Search

Objective To identify, screen, highlight, review, and summarize some of the most rigorously conducted and impactful original research and review articles in global emergency medicine (EM) published in 2020 in the peer-reviewed and gray literature. Methods A broad systematic search of peer-reviewed publications related to global EM indexed on PubMed and in the gray literature was conducted. The titles and abstracts of the articles on this list were screened by members of the Global Emergency Medicine Literature Review team to identify those that met our criteria of original research or review articles in the domains of Disaster and Humanitarian Response, Emergency Care in Resource-Limited Settings, and Emergency Medicine Development. Those articles that met these screening criteria were then scored using one of three scoring templates appropriate to the article type. Those articles that scored in the top 5% then underwent in-depth narrative summarization. Results The 2020 GEMLR search initially identified 35,970 articles, more than 50% more than last year's search. From these, 364 were scored based on their full text. Nearly three-fourths of the scored articles constituted original research, of which nearly three-fourths employed quantitative research methods. Nearly 10% of the articles identified this year were directly related to COVID-19. Research involving Emergency Care in Resource-Limited Settings again constituted most of the articles in this year's review, accounting for more than 60% of the literature scored. A total of 20 articles underwent in-depth narrative critiques. Conclusions The number of studies relevant to global EM identified by our search was very similar to last year. Revisions to our methodology to identify a broader range of research were successful in identifying more qualitative research and studies related to Disaster and Humanitarian Response. The number of COVID-19-related articles is likely to continue to increase in subsequent years.

Selective attention is well known for 2D patterns and perceptual alternations are well established for 3D structures projected into 2D, such as the Necker cube. Here, these concepts are extended to the spatial fourth dimension in the form of the mathematical structure of the 4D hypercube. In orthographic projection, its 2D outline figure has multiple and highly dynamic percepts of up to 28 different 3D interpretations, which correspond to local 3D views of the 4D hypercube. Thus, the spontaneous operations of perceptual processing can provide direct insight into conceptual structure in the fourth dimension.

In the time of the Renaissance, a major aspect of vision science was understanding how spatial information projected to the viewpoint of the observer, that is, visual perspective, which is one of the primary cues to depth perception. Perspective representation was thus an early form of virtual reality. Although accurate perspective representation was developed earlier in the 15th century, the first analytic perspective scheme was developed by Piero della Francesca, whose chef d’oeuvre is in the Church of San Francesco, Arezzo, in which the present lecture took place. The focus of the lecture was to evaluate some of the contributions of Piero della Francesca and his 15th-century contemporaries to the visual science, art and symbolism of his era, and its significance for the perception of depth structure from two-dimensional images.

The aim of this study is to compare intrafractional motion using two commercial non-invasive immobilization systems for linac-based intracranial stereotactic radiosurgery (SRS) under guidance with a surface-guided radiotherapy (SGRT) system.Twenty-one patients who received intracranial SRS were retrospectively selected. Ten patients were immobilized with a vacuum fixation biteplate system, while 11 patients were immobilized with an open-face mask system. A setup margin of 1 mm was used in treatment planning. Real-time surface motion data in 37 treatment fractions using the vacuum fixation system and 44 fractions using the open-face mask were recorded by an SGRT system. Variances of intrafractional motion along three translational directions and three rotational directions were compared between the two immobilization techniques with Levene's tests. Intrafractional motion variation over time during treatments was also evaluated.Using the vacuum fixation system, the average and standard deviations of the shifts were 0.01 ± 0.18 mm, -0.06 ± 0.30 mm, and 0.02 ± 0.26 mm in the anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions, and -0.02 ± 0.19°, -0.01 ± 0.13°, and 0.01 ± 0.13° for rotations in yaw, roll, and pitch, respectively; using the open-face mask system, the average and standard deviations of the shifts were -0.06 ± 0.20 mm, -0.02 ± 0.35 mm, and 0.01 ± 0.40 mm in the AP, SI, and LR directions, and were 0.05 ± 0.23°, 0.02 ± 0.21°, and 0.00 ± 0.16° for rotations in yaw, roll, and pitch, respectively. There was a significant increase in intrafractional motion variance over time during treatments.Patients with the vacuum fixation system had significantly smaller intrafractional motion variation compared to those with the open-face mask system. Using intrafractional motion techniques such as surface imaging system is recommended to minimize dose deviation due to intrafractional motion. The increase in intrafractional motion over time indicates clinical benefits with shorter treatment time.

Objectives:This review systematically explores the current available evidence on the effectiveness of interventions provided to first responders to prevent and/or treat the mental health effects of responding to a disaster.Methods:A systematic review of Medline, Scopus, PsycINFO, and gray literature was conducted. Studies describing the effectiveness of interventions provided to first responders to prevent and/or treat the mental health effects of responding to a disaster were included. Quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, and the Critical Appraisal Skills Programme (CASP) checklist.Results:Manuscripts totaling 3869 met the initial search criteria; 25 studies met the criteria for in-depth analysis, including 22 quantitative and 3 qualitative studies; 6 were performed in low- and middle-income countries (LMICs); 18 studies evaluated a psychological intervention; of these, 13 found positive impact, 4 found no impact, and 1 demonstrated worsened symptoms after the intervention. Pre-event trainings decreased psychiatric symptoms in each of the 3 studies evaluating its effectiveness.Conclusions:This review demonstrates that there are likely effective interventions to both prevent and treat psychiatric symptoms in first responders in high-, medium-, and low-income countries.

Language function in the brain, once thought to be highly localized, is now appreciated as relying on a connected but distributed network. The semantic system is of particular interest in the language domain because of its hypothesized integration of information across multiple cortical regions. Previous work in healthy individuals has focused on group-level functional connectivity (FC) analyses of the semantic system, which may obscure interindividual differences driving variance in performance. These studies also overlook the contributions of white matter networks to semantic function. Here, we identified semantic network nodes at the individual level with a semantic decision fMRI task in 53 typically aging adults, characterized network organization using structural connectivity (SC), and quantified the segregation and integration of the network using FC. Hub regions were identified in left inferior frontal gyrus. The individualized semantic network was composed of three interacting modules: (1) default-mode module characterized by bilateral medial prefrontal and posterior cingulate regions and also including right-hemisphere homotopes of language regions; (2) left frontal module extending dorsally from inferior frontal gyrus to pre-motor area; and (3) left temporoparietal module extending from temporal pole to inferior parietal lobule. FC within Module3 and integration of the entire network related to a semantic verbal fluency task, but not a matched phonological task. These results support and extend the tri-network semantic model (Xu in Front Psychol 8: 1538 1538, 2017) and the controlled semantic cognition model (Chiou in Cortex 103: 100 116, 2018) of semantic function.

