Publications by authors named "Kyle A"

Ultrasound-guided erector spinae plane block (ESPB) has emerged as a valuable technique in pain management. Though frequently used in chronic and postoperative pain, it remains underutilized in the emergency department (ED) setting. In particular, this block has become attractive because it is rapid, safe, and efficacious for a variety of different pain syndromes that are commonly encountered in the emergency department setting.

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Background: The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes.

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Background/aim: The aim of this study was to develop an enhanced intestinal toxicity assay with three outputs assessing proliferation, villi morphology and DNA damage after irradiation.

Materials And Methods: Whole 5 cm jejunal lengths were collected from mice following total body x-ray irradiation (0-15 Gy) at 0-84 h. Tissues were wrapped into swirls for cryopreservation and immunohistochemically stained for EdU, CD31, and γH2AX.

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Inhibitors of DNA-dependent protein kinase (PRKDC; DNA-PK) sensitize cancers to radiotherapy and DNA-damaging chemotherapies, with candidates in clinical trials. However, the degree to which DNA-PK inhibitors also sensitize normal tissues remains poorly characterized. In this study, we compare tumor growth control and normal tissue sensitization following DNA-PK inhibitors in combination with radiation and etoposide.

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The effectiveness of radiotherapy depends on the sensitivities of 'normal' and cancer cells to the administered radiation dose. Increasing the radiosensitivity of cancers by inhibiting DNA damage repair is a goal of much current research, however success depends on avoiding concomitant sensitization of normal tissues inevitably irradiated during therapy. In this study we investigated the mechanisms of radiosensitization for DNA-PK and PARP inhibitors by examining the impacts on proliferating vs quiescent cell populations.

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Article Synopsis
  • - The study investigates the oxygen depletion hypothesis to explain how FLASH-radiotherapy (FLASH-RT) protects normal tissues while maintaining tumor control, focusing on the DNA Damage Response (DDR) in 3D multicellular spheroids.
  • - Experiments were conducted using a Truebeam linear accelerator on spheroids with varying oxygen and temperature conditions, with findings showing different responses of DDR markers (pDNA-PK and γH2AX) to FLASH vs. standard dose rates.
  • - Results indicate that FLASH-RT protection is more effective in well-oxygenated tissues and that transient oxygen depletion influences DNA damage markers, suggesting better outcomes for FLASH-RT in tissues with higher oxygen levels.
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Joint Gaussian measurements of two quantum systems are important for quantum communication between remote parties and are often used in continuous-variable teleportation or entanglement-swapping protocols. Many of the errors in real-world implementations can be modeled by independent Gaussian error channels acting prior to measurement. In this work we study independent single-mode Gaussian error channels on two modes A and B that take place prior to a joint Gaussian measurement.

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Type II topoisomerase (Top2) poisoning therapy is used to treat a broad range of cancers via induction of double strand breaks (DSBs) in cells undergoing replication and transcription. Preventing the repair of DSBs via inhibition of DNA-PK, an inhibitor of non-homologous end-joining (NHEJ), increases cell kill with Top2 poisons and has led to the initiation of several clinical trials. To elucidate the cellular mechanisms leading to synergistic activity of dual DNA-PK/Top2 inhibition we looked at their effects in cycling versus non-cycling cells, in 3D spheroids and in xenograft models.

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Purpose: There is a significant need for a widely available, translatable, sensitive and non-invasive imaging biomarker for tumor hypoxia in radiation oncology. Treatment-induced changes in tumor tissue oxygenation can alter the sensitivity of cancer tissues to radiation, but the relative difficulty in monitoring the tumor microenvironment results in scarce clinical and research data. Oxygen-Enhanced MRI (OE-MRI) uses inhaled oxygen as a contrast agent to measure tissue oxygenation.

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Objectives: Consenting donors for remnant clinical biospecimen donation is critical for scaling research biorepositories. Opt-in, low-cost, self-consenting for donations that solely relied on clinical staff and printed materials was recently shown to yield ∼30% consent rate. We hypothesized that adding an educational video to this process would improve consent rates.

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The advent of COVID-19, caused by the SARS-CoV-2 virus, has resulted in over 541 million cases with 6.32 million deaths worldwide as of June 2022. The devastating consequences of this global pandemic resulted in the expedited generation of mRNA-based vaccines such as the Pfizer-BioNTech and Moderna vaccines.

