4,497 research outputs found
Systems 1 and 2 thinking processes and cognitive reflection testing in medical students
Background: Diagnostic decision-making is made through a combination of Systems 1 (intuition or pattern-recognition) and Systems 2 (analytic) thinking. The purpose of this study was to use the Cognitive Reflection Test (CRT) to evaluate and compare the level of Systems 1 and 2 thinking among medical students in pre-clinical and clinical programs.Methods: The CRT is a three-question test designed to measure the ability of respondents to activate metacognitive processes and switch to System 2 (analytic) thinking where System 1 (intuitive) thinking would lead them astray. Each CRT question has a correct analytical (System 2) answer and an incorrect intuitive (System 1) answer. A group of medical students in Years 2 & 3 (pre-clinical) and Years 4 (in clinical practice) of a 5-year medical degree were studied.Results: Ten percent (13/128) of students had the intuitive answers to the three questions (suggesting they generally relied on System 1 thinking) while almost half (44%) answered all three correctly (indicating full analytical, System 2 thinking). Only 3-13% had incorrect answers (i.e. that were neither the analytical nor the intuitive responses). Non-native English speaking students (n = 11) had a lower mean number of correct answers compared to native English speakers (n = 117: 1.0 s 2.12 respectfully: p < 0.01). As students progressed through questions 1 to 3, the percentage of correct System 2 answers increased and the percentage of intuitive answers decreased in both the pre-clinical and clinical students. Conclusions: Up to half of the medical students demonstrated full or partial reliance on System 1 (intuitive) thinking in response to these analytical questions. While their CRT performance has no claims to make as to their future expertise as clinicians, the test may be used in helping students to understand the importance of awareness and regulation of their thinking processes in clinical practice
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Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.
Acetaminophen (APAP)-induced liver injury is clinically significant, and APAP overdose in mice often serves as a model for drug-induced liver injury in humans. By specifying that APAP metabolism, reactive metabolite formation, glutathione depletion, and mitigation of mitochondrial damage within individual hepatocytes are functions of intralobular location, an earlier virtual model mechanism provided the first concrete multiattribute explanation for how and why early necrosis occurs close to the central vein (CV). However, two characteristic features could not be simulated consistently: necrosis occurring first adjacent to the CV, and subsequent necrosis occurring primarily adjacent to hepatocytes that have already initiated necrosis. We sought parsimonious model mechanism enhancements that would manage spatiotemporal heterogeneity sufficiently to enable meeting two new target attributes and conducted virtual experiments to explore different ideas for model mechanism improvement at intrahepatocyte and multihepatocyte levels. For the latter, evidence supports intercellular communication via exosomes, gap junctions, and connexin hemichannels playing essential roles in the toxic effects of chemicals, including facilitating or counteracting cell death processes. Logic requiring hepatocytes to obtain current information about whether downstream and lateral neighbors have triggered necrosis enabled virtual hepatocytes to achieve both new target attributes. A virtual hepatocyte that is glutathione-depleted uses that information to determine if it will initiate necrosis. When a less-stressed hepatocyte is flanked by at least two neighbors that have triggered necrosis, it too will initiate necrosis. We hypothesize that the resulting intercellular communication-enabled model mechanism is analogous to the actual explanation for APAP-induced hepatotoxicity at comparable levels of granularity
Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of Pregabalin
Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex, however under neuropathic conditions, it is unclear how hyperexcitability of spinal neurones converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity, and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurones in anaesthetised spinal nerve-ligated (SNL), sham-operated and naïve rats. In neuropathic rats, WDR neurones had elevated evoked responses to low and high intensity punctate mechanical stimuli, dynamic brushing, innocuous and noxious cooling, but less so to heat stimulation of the receptive field. NS neurones in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling and noxious heat. Additionally, WDR, but not NS, neurones in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR:NS neurones was comparable between SNL and naïve/sham groups suggesting relatively few NS neurones gain sensitivity to low intensity stimuli leading to a 'WDR phenotype'. After neuropathy, the proportion of cold sensitive WDR and NS neurones increased, supporting that changes in frequency dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold evoked or elevated spontaneous activity
Ideology, Qualifications, and Covert Senate Obstruction of Federal Court Nominations
Scholars, policymakers, and journalists have bemoaned the emphasis on ideology over qualifications and party over performance in the judicial appointment process. Though, for years, the acrimony between the two parties and between the Senate and President remained limited to appointments to the United States Supreme Court, the modern era of judicial appointments has seen the so-called “appointments rigor mortis” spread throughout all levels of judicial appointments. A host of studies have examined the causes and consequences of the growing acrimony and obstruction of lower federal court appointments, but few rely on archival data and empirical evidence to examine the underlying friction between the parties and the two branches.
