PTBP1 controls intestinal epithelial regeneration through post-transcriptional regulation of gene expression.

The intestinal epithelial regeneration is driven by intestinal stem cells under homeostatic conditions. Differentiated intestinal epithelial cells, such as Paneth cells, are capable of acquiring multipotency and contributing to regeneration upon the loss of intestinal stem cells. Paneth cells also support intestinal stem cell survival and regeneration. We report here that depletion of an RNA-binding protein named polypyrimidine tract binding protein 1 (PTBP1) in mouse intestinal epithelial cells causes intestinal stem cell death and epithelial regeneration failure. Mechanistically, we show that PTBP1 inhibits neuronal-like splicing programs in intestinal crypt cells, which is critical for maintaining intestinal stem cell stemness. This function is achieved at least in part through promoting the non-productive splicing of its paralog PTBP2. Moreover, PTBP1 inhibits the expression of an AKT inhibitor PHLDA3 in Paneth cells and permits AKT activation, which presumably maintains Paneth cell plasticity and function in supporting intestinal stem cell niche. We show that PTBP1 directly binds to a CU-rich region in the 3' UTR of Phlda3, which we demonstrate to be critical for downregulating the mRNA and protein levels of Phlda3. Our results thus reveal the multifaceted in vivo regulation of intestinal epithelial regeneration by PTBP1 at the post-transcriptional level.

Preclinical Models of Anal Cancer Combined-Modality Therapy.

INTRODUCTION: There have been no significant changes in anal cancer treatment options in 4 decades. In this study, we highlight two preclinical models designed to assess anal cancer treatments. MATERIALS AND METHODS: Transgenic K14E6/E7 mice were treated with 7, 12-dimethylbenz(a)anthracene until anal tumors developed. Mice were treated with localized radiation in addition to chemotherapy (combined-modality therapy [CMT]) and compared to no treatment control (NTC). K14E6/E7 mouse anal spheroids with and without Pik3ca mutations were isolated and treated with vehicle, LY3023414 (LY3) (a drug previously shown to be effective in cancer prevention), CMT, or CMT + LY3. RESULTS: In the in vivo model, there was a significant increase in survival in the CMT group compared to the NTC group (P = 0.0392). In the ex vivo model, there was a significant decrease in the mean diameter of CMT and CMT + LY3-treated spheroids compared to vehicle (P ≤ 0.0001). For LY3 alone compared to vehicle, there was a statistically significant decrease in spheroid size in the K14E6/E7 group without mutation (P = 0.0004). CONCLUSIONS: We have provided proof of concept for two preclinical anal cancer treatment models that allow for the future testing of novel therapies for anal cancer.

Mercury (Hg) concentration in fish commercialized in the São Luís fish market (MA) and potential exposure of consumers.

Fish consumption is the main path of human exposure to Hg and may represent a risk to public health, even with low Hg concentrations in fish, if consumption rates are high. This study quantifies, for the first time, the Hg concentrations in nine most commercialized species in the São Luís (MA) fish market, where fish consumption is high, and estimates human exposure. Average Hg concentrations were highest in carnivorous species, yellow hake (Cynoscion acoupa) (0.296 mg kg-1), the Atlantic croaker (Micropogonias undulatus) (0.263 mg kg-1), whereas lowest concentrations were recorded in iliophagous Mullets (Mugil curema) (0.021 mg kg-1) and the Shorthead drum Larimus breviceps (0.025 mg kg-1). Significant correlations were observed between Hg concentrations and fish length in two species: the Coco-Sea catfish (Bagre bagre) and the Atlantic bumper (Chloroscombrus crysurus), but not in the other species, since they presented relatively uniform size of individuals and/or a small number of samples. Risk coefficients, despite the relatively low Hg concentrations, suggest that consumers should limit their consumption of Yellow hake and Atlantic croaker, as they can present some risk to human health (EDI > RfD and THQ > 1), depending on the frequency of their consumption and the consumer's body weight.