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Doubly parametric quantum transducers, such as electro-optomechanical devices, show promise for providing the critical link between quantum information encoded in highly disparate frequencies such as in the optical and microwave domains. This technology would enable long-distance networking of superconducting quantum computers. Rapid experimental progress has resulted in impressive reductions in decoherence from mechanisms such as thermal noise, loss, and limited cooperativities.

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Major trauma networks reduce mortality in critically injured patients. Trauma patients should be appropriately triaged straight from the scene of injury, avoiding secondary transfer from a trauma unit. Selection criteria in regionally agreed triage tools are designed to identify which patients should be taken directly to the major trauma centre.

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Antibody-drug conjugates (ADCs) have begun to fulfil their promise as targeted cancer therapeutics with ten clinical approvals to date. As the field matures, much attention has focused upon the key factors required to produce safe and efficacious ADCs. Recently the role that linker-payload reagent design has on the properties of ADCs has been highlighted as an important consideration for developers.

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Objective: Intraosseous (IO) access is critical in resuscitation, providing rapid access when peripheral vascular attempts fail. Unfortunately, misplacement commonly occurs, leading to possible fluid extravasation and tissue necrosis. Current research exploring the utility of bedside ultrasound in confirming IO line placement is limited by small sample sizes of skeletally immature subjects or geriatric cadaveric models.

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Background: Disparities in trauma outcomes and care are well established for adults, but the extent to which similar disparities are observed in pediatric trauma patients requires further investigation. The objective of this study was to evaluate the unique contributions of social determinants (race, gender, insurance status, community distress, rurality/urbanicity) on trauma outcomes after controlling for specific injury-related risk factors.

Study Design: All pediatric (age < 18) trauma patients admitted to a single level 1 trauma center with a statewide, largely rural, catchment area from January 2010 to December 2020 were retrospectively reviewed (n = 14,398).

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Background: Racial disparities in trauma care have been reported for a range of outcomes, but the extent to which these remain after accounting for socioeconomic and environmental factors remains unclear. The objective of this study was to evaluate the unique contributions of race, health insurance, community distress, and rurality/urbanicity on trauma outcomes after carefully controlling for specific injury-related risk factors.

Methods: All adult (age, ≥18 years) trauma patients admitted to a single Level I trauma center with a statewide, largely rural, catchment area from January 2010 to December 2020 were retrospectively reviewed.

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A wide range of diseases have been shown to be influenced by the accumulation of senescent cells, from fibrosis to diabetes, cancer, Alzheimer's and other age-related pathologies. Consistent with this, clearance of senescent cells can prolong healthspan and lifespan in in vivo models. This provided a rationale for developing a new class of drugs, called senolytics, designed to selectively eliminate senescent cells in human tissues.

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Introduction: Point-of-care ultrasound (POCUS) is an integral aspect of critical care and emergency medicine curriculums throughout the country, but it has been slow to integrate into internal medicine residency programs. POCUS has many benefits for internal medicine providers, guiding diagnostic decisions and aiding in procedures. Additionally, POCUS is a convenient and portable resource specifically for internal medicine providers in the military when practicing in deployed or critical care settings.

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Background: Preclinical drug development studies rarely consider the impact of a candidate drug on established metastatic disease. This may explain why agents that are successful in subcutaneous and even orthotopic preclinical models often fail to demonstrate efficacy in clinical trials. It is reasonable to anticipate that sites of metastasis will be phenotypically unique, as each tumor will have evolved heterogeneously with respect to gene expression as well as the associated phenotypic outcome of that expression.

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Background: Open lower limb fractures are serious injuries requiring combined ortho-plastic surgery and have significantly worse outcomes than similar closed fractures. There is little objective published data to determine which functional outcome measures best reflect progress or completeness of physical recovery. Our hypothesis was that objective measures combining strength, mobility and balance would better reflect recovery than isolated parameters (e.

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Purpose: To assess dosimetric properties and identify required updates to commonly used protocols (including use of film and ionization chamber) pertaining to a clinical linac configured into FLASH (ultra-high dose rate) electron mode.

Methods: An 18MV photon beam of a Varian iX linac was converted to FLASH electron beam by replacing the target and the flattening filter with an electron scattering foil. The dose was prescribed by entering the MUs through the console.

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We collected questing Haemaphysalis longicornis ticks from southeastern counties of Pennsylvania, USA. Of 263 ticks tested by PCR for pathogens, 1 adult female was positive for Borrelia burgdorferi sensu stricto, yielding a 0.4% infection rate.

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