The language system is perhaps the most unique feature of the human brain's cognitive architecture. It has long been a quest of cognitive neuroscience to understand the neural components that contribute to the hierarchical pattern processing and advanced rule learning required for language. The most important goal of this research is to understand how language becomes impaired when these neural components malfunction or are lost to stroke, and ultimately how we might recover language abilities under these circumstances. Additionally, understanding how the language system develops and how it can reorganize in the face of brain injury or dysfunction could help us to understand brain plasticity in cognitive networks more broadly. In this chapter we will discuss the earliest features of language organization in infants, and how deviations in typical development can-but in some cases, do not-lead to disordered language. We will then survey findings from adult stroke and aphasia research on the potential for recovering language processing in both the remaining left hemisphere tissue and in the non-dominant right hemisphere. Altogether, we hope to present a clear picture of what is known about the capacity for plastic change in the neurobiology of the human language system.

To describe the technique of combined center of rotation of angulation (CORA)-based leveling osteotomy (CBLO) with tibial tuberosity transposition (TTT) and to compare the load to failure between CBLO combined with TTT and CBLO or TTT alone.Ex vivo study.Twelve pairs of cadaveric pelvic limbs.Six pairs of cadaveric tibia were tested in each group (CBLO-TTT versus CBLO) and (CBLO-TTT versus TTT) with each limb randomly assigned to a treatment group. Construct stability was determined by applying a tensile force to each patellar tendon until failure occurred. Load at failure and mode of failure were recorded for each specimen.No difference in mean load to failure was identified between CBLO-TTT (897 N) and CBLO alone (943 N) (P = .81). There was also no difference in the mean load to failure between the CBLO-TTT (928 N) and TTT alone (1046 N) (P = .12).Performing a TTT in combination with a CBLO does not weaken the construct failure to load when compared with each procedure performed alone.A combined CBLO and TTT could be considered a viable option for concurrent management of a cranial cruciate ligament deficient stifle and medial patella luxation.

Background Concussion-induced light sensitivity, or traumatic photalgia, is a lifelong debilitating problem for upwards of 50% of mild traumatic brain injury (mTBI) cases, though of unknown etiology. We employed spectral analysis of electroretinographic (ERG) responses to assess retinal changes in mTBI as a function of the degree of photalgia. Methods The design was a case–control study of the changes in the ERG waveform as a function of level of light sensitivity in individuals who had suffered incidents of mild traumatic brain injury. The mTBI participants were categorized into non-, mild-, and severe-photalgic groups based on their spectral nociophysical settings. Light-adapted ERG responses were recorded from each eye for 200 ms on–off stimulation of three spectral colors (R:red, G:green, and B:blue) and their sum (W:white) at the highest pain-free intensity level for each participant. The requirement of controls for testing hypersensitive individuals at lower light levels was addressed by recording a full light intensity series in the control group. Results Both the b-wave and the photopic negative response (PhNR) were significantly reduced in the non-photalgic mTBI group relative to controls. In the photalgic groups, the main b-wave peak shifted to the timing of the rod b-wave, with reduced amplitude at the timing of the cone response. Conclusion These results suggest the interpretation that the primary etiology of the painful light sensitivity in mTBI is release of the rod pathway from cone-mediated inhibition at high light levels, causing overactivation of the rod pathway.

To measure the effects of a quality improvement intervention on length of stay and benzodiazepine use among patients admitted for alcohol use disorder.This retrospective cohort study was performed at the Salt Lake City Veterans Affairs Medical Center. Patients 18 years and older admitted to a general medical ward with a diagnosis of alcohol related disorders who were treated for alcohol withdrawal were included. The baseline cohort included patients admitted over 12 months. The post-intervention cohort included patients admitted over 12 months. Primary outcomes were total benzodiazepine dose and length of stay. Secondary outcomes included episodes of delirium tremens and seizures.Total benzodiazepine dose decreased significantly over the intervention period. Length of stay also decreased. No episodes of delirium tremens or seizures were observed.A quality improvement intervention directed at general medicine inpatients admitted for alcohol withdrawal was associated with reductions in total benzodiazepine administration and length of stay.

Introduction The Accreditation Council for Graduate Medical Education stipulates that residents should participate in scholarly activity. As of 2019 that verbiage will be changed to, “Residents must participate in scholarship.” However, scholarly activity is not clearly defined. We set out to define our graduation research requirement in a measurable way and structure a research curriculum that better prepared residents to conduct scholarly activity. Materials and Methods This study compares resident scholarly output in several categories before and after the initiation of a revised research curriculum and graduation requirement. Scholarly activity was measured by comparing the production of Pubmed Indexed (PMID) publications, online publications, and conference presentations of two Emergency Medicine Residency classes. The intervention class was represented by the class of 2018 which exposed 16 residents to the new curriculum and graduation requirement for the full three years of their residency. The comparison class was represented by the class of 2015 which exposed 16 residents to the old curriculum and old graduation requirement. The old graduation requirement and curriculum were undefined. The new requirement involved two options, participate in original research starting from the process of question formulation and carried through manuscript drafting or publishing at first author PMID of any kind. The new curriculum involved monthly journal clubs, two annual deep dives, and an 8-day Intern Research Course modeled after the Emergency Medicine Basic Research Skills workshop sponsored by the American College of Emergency Physicians. In addition to the new curriculum, several new leadership positions were created at both the staff and resident level that solely focused on the promotion of scholarly activity. In addition to creating a culture within the department that encouraged scholarship, these overlapping leadership positions also helped create continuity in a program that could easily be hampered by frequent staff turnover due to new military assignments and military deployments. Results Resident scholarly activity in the form of PMIDs increased from 4 to 22. The production of online publications was 0 and 12, respectively. There were 2 and 11 conference presentations, respectively. Conclusion Resident scholarly activity increased following the institution of a new research curriculum and graduation requirement.