ProteoDisco: a flexible R approach to generate customized protein databases for extended search space of novel and variant proteins in proteogenomic studies.

SUMMARY: We present an R-based open-source software termed ProteoDisco that allows for flexible incorporation of genomic variants, fusion genes and (aberrant) transcriptomic variants from standardized formats into protein variant sequences. ProteoDisco allows for a flexible step-by-step workflow allowing for in-depth customization to suit a myriad of research approaches in the field of proteogenomics, on all organisms for which a reference genome and transcript annotations are available. AVAILABILITY AND IMPLEMENTATION: ProteoDisco (R package version ≥ 1.0.0) is available on Bioconductor at https://doi.org/doi:10.18129/B9.bioc.ProteoDisco and from https://github.com/ErasmusMC-CCBC/ProteoDisco/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Retrograde labeling correlates with motor unit number estimation in rapid-stretch nerve injury.

INTRODUCTION/AIMS: Rapid-stretch nerve injuries represent a substantial treatment challenge. No study has examined motor neuron connection after rapid-stretch injury. Our objective in this study was to characterize the electrophysiological properties of graded rapid-stretch nerve injury and assess motor neuron health using retrograde labeling and muscle adenosine triphosphatase (ATPase) histology. METHODS: Male C57BL/6 mice (n = 6 per group) were rapid-stretch injured at four levels of severity: sham injury, stretch within elastic modulus, inelastic deformation, and stretch rupture. Serial compound muscle action potential (CMAP) and motor unit number estimation (MUNE) measurements were made for 48 days, followed by retrograde labeling and muscle ATPase histology. RESULTS: Elastic injuries showed no durable abnormalities. Inelastic injury demonstrated profound initial reduction in CMAP and MUNE (P < .036) on day 2, with partial recovery by day 14 after injury (CMAP: 40% baseline, P = .003; MUNE: 55% baseline, P = .033). However, at the experimental endpoint, CMAP had recovered to baseline with only limited improvement in MUNE. Inelastic injury led to reduced retrograde-labeled neurons and grouped fiber type histology. Rupture injury had severe and nonrecovering electrophysiological impairment, dramatically reducing labeled neurons (P = .005), and atrophic or type 1 muscle fibers. There was an excellent correlation between MUNE and retrograde-labeled tibial motor neurons across injury severities (R2  = 0.96). DISCUSSION: There was no significant electrophysiological derangement in low-severity injuries but there was recoverable conduction block in inelastic injury with slow recovery, potentially due to collateral sprouting. Rupture injuries yielded permanent failure of injured axons to reinnervate. These results provide insight into the pathophysiology of clinical injuries and recovery.

Surgical Site Infections in Colorectal Resections: What is the Cost?

INTRODUCTION: Although surgical site infections (SSIs) associated with colectomy are tracked by the National Healthcare Safety Network/Center for Disease Control, untracked codes, mainly related to patients undergoing proctectomy, are not. These untracked codes are performed less often yet they may be at a greater risk of SSI due to their greater complexity. Determining the impact and predictors of SSI are critical in the development of quality improvement initiatives. METHODS: Following an institutional review board approval, National Surgery Quality Improvement Program, institutional National Surgery Quality Improvement Program, and financial databases were queried for tracked colorectal resections and untracked colorectal resections (UCR). National data were obtained for January 2019-December 2019, and local procedures were identified between January 2013 and December 2019. Data were analyzed for preoperative SSI predictors, operative characteristics, outcomes, and 30-day postdischarge costs (30dPDC). RESULTS: Nationally, 71,705 colorectal resections were identified, and institutionally, 2233 patients were identified. UCR accounted for 7.9% nationally and 11.8% of all colorectal resections institutionally. Tracked colorectal resection patients had a higher incidence of SSI predictors including sepsis, hypoalbuminemia, coagulopathy, hypertension, and American Society of Anesthesiologists class. UCR patients had a higher rate of SSIs [12.9% (P < 0.001), 15.2% (P = 0.064)], readmission, and unplanned return to the operating room. Index hospitalization and 30dPDC were significantly higher in patients experiencing an SSI. CONCLUSIONS: SSI was associated with nearly a two-fold increase in index hospitalization costs and six-fold in 30dPDC. These data suggest opportunities to improve hospitalization costs and outcomes for patients undergoing UCR through protocols for SSI reduction and preventing readmissions.