In a unique study, the authors examine archival data to determine the conditions under which Senators obstruct judicial nominations to lower federal courts. More specifically, the authors examine one form of Senate obstruction — the blue slip — and find that Senators use their blue slips to block ideologically distant nominees as well as unqualified nominees. More importantly, however, the authors find that among nominations to federal circuit courts, Senators block highly qualified nominees who are ideologically distant from them just as often as they block unqualified nominees who are ideologically distant from them. That is, stellar qualifications do not appear to mitigate the negative effects of ideological distance. The fact that blue slips occur in private, away from public view, allows Senators to block nominees entirely on ideological grounds, without fear of individualized public retribution. Senators, in short, have taken an aggressive role in blocking highly qualified nominees who would otherwise make significant — but opposing — policy and who might one day become credible nominees to the Supreme Court were their nominations to move forward. By killing these nominations in the cradle, and outside the public view, Senators can block or delay the confirmation of judges with whom they disagree ideologically.
The authors point out that policymakers and scholars who seek to reform the judicial appointment process must therefore be very clear about their goals. If a reform’s goal is to minimize the role of Senate ideology in the appointment process, then proposals that insulate the process from the public eye are likely to backfire. For, as the data show, Senators take advantage of insulation to achieve ideological goals. On the other hand, if a reform’s goal is to maximize the role of Senate ideology — perhaps to offset the President’s first mover advantage or to recognize and directly address the fact that courts are policymaking bodies — then proposals that insulate the process from the public eye are likely to accomplish that goal
Neonatal resuscitation training in Ireland integrating teaching and research: a quality of care initiative in health services research
Resuscitation training is a vital area of education that could have a significant impact on patient outcome. This is especially true in the newborn period where inexperienced, inadequate or inappropriate resuscitation responses could affect the entire life span of a newborn infant. In addition, neonates are more often subject to asphyxia and are far more likely to be in need of resuscitation than any other age group. The World Health Organization (1995) estimates that every year there are one million neonatal deaths attributable to birth asphyxia. Due to the unique aetiology and pathophysiology of neonatal arrests, successful resuscitation requires the application of knowledge and skills that require special training. The purpose of resuscitation training is to transfer the science of resuscitation into classroom performance, with the objective of transferring knowledge and skills into clinical practice. The ultimate goal of the process is to improve neonatal survival and decrease handicap. While it is the responsibility of the Health Services to provide the necessary training for its employees, it is the function of Universities to design, develop, evaluate and promote effective educational programmes that improve patient care
Synthetic and Evolutionary Construction of a Chlorate-Reducing Shewanella oneidensis MR-1.
UnlabelledDespite evidence for the prevalence of horizontal gene transfer of respiratory genes, little is known about how pathways functionally integrate within new hosts. One example of a mobile respiratory metabolism is bacterial chlorate reduction, which is frequently encoded on composite transposons. This implies that the essential components of the metabolism are encoded on these mobile elements. To test this, we heterologously expressed genes for chlorate reduction from Shewanella algae ACDC in the non-chlorate-reducing Shewanella oneidensis MR-1. The construct that ultimately endowed robust growth on chlorate included cld, a cytochrome c gene, clrABDC, and two genes of unknown function. Although strain MR-1 was unable to grow on chlorate after initial insertion of these genes into the chromosome, 11 derived strains capable of chlorate respiration were obtained through adaptive evolution. Genome resequencing indicated that all of the evolved chlorate-reducing strains replicated a large genomic region containing chlorate reduction genes. Contraction in copy number and loss of the ability to reduce chlorate were also observed, indicating that this phenomenon was extremely dynamic. Although most strains contained more than six copies of the replicated region, a single strain with less duplication also grew rapidly. This strain contained three additional mutations that we hypothesized compensated for the low copy number. We remade the mutations combinatorially in the unevolved strain and determined that a single nucleotide polymorphism (SNP) upstream of cld enabled growth on chlorate and was epistatic to a second base pair change in the NarP binding sequence between narQP and nrfA that enhanced growth.ImportanceThe ability of chlorate reduction composite transposons to form functional metabolisms after transfer to a new host is an important part of their propagation. To study this phenomenon, we engineered Shewanella oneidensis MR-1 into a chlorate reducer. We defined a set of genes sufficient to endow growth on chlorate from a plasmid, but found that chromosomal insertion of these genes was nonfunctional. Evolution of this inoperative strain into a chlorate reducer showed that tandem duplication was a dominant mechanism of activation. While copy number changes are a relatively rapid way of increasing gene dosage, replicating almost 1 megabase of extra DNA is costly. Mutations that alleviate the need for high copy number are expected to arise and eventually predominate, and we identified a single nucleotide polymorphism (SNP) that relieved the copy number requirement. This study uses both rational and evolutionary approaches to gain insight into the evolution of a fascinating respiratory metabolism
The Gut Microbiota Composition in Dichorionic Triplet Sets Suggests a Role for Host Genetic Factors
