A contact binary satellite of the asteroid (152830) Dinkinesh.

Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky-O'Keefe-Radzievskii-Paddack effect)1 to be a notable factor in their evolution2. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 AU; its S-type spectrum3,4 is typical of bodies in this part of the main belt5. Here we report observations by the Lucy spacecraft6,7 as it passed within 431 km of Dinkinesh. Lucy revealed Dinkinesh, which has an effective diameter of only 720 m, to be unexpectedly complex. Of particular note is the presence of a prominent longitudinal trough overlain by a substantial equatorial ridge and the discovery of the first confirmed contact binary satellite, now named (152830) Dinkinesh I Selam. Selam consists of two near-equal-sized lobes with diameters of 210 m and 230 m. It orbits Dinkinesh at a distance of 3.1 km with an orbital period of about 52.7 h and is tidally locked. The dynamical state, angular momentum and geomorphologic observations of the system lead us to infer that the ridge and trough of Dinkinesh are probably the result of mass failure resulting from spin-up by YORP followed by the partial reaccretion of the shed material. Selam probably accreted from material shed by this event.

The big business of sustainable food production and consumption: Exploring the transition to alternative proteins.

A widespread sense of the unsustainability of the food system has taken hold in recent years, leading to calls for fundamental change. The role of animal agriculture is central to many of these debates, leading to interest in the possibility of a "protein transition," whereby the production and consumption of animal-derived foods is replaced with plant-based substitutes or "alternative proteins." Despite the potential sustainability implications of this transition, the developmental trajectories and transformative potential of the associated technologies remain underexplored. This article sheds light on these dynamics by addressing two questions: 1) how have alternative protein innovations developed over the past three decades, and 2) what explains their more recent acceleration? To answer these questions, the article makes an empirical analysis of four alternative protein innovations, and the partial destabilization of the animal agriculture system between 1990 and 2021, guided by the multi-level perspective. The analysis highlights an intensification in corporate engagement with alternative protein development and diffusion. This intensification is judged to be consistent with the beginnings of a wider corporate reorientation, occurring alongside a rise in pressures on the animal agriculture system, notably an increasing scientific consensus and societal awareness of the links between climate change and meat-intensive diets. The paper demonstrates how differences in technological maturity across the niche innovations have resulted in potentially transformative pressures, which are consistent with an emerging sustainability transition, manifesting differently in terms of the extent of diffusion of the alternative protein niches.

Single-level laminoplasty approach to selective dorsal rhizotomy with conus localization by rapid spine MRI.

INTRODUCTION: While selective dorsal rhizotomy (SDR) was originally described as a multilevel approach, single-level approaches are now popularized. Conus localization is beneficial for operative planning in single-level selective dorsal rhizotomy. Our approach to SDR involves minimal exposure for a single-level laminoplasty, preserving one attached interspinous ligament. Pre-operative conus localization is required for this tailored approach to determine the laminoplasty level and dictate rostral or caudal division of the superior spinus ligament. While rapid MRI sequences have been popularized for pediatric cranial imaging, its utility for spinal imagining is less well-described, and specific application for conus localization has not been reported. OBJECTIVE: Illustrate that rapid MRI without sedation is sufficient to identify conus level for tailored single-level laminoplasty SDR. MATERIAL AND METHODS: Patients undergoing SDR from 2014 to 2022 at one institution were reviewed for type of pre-operative MRI (rapid vs full), conus level, procedural time for MRI, and radiology report. The typical rapid MRI has four sequences utilizing single-shot technique (scout, sagittal T2, axial T2, and axial T1) that typically take less than 1 min each of acquisition time, with non-single-shot sequences added periodically in cooperative patients. To include time for patient positioning, pre-scan shimming, procedural incidentals, and other patient-specific variations, MRI procedure length was recorded as documented in the electronic medical record. RESULTS: N = 100 patients had documentation of an MRI for pre-operative imaging. Seventy-nine of these had a rapid MRI, and 21 required a full MRI with anesthesia for their treatment plan. Mean total procedure time for rapid MRI was 21.5 min (median 17). Mean procedure time for MRI under general anesthesia was 91.2 min (median 94). Of patients with rapid MRI imaging, 2/79 had an ambiguous conus level (1 from motion artifact, 1 from spinal hardware) vs 1/21 with a full MRI under anesthesia (due to spinal hardware). CONCLUSION: Rapid spinal MRI without sedation can be used for conus localization in a pediatric population. This may be routinely used as pre-operative imaging for a single-level approach to selective dorsal rhizotomy, without sedation or intubation procedures.

