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Multidrug resistant organisms (MDROs) are a public health threat that have reduced the effectiveness of many available antibiotics. Antimicrobial stewardship programs (ASPs) have been tasked with reducing antibiotic use and therefore the emergence of MDROs. While fecal microbiota transplant (FMT) has been proposed as therapy to reduce patient colonization of MDROs, this will require additional evidence to support an expansion of the current clinical indication for FMT. This article discusses the evidence and ethics of the expanded utilization of FMT by ASPs for reasons other than severe recurrent or refractory Clostridioides (formerly Clostridium) difficile infection.
Bone healing is an important survival mechanism, allowing vertebrates to recover from injury and disease. Here we describe newly recognized paleopathologies in the hindlimbs of the early tetrapods Crassigyrinus scoticus and Eoherpeton watsoni from the early Carboniferous of Cowdenbeath, Scotland. These pathologies are among the oldest known instances of bone healing in tetrapod limb bones in the fossil record (about 325 Ma). X-ray microtomographic imaging of the internal bone structure of these lesions shows that they are characterized by a mass of trabecular bone separated from the shaft's trabeculae by a layer of cortical bone. We frame these paleopathologies in an evolutionary context, including additional data on bone healing and its pathways across extinct and extant sarcopterygians. These data allowed us to synthesize information on cell-mediated repair of bone and other mineralized tissues in all vertebrates, to reconstruct the evolutionary history of skeletal tissue repair mechanisms. We conclude that bone healing is ancestral for sarcopterygians. Furthermore, other mineralized tissues (aspidin and dentine) were also capable of healing and remodeling early in vertebrate evolution, suggesting that these repair mechanisms are synapomorphies of vertebrate mineralized tissues. The evidence for remodeling and healing in all of these tissues appears concurrently, so in addition to healing, these early vertebrates had the capacity to restore structure and strength by remodeling their skeletons. Healing appears to be an inherent property of these mineralized tissues, and its linkage to their remodeling capacity has previously been underappreciated.
The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
As Israel's National Emergency Medical Services (EMS) provider, Magen David Adom (MDA) is constantly looking for ways to improve the response to mass casualty incidents (MCIs). Previous research has shown that in an MCI situation, the demand for resources is disproportionate to the available resources, thus creating a dilemma of how to triage and treat the patients, as well as how to best prioritize and treat the critical patients.
Smartwatches have become an integral part of society. MDA constantly looks for ways to integrate new technologies into their emergency response protocols. Smartwatches were used in this experiment to determine if in an MCI, relaying live information to the dispatch center would improve the time it takes for emergency crews to effectively treat and transport critical patients.
A drill and scenario were designed to simulate an MCI in which there were 3 severe, 2 moderate, and 5 lightly wounded patients. There were then different colored smartwatches placed on each victim. The watches transmitted real-time blood pressure, pulse, and oxygen saturation readings to the dispatch center. The live information was transferred directly to responding teams. A second drill was conducted using the same scenario, same number of patients, but without watches to examine the differences in response times.
MDA found that the use of smartwatches directly improved the times (by 3.27 minutes) in which emergency teams were able to reach the most severely wounded patients and evacuate them to the hospital in a timely manner.
Using smartwatches to transmit live information to the dispatch center allowed for effective treatment and transport of patients in an MCI. Use of such information allows the dispatch center to direct teams to provide accurate treatment to the patients according to their needs.
During a mass casualty incident (MCI) seminar in Rome, Italy a survey was used to gauge the self-efficacy and confidence of the participants in managing an MCI. Following the course, a follow-up presentation was held by the Torino EMS Medical Director to evaluate and debrief the Torino Railway incident that occurred one day prior. Students partook in a seminar on MCI management, as well as a debriefing of the Turin Railway accident in which they evaluated the skills used by teams on the scene to manage the incident.
