Members of the cytochrome P450 superfamily catalyze the addition of molecular oxygen to nonactivated hydrocarbons at physiological temperature-a reaction that requires high temperature to proceed in ...the absence of a catalyst. Structures were obtained for three intermediates in the hydroxylation reaction of camphor by P450cam with trapping techniques and cryocrystallography. The structure of the ferrous dioxygen adduct of P450cam was determined with 0.91 angstrom wavelength x-rays; irradiation with 1.5 angstrom x-rays results in breakdown of the dioxygen molecule to an intermediate that would be consistent with an oxyferryl species. The structures show conformational changes in several important residues and reveal a network of bound water molecules that may provide the protons needed for the reaction.
One often observes small but measurable differences in the diffraction data measured from different crystals of a single protein. These differences might reflect structural differences in the protein ...and may reveal the natural dynamism of the molecule in solution. Partitioning these mixed‐state data into single‐state clusters is a critical step that could extract information about the dynamic behavior of proteins from hundreds or thousands of single‐crystal data sets. Mixed‐state data can be obtained deliberately (through intentional perturbation) or inadvertently (while attempting to measure highly redundant single‐crystal data). To the extent that different states adopt different molecular structures, one expects to observe differences in the crystals; each of the polystates will create a polymorph of the crystals. After mixed‐state diffraction data have been measured, deliberately or inadvertently, the challenge is to sort the data into clusters that may represent relevant biological polystates. Here, this problem is addressed using a simple multi‐factor clustering approach that classifies each data set using independent observables, thereby assigning each data set to the correct location in conformational space. This procedure is illustrated using two independent observables, unit‐cell parameters and intensities, to cluster mixed‐state data from chymotrypsinogen (ChTg) crystals. It is observed that the data populate an arc of the reaction trajectory as ChTg is converted into chymotrypsin.
The dynamics of proteins can be explored from polymorphs observed by the clustering of multiple data wedges.
The use of simulation as an assessment tool is much more controversial than is its utility as an educational tool. However, without valid simulation-based assessment tools, the ability to objectively ...assess technical skill competencies in a competency-based medical education framework will remain challenging. The current literature in urologic simulation-based training and assessment uses a definition and framework of validity that is now outdated. This is probably due to the absence of awareness rather than an absence of comprehension. The following review article provides the urologic community an updated taxonomy on validity theory as it relates to simulation-based training and assessments and translates our simulation literature to date into this framework. While the old taxonomy considered validity as distinct subcategories and focused on the simulator itself, the modern taxonomy, for which we translate the literature evidence, considers validity as a unitary construct with a focus on interpretation of simulator data/scores.
Adaptive radiation is an important mechanism of organismal diversification and can be triggered by new ecological opportunities. Although poorly studied in this regard, parasites are an ideal group ...in which to study adaptive radiations because of their close associations with host species. Both experimental and comparative studies suggest that the ectoparasitic wing lice of pigeons and doves have adaptively radiated, leading to differences in body size and overall coloration. Here, we show that long-distance dispersal by dove hosts was central to parasite diversification because it provided new ecological opportunities for parasites to speciate after host-switching. We further show that among extant parasite lineages host-switching decreased over time, with cospeciation becoming the more dominant mode of parasite speciation. Taken together, our results suggest that host dispersal, followed by host-switching, provided novel ecological opportunities that facilitated adaptive radiation by parasites.
The Bemisia tabaci complex of whiteflies contains globally important pests thought to contain cryptic species corresponding to geographically structured phylogenetic clades. Although mostly ...morphologically indistinguishable, differences have been shown to exist among populations in behavior, plant virus vector capacity, ability to hybridize, and DNA sequence divergence. These differences allow for certain populations to become invasive and cause great economic damage in a monoculture setting. Although high mitochondrial DNA divergences have been reported between putative conspecifics of the B. tabaci species complex, there is limited data that exists across the whole genome for this group. Using data from 2184 orthologs obtained from whole genome sequencing (Illumina), a phylogenetic analysis using maximum likelihood and coalescent methodologies was completed on ten individuals of the B. tabaci complex. In addition, automatic barcode gap discovery methods were employed, and results suggest the existence of five species. Although the divergences of the mitochondrial cytochrome oxidase I gene are high among members of this complex, nuclear divergences are much lower in comparison. Single-copy orthologs from whole genome sequencing demonstrate divergent population structures among members of the B. tabaci complex and the sequences provide an important resource to aid in future genomic studies of the group.
To assess the effect of the changing landscape of urologic residency education and training on resident operative exposure and inter-resident variability.
The Accreditation Council for Graduate ...Medical Education (ACGME) case logs for graduating urology chief residents were reviewed from Academic Year (AY) 2009-2010 to 2016-2017. Cases were stratified into the 4 ACGME categories – general urology, endourology, oncology, and reconstruction. Linear regression models analyzed the association between training year, volume, and type of cases performed. Inter-resident variability in case exposure was calculated by the difference between the ACGME reported 10th and 90th percentiles.
During the study period, the mean number of cases performed per resident was 1092 (standard deviation 32.7). Although there was no significant change in total case volume, there were changes within case categories. Endoscopic, retroperitoneal oncology, and male reconstruction case volume all increased significantly (Δ20.1%, Δ 5.1%, Δ 8.2%, respectively, all P < .05). This was balanced with a concomitant decrease in pelvic oncology and female reconstruction cases (Δ 10.0% and Δ 14.5%, respectively, both P < .05). There was a 27.8% increase in laparoscopic/robotic cases (P < .001). The ratio difference between the 10th percentile and 90th percentile ranged from a low of 2.5 for retroperitoneal oncology cases to a high of 5.2 for extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy.