Preventing translational inhibition from ribosomal protein insufficiency by a herpes simplex virus-encoded ribosome-associated protein.

In addition to being required for protein synthesis, ribosomes and ribosomal proteins (RPs) also regulate messenger RNA translation in uninfected and virus-infected cells. By individually depleting 85 RPs using RNA interference, we found that overall protein synthesis in uninfected primary fibroblasts was more sensitive to RP depletion than those infected with herpes simplex virus-1 (HSV-1). Although representative RP depletion (uL3, uS4, uL5) inhibited protein synthesis in cells infected with two different DNA viruses (human cytomegalovirus, vaccinia virus), HSV-1-infected cell protein synthesis unexpectedly endured and required a single virus-encoded gene product, VP22. During individual RP insufficiency, VP22-expressing HSV-1 replicated better than a VP22-deficient variant. Furthermore, VP22 promotes polysome accumulation in virus-infected cells when uL3 or ribosome availability is limiting and cosediments with initiating and elongating ribosomes in infected and uninfected cells. This identifies VP22 as a virus-encoded, ribosome-associated protein that compensates for RP insufficiency to support viral protein synthesis and replication. Moreover, it reveals an unanticipated class of virus-encoded, ribosome-associated effectors that reduce the dependence of protein synthesis upon host RPs and broadly support translation during physiological stress such as infection.

Mucinous ovarian carcinoma: A survey of practice in Australia and New Zealand.

BACKGROUND: Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer with limited evidence to support clinical care. AIMS: We undertook a clinician survey to better understand current practice in treating MOC in Australia and New Zealand, and to determine any features associated with variation in care. In addition, we aimed to understand future research priorities. METHODS: A RedCap survey was distributed to clinician members of the Australia New Zealand Gynaecological Oncology Group (ANZGOG). Questions included respondent demographics, three case studies and future research priorities. Clinicians were asked questions specific to their speciality. RESULTS: Respondents (n = 47) were commonly experienced gynae-oncology specialists, most often surgical (38%) or medical (30%) oncologists. There was good consensus for surgical approaches for stage I disease; however, variation in practice was noted for advanced or recurrent MOC. Variation was also observed for medical oncologists; in early-stage disease there was no clear consensus on whether to offer chemotherapy, or which regimen to recommend. For advanced and recurrent disease a wide range of chemotherapy options was considered, with a trend away from an ovarian-type toward gastrointestinal (GI)-type regimens in advanced MOC. This practice was reflected in future research priorities, with 'Is a GI chemotherapy regimen better than an ovarian regimen?' the most highly ranked option, followed by 'Should stage 1C patients receive chemotherapy?' CONCLUSIONS: Although the number of respondents limited the analyses, it was clear that chemotherapy selection was a key point of divergence for medical oncologists. Future research is needed to establish well-evidenced guidelines for clinical care of MOC.

Impacts of the COVID-19 pandemic on population management in AZA.

Soon after the onset of the COVID-19 pandemic, almost all Association of Zoos and Aquariums (AZA) facilities closed to the public. Resulting cost-saving and safety measures led some facilities to temporarily cease or reduce animal breeding and/or transfers. We surveyed AZA facilities and Species Survival Plan® (SSP) Coordinators for AZA's cooperative population management programs to evaluate how widespread these decisions were, if impacts varied by taxa, and how the AZA community navigated related challenges during the pandemic. We found that 60% of responding facilities did not suspend breeding and 22% did not suspend transfers. About 50% of responding zoos increased their reliance on ground transportation to move animals, while aquariums reported no change to transportation methods. SSP Coordinators reported the main reason why breeding decreased, regardless of taxa, was due to canceled or delayed transfers. The reasons transfers decreased differed by taxa, such as limited financial resources and lack of access to air transportation. The majority of respondents for both surveys stated transfers were the greatest challenge they faced. To address this, facilities utilized alternative transportation methods and worked closely with nearby zoos and aquariums for the movement of animals, while SSP Coordinators issued alternative transfer recommendations. If another pandemic or other widespread facility closure occurs, our research highlights the importance of communication, collaboration, and flexibility to fulfill breeding and transfer recommendations to maintain sustainable zoo and aquarium populations.