Medical students partook in a seminar to learn to manage an MCI scene, as well as a debriefing of the Turin Railway accident. Following both seminars, the students were given a survey to assess their sense of self-confidence in managing such a situation.
The mean level of self-efficacy prior to the MCI training (M=3.43, SD+0.42) increased after the training (M=3.71, SD+0.37) and remained at the same higher level (M=3.71, SD+0.51) after the medical students were exposed to the details of the Turin train accident. The overall difference between the mean self-efficacy scores in the three time frames was not found to be significant. The mean level of confidence in managing MCIs prior to the training (M=2.83; SD+0.89) increased after the training (M=3.56; SD+0.53) and remained higher following the presentation of the Turin train accident, despite a slight decrease (M=3.52, SD+0.63).
The participants’ surveys showed an increase in their self-efficacy and confidence following the course and follow-up presentation. It is our professional recommendation that real-life events be used in such seminars to increase self-efficacy and confidence. The topic will continue to be evaluated further.
Following a mass casualty incident (MCI), it can take several minutes for emergency medical services (EMS) to arrive. The course was developed by Magen David Adom (MDA) based on unique experience in dealing with MCIs, and the time between alerting emergency services to such an incident until they arrive. The course is focused on teaching the general public to channel their desire to help in such a situation into useful skills which can potentially improve patient outcomes. The seminar focuses on key principles such as safety, calling for help, providing an accurate picture of the scene, and initiating basic treatment with an emphasis on hemorrhage control.
MDA examined the ability of the general public with no previous medical training to perform a basic triage and treatment in an MCI situation. Additionally, the study examined the abilities of the study groups to manage a scene until the arrival of EMS based on the principles taught in the course.
MDA has sent teams of instructors around the world to teach over 1,000 participants. Upon completing the course, the participants partake in a drill that assesses their ability to manage a scene of 20 patients. Their ability to initiate the call for help, provide an accurate picture, initiate treatment, and give an accurate report to arriving emergency responders are examined.
The average times were recorded. Within 38 seconds, dispatch was alerted to the situation. Within 2:30 minutes, treatment was initiated for all patients. Within 4:37 minutes, the scene was fully under control, and within 6:37 minutes, an accurate report was transferred to EMS on the scene.
The participants demonstrated an unexpected willingness to learn, practice, and partake in the drills, and the results were unexpected.
Emergency medical services (EMS) is a high-stress profession, which can lead to deterioration in provider mental health over time. EMS providers may find themselves in a situation where they are not only treating the general public, but also each other. Until now, there has been no active training or emphasis on provider mental health. This has taken its toll and can lead to PTSD (post-traumatic stress disorder) in field providers and managers alike.
Identifying and managing stressors is crucial to longevity in the field of EMS. Managers must have the ability to broach sensitive matters with their subordinates, and effectively debrief them following such stressful incidents.
Magen David Adom held a two-day seminar for its administration, from which they learned signs and symptoms of PTSD, how to approach teams who had been in stressful situations, and how to properly debrief the teams. The seminar culminated in mass casualty incident (MCI) drills, where there were 4 active scenes. Scene 1 had a team that was physically injured. Scene 2 had a team which cared for the team from scene 1. Scene 3 had a team suffering from emotional stress and ceased to function. Scene 4 had only wounded civilians. The drill focused on provider emotions and used actors and props to simulate an exceedingly complex MCI situation.
Following the drill, a debriefing was held and it was found that all of the points of interest had been noted and properly dealt with.
Holding a successful drill assisted in providing participants with an accurate sense of such stressful situations in which their subordinates find themselves on a daily basis. The debriefing session succeeded in identifying potential stressors for field providers and teaching the participants the appropriate way to approach such sensitive matters.