Development of skeletal muscle fibrosis in a rodent model of cancer cachexia.

Cachexia is characterized by losses in lean body mass and its progression results in worsened quality of life and exacerbated outcomes in cancer patients. However, the role and impact of fibrosis during the early stages and development of cachexia in under-investigated. The purpose of this study was to determine if fibrosis occurs during cachexia development, and to evaluate this in both sexes. Female and male C57BL6/J mice were injected with phosphate-buffered saline or Lewis Lung Carcinoma (LLC) at 8-week of age, and tumors were allowed to develop for 1, 2, 3, or 4 weeks. 3wk and 4wk female tumor-bearing mice displayed a dichotomy in tumor growth and were reassigned to high tumor (HT) and low tumor (LT) groups. In vitro analyses were also performed on cocultured C2C12 and 3T3 cells exposed to LLC conditioned media. Immunohistochemistry and quantitative polymerase chain reaction (qPCR) analysis were used to investigate fibrosis and fibrosis-related signaling in skeletal muscle. Collagen deposition in skeletal muscle was increased in the 1wk, LT, and HT groups in female mice. However, collagen deposition was only increased in the 4wk group in male mice. In general, female mice displayed earlier alterations in extracellular matrix (ECM)-related genes beginning at 1wk post-LLC injection. Whereas this was not seen in males. While overall tumor burden is tightly correlated to cachexia development in both sexes, fibrotic development is not. Male mice did not exhibit early-stage alterations in ECM-related genes contrary to what was noted in female mice.

Ineffectiveness of Paramedic Naloxone Administration as a Standalone Metric for Community Opioid Overdoses and the Increasing Use of Naloxone by Community Members.

INTRODUCTION: With Canada's growing opioid crisis, many communities are attempting to monitor cases in real-time. Paramedic Naloxone Administration (PNA) has become a common metric for monitoring overdoses. We evaluate whether the use of naloxone administration counts represents an effective monitoring tool for community opioid overdoses. METHODS: The electronic ambulance call report database of Peterborough Paramedics (Ontario, Canada) was examined. De-identified records from 2016-2019 with problem codes of "Opioid Overdose", along with all patients documented as receiving naloxone were extracted. Chi-square and Bonferroni-adjusted post hoc proportion tests were used for comparison of counts. RESULTS: 558 opioid overdoses were identified, 124 (22%) of which had PNA documented, 181(32%) had naloxone prior to arrival documented and 264 (47%) received no naloxone. Over the three years, the annual number of overdose cases increased, while the proportion of patients receiving PNA decreased significantly each year. PNA was also associated with calls in a residence. Naloxone was administered by a non-paramedic in 262 cases, with 181 of these identified as opioid overdoses and was more common in later years and in cases occurring in public places. CONCLUSION: PNA calls did not account for a significant percentage of opioid overdoses attended to by paramedics. The strong association between PNA and call location being a residence, along with increasing use of community naloxone kits, may cause certain populations to be under-represent if PNA is used as a standalone metric. The decreasing association with time may also lead to a falsely improving metric further reducing its effectiveness. Thus, PNA when used alone may no longer be a suitable metric for opioid overdose tracking.

Modified nucleotides may have enhanced early RNA catalysis.

The modern version of the RNA World Hypothesis begins with activated ribonucleotides condensing (nonenzymatically) to make RNA molecules, some of which possess (perhaps slight) catalytic activity. We propose that noncanonical ribonucleotides, which would have been inevitable under prebiotic conditions, might decrease the RNA length required to have useful catalytic function by allowing short RNAs to possess a more versatile collection of folded motifs. We argue that modified versions of the standard bases, some with features that resemble cofactors, could have facilitated that first moment in which early RNA molecules with catalytic capability began their evolutionary path toward self-replication.