In vitro evolution of antibody affinity via insertional scanning mutagenesis of an entire antibody variable region.

We report a systematic combinatorial exploration of affinity enhancement of antibodies by insertions and deletions (InDels). Transposon-based introduction of InDels via the method TRIAD (transposition-based random insertion and deletion mutagenesis) was used to generate large libraries with random in-frame InDels across the entire single-chain variable fragment gene that were further recombined and screened by ribosome display. Knowledge of potential insertion points from TRIAD libraries formed the basis of exploration of length and sequence diversity of novel insertions by insertional-scanning mutagenesis (InScaM). An overall 256-fold affinity improvement of an anti-IL-13 antibody BAK1 as a result of InDel mutagenesis and combination with known point mutations validates this approach, and suggests that the results of this InDel mutagenesis and conventional exploration of point mutations can synergize to generate antibodies with higher affinity.

Institutional networks in cooperative population management: Exploring patterns in transfer fulfillment.

Long-term sustainability of ex-situ animal populations is important for zoos and aquariums, but challenging due to inconsistent compliance with Breeding and Transfer Plans. Transfer recommendations are key to promoting the sustainability of ex-situ animal populations by ensuring cohesive populations, genetic diversity, and demographic stability, but factors affecting their fulfillment are poorly understood. We used a network analysis framework to analyze data compiled from PMCTrack from 2011 to 2019 for three taxonomic classes (mammals, birds, and reptiles/amphibians) within the Association of Zoos and Aquariums to assess factors affecting transfer recommendation fulfillment. Of 2505 compiled transfer recommendations spanning 330 Species Survival Plan® (SSP) Programs and 156 institutions, 1628 (65%) of them were fulfilled. Transfers were most likely to be fulfilled between institutions in close proximity with an established relationship. Annual operating budget, SSP Coordinator experience, number of staff, and diversity of Taxonomic Advisory Groups in which an institution participates also influenced transfer recommendations and/or fulfillment, but effects varied with taxonomic class. Our results suggest that current practices of focusing on transfers between institutions in close proximity are working to maximize transfer success and that institutions with larger budgets and some degree of taxonomic specialization play important roles in promoting success. Success could be further enhanced by building reciprocal transfer relationships and encouraging further development of relationships between smaller institutions and larger ones. These results emphasize the utility of examining animal transfers using a network approach, which accounts for attributes of both sending and receiving institutions, describing novel patterns otherwise left undetected.

Clinical characteristics of Plasmodium falciparum infection among symptomatic patients presenting to a major urban military hospital in Cameroon.

BACKGROUND: Urban malaria has received insufficient attention in the literature. The prevalence and clinical characteristics of Plasmodium falciparum infection amongst patients presenting with suspected malaria were investigated at a major urban hospital in Douala, Cameroon with a particular focus on anaemia. METHODS: A cross-sectional, 18-week demographic and clinical survey was conducted of patients presenting to the Emergency Department of Douala Military Hospital with suspected malaria, largely defined by the presence or recent history of fever. Venous samples were tested for P. falciparum using rapid diagnostic tests and PCR, and anaemia was defined by haemoglobin level according to WHO definitions. Likelihood ratios (LR), odds ratios (OR), and population attributable risk percent (PARP) were calculated. RESULTS: Participants were ages 8 months to 86 years, 51% were women (257/503), and all districts of Douala were represented. Overall, 38.0% (n = 189/497) were anaemic, including 5.2% (n = 26/497) with severe anaemia. Anaemia prevalence was significantly higher (OR: 2.20, 95% CI 1.41-3.45) among children < 15 years (53.1%, n = 52/98) compared to adults (34%, n = 133/392). Plasmodium falciparum was detected in 37.2% by nested PCR. Among all participants, several factors were associated with clinically significant LR for P. falciparum infection, including age 10-14 years (positive LR: 3.73), living in the island district of Douala VI (positive LR: 3.41), travel to any of three northern regions (positive LR: 5.11), and high fever > 40 °C at presentation (positive LR: 4.83). Among all participants, 8.7% of anaemia was associated with P. falciparum infection, while the PARP was 33.2% among those < 15 years of age and 81.0% among 10-14-year-olds. CONCLUSIONS: The prevalence of P. falciparum infection in the urban hospital was high. Mirroring trends in many rural African settings, older children had the highest positivity rate for P. falciparum infection. Anaemia was also common in all age groups, and for those 10-14 years of age, 80% of the risk for anaemia was associated with P. falciparum infection. Malaria rates in major urban population centres can be high, and more research into the multifactorial causes of anaemia across the age spectrum are needed.

