating CD4⁺ T cells were positively correlated. Following BCG vaccination, there was no demonstrable effect of HIV exposure or maternal Mtb infection on infant BCG-specific T-cell proliferative responses or concentrations of secreted cytokines and chemokines. CONCLUSION: Effects of maternal HIV and Mtb infection on infant immune profiles at birth are transient only, and HIV-exposed, noninfected infants have the same potential to respond to and be protected by BCG vaccination as HIV-unexposed infants

Emotional responses to the experience of cancer 'alarm' symptoms

To qualitatively explore associations between emotional responses to experience of cancer 'alarm' symptoms and help-seeking in a community sample of adults