Luminance contrast is one of the key factors in the visibility of objects in the world around us. Previous work has shown that the perceived depth from binocular disparity depends profoundly on the luminance contrast of the image. This dependence cannot be explained by existing disparity models, such as the well-established disparity energy model, because they predict no effect of luminance contrast on depth perception. Here, we develop a model for disparity processing that incorporates contrast normalization of the neural response into the disparity energy model to account for the contrast dependence of perceived depth from disparity. Our model contains an array of disparity channels, each with a different disparity selectivity. The binocular images are first processed by the left- and right-eye receptive fields of each channel. The outputs of the two receptive fields are combined linearly as the excitatory disparity sensitivity and then fed into a nonlinear contrast gain control mechanism. The perceived depth is determined by the weighted average of all the disparity channels that respond to the binocular images. This model provides the first analytic account of how luminance contrast affects perceived depth from disparity.

Lack of organized prehospital care may contribute to the disproportionate burden of trauma-related deaths in low- and middle-income countries (LMICs). The World Health Organization (WHO) recommends bystander training in basic principles of first aid and victim transport; however, prevalence of bystander or layperson assistance to trauma victims in LMICs has not been well-described, and organized reviews of existing evidence for bystander training are lacking. This systematic review aims to 1) describe the prevalence of bystander or layperson aid or transport for trauma victims in the prehospital setting in LMICs and 2) ascertain impacts of bystander training interventions in these settings.A systematic search of OVID Medline, Cochrane Library, and relevant gray literature was conducted. We included 1) all studies detailing prevalence of bystander-administered aid or transport for trauma victims in LMICs and 2) all randomized controlled trials and observational studies evaluating bystander training interventions. We extracted study characteristics, interventions, and outcomes data. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.Sixty-two studies detailed prevalence of bystander transport and aid. Family members, police, and bus or taxi drivers commonly transported patients; a majority of patients, up to94%, received aid from bystanders. Twenty-four studies examined impacts of training interventions. Only one study looked at transport interventions; the remainder addressed first aid training. Interventions varied in content, duration, and target learners. Evidence was generally of low quality, but all studies demonstrated improvements in layperson knowledge and skills. Five studies reported a mortality reduction.Heterogeneity in data reporting and outcomes limited formal meta-analysis. However, this review shows high rates of bystander involvement in prehospital trauma care and transport in LMICs and highlights the need for bystander training. Bystander training in these settings is feasible and may have an important impact on meaningful outcomes such as mortality. Categories of involved bystanders varied by region and training interventions should be targeted at relevant groups. "Train the trainer" models appear promising in securing community engagement and maximizing participation. Further research is needed to examine the value of bystander transport networks in trauma.

Ketamine, a molecule of many faces, has contributed immeasurably to numerous realms of clinical practice and scientific inquiry. From anesthesia and analgesia to depression and schizophrenia, it continues to shed light on the molecular underpinnings of pain, consciousness, and the pathophysiology of neuropsychiatric disorders. In particular, research on ketamine's mechanism of action is providing new hope in the search for therapies for treatment-resistant depression and affords insights into disorders of glutamatergic dysfunction. In this Review, we will cover aspects of ketamine's synthesis, manufacturing, metabolism, pharmacology, approved and off-label indications, and adverse effects. We will also discuss the captivating history of this molecule, its influence on neuropsychiatry, and its potential to advance the fields of chemical neuroscience and neuropharmacology.

PURPOSE Photophobia is a debilitating clinical condition that disrupts the ability to use vision for everyday tasks in bright lighting conditions. The goal of the study is to develop a methodology to study the neural basis of photophobia and the contribution of the melanopic pathway to its etiology with differential chromatic responses by means of standard electroencephalographic recording equipment. METHODS We introduce and validate the approach of recording wavelength-specific electroretinographic (ERG) responses from the face electrodes of the high-density whole-head electroencephalography recording system under light-adapted conditions. RESULTS ERGs recorded in this way to whole-field chromatic stimuli exhibit striking differences between the photophobic and non-photophobic groups. The control responses were consistent with photopic intensity in peak time, and in the ordering of peak times as a function of wavelength condition, indicating a predominantly cone source of the signals. The photophobic responses, on the other hand, were substantially slowed relative to controls, with the peak times conforming to a different order as a function of wavelength condition than controls, implying that the cone response has been suppressed and that the responses derived from a different photoreceptor system consistent with mediation by melanopic retinal ganglion cells. CONCLUSIONS The results will be important for determining the neural pathways involved in photophobia and potential approaches to its treatment on the basis of this etiology.

The discovery of haloperidol catalyzed a breakthrough in our understanding of the biochemical basis of schizophrenia, improved the treatment of psychosis, and facilitated deinstitutionalization. In doing so, it solidified the role for chemical neuroscience as a means to elucidate the molecular underpinnings of complex neuropsychiatric disorders. In this Review, we will cover aspects of haloperidol's synthesis, manufacturing, metabolism, pharmacology, approved and off-label indications, and adverse effects. We will also convey the fascinating history of this classic molecule and the influence that it has had on the evolution of neuropsychopharmacology and neuroscience.

Objectives Trauma is a leading cause of morbidity and mortality worldwide, with a disproportionate burden of illness in low- and middle- income countries. This study sought to provide a proof-of-concept pilot study to evaluate the feasibility of a trauma registry in the Western Honduras Hospital. Methods A cross-sectional, observation study was performed that included all admitted, transferred, or deceased trauma patients presenting to the Western Honduras Hospital from February 4, 2019 until April 4, 2019. Descriptive statistics were utilized to describe patient demographics and injury characteristics. Results 268 patients were enrolled. The average age was 27.5 years (SD ±21.3). 10% of injuries were due to interpersonal violence. The most common mechanisms of injury were falls (33.6%) and motor vehicle collisions (MVCs) (22.4%). The mean Modified Kampala Trauma Score (M-KTS) was 12 (SD ±1.4). The mortality rate was 1.1% (N = 3). 94.5% of data points were complete. Conclusions A continuous injury surveillance system in the Western Honduras Hospital is feasible and provides valuable information. The data completeness was suboptimal, but the current data collection system may be improved via modifying and utilizing the registry form as both a clinical and data collection instrument.