Muscle development and regeneration controlled by AUF1-mediated stage-specific degradation of fate-determining checkpoint mRNAs.

AUF1 promotes rapid decay of mRNAs containing 3' untranslated region (3'UTR) AU-rich elements (AREs). AUF1 depletion in mice accelerates muscle loss and causes limb girdle muscular dystrophy. Here, we demonstrate that the selective, targeted degradation by AUF1 of key muscle stem cell fate-determining checkpoint mRNAs regulates each stage of muscle development and regeneration by reprogramming each myogenic stage. Skeletal muscle stem (satellite) cell explants show that Auf1 transcription is activated with satellite cell activation by stem cell regulatory factor CTCF. AUF1 then targets checkpoint ARE-mRNAs for degradation, progressively reprogramming the transcriptome through each stage of myogenesis. Transition steps in myogenesis, from stem cell proliferation to differentiation to muscle fiber development, are each controlled by fate-determining checkpoint mRNAs, which, surprisingly, were found to be controlled in their expression by AUF1-targeted mRNA decay. Checkpoint mRNAs targeted by AUF1 include Twist1, decay of which promotes myoblast development; CyclinD1, decay of which blocks myoblast proliferation and initiates differentiation; and RGS5, decay of which activates Sonic Hedgehog (SHH) pathway-mediated differentiation of mature myotubes. AUF1 therefore orchestrates muscle stem cell proliferation, self-renewal, myoblast differentiation, and ultimately formation of muscle fibers through targeted, staged mRNA decay.

Thalamic Stimulation Improves Postictal Cortical Arousal and Behavior.

The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. Previous work in disorders of consciousness including the postictal state suggests that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) may improve level of arousal. We tested the effects of postictal thalamic CL DBS in a rat model of secondarily generalized seizures elicited by electrical hippocampal stimulation. Thalamic CL DBS was delivered at 100 Hz during the postictal period in 21 female rats while measuring cortical electrophysiology and behavior. The postictal period was characterized by frontal cortical slow waves, like other states of depressed consciousness. In addition, rats exhibited severely impaired responses on two different behavioral tasks in the postictal state. Thalamic CL stimulation prevented postictal cortical slow wave activity but produced only modest behavioral improvement on a spontaneous licking sucrose reward task. We therefore also tested responses using a lever-press shock escape/avoidance (E/A) task. Rats achieved high success rates responding to the sound warning on the E/A task even during natural slow wave sleep but were severely impaired in the postictal state. Unlike the spontaneous licking task, thalamic CL DBS during the E/A task produced a marked improvement in behavior, with significant increases in lever-press shock avoidance with DBS compared with sham controls. These findings support the idea that DBS of subcortical arousal structures may be a novel therapeutic strategy benefitting patients with medically and surgically refractory epilepsy.SIGNIFICANCE STATEMENT The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. For the first time, we developed two behavioral tasks and demonstrate that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) decreased cortical slow wave activity and improved task performance in the postictal period. Because preclinical task performance studies are crucial to explore the effectiveness and safety of DBS treatment, our work is clinically relevant as it could support and help set the foundations for a human neurostimulation trial to improve postictal responsiveness in patients with medically and surgically refractory epilepsy.

Therapeutic Drug Monitoring for Current and Investigational Inflammatory Bowel Disease Treatments.

This article reviews therapeutic drug monitoring (TDM) use for current inflammatory bowel disease (IBD) treatments. IBD comprises Crohn's disease and ulcerative colitis-chronic gastrointestinal inflammatory disorders. Treatment options for moderate to severe IBD include thiopurines; methotrexate; biologic agents targeting tumor necrosis factor, α4ß7 integrin or interleukins 12 and 23; and Janus kinase inhibitors. TDM is recommended to guide treatment decisions for some of these agents. Published literature concerning TDM for IBD treatments was reviewed. S.D.L., R.S., and E.V.L. drew on their clinical experiences. Polymorphisms resulting in altered enzymatic activity inactivating thiopurine metabolites can lead to myelotoxicity and hepatotoxicity. Increased elimination of biologic agents can result from immunogenicity or higher disease activity, leading to low drug concentration and consequent nonresponse or loss of response. TDM may aid treatment and dose decisions for individual patients, based on monitoring metabolite levels for thiopurines, or serum drug trough concentration and antidrug antibody levels for biologic agents. Challenges remain around TDM implementation in IBD, including the lack of uniform assay methods and guidance for interpreting results. The Janus kinase inhibitor tofacitinib is not impacted by enzyme polymorphisms or disease activity, and is not expected to stimulate the formation of neutralizing antidrug antibodies. TDM is associated with implementation challenges, despite the recommendation of its use for guiding many IBD treatments. Newer small molecules with less susceptibility to patient variability factors may fulfill the unmet need of treatment options that do not require TDM, although further study is required to confirm this.