Most interstellar and planetary environments are suffused by a continuous flux of several types of ionizing radiation, including cosmic rays, stellar winds, x-rays, and gamma-rays from radionuclide decay. There is now a large body of experimental work showing that these kinds of radiation can trigger significant physicochemical changes in ices, including the dissociation of species (radiolysis), sputtering of surface species, and ice heating. Even so, modeling the chemical effects that result from interactions between ionizing radiation and interstellar dust grain ice mantles has proven challenging due to the complexity and variety of the underlying physical processes. To address this shortcoming, we have developed a method whereby such effects could easily be included in standard rate-equations-based astrochemical models. Here, we describe how such models, thus improved, can fruitfully be used to simulate experiments in order to better understand bulk chemistry at low temperatures.
In response to the economic vulnerability of single mothers and in keeping with a neoliberal ideology, many Western countries have encouraged increased labour-market participation, often through welfare-to-work (WTW) programmes. One practice adopted in these programmes is deepening knowledge of pension savings and increasing financial savviness. Feminist research points to women's lower economic status than men at retirement, especially divorcees and widows. Based on perceptions of single mothers participating in a WTW programme in Israel and their trainers, this study examines how such mothers, in a framework of vulnerability, experience policy imperatives regarding paid labour and examines their attitudes to pension savings. Findings reveal that, in reaction to the imperative of pension savings, some single mothers believed their present employment provided them with a more secure economic future, while others rejected this belief. The trainers also had divided opinions, despite their role in encouraging mothers to follow the imperative.
The initial mass function (IMF) is a profoundly studied subject, however its origin is still unclear and heavily disputed. The Core Mass Function (CMF) has a remarkable resemblance to a shifted IMF along the mass axis of a factor of 3. This CMF has been observed amongst others in the Pipe Nebula, a calm molecular cloud at approximately 130 pc. We study the origin of the CMF under the assumption that collisions and merging of prestellar cores shape the CMF. We present our preliminary results of core collisions for the well known FeSt 1-457.
Carbon-doped titania was fabricated via carbothermal treatment in nitrogen–acetylene gas flow and further used as a precursor for multiwalled titanate nanotube (TNT) synthesis via alkaline hydrothermal route. Investigation of the reaction products after hydrothermal treatment of carbon-doped titania using Transmission electron microscopy, X-ray diffraction, and Brunauer–Emmett–Teller method shows the successful formation of TNTs. The presence of carbon was proved although the type of incorporation could not be certified. All samples show approximately the same carbon content before and after hydrothermal treatment. An increasing pretreatment temperature of titania precursor powders yields more secondary products in the nanotube samples, indicating lower reactivity of the titanium oxycarbide phase during hydrothermal treatment. In this study, TNTs with 6 wt% carbon and with the highest specific surface area of 340 m2/g were formed via hydrothermal treatment of carbon-doped titania precursor powder exposed to 700 °C during carbothermal pretreatment.
The Carboniferous tetrapod Crassigyrinus scoticus is an enigmatic animal in terms of its morphology and its phylogenetic position. Crassigyrinus had extremely reduced forelimbs, and was aquatic, perhaps secondarily. Recent phylogenetic analyses tentatively place Crassigyrinus close to the whatcheeriids. Many Carboniferous tetrapods exhibit several characteristics associated with terrestrial locomotion, and much research has focused on how this novel locomotor mode evolved. However, to estimate the selective pressures and constraints during this important time in vertebrate evolution, it is also important to study early tetrapods like Crassigyrinus that either remained aquatic or secondarily became aquatic. We used computed tomographic scanning to search for more data about the skeletal morphology of Crassigyrinus and discovered several elements previously hidden by the matrix. These elements include more ribs, another neural arch, potential evidence of an ossified pubis and maybe of pleurocentra. We also discovered several additional metatarsals with interesting asymmetrical morphology that may have functional implications. Finally, we reclassify what was previously thought to be a left sacral rib as a left fibula and show previously unknown aspects of the morphology of the radius. These discoveries are examined in functional and phylogenetic contexts.