IMRT QA result prediction via MLC transmission decomposition.

BACKGROUND: Quality assurance measurement of IMRT/VMAT treatment plans is resource intensive, and other more efficient methods to achieve the same confidence are desirable. PURPOSE: We aimed to analyze treatment plans in the context of the treatment planning systems that created them, in order to predict which ones will fail a standard quality assurance measurement. To do so, we sought to create a tool external to the treatment planning system that could analyze a set of MLC positions and provide information that could be used to calculate various evaluation metrics. METHODS: The tool was created in Python to read in DICOM plan files and determine the beam fluence fraction incident on each of seven different zones, each classified based on the RayStation MLC model. The fractions, termed grid point fractions, were validated by analyzing simple test plans. The average grid point fractions, over all control points for 46 plans were then computed. These values were then compared with gamma analysis pass percentages and median dose differences to determine if any significant correlations existed. RESULTS: Significant correlation was found between the grid point fraction metrics and median dose differences, but not with gamma analysis pass percentages. Correlations were positive or negative, suggesting differing model parameter value sensitivities, as well as potential insight into the treatment planning system dose model. CONCLUSIONS: By decomposing MLC control points into different transmission zones, it is possible to create a metric that predicts whether the analyzed plan will pass a quality assurance measurement from a dose calculation accuracy standpoint. The tool and metrics developed in this work have potential applications in comparing clinical beam models or identifying their weak points. Implementing the tool within a treatment planning system would also provide more potential plan optimization parameters.

AAPM medical physics practice guideline 13.a: HDR brachytherapy, part A.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines (MPPGs) will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: (1) Must and must not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. (2) Should and should not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM's Executive Committee April 28, 2022.

A dependent Bayesian Dirichlet process model for source apportionment of particle number size distribution.

The relationship between particle exposure and health risks has been well established in recent years. Particulate matter (PM) is made up of different components coming from several sources, which might have different level of toxicity. Hence, identifying these sources is an important task in order to implement effective policies to improve air quality and population health. The problem of identifying sources of particulate pollution has already been studied in the literature. However, current methods require an a priori specification of the number of sources and do not include information on covariates in the source allocations. Here, we propose a novel Bayesian nonparametric approach to overcome these limitations. In particular, we model source contribution using a Dirichlet process as a prior for source profiles, which allows us to estimate the number of components that contribute to particle concentration rather than fixing this number beforehand. To better characterize them we also include meteorological variables (wind speed and direction) as covariates within the allocation process via a flexible Gaussian kernel. We apply the model to apportion particle number size distribution measured near London Gatwick Airport (UK) in 2019. When analyzing this data, we are able to identify the most common PM sources, as well as new sources that have not been identified with the commonly used methods.

An illustration of model agnostic explainability methods applied to environmental data.

Historically, two primary criticisms statisticians have of machine learning and deep neural models is their lack of uncertainty quantification and the inability to do inference (i.e., to explain what inputs are important). Explainable AI has developed in the last few years as a sub-discipline of computer science and machine learning to mitigate these concerns (as well as concerns of fairness and transparency in deep modeling). In this article, our focus is on explaining which inputs are important in models for predicting environmental data. In particular, we focus on three general methods for explainability that are model agnostic and thus applicable across a breadth of models without internal explainability: "feature shuffling", "interpretable local surrogates", and "occlusion analysis". We describe particular implementations of each of these and illustrate their use with a variety of models, all applied to the problem of long-lead forecasting monthly soil moisture in the North American corn belt given sea surface temperature anomalies in the Pacific Ocean.

Characterization of imaging performance of a novel helical kVCT for use in image-guided and adaptive radiotherapy.