Purpose To introduce the definite target volume (DTV) and evaluate dosimetric consequences of boosting dose to this region of high clinical target volume (CTV)- and low organs at risk (OAR)-probability. Methods This work defines the DTV via occupancy probability and via contraction of the CTV by margin M less any planning risk volume (PRV) volumes. The equivalence to within varying occupancy probability of the two methods is established for spherical target volumes. We estimate a margin for four radiation treatment sites based on modern images guided radiation therapy-literature utilizing repeat volumetric imaging. Based on margins and patient-specific DTV targets, the ability to dose escalate the DTV including the effects of spatial uncertainty was evaluated. We simulate delivery assuming violation of the underlying spatial uncertainty of 130%. Results Contracting the planning target volume (PTV) by M and excluding PRV volumes, the DTV ranged from 7.3 to 93.6 cc. In a brain treatment, DTV-Dmax increased to 66.8 Gy (145% of prescription isodose); in advanced lung DTV-Dmax increased to 122.2 Gy (204% of prescription isodose), in a pancreatic case DTV-Dmax was boosted up to 87.3 Gy (173% or prescription isodose), and in retroperitoneal sarcoma to 74.6 Gy (249% of prescription isodose). The high point doses were not associated with increased dose to OARs, even when considering the effects of spatial uncertainty. Simulated delivery at 130% of assumed spatial uncertainties revealed DTV-based planning can result in minor increases in OAR Dmean/Dmax of 2.7 ± 2.1 Gy/1.8 ± 2.2 Gy with duodenum Dmax > 110% of prescription isodose in the pancreatic case. These dose increases were consistent with simulation of clinical, homogenous PTV-dose distributions. Conclusion We have proposed and tested a method to deliver extremely high doses to subvolumes of target volumes in multiple treatment sites by defining a new target volume, the DTV. Based on simulated delivery, the method does not result in significant increases in dose to OARs if spatial uncertainty can be estimated.

To investigate the effect of background noise on visual summation, we measured the contrast detection thresholds for targets with or without a white noise mask in luminance contrast. The targets were Gabor patterns placed at 3° eccentricity to either the left or right of the fixation and elongated along an arc of the same radius to ensure equidistance from fixation for every point along the long axis. The task was a spatial two-alternative forced-choice (2AFC) paradigm in which the observer had to indicate whether the target was on the left or the right of the fixation. The threshold was measured at 75% accuracy with a staircase procedure. The detection threshold decreased with target length with slope −1/2 on log-log coordinates for target lengths between 30′ and 300′ half-height full-width (HHFW), defining a range of ideal matched-filter summation extending up to about 200′ (or about 16× the center width of the Gabor targets). The summation curves for different noise contrasts were shifted copies of each other. For the threshold versus mask contrast (TvN) functions, the target threshold was constant for noise levels up to about −22 dB, then increased with noise contrast to a linear asymptote on log-log coordinates. Since the “elbow” of the target threshold versus noise function is an index of the level of the equivalent noise experienced by the visual system during target detection, our results suggest that the signal-to-noise ratio was invariant with target length. We further show that a linear-nonlinear-linear gain-control model can fully account for these results with far fewer parameters than a matched-filter model.

Eye movements are an important index of the neural functions of visual information processing, decision making, visuomotor coordination, sports performance, and so forth. However, the available optical tracking methods are impractical in many situations, such as the wearing of eyeglasses or the presence of ophthalmic disorders, and this can be overcome by accurate recording of eye movements by electrooculography (EOG). In this study we recorded eye movements by EOG simultaneously with high-density electroencephalogram (EEG) recording using a 128-channel EGI electrode net at a 500-Hz sampling rate, including appropriate facial electrodes. The participants made eye movements over a calibration target consisting of a 5×5 grid of stimulus targets. The results showed that the EOG methodology allowed accurate analysis of the amplitude and direction of the fixation locations and saccadic dynamics with a temporal resolution of 500 Hz, under both cued and uncued analysis regimes. Blink responses could be identified separately and were shown to have a more complex source derivation than has previously been recognized. The results also showed that the EOG signals recorded through the EEG net can achieve results as accurate as typical optical eye-tracking devices, and also allow for simultaneous assessment of neural activity during all types of eye movements. Moreover, the EOG method effectively avoids the technical difficulties related to eye-tracker positioning and the synchronization between EEG and eye movements. We showed that simultaneous EOG/EEG recording is a convenient means of measuring eye movements, with an accuracy comparable to that of many specialized eye-tracking systems.

Purpose\ud Describing the psychometric characteristics and diagnostic accuracy of the Accelerator 4‐Alternative Forced‐Choice Flicker Test prototype (A4FTp) for detecting chronic open angle glaucoma (COAG).\ud \ud Methods\ud A4FTp measures temporally‐modulated flicker thresholds in regions of the visual field with high susceptibility to glaucomatous loss. We initially evaluated its psychometric properties on 20 normals (aged 33.8 ± 8.5 years) who were tested multiple times over a period of 3 months. All subjects underwent four repetitions for shorter (T8) and longer (T12) staircase termination criteria, to determine the most suitable threshold criterion. Four randomly selected subjects underwent a total of 10 repetitions to study test‐retest repeatability and learning effects. To determine its diagnostic accuracy, one eye of 40 participants with COAG and 38 normal controls were tested with the A4FTp in comparison with the Frequency Doubling Technology (FDT; C20‐5 programme) and iVue Spectral Domain Optical Coherence Tomography (SD‐OCT). Tests were conducted in a random order with results masked to the clinician conducting the reference ophthalmic examination. The accuracy of each test was determined by analysis of the area under the receiver operator characteristic curve (AUROC).\ud \ud Results\ud A4FTp flicker thresholds were stable, with standard deviations of only 0.52 decilog (dL) for T8, increasing to 1.32 dL for T12, and no significant flicker sensitivity threshold improvement over the 10 repeat runs. T8 was superior to T12 on several other measures, so it was used for the remaining comparisons. In terms of diagnostic accuracy, the mean AUROC for the three tests were A4FTp [T8 criterion; 0.82, 95% confidence interval (0.73–0.92)]; SD‐OCT [any RNFL parameter p < 1% level; 0.90 (0.83–0.97)]; and FDT [one or more locations missed at p < 5% level; 0.91 (0.82–0.96)]. There was no statistical difference in AUROC between A4FTp and SD‐OCT (p = 0.18) or FDT (p = 0.12). The A4FTp test duration averaged just over 2 min per eye, taking approximately one‐third of the time for completion of the HFA SITA 24‐2 algorithm (conducted as part of the reference examination) and twice the time for the suprathreshold FDT.\ud \ud Conclusion\ud Test accuracy for the A4FTp was comparable to those of the FDT and SD‐OCT for the detection of COAG. Time taken to complete the A4FTp was relatively short and initial results are promising. With further refinement, the A4FTp could have a future role in glaucoma detection.