Halophilic Archaea are known to tolerate multiple extreme conditions on Earth and have been proposed as models for astrobiology. In order to assess the importance of cold-adaptation of these microorganisms in surviving stratospheric conditions, we launched live, liquid cultures of two species, the mesophilic model Halobacterium sp. NRC-1 and the cold-adapted Antarctic isolate Halorubrum lacusprofundi ATCC 49239, on helium balloons. After return to Earth, the cold-adapted species showed nearly complete survival while the mesophilic species exhibited slightly reduced viability. Parallel studies found that the cold-adapted species was also better able to survive freezing and thawing in the laboratory. Genome-wide transcriptomic analysis was used to compare the two haloarchaea at optimum growth temperatures versus low temperatures supporting growth. The cold-adapted species displayed perturbation of a majority of genes upon cold temperature exposure, divided evenly between up-regulated and down-regulated genes, while the mesophile exhibited perturbation of only a fifth of its genes, with nearly two-thirds being down-regulated. These results underscore the importance of genetic responses of H. lacusprofundi to cold temperature for enhanced survival in the stratosphere.
Lawyers are most often portrayed and understood to be zealous advocates for individual clients in adversarial litigation or zero-sum transactions. Law schools provide excellent preparation for this type of lawyer role, but lawyers' unique understanding of the law is also needed for systemic advocacy, policymaking, and legal education to solve the most difficult societal problems. An interdisciplinary public health law class is one way for law schools to provide students an opportunity to explore and develop these other professional identities.
The vasa vasorum (VV) of explanted segments of the human great saphenous vein (Vena saphena magna; HGSV), harvested during dissection for coronary bypass grafts or diseased vein segments from the “Salzburger Landesklinikum,” were studied by scanning electron microscopy and three-dimensional morphometry of microvascular corrosion casts. The main objective of this study was to examine the VV’s structural arrangement in order to find the most vital segments of the HGSV and in turn to improve the results of coronary bypass surgeries. The study presents a meticulous analysis of the whole microvascular system of the VV of the HGSV and its three-dimensional arrangement. It is one of the first studies yielding detailed quantitative data on geometry of the VV of the HGSV. A detailed insight into different vascular parameters such as vessel diameter, interbranching, intervascular distances, and branching angles at different levels of the VV’s angioarchitecture and in different parts of the HGSV in health and disease is given. Further, the geometry of bifurcations was examined in order to compute the physiological optimality principles of this delicate vascular system based on its construction, maintenance, and function.
In the past decade, delivering personalized medicine via molecularly targeted therapies has become a major focus in the field of cancer therapeutics. Tyrosine kinases regulate angiogenesis and cell proliferation, invasion, and apoptosis. Tyrosine-kinase inhibitors (TKIs) are small-molecule inhibitors that permeate through the cell membrane and target specific portions of kinase receptors in cancer cells and/or the surrounding endothelium and vasculature. In this chapter, we review the TKIs currently used to treat cancer, including targeted agents, angiogenesis inhibitors, and Her family inhibitors (Figure 82.1).
Imatinib mesylate (STI-571; Gleevec/Glivec, Novartis Pharmaceuticals), the first TKI developed for Philadelphia-chromosome-positive (Ph+) chronic myeloid leukemia (CML), specifically targets the translocation that encodes the breakpoint cluster region–Abelson (BCR–ABL) tyrosine kinase (Figure 82.2). Imatinib also inhibits normal ABL. The BCR–ABL fusion gene is found in 90% of patients with CML and 15–30% of patients with acute lymphoblastic leukemia (ALL; 1). BCR–ABL activates multiple cytoplasmic and nuclear signal-transduction pathways, including Ras, phosphatidylinositol-3 kinase (PI3K), protein kinase B (AKT), and Jak/Stat, and up-regulates interleukin-3 and focal adhesion kinase. BCR–ABL is associated with an impaired DNA-repair response that promotes genetic abnormalities (2–10). In addition, imatinib inhibits c-Kit receptor and platelet-derived growth-factor receptor (PDGFR)-α and -β.