From AY2009-2010 to 2016-2017, residency case volume has remained constant, but there has been a change in types of cases performed and proliferation of minimally invasive techniques. Significant variability of inter-resident operative experience was noted.
The highly automated macromolecular crystallography beamline AMX/17‐ID‐1 is an undulator‐based high‐intensity (>5 × 1012 photons s−1), micro‐focus (7 µm × 5 µm), low‐divergence (1 mrad × 0.35 mrad) ...energy‐tunable (5–18 keV) beamline at the NSLS‐II, Brookhaven National Laboratory, Upton, NY, USA. It is one of the three life science beamlines constructed by the NIH under the ABBIX project and it shares sector 17‐ID with the FMX beamline, the frontier micro‐focus macromolecular crystallography beamline. AMX saw first light in March 2016 and started general user operation in February 2017. At AMX, emphasis has been placed on high throughput, high capacity, and automation to enable data collection from the most challenging projects using an intense micro‐focus beam. Here, the current state and capabilities of the beamline are reported, and the different macromolecular crystallography experiments that are routinely performed at AMX/17‐ID‐1 as well as some plans for the near future are presented.
AMX (17‐ID‐1) is the highly automated macromolecular crystallography beamline at the NSLS‐II. Photon delivery system, beamline instrumentation, high‐performance computing environment and suites of applications are described for beamline scientists and users. AMX's primary mission is to support routine structure determination from the most challenging projects.
To review the literature regarding the epidemiology of stone disease and develop a management algorithm based on current evidence and societal guidelines.
A structured literature review was performed ...to determine highest quality of evidence guiding care for pregnant patients with symptomatic nephrolithiasis. PUBMED and EMBASE databases were searched using terms “pregnancy,” “nephrolithiasis,” or “pregnancy” and “renal colic” alone and in combination with “stone”, “kidney stone,” “ultrasound,” “MRI,” “CT,” “percutaneous nephrostomy,” “ureteral stent,” or “ureteroscopy.” All English-language abstracts were reviewed for relevance and full-length articles were reviewed for content. Articles published prior to 1990 were excluded, and priority for inclusion was given to multi-institutional studies and larger institutional studies, reflecting the highest level of current available evidence and most contemporaneous practice patterns.
Symptomatic nephrolithiasis affects less than 1% of pregnancies but poses unique diagnostic challenges due to the physiologic changes of pregnancy and risks of ionizing radiation exposure to the fetus. Ultrasound remains the imaging modality of choice. Most patients may be managed non-operatively, but drainage with percutaneous nephrostomy or ureteral stent may be performed if warranted. Growing evidence also supports the safety and efficacy of definitive stone treatment.
Though rare, symptomatic nephrolithiasis poses significant clinical challenges due to the need to minimize risk for both mother and fetus with diagnostic and therapeutic interventions. A multi-disciplinary approach is paramount, as is shared decision making with the patient at each step of care.
Purpose Surgical education is changing rapidly as several factors including budget constraints and medicolegal concerns limit opportunities for urological trainees. New methods of skills training ...such as low fidelity bench trainers and virtual reality simulators offer new avenues for surgical education. In addition, surgical simulation has the potential to allow practicing surgeons to develop new skills and maintain those they already possess. We provide a review of the background, current status and future directions of surgical simulators as they pertain to urology. Materials and Methods We performed a literature review and an overview of surgical simulation in urology. Results Surgical simulators are in various stages of development and validation. Several simulators have undergone extensive validation studies and are in use in surgical curricula. While virtual reality simulators offer the potential to more closely mimic reality and present entire operations, low fidelity simulators remain useful in skills training, particularly for novices and junior trainees. Surgical simulation remains in its infancy. However, the potential to shorten learning curves for difficult techniques and practice surgery without risk to patients continues to drive the development of increasingly more advanced and realistic models. Conclusions Surgical simulation is an exciting area of surgical education. The future is bright as advancements in computing and graphical capabilities offer new innovations in simulator technology. Simulators must continue to undergo rigorous validation studies to ensure that time spent by trainees on bench trainers and virtual reality simulators will translate into improved surgical skills in the operating room.
ABSTRACT
Introduction
Current thinking in healthcare education stipulates a holistic approach with a focus on patient management, bringing together technical skills, decision-making, and team ...performance. In parallel, training opportunities with actual patients have diminished, and the number of different interventions to master has increased. Training on simulators has become broadly accepted; however, requirements for such training devices have outpaced the development of new simulators. The Department of Defense (DoD) targeted this gap with a development challenge. This article introduces the Advanced Modular Manikin (AMM) platform and describes the path followed to address the challenge.
Materials and Methods
Under Contract # W81XWH-14-C-0101, our interdisciplinary team of healthcare providers, educators, engineers, and scientists, together with partners in industry and the government collaborated to establish a set of comprehensive requirements and develop an overarching system architecture and specifications to meet healthcare simulation needs. In order to instantiate the architecture and investigate usability of the platform, a demonstration modular manikin was created that incorporated physical and digital peripherals.
Results
The system architecture and corresponding data models have been completed and published as open source. A developer’s tool kit has been created, including instructional materials and required hardware and software for interested parties to develop AMM-compatible modules. A reference manikin was created based on the platform specifications and successfully supported a usability study that was performed by the American College of Surgeons, Education Division at the Naval Medical Center San Diego.
Conclusions
The formal release of a functional modular, interoperable open-source healthcare simulation platform is complete. Next steps involve a strategy for maintaining the open standards and verification of AMM-compatibility for modules. Increasing awareness of this powerful tool and prioritization of module-development to address the wide range of healthcare education needs could lead to a renaissance in military and civilian healthcare simulation-based training.
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