ClearRT helical kVCT imaging for the Radixact helical tomotherapy system recently received FDA approval and is available for clinical use. The system is intended to enhance image fidelity in radiation therapy treatment planning and delivery compared to the prior MV-based onboard imaging approach. The purpose of this work was to characterize the imaging performance of this system and compare this performance with that of clinical systems used in image-guided and/or adaptive radiotherapy (ART) or computed tomography (CT) simulation, including Radixact MVCT, TomoTherapy MVCT, Varian TrueBeam kV OBI CBCT, and the Siemens SOMATOM Definition Edge kVCT. A CT image quality phantom was scanned across clinically relevant acquisition modes for each system to evaluate image quality metrics, including noise, uniformity, contrast, spatial resolution, and CT number linearity. Similar noise levels were observed for ClearRT and Siemens Edge, whereas noise for the other systems was ∼1.5-5 times higher. Uniformity was best for Siemens Edge, whereas most scans for ClearRT exhibited a slight "cupping" or "capping" artifact. The ClearRT and Siemens Edge performed best for contrast metrics, which included low-contrast visibility and contrast-to-noise ratio evaluations. Spatial resolution was best for TrueBeam and Siemens Edge, whereas the three kVCT systems exhibited similar CT number linearity. Overall, these results provide an initial indication that ClearRT image quality is adequate for image guidance in radiotherapy and sufficient for delineating anatomic structures, thus enabling its use for ART. ClearRT also showed significant improvement over MVCT, which was previously the only onboard imaging modality available on Radixact. Although the acquisition of these scans does come at the cost of additional patient dose, reported CTDI values indicate a similar or generally reduced machine output for ClearRT compared to the other systems while maintaining comparable or improved image quality overall.

Using 4D dose accumulation to calculate organ-at-risk dose deviations from motion-synchronized liver and lung tomotherapy treatments.

Tracking systems such as Radixact Synchrony change the planned delivery of radiation during treatment to follow the target. This is typically achieved without considering the location changes of organs at risk (OARs). The goal of this work was to develop a novel 4D dose accumulation framework to quantify OAR dose deviations due to the motion and tracked treatment. The framework obtains deformation information and the target motion pattern from a four-dimensional computed tomography dataset. The helical tomotherapy treatment plan is split into 10 plans and motion correction is applied separately to the jaw pattern and multi-leaf collimator (MLC) sinogram for each phase based on the location of the target in each phase. Deformable image registration (DIR) is calculated from each phase to the references phase using a commercial algorithm, and doses are accumulated according to the DIR. The effect of motion synchronization on OAR dose was analyzed for five lung and five liver subjects by comparing planned versus synchrony-accumulated dose. The motion was compensated by an average of 1.6 cm of jaw sway and by an average of 5.7% of leaf openings modified, indicating that most of the motion compensation was from jaw sway and not MLC changes. OAR dose deviations as large as 19 Gy were observed, and for all 10 cases, dose deviations greater than 7 Gy were observed. Target dose remained relatively constant (D95% within 3 Gy), confirming that motion-synchronization achieved the goal of maintaining target dose. Dose deviations provided by the framework can be leveraged during the treatment planning process by identifying cases where OAR doses may change significantly from their planned values with respect to the critical constraints. The framework is specific to synchronized helical tomotherapy treatments, but the OAR dose deviations apply to any real-time tracking technique that does not consider location changes of OARs.

The effect of autologous repair and voluntary wheel running on force recovery in a rat model of volumetric muscle loss.