Through epigenetic and other regulatory functions, the histone deacetylase (HDAC) family of enzymes has emerged as a promising therapeutic target for central nervous system and other disorders. Here we report on the synthesis and functional characterization of new HDAC inhibitors based structurally on tianeptine, a drug used primarily to treat major depressive disorder (MDD) that has a poorly understood mechanism of action. Since the chemical structure of tianeptine resembles certain HDAC inhibitors, we profiled the in vitro HDAC inhibitory activity of tianeptine and demonstrated its ability to inhibit the lysine deacetylase activity of a subset of class I HDACs. Consistent with a model of active site Zn2+ chelation by the carboxylic acid present in tianeptine, newly synthesized analogues containing either a hydroxamic acid or ortho-aminoanilide exhibited increased potency and selectivity among the HDAC family. This in vitro potency translated to improved efficacy in a panel of high-content imaging assays designed to assess HDAC target engagement and functional effects on critical pathways involved in neuroplasticity in both primary mouse neurons and, for the first time, human neurons differentiated from pluripotent stem cells. Most notably, tianeptinaline, a class I HDAC-selective analogue of tianeptine, but not tianeptine itself, increased histone acetylation, and enhanced CREB-mediated transcription and the expression of Arc (activity-regulated cytoskeleton-associated protein). Systemic in vivo administration of tianeptinaline to mice confirmed its brain penetration and was found to enhance contextual fear conditioning, a behavioral test of hippocampal-dependent memory. Tianeptinaline and its derivatives provide new pharmacological tools to dissect chromatin-mediated neuroplasticity underlying memory and other epigenetically related processes implicated in health and disease.

Background Advances in genomics technologies are making it increasingly feasible to characterize breeding lines that carry traits of agronomic interest. Tobacco germplasm lines that carry loci designated VAM and va have been extensively investigated due to their association with potyvirus resistance (both VAM and va) and defects in leaf surface compounds originating from glandular trichomes (VAM only). Molecular studies and classical genetic analyses are consistent with the model that VAM and va represent deletion mutations in the same chromosomal region. In this study, we used RNA-seq analysis, together with emerging tobacco reference genome sequence information to characterize the genomic regions deleted in tobacco lines containing VAM and va. Results Tobacco genotypes TI 1406 (VAM), K326-va and K326 (wild type) were analyzed using RNA-seq to generate a list of genes differentially expressed in TI 1406 and K326-va, versus the K326 control. Candidate genes were localized onto tobacco genome scaffolds and validated as being absent in only VAM, or missing in both VAM and va, through PCR analysis. These results enabled the construction of a map that predicted the relative extent of the VAM and va mutations on the distal end of chromosome 21. The RNA-seq analyses lead to the discovery that members of the cembratrienol synthase gene family are deleted in TI 1406. Transformation of TI 1406 with a cembratrienol synthase cDNA, however, did not recover the leaf chemistry phenotype. Common to both TI 1406 and K326-va was the absence of a gene encoding a specific isoform of a eukaryotic translation initiation factor (eiF4E1.S). Transformation experiments showed that ectopic expression of eiF4E1.S is sufficient to restore potyvirus susceptibility in plants possessing either the va or VAM mutant loci. Conclusions We have demonstrated the feasibility of using RNA-seq and emerging whole genome sequence resources in tobacco to characterize the VAM and va deletion mutants. These results lead to the discovery of genes underlying some of the phenotypic traits associated with these historically important loci. Additionally, initial size estimations were made for the deleted regions, and dominant markers were developed that are very close to one of the deletion junctions that defines va. Electronic supplementary material The online version of this article (10.1186/s12864-018-4839-y) contains supplementary material, which is available to authorized users.

Traumatic brain injury is an increasingly common affliction, although many of its serious repercussions are still underappreciated. A frequent consequence is the development of light-induced pain, or ‘photalgia’, which can often lead to prolonged debilitation. The mechanism underlying the sensitivity to light, however, remains unresolved. Since tissue oedema (swelling) is a common feature of traumatic brain injury, we propose that the brainstem oedema, in particular, might sensitize the brainstem trigeminal complex to signals from ocular mechanisms activated in bright light. To assess this hypothesis, we ran high-resolution Magnetic Resonance Imaging of the brainstems of concussion groups with mild and severe photalgia, without photalgia, and healthy controls. The 3D configuration of the brainstem was determined by Tensor-Based Morphometry (TBM) for each participant. The TBM revealed significant deviations in the brainstem morphology of all concussion groups, with a characteristic signature for each group. In particular, concussion without photalgia showed bilateral expansion at the pontine/medulla junction, whereas concussion with photalgia showed mid-pontine shrinkage, consistent with degeneration of nuclei of the trigeminal complex. These results support the hypothesis that brainstem shrinkage/degeneration represents a morphological substrate of the photalgic sensitization of the trigeminal pathway.

Objectives Malnutrition contributes to paediatric morbidity and mortality in disasters and complex emergencies, but summary data describing specific nutritional interventions in these settings are lacking. This systematic review aimed to characterise such interventions and their effects on paediatric mortality, anthropometric measures and serum markers of nutrition. Methods A systematic search of OVID MEDLINE, Cochrane Library and relevant grey literature was conducted. We included all randomised controlled trials and observational controlled studies evaluating effectiveness of nutritional intervention(s) on defined health outcomes in children and adolescents (0–18 years) within a disaster or complex emergency. We extracted study characteristics, interventions and outcomes data. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Results A total of 31 studies met inclusion criteria. Most were conducted in Africa (17), during periods of conflict or hunger gaps (14), and evaluated micronutrient supplementation (14) or selective feeding (10). Overall study quality was low, with only two high and four moderate quality studies. High- and medium-quality studies demonstrated positive impact of fortified spreads, ready-to-use therapeutic foods, micronutrient supplementation, and food and cash transfers. Conclusion In disasters and complex emergencies, high variability and low quality of controlled studies on paediatric malnutrition limit meaningful data aggregation. If existing research gaps are to be addressed, the inherent unpredictability of humanitarian emergencies and ethical considerations regarding controls may warrant a paradigm shift in what constitutes adequate methods. Periodic hunger gaps may offer a generalisable opportunity for robust trials, but consensus on meaningful nutritional endpoints is needed.