peer-reviewedMonozygotic and dizygotic twin studies investigating the relative roles of host genetics and environmental factors in shaping gut microbiota composition have produced conflicting results. In this study, we investigated the gut microbiota composition of a healthy dichorionic triplet set. The dichorionic triplet set contained a pair of monozygotic twins and a fraternal sibling, with similar pre- and post-natal environmental conditions including feeding regime. V4 16S rRNA and rpoB amplicon pyrosequencing was employed to investigate microbiota composition, and the species and strain diversity of the culturable bifidobacterial population was also examined. At month 1, the monozygotic pair shared a similar microbiota distinct to the fraternal sibling. By month 12 however, the profile was more uniform between the three infants. Principal coordinate analysis (PCoA) of the microbiota composition revealed strong clustering of the monozygotic pair at month 1 and a separation of the fraternal infant. At months 2 and 3 the phylogenetic distance between the monozygotic pair and the fraternal sibling has greatly reduced and by month 12 the monozygotic pair no longer clustered separately from the fraternal infant. Pulse field gel electrophoresis (PFGE) analysis of the bifidobacterial population revealed a lack of strain diversity, with identical strains identified in all three infants at month 1 and 12. The microbiota of two antibiotic-treated dichorionic triplet sets was also investigated. Not surprisingly, in both triplet sets early life antibiotic administration appeared to be a major determinant of microbiota composition at month 1, irrespective of zygosity. By month 12, early antibiotic administration appeared to no longer exert such a strong influence on gut microbiota composition. We hypothesize that initially host genetics play a significant role in the composition of an individual’s gut microbiota, unless an antibiotic intervention is given, but by month 12 environmental factors are the major determinant.This study was performed as part of the INFANTMET project (10/RD/Infantmet/MFRC/705) and was funded by the Government of Ireland's Department of Agriculture Fisheries and in part by Alimentary Pharmabiotic Centre. KM is a Teagasc Walsh Fellow. CS, RPR and PWOT are members of The Alimentary Pharmabiotic Centre, which is a Centre for Science and Technology (CSET) funded by the Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan (Grant no. 02/CE/B124 and 07/CE/B1368)
Microbial therapeutics designed for infant health
Acknowledgment of the gut microbiome as a vital asset to health has led to multiple studies attempting to elucidate its mechanisms of action. During the first year of life, many factors can cause fluctuation in the developing gut microbiome. Host genetics, maternal health status, mode of delivery, gestational age, feeding regime, and perinatal antibiotic usage, are known factors which can influence the development of the infant gut microbiome. Thus, the microbiome of vaginally born, exclusively breastfed infants at term, with no previous exposure to antibiotics, either directly or indirectly from the mother, is to be considered the “gold standard.” Moreover, the use of prebiotics as an aid for the development of a healthy gut microbiome is equally as important in maintaining gut homeostasis. Breastmilk, a natural prebiotic source, provides optimal active ingredients for the growth of beneficial microbial species. However, early life disorders such as necrotising enterocolitis, childhood obesity, and even autism have been associated with an altered/disturbed gut microbiome. Subsequently, microbial therapies have been introduced, in addition to suitable prebiotic ingredients, which when administered, may aid in the prevention of a microbial disturbance in the gastrointestinal tract. The aim of this mini-review is to highlight the beneficial effects of different probiotic and prebiotic treatments in early life, with particular emphasis on the different conditions which negatively impact microbial colonisation at birth
Poly Spotlight Control
When this project began, The Cambria Center for the Arts Theater used a manually-operated spotlight. The sound created by the fans, along with the sheer size of the spotlight, required that it be housed in an attic room above the theater and shined through a closed window. This trapped a lot of heat in the room and involved some risk with climbing into and out of the attic room. This project sought to remedy those issues by mounting a pair of newer LED spotlights inside the theater. Doing this required a method for remotely controlling and actuating the angular position of each spotlight in two axes. Over the course of one year, the Dynalux team researched, designed, and built a solution to CCAT’s problem. The process by which they completed those steps is written in detail within this report. The first third of the year was spent in research and development. The team compared commercial and industry options to determine the best practices and designs. Many of the available options were too complicated or expensive and this reiterated that a cheaper and easier system was needed. At this point, Team Dynalux came up with a preliminary design that met all the design constraints. The next third of the year was dedicated to detailed analysis and proving that the design would work as intended. This included looking at all aspects of the system from motor torque requirements to strength and material properties. At this stage, the design was presented to the sponsor and advisors to begin manufacturing. The remainder of the project consisted of manufacturing, assembling, and testing. Some aspects had to be changed on-the-fly but the majority of the design remained the same throughout. Upon concluding machining and welding, the metal parts were finished and assembled with off-the-shelf components. When the mounts were complete, the electronics were added and tested in the overall system. Testing and manufacturing were time intensive but kept safety and reliability as the highest priority. The contents of this report are intended to document the process by which the project was completed but also provide reference to the parts and techniques used to build the system. Also included are comprehensive drawings and instructions to make sure the system is running smoothly, and if needed, provide maintenance
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