NEW FINDINGS: What is the central question of this study? Following large traumatic loss of muscle tissue (volumetric muscle loss; VML), permanent functional and cosmetic deficits present themselves and regenerative therapies alone have not been able to generate a robust regenerative response: how does the addition of rehabilitative therapies affects the regenerative response? What is the main finding and its importance? Using exercise along with autologous muscle repair, we demonstrated accelerated muscle force recovery response post-VML. The accentuated force recovery 2 weeks post-VML would allow patients to return home sooner than allowed with current therapies. ABSTRACT: Skeletal muscle can regenerate from damage but is overwhelmed with extreme tissue loss, known as volumetric muscle loss (VML). Patients suffering from VML do not fully recover force output in the affected limb. Recent studies show that replacement tissue (i.e., autograph) into the VML defect site plus physical activity show promise for optimizing force recovery post-VML. The purpose of this study was to measure the effects of autologous repair and voluntary wheel running on force recovery post-VML. Thirty-two male Sprague-Dawley rats had 20% of their left tibialis anterior (LTA) excised then replaced and sutured into the intact muscle (autologous repair). The right tibialis anterior (RTA) acted as the contralateral control. Sixteen rats were given free access to a running wheel (Wheel) whereas the other 16 remained in a cage with the running wheel locked (Sed). At 2 and 8 weeks post-VML, the LTA underwent force testing; then the muscle was removed and morphological and gene expression analysis was conducted. At 2 weeks post-injury, normalized LTA force was 58% greater in the Wheel group compared to the Sed group. At 8 weeks post-VML, LTA force was similar between the Wheel and Sed groups but was still lower than the uninjured RTA. Gene expression analysis at 2 weeks post-VML showed the wheel groups had lower mRNA content of interleukin (IL)-1ß, IL-6 and tumour necrosis factor α compared to the Sed group. Overall, voluntary wheel running promoted early force recovery, but was not sufficient to fully restore force. The accentuated early force recovery is possibly due to a more pro-regenerative microenvironment.

Trainee Experience in Simulation-Based Education of Open Vascular Surgery.

BACKGROUND: Simulation continues to be an important adjunct to vascular surgery training, yet the optimal implementation of simulation to complement conventional surgical training continues to evolve. This study aims to find areas for improvement in current simulation-based training of open vascular skills by characterizing the experience of vascular trainees attending a national simulation-based course. METHOD: This was a survey study conducted at the simulation course of the Annual UCLA/SVS Symposium: A Comprehensive Review and Update of What's New in Vascular and Endovascular Surgery, a national vascular surgery meeting. The survey consisted of 17 questions and was administered on paper or electronically via the Audience Response System, before the start of the course. The survey assessed the participants' experience in formal training, simulation training, and comfort with open surgical procedures. RESULTS: Between 2013 and 2018, the survey was completed by 150 participants of which 65% were vascular fellows. Only 48% of the participants had formal training in suturing and surgical instruments. Most participants had formal training in basic vascular techniques and advanced vascular operations. In 71%, simulation was incorporated into basic technique training and 60% in open surgical training. Simulation training was most commonly utilized in learning anastomotic techniques and open abdominal aortic aneurysm repair. Simulation skills were deemed translatable to the operating room by 59% of participants. Most participants were comfortable performing open vascular procedures. However, 68% of participants were uncomfortable performing an abdominal aortic aneurysm repair. CONCLUSIONS: There continues to be a significant portion of trainees who do not undergo a simulation-based education. Current simulation training is being targeted to meet trainee needs in open vascular surgery, specifically open aneurysm repair. Nonetheless, trainees continue to have doubts regarding applicability of simulation-based skills to the operating theater. Further studies investigating access to simulation education as well as its translatability are needed.

Technical note: On the impact of the kV imaging configuration on doses from planar images during motion-synchronized treatments on Radixact®.

Kilovoltage radiographs are acquired during motion-synchronized treatments on Radixact to localize the tumor during the treatment. Several previous publications have provided estimates of patient dose from these planar radiographs. However, a recent hardware update changed several aspects of the kV imaging system, including a new X-ray tube, an extended source-to-axis distance (SAD), and a larger field size. This is denoted the extended configuration. The purpose of this work was to assess the impact of the configuration change on patient dose from these procedures. Point doses in water were measured using the TG-61 protocol for tube potentials between 100 and 140 kVp for both the standard and extended configurations under the same water tank setup. Comparisons were made for equal mAs since the same protocols (kVp, mAs) will be used for both configurations. In comparison to the standard configuration, doses per mAs from the extended configuration were found to be ~66% less and falloff less steep due to the increased SAD. However, a larger volume of tissue is irradiated due to the larger field size. Beam quality for a given tube potential was the same as determined by half-value layer measurements. Both kV configurations are available from the vendor, therefore, the values in this work can be used to compare values previously published in the literature for the standard configuration or to intercompare doses from these two system configurations.