Earlier work by one of us examined a historical corpus of portraits and found that artists often paint the subject such that one eye is centred horizontally. If due to psychological mechanisms constraining artistic composition, this eye-centring bias should be detectable also in portraits by non-professionals. However, this finding has been questioned both on theoretical and empirical grounds. Here we tested eye-centring in a larger (N ~ = 4000) and more representative set of selfies spontaneously posted on Instagram from six world cities. In contrast with previous selfie results, the distribution of the most-centred eye position peaked almost exactly at the horizontal centre of the image and was statistically different from predictions based on realistic Monte-Carlo predictions. In addition, we observed a small but statistically reliable pseudoneglect effect as well as a preference for centring the left-eye. An eye-centring tendency appears to exist in self-portraits by non-artists.

IMPORTANCE: Strabismus is a binocular vision disorder characterized by the partial or complete inability to maintain eye alignment on the object that is the target of fixation, usually accompanied by suppression of the deviating eye and consequent 2-dimensional monocular vision. This cue has been used to infer the presence of strabismus in a substantial number of famous artists. OBJECTIVE: To provide evidence that Leonardo da Vinci had strabismus. DESIGN, SETTING, AND PARTICIPANTS: In exotropia, the divergent eye alignment is typically manifested as an outward shift in the locations of the pupils within the eyelid aperture. The condition was assessed by fitting circles and ellipses to the pupils, irises, and eyelid apertures images identified as portraits of Leonardo da Vinci and measuring their relative positions. MAIN OUTCOMES AND MEASURES: Geometric angle of alignment of depicted eyes. RESULTS: This study assesses 6 candidate images, including 2 sculptures, 2 oil paintings, and 2 drawings. The mean relative alignments of the pupils in the eyelid apertures (where divergence is indicated by negative numbers) showed estimates of −13.2° in David, −8.6° in Salvator Mundi, −9.1° in Young John the Baptist, −12.5° in Young Warrior, 5.9° in Vitruvian Man, and −8.3° in an elderly self-portrait. These findings are consistent with exotropia (t(5) = 2.69; P = .04, 2-tailed). CONCLUSIONS AND RELEVANCE: The weight of converging evidence leads to the suggestion that da Vinci had intermittent exotropia with the resulting ability to switch to monocular vision, which would perhaps explain his great facility for depicting the 3-dimensional solidity of faces and objects in the world and the distant depth-recession of mountainous scenes.

Intuition suggests that increased viewing time should allow for the accumulation of more visual information, but scant support for this idea has been found in studies of voluntary averaging, where observers are asked to make decisions based on perceived average size. In this paper we examine the dynamics of information accrual in an orientation-averaging task. With orientation (unlike intensive dimensions such as size), it is relatively safe to use an item's physical value as an approximation for its average perceived value. We displayed arrays containing eight iso-eccentric Gabor patterns, and asked six trained psychophysical observers to compare their average orientation with that of probe stimuli that were visible before, during, or only after the presentation of the Gabor array. From the relationship between orientation variance and human performance, we obtained estimates of effective set size, i.e., the number of items that an ideal observer would need to assess in order to estimate average orientation as well as our human observers did. We found that display duration had only a modest influence on effective set size. It rose from an average of ∼2 for 0.1-s displays to an average of ∼3 for 3.3-s displays. These results suggest that the visual computation is neither purely serial nor purely parallel. Computations of this nature can be made with a hybrid process that takes a series of subsamples of a few elements at a time.

The objective was to compare intensity‐modulated radiation therapy (IMRT) with 3D conformal proton therapy (3DCPT) in the treatment of cervical cancer. In particular, each technique's ability to spare pelvic bone marrow (PBM) was of primary interest in this study. A total of six cervical cancer patients (3 postoperative and 3 intact) were planned and analyzed. All plans had uniform 1.0 cm CTV‐PTV margin and satisfied the 95% PTV with 100% isodose (prescription dose=45Gy) coverage. Dose‐volume histograms (DVH) were analyzed for comparison. The overall PTV and PBM volumes were 1035.9±192.2 cc and 1151.4±198.3 cc, respectively. In terms of PTV dose conformity index (DCI) and dose homogeneity index (DHI), 3DCPT was slightly superior to IMRT with 1.00±0.001,1.01±0.02, and 1.10±0.02,1.13±0.01, respectively. In addition, 3DCPT demonstrated superiority in reducing lower doses (i.e., V30 or less) to PBM, small bowel and bladder. Particularly in PBM, average V10 and V20 reductions of 10.8% and 7.4%(p=0.001 and 0.04), respectively, were observed. However, in the higher dose range, IMRT provided better sparing (>V30). For example, in small bowel and PBM, average reductions in V45 of 4.9% and 10.0%(p=0.048 and 0.008), respectively, were observed. Due to its physical characteristics such as low entrance dose, spread‐out Bragg peak and finite particle range of protons, 3DCPT illustrated superior target coverage uniformity and sparing of the lower doses in PBM and other organs. Further studies are, however, needed to fully exploit the benefits of protons for general use in cervical cancer. PACS number: 87.55.D‐, 87.55.dk

Algorithms for direct tumor tracking in rotational cone-beam projections and for reconstruction of phase-binned 3D tumor trajectories were developed. The feasibility of the algorithm was demonstrated on a digital phantom, a physical phantom and two patients. Tracking results were obtained by comparing reference templates generated from 4DCT to rotational cone-beam projections. The 95th percentile absolute errors (e(95)) in phantom tracking results did not exceed 1.7 mm in either imager dimension, while e(95) in the patients was 3.3 mm or less. Accurate phase-binned trajectories were reconstructed in each case, with 3D maximum errors of no more than 1.0 mm in the phantoms and 2.0 mm in the patients. This work shows the feasibility of a direct tumor tracking technique for rotational images, and demonstrates that an accurate 3D tumor trajectory can be reconstructed from relatively less accurate tracking results. The ability to reconstruct the tumor's average trajectory from a 3D cone-beam CT scan on the day of treatment could allow for better patient setup and quality assurance, while direct tumor tracking in rotational projections could be clinically useful for rotational therapy such as volumetric modulated arc therapy (VMAT).