Up and Down States of Cortical Neurons in Focal Limbic Seizures.

Recent work suggests an important role for cortical-subcortical networks in seizure-related loss of consciousness. Temporal lobe seizures disrupt subcortical arousal systems, which may lead to depressed cortical function and loss of consciousness. Extracellular recordings show ictal neocortical slow waves at about 1 Hz, but it is not known whether these simply represent seizure propagation or alternatively deep sleep-like activity, which should include cortical neuronal Up and Down states. In this study, using in vivo whole-cell recordings in a rat model of focal limbic seizures, we directly examine the electrophysiological properties of cortical neurons during seizures and deep anesthesia. We found that during seizures, the membrane potential of frontal cortical secondary motor cortex layer 5 neurons fluctuates between Up and Down states, with decreased input resistance and increased firing rate in Up states when compared to Down states. Importantly, Up and Down states in seizures are not significantly different from those in deep anesthesia, in terms of membrane potential, oscillation frequency, firing rate, and input resistance. By demonstrating these fundamental similarities in cortical electrophysiology between deep anesthesia and seizures, our results support the idea that a state of decreased cortical arousal may contribute to mechanisms of loss of consciousness during seizures.

Clinical trials site recruitment optimisation: Guidance from Clinical Trials: Impact and Quality.

BACKGROUND/AIMS: Participants are integral to the success of any clinical research study, yet participant recruitment into clinical trials poses ongoing and complex challenges. It is widely accepted and recognised that clinical trial sites often find it difficult to meet recruitment goals, both in terms of accrual targets and timelines. This can impact the validity of trials or cause major delays for research. There are very few frameworks available to clinical trial sites to improve recruitment. The GREET project (Guidance to Recruitment: Examining Experiences at clinical Trial sites) sought to identify barriers to recruitment and produce formal guidance to optimise recruitment outcomes. METHODS: Clinical Trials: Impact and Quality, a collaborative of sector stakeholders, convened a project team with comprehensive knowledge of the Australian clinical trials sector to undertake the GREET project. The project scope included exploration of recruitment issues at a site level across all phases of clinical trials and all types of trial sites. The scope excluded upstream issues such as protocol design and general public clinical trial awareness, participant retention and elements of recruitment outside a site's capacity to directly influence or control. The project team's extensive knowledge and experience conducting clinical trials in Australia was used to collaboratively identify a list of 24 key barriers and 12 enablers to site recruitment which formed the basis of the project. Key stakeholder groups were surveyed to challenge project team assumptions. A national and international environmental scan and literature review was conducted to identify best-practice recruitment solutions. RESULTS: A total of 343 people responded to a survey sent to sites, sponsors, and contract research organisations, and 162 people responded to a survey sent to consumers via consumer networks. The key barriers and enablers initially identified by the project team aligned with the key outcomes of the surveys, which in turn assisted in the development of best-practice recommendations in the form of a Clinical Trial Site Recruitment Guide. Recommendations were grouped into four key themes; conducting accurate study feasibility; proactive planning during start-up; selecting optimal recruitment methods; and participant involvement. Early intervention was identified as a key facilitator in maximising improved recruitment outcomes. The GREET Clinical Trial Site Recruitment Guide is publicly accessible on the Clinical Trials: Impact and Quality website. CONCLUSION: Participant recruitment challenges experienced at a site level are widespread and varied, and there is no universal recruitment solution. However, this project identified that there are interventions and assessments that can be proactively implemented and selectively applied to facilitate improved recruitment outcomes.

Expanding innovation from undergraduate to graduate medical education: A path of continuous professional development.