Effects of variable-width jaw motion on beam characteristics for Radixact Synchrony®.

PURPOSE: Radixact Synchrony corrects for target motion during treatment by adjusting the jaw and MLC positions in real time. As the jaws move off axis, Synchrony attempts to adjust for a loss in output due to the un-flattened 6 MV beam by increasing the jaw aperture width. The purpose of this work was to assess the impact of the variable-width aperture on delivered dose using measurements and simulations. METHODS: Longitudinal beam profile measurements were acquired using an Edge diode with static gantry. Jaw-offset peak, width, and integral factors were calculated for profiles with the jaws in the extreme positions using both variable-width (Synchrony) and fixed-width apertures. Treatment plans with target motion and compensation were compared to planned doses to study the impact of the variable aperture on volumetric dose. RESULTS: The jaw offset peak factor (JOPF) for the Synchrony jaw settings were 0.964 and 0.983 for the 1.0- and 2.5-cm jaw settings, respectively. These values decreased to 0.925 and 0.982 for the fixed-width settings, indicating that the peak value of the profile would decrease by 7.5% compared to centered if the aperture width was held constant. The IMRT dose distributions reveal similar results, where gamma pass rates are above tolerance for the Synchrony jaw settings but fall significantly for the fixed-width 1-cm jaws. CONCLUSIONS: The variable-width behavior of Synchrony jaws provides a larger output correction for the 1-cm jaw setting. Without the variable-aperture correction, plans with the 1-cm jaw setting would underdose the target if the jaws spend a significant amount of time in the extreme positions. This work investigated the change in delivered dose with jaws in the extreme positions, therefore overall changes in dose due to offset jaws are expected to be less for composite treatment deliveries.

Impact of a Multiplexed Polymerase Chain Reaction Panel on Identifying Diarrheal Pathogens in Hematopoietic Cell Transplant Recipients.

BACKGROUND: Diarrhea is common and associated with substantial morbidity among hematopoietic cell transplant (HCT) recipients, but the etiology is often not identified. Multiplexed polymerase chain reaction (PCR) assays increase the detection of diarrheal pathogens, but the impact of this technology in this population has not been evaluated. METHODS: Our center replaced stool cultures and other conventional microbiologic methods with the FilmArray Gastrointestinal Panel (GI PCR) in June 2016. We reviewed all adult patients who received an HCT from June 2014-May 2015 (pre-GI PCR, n = 163) and from June 2016-May 2017 (post-GI PCR, n = 182) and followed them for 1 year after transplantation. Clostridioides difficile infection was diagnosed by an independent PCR test in both cohorts. RESULTS: The proportion of patients with ≥1 identified infectious diarrheal pathogen increased from 25% to 37% after implementation of GI PCR (P = .01). Eight patients (5%) in the pre-GI PCR cohort tested positive for a pathogen other than C. difficile versus 49 patients (27%) in the post-GI PCR cohort (P < .001). The most common non-C. difficile diarrheal pathogens in the post-GI PCR cohort were enteropathogenic Escherichia coli (n = 14, 8%), norovirus (n = 14, 8%), and Yersinia enterocolitica (n = 7, 4%). The percentage of diarrheal episodes with an identified infectious etiology increased from 14% to 23% (P = .001). Median total costs of stool testing per patient did not increase (pre: $473; post: $425; P = .25). CONCLUSIONS: Infectious etiologies of diarrhea were identified in a higher proportion of HCT recipients after replacing conventional stool testing with a multiplexed PCR assay, without an increase in testing costs.