The encoding of the objects from the world around us is one of the major topics of cognitive psychology, yet the principles of object coding in the human brain remain unresolved. Beyond referring to the particular features commonly associated with objects, our ability to categorize and discuss objects in detailed linguistic propositions implies that we have access to generic concepts of each object category with well-specified boundaries between them. Consideration of the nature of generic object concepts reveals that they must have the structure of a probabilistic list array specifying the Bayesian prior on all possible features that the object can possess, together with mutual covariance matrices among the features. Generic object concepts must also be largely context independent for propositions to have communicable meaning. Although, there is good evidence for local feature processing in the occipital lobe and specific responses for a few basic object categories in the posterior temporal lobe, the encoding of the generic object concepts remains obscure. We analyze the conceptual underpinnings of the study of object encoding, draw some necessary clarifications in relation to its modality-specific and amodal aspects, and propose an analytic algebra with specific reference to functional Magnetic Resonance Imaging approaches to the issue of how generic (amodal) object concepts are encoded in the human brain.

Although a high proportion of the motion selective cells in primate motion area, MT, are disparity-selective, there is no convincing evidence for cells in this area specific to stereomotion-in-depth and the neural basis of stereomotion processing remains obscure. With functional magnetic resonance imaging (fMRI), we identify an occipito-temporal region activated by cyclopean stereomotion-in-depth stimulation, centered anterior to the human motion complex hMT+. This discovery suggests a reconceptualization of the architecture of the motion complex to incorporate the processing of motion in the third dimension.

Rules of composition in paintings form a rich probe into the principles of perceptual processing that have been discussed for centuries. These principles can be studied by controlled scientific experiments, but an alternative approach is to use the art works themselves as a database for direct analysis. This paper focuses on the analysis of composition in relation to the canvas frame. An underlying principle is the compositional pyramid rising from the bottom of the frame to a center of consciousness high on the midline, which also finds its expression in the configuration of portrait paintings. The analyses presented reveal a dominant positioning principle for one eye in a portrait to lie on the vertical axis with an unbiased accuracy of the order of +/-5%. Analysis of the vertical location shows that the dominant height is at or above the Golden Section level on the vertical axis. In general, the layout of the portrait follows the principle of the compositional pyramid, with a center of consciousness at its apex, but there are many other compositional principles at work in the corpus of portraits in general. Analysis of the portraits of particular artists reveals that special features of their work must be considered in order to identify those that do and do not conform to the eye-centering principle.

Magnetic resonance imaging (MRI)-based intracavitary brachytherapy offers several advantages over computed tomography (CT)-based brachytherapy, but many centers are unable to offer it at the time of brachytherapy because of logistic and/or financial considerations. We have implemented a method of integrating MRI into a CT-guided, high-dose-rate intracavitary brachytherapy workflow in clinics that do not have immediately available MRI capability.At our institution, patients receiving high-dose-rate intracavitary brachytherapy as a component of the definitive treatment of cervical cancer have a Smit sleeve placed during the first brachytherapy fraction in a dedicated suite with in-room CT-on-rails. After the first fraction of brachytherapy, an MRI is obtained with the Smit sleeve, but no applicator, in place. For each subsequent fraction, CT scans are coregistered to the MRI scan by the Smit sleeve. The gross target volume is defined by MRI and overlaid on the CT images for each brachytherapy treatment for dose optimization.This MRI-integrated workflow adds5 minutes to the brachytherapy session for image fusion. Our initial clinical experience suggests that this approach is feasible and results in target volume reductions compared with CT-alone brachytherapy.Our proposed combination MRI and/or CT workflow is a feasible compromise to preserve an efficient workflow while integrating MRI target delineation, and it provides many of the advantages of both MRI- and CT-based brachytherapy. The future collection and analysis of clinical data will serve to compare the proposed approach to non-MRI containing techniques.

Purpose To describe a parallelized patient-specific quality assurance (QA) program designed to ensure safety and quality in image-guided high-dose-rate brachytherapy in an integrated computed tomography (CT)–on-rails brachytherapy suite. Materials and Methods A patient-specific QA program has been modified for the image-guided brachytherapy (IGBT) program in an integrated CT-on-rails brachytherapy suite. In the modification of the QA procedures of Task Group-59, the additional patient-specific QA procedures are included to improve rapid IGBT workflow with applicator placement, imaging, planning, treatment, and applicator removal taking place in one room. Results The IGBT workflow is partitioned into two groups of tasks that can be performed in parallel by two or more staff members. One of the unique components of our implemented workflow is that groups work together to perform QA steps in parallel and in series during treatment planning and contouring. Coordinating efforts in this systematic way enable rapid and safe brachytherapy treatment while incorporating 3-dimensional anatomic variations between treatment days. Conclusions Implementation of these patient-specific QA procedures in an integrated CT-on-rails brachytherapy suite ensures confidence that a rapid workflow IGBT program can be implemented without sacrificing patient safety or quality and deliver highly-conformal dose to target volumes. These patient-specific QA components may be adapted to other IGBT environments that seek to provide rapid workflow while ensuring quality.

To study the spatial extent and shape of the binocular disparity mechanisms subserving depth perception, we employ the spatial summation paradigm of contrast threshold for front/back depth discrimination at a fixed binocular disparity. The stimuli were Gabor patches with disparity set at either 4 or 8 arcmin and spatial frequency set at an optimal value of 4 cy/deg. Contrast threshold was measured as a function of length and width of the Gabor patches to determine the aspect ratio of greatest efficiency. The space constant of the Gaussian envelope varied between 0.0375 degrees and 0.9 degrees in either vertical or horizontal directions, or both simultaneously. For vertical elongation of the Gabor patches, discrimination sensitivity improved by 4-6 dB for a doubling of the length of the Gabor patches, then reduced more slowly as the length further increased. However, extending the Gabor patches horizontally across cycles produced little or no sensitivity improvement. Instead, discrimination performance collapsed in a fashion that is incompatible with many models of disparity processing. The results imply that the main mechanisms subserving stereoscopic depth discrimination are vertically elongated for vertical-bar Gabors and encounter special difficulties integrating horizontal disparity information. Disparity discrimination sensitivity for very small targets was also much greater than predicted by the single-mechanism fit, implying the presence of a second, independent mechanism with a very small summation field, which may underlie the fine stereoscopic processing system.