A hundred years after the Flexner report laid the foundation for modern medical education, a number of authors commemorated the occasion by commenting on how the medical education system had to change once more to serve 21st century patients. Experts called for standardized outcomes and individualized learner pathways, integration of material across traditional areas, attention to an environment of inquiry, and professional identity formation. The medical education community responded and much has been achieved in the last decade, but much work remains to be done. In this paper we outline how the American Medical Association Accelerating Change in Medical Education Consortium, launched in 2013 through significant funding of transformation projects in undergraduate medical education, expanded its work into graduate medical education, and we look to the future of innovation in medical education.

Realizing the vision of the Lancet Commission on Education of Health Professionals for the 21st Century: Transforming medical education through the Accelerating Change in Medical Education Consortium.

In the last two decades, prompted by the anticipated arrival of the 21st Century and on the centenary of the publication of the Flexner Report, many in medical education called for change to address the expanding chasm between the requirements of the health care system and the educational systems producing the health care workforce. Calls were uniform. Curricular content was missing. There was a mismatch in where people trained and where they were needed to practice, legacy approaches to pedagogical methods that needed to be challenged, an imbalance in diversity of trainees, and a lack of research on educational outcomes, resulting in a workforce that was described as ill-equipped to provide health care in the current and future environment. The Lancet Commission on Education of Health Professionals for the 21st Century published a widely acclaimed report in 2010 that called for a complete and authoritative re-examination of health professional education. This paper describes the innovations of the American Medical Association Accelerating Change in Medical Education Consortium schools as they relate to the recommendations of the Lancet Commission. We outline the successes, challenges, and lessons learned in working to deeply reform medical education.

Early seizure spread and epilepsy surgery: A systematic review.

OBJECTIVE: A fundamental question in epilepsy surgery is how to delineate the margins of cortex that must be resected to result in seizure freedom. Whether and which areas showing seizure activity early in ictus must be removed to avoid postoperative recurrence of seizures is an area of ongoing research. Seizure spread dynamics in the initial seconds of ictus are often correlated with postoperative outcome; there is neither a consensus definition of early spread nor a concise summary of the existing literature linking seizure spread to postsurgical seizure outcomes. The present study is intended to summarize the literature that links seizure spread to postoperative seizure outcome and to provide a framework for quantitative assessment of early seizure spread. METHODS: A systematic review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A Medline search identified clinical studies reporting data on seizure spread measured by intracranial electrodes, having at least 10 subjects and reporting at least 1-year postoperative outcome in the English literature from 1990 to 2019. Studies were evaluated regarding support for a primary hypothesis: Areas of early seizure spread represent cortex with seizure-generating potential. RESULTS: The search yielded 4562 studies: 15 studies met inclusion criteria and 7 studies supported the primary hypothesis. The methods and metrics used to describe seizure spread were heterogenous. The timeframe of seizure spread associated with seizure outcome ranged from 1-14 seconds, with large, well-designed, retrospective studies pointing to 3-10 seconds as most likely to provide meaningful correlates of postoperative seizure freedom. SIGNIFICANCE: The complex correlation between electrophysiologic seizure spread and the potential for seizure generation needs further elucidation. Prospective cohort studies or trials are needed to evaluate epilepsy surgery targeting cortex involved in the first 3-10 seconds of ictus.

Improving Our Ability to Predict Resident Applicant Performance: Validity Evidence for a Situational Judgment Test.

Construct: We investigated whether a situational judgment test (SJT) designed to measure professionalism in physicians predicts residents' performance on (a) Accreditation Council for Graduate Medical Education (ACGME) competencies and (b) a multisource professionalism assessment (MPA). Background: There is a consensus regarding the importance of assessing professionalism and interpersonal and communication skills in medical students, residents, and practicing physicians. Nonetheless, these noncognitive competencies are not well measured during medical education selection processes. One promising method for measuring these noncognitive competencies is the SJT. In a typical SJT, respondents are presented with written or video-based scenarios and asked to make choices from a set of alternative courses of action. Interpersonally oriented SJTs are commonly used for selection to medical schools in the United Kingdom and Belgium and for postgraduate selection of trainees to medical practice in Belgium, Singapore, Canada, and Australia. However, despite international evidence suggesting that SJTs are useful predictors of in-training performance, end-of-training performance, supervisory ratings of performance, and clinical skills licensing objective structured clinical examinations, the use of interpersonally oriented SJTs in residency settings in the United States has been infrequently investigated. The purpose of this study was to investigate whether residents' performance on an SJT designed to measure professionalism-related competencies-conscientiousness, integrity, accountability, aspiring to excellence, teamwork, stress tolerance, and patient-centered care-predicts both their current and future performance as residents on two important but conceptually distinct criteria: ACGME competencies and the MPA. Approach: We developed an SJT to measure seven dimensions of professionalism. During calendar year 2017, 21 residency programs from 2 institutions administered the SJT. We conducted analyses to determine the validity of SJT and USMLE scores in predicting milestone performance in ACGME core competency domains and the MPA in June 2017 and 3 months later in September 2017 for the MPA and 1 year later, in June 2018, for ACGME domains. Results: At both periods, the SJT score predicted overall ACGME milestone performance (r = .13 and .17, respectively; p < .05) and MPA performance (r = .19 and .21, respectively; p < .05). In addition, the SJT predicted ACGME patient care, systems-based practice, practice-based learning and improvement, interpersonal and communication skills, and professionalism competencies (r = .16, .15, .15, .17, and .16, respectively; p < .05) 1 year later. The SJT score contributed incremental validity over USMLE scores in predicting overall ACGME milestone performance (ΔR = .07) 1 year later and MPA performance (ΔR = .05) 3 months later. Conclusions: SJTs show promise as a method for assessing noncognitive attributes in residency program applicants. The SJT's incremental validity to the USMLE series in this study underscores the importance of moving beyond these standardized tests to a more holistic review of candidates that includes both cognitive and noncognitive measures.

Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs).

Non-communicable diseases (NCDs) are medical conditions that, by definition, are non-infectious and non-transmissible among people. Much of current NCDs are generally due to genetic, behavioral, and metabolic risk factors that often include excessive alcohol consumption, smoking, obesity, and untreated elevated blood pressure, and share many common signal transduction pathways. Alterations in cell and physiological signaling and transcriptional control pathways have been well studied in several human NCDs, but these same pathways also regulate expression and function of the protein synthetic machinery and mRNA translation which have been less well investigated. Alterations in expression of specific translation factors, and disruption of canonical mRNA translational regulation, both contribute to the pathology of many NCDs. The two most common pathological alterations that contribute to NCDs discussed in this review will be the regulation of eukaryotic initiation factor 2 (eIF2) by the integrated stress response (ISR) and the mammalian target of rapamycin complex 1 (mTORC1) pathways. Both pathways integrally connect mRNA translation activity to external and internal physiological stimuli. Here, we review the role of ISR control of eIF2 activity and mTORC1 control of cap-mediated mRNA translation in some common NCDs, including Alzheimer's disease, Parkinson's disease, stroke, diabetes mellitus, liver cirrhosis, chronic obstructive pulmonary disease (COPD), and cardiac diseases. Our goal is to provide insights that further the understanding as to the important role of translational regulation in the pathogenesis of these diseases.

Projected Landscape Impacts from Oil and Gas Development Scenarios in the Permian Basin, USA.

Projecting landscape impacts from energy development is essential to land management decisions. We forecast landscape alteration resulting from oil and gas well-pad construction across the economically important Permian Basin of Texas and New Mexico, USA, by projecting current landscape trends through 2050. We modeled three landscape-impact scenarios (low, medium, and high) using recent (2008-2017) trends in well-pad construction and energy production. The results of low-, medium-, and high-impact scenarios suggest that ~60,000, ~180,000, and ~430,000 new well pads could be constructed, potentially causing ~1000, ~2800, and ~6700 km2 of new direct landscape alteration. Almost two-thirds of all new well pads will be constructed within the geologic boundaries of the Delaware and Midland Basins. This translates into a 40, 120, and 300% increase in direct landscape alteration compared with direct alteration from existing well pads. We found that indirect effects (from edges) could increase by twofold, and that the ratio between indirect and direct alteration could decline by half as alteration intensifies and overlaps with existing alteration. The Chihuahuan Desert occupies the largest portion of the study area, and is projected to experience the largest area of alteration from future well-pad construction in the Permian Basin; the degree of direct alteration could increase by 70, 200, and 500% in this desert region, under low-, medium-, and high-impact scenarios. These scenarios can be used to design proactive conservation strategies to reduce landscape impacts from future oil and gas development.