Humans often create and appreciate visual symmetry in their environment, and the underlying brain mechanisms have been a topic of increasing interest. Here, symmetric versus random dot stimuli produced robust functional MRI (fMRI) activity in higher-order regions of human visual cortex (especially areas V3A, V4, V7, and LO) but little activity elsewhere in brain. This fMRI response was found both with and without attention controls. Moreover, it was highly correlated with the psychophysical perception of symmetry. Similar symmetry responses were found by using line-based and dot stimuli and were found at a wide range of stimulus sizes and geometric configurations. Weaker symmetry responses were found in analogous regions of macaque visual cortex by using fMRI techniques with higher sensitivity. This evidence suggests that visual symmetry is specifically enhanced in the human brain, but that the underlying neural mechanisms may nevertheless be resolvable in nonhuman primates.

Symmetry along one or more axes is a key property of objects and biological organisms. We report on a bilateral visual region of occipital cortex that responds strongly to the presence of multiple symmetries in the viewed image. The stimuli consisted of random dots organized in fourfold and onefold mirror-symmetric patterns, against random control stimuli. The contrast between symmetric and random patterns produced negligible or inconsistent activation of the primary visual projection area V1 or of other medial occipital projection areas. However, there was strong symmetry-specific activation in extra-retinotopic lateral occipital cortex. The high level of activation in this region of cortex may represent part of a general class of computations that require integration of information across a large span of the visual field.

This analysis addresses the issue that texture properties are defined on ensembles of possible textures, while psychophysical judgments of texture properties must be made on individual texture samples, or regions of uniform texture within a larger texture field. Since the basic discrimination task requires comparison of two sample images (or regions) specified by different ensemble rules, the viewer is thus required to compare the estimates of their ensemble statistics of single textures. This paper develops a theory of texture discrimination incorporating a roving local sampling window that allows the visual system to derive an estimate of the ensemble statistics over the window from any particular texture image, without the need to present multiple samples for evaluation. This approach to texture explains how we can have a clear sense that two patterns derive from different statistical generation rules even though we see only one example of each type. In providing the theoretical basis for texture discrimination of individual samples, this analysis goes beyond previous work to account for our intuitive sense that we can estimate the generation rule underlying particular textures. It also analyzes the decision process for discriminating texture boundaries in extended images, defining a novel “Gregorian attractor” that replaces and extends standard Bayesian decision rules.

We investigated the random variability of BOLD (blood oxygen level dependent) activation during rest, or null-hypothesis, conditions in which the observers were neither receiving controlled sensory stimuli nor performing cognitive tasks. The data indicate that the distributions for the BOLD variation across space are skewed, with non-Gaussian tails, while the distributions for the temporal variation within individual voxels are predominantly Gaussian. The proportion of voxels that show non-Gaussian properties is highly correlated with the magnitude of head movement of the observers. In all observers, the white matter showed less variability than the gray matter. The distributions for the spatial and the temporal variations are robust across observers despite differences in the data acquisition methods (EPI vs. spiral) and magnetic field strength (1.5 vs. 3 T). In most cases, the non-Gaussian tails of the spatial distribution can be eliminated by normalizing the amplitude in each voxel to its standard deviation before cumulating across voxels. We therefore recommend such a normalization procedure before any data manipulations are performed on fMRI data.

In forced-choice detection, incorrect responses are routinely ascribed to internal noise, because experienced psychophysical observers do not act as if they have a sensory threshold, below which all perceived intensities would be identical. To determine whether inexperienced observers have sensory thresholds, we examined psychometric functions (percent correct versus log contrast) for detection and detection in full-screen, dynamic visual noise. Over five days, neither type of psychometric function changed shape, but both shifted leftwards, indicating increased sensitivity. These results are not consistent with a lowered sensory threshold, which would decrease psychometric slope. Our results can be understood within the context of Dosher and Lu's "stochastic" perceptual template model [Vis. Res.40, 1269 (2000)], augmented to allow intrinsic uncertainty. Specifically, our results are consistent with a combination of reduced internal additive noise and improved filtering of external noise.

To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach.MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated.By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery.MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

Purpose The purposes of this analysis are to report a modern series of severe gastrointestinal toxic effects after definitive chemoradiotherapy in the treatment of locally advanced cervical cancer at our institution and to review the existing literature on factors that contribute to toxic effects and preventive strategies and management. Methods Our institution’s cervical cancer cohort was evaluated for patients with late grade 3 to 4 gastrointestinal toxic effects who were retrospectively reviewed for clinical or dosimetric parameters that could have contributed to late toxic effects. A review of the published literature was performed to identify factors associated with late toxic effects, prophylactic agents, and corrective therapy. Findings Five of 85 patients were identified as having late grade 3 to 4 gastrointestinal toxic effects with a median follow-up of 13.3 months. Two of 5 patients developed late grade 3 toxic effects, and 3 of 5 developed late grade 4 toxic effects. Three of the 5 patients reviewed ultimately required permanent colostomies. Cumulative median dose (in equivalent dose in 2-Gy fractions) of clinical target volume to the hottest 90% was 107.2 Gy, rectal dose to the hottest 2 cc (D2cc) was 81.7 Gy, sigmoid D2cc was 61.7 Gy, and bladder D2cc was 79.5 Gy. No patient had evidence of disease recurrence in the pelvis. One patient developed oligometastatic disease in the suprarenal gland and was successfully salvaged with adrenalectomy. Implications Despite its risk of toxic effects, intracavitary brachytherapy remains a critical component of the treatment of locally advanced cervical cancer. Even with modern radiotherapy planning and delivery techniques, extra attention is warranted to continue to strive for optimal outcomes.