Publications by authors named "Ryan Schofield"

Nanofibrous active layers offer hierarchical control over molecular structure, and the size and distribution of electron donor:acceptor domains, beyond conventional organic photovoltaic architectures. This structure is created by forming donor pathways via electrospinning nanofibers of semiconducting polymer, then infiltrating with an electron acceptor. Electrospinning induces chain and crystallite alignment, resulting in enhanced light-harvesting and charge transport.

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Article Synopsis
  • * A study tested the feasibility of administering HD-MTX in an outpatient setting with the aid of low-dose glucarpidase to help clear the drug more quickly.
  • * Results showed that all treatments were effective and safe, with no hospitalizations needed, suggesting that outpatient HD-MTX with glucarpidase could change how CNS lymphoma is treated.
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Electrospinning has been applied to produce ceramic fibers using sol gel-based spinning solutions consisting of ceramic precursors, a solvent, and a polymer to control the viscosity of the solution. However, the addition of polymers to the spinning solution makes the process more complex, increases the processing time, and results in porous mechanically weak ceramic fibers. Herein, we develop a coelectrospinning technique, where a nonspinnable sol (<10 mPa s) consisting of only the ceramic precursor(s) and solvent(s) is encapsulated inside a polymeric shell, forming core-shell precursor fibers that are further calcined into ceramic fibers with reduced porosity, decreased surface defects, uniform crystal packing, and controlled diameters.

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Treosulfan is a structural analog of the alkylating agent busulfan which has been shown in clinical trials to exhibit comparable myeloablative activity while causing fewer serious side effects. Treosulfan is currently being considered for FDA approval in combination with fludarabine, one of the most commonly used myeloablative agents, as a conditioning regimen prior to hematopoietic stem cell transplantation (HSCT). Because plasma concentrations of both treosulfan and fludarabine exhibit significant interindividual variability, therapeutic drug monitoring (TDM) is indicated to ensure dosages are administered that maximize efficacy while minimizing toxicity.

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N,N',N''-Triethylenethiophosphoramide (thioTEPA) is a polyfunctional, organophosphorus alkylating agent that has been a primary treatment of multiple solid malignancies for many years and more recently as part of conditioning regimens prior to hematopoietic stem cell transplantation for a variety of hematologic malignancies. In vivo, thioTEPA is quickly metabolized to N,N',N″-triethylenephosphoramide (TEPA). ThioTEPA and TEPA have similar alkylating activity and both exhibit outstanding central nervous system penetration.

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Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapeutic treatment for patients with high-risk hematologic malignancies and bone marrow failure syndromes. While allo-HCT can be highly effective, it is met with significant regimen-related toxicities and complications such as graft-versus-host disease (GVHD), poor immune reconstitution, and infections. Prednisone is the preferred treatment for patients with both acute and chronic GVHD.

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Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapeutic treatment for many patients with high-risk hematologic malignancies and bone marrow failure syndromes. While allo-HCT can be highly effective, it is met with significant bone marrow conditioning regimen-related toxicities and complications such as infections related to poor immune reconstitution. This chapter describes the measurement of clofarabine and fludarabine concentrations to support clinical trials whose goal is to determine the optimal therapeutic ranges in order to maximize effectiveness while minimizing variability and regimen-related adverse events and toxicities.

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Melphalan and busulfan are DNA-alkylating agents that are often used concurrently in hematopoietic stem cell transplant (HCT) conditioning regimens. Studies have demonstrated that this combination of alkylating agents is very effective and well-tolerated prior to HCT. This combination is widely used for acute leukemia, advanced lymphoid malignancies, and multiple myeloma.

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Objective: To estimate vaccine effectiveness for preventing covid-19 related hospital admission in individuals first infected with the SARS-CoV-2 virus during pregnancy compared with those of reproductive age who were not pregnant when first infected with the virus.

Design: Population based cohort study.

Setting: Office for National Statistics Public Health Data Asset linked dataset, providing national linked census and administrative data in England, 8 December 2020 to 31 August 2021.

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Objective: To examine sociodemographic inequalities in people with SARS-CoV-2 during the second (alpha) and third (delta) waves of the covid-19 pandemic.

Design: Retrospective, population based cohort study.

Setting: Resident population of England.

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Adult and pediatric endocrinology and oncology often requires measuring serum estrogens and testosterone at very low concentrations. Conventional immunoassay methods often lack the required performance to meet this analytical need, and mass spectrometry techniques must be employed. Our aim was to develop a sensitive HPLC-MS/MS assay for both estradiol (E2) and testosterone (Te) in serum, utilizing commercially available calibrators and without the need for chemical derivatization.

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Background: Dysgeusia is a common but understudied complication in patients undergoing autologous hematopoietic cell transplantation (auto-HCT). We assessed the feasibility of using chemical gustometry (CG) to measure dysgeusia and explored its associations with symptom burden, nutrition, chemotherapy pharmacokinetics (PK), and the oral microbiome.

Methods: We conducted a single-center, prospective feasibility study (NCT03276481) of patients with multiple myeloma undergoing auto-HCT.

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Background: High-dose methotrexate (HD-MTX) has broad use in the treatment of central nervous system (CNS) malignancies but confers significant toxicity without inpatient hydration and monitoring. Glucarpidase is a bacterial recombinant enzyme dosed at 50 units (u)/kg, resulting in rapid systemic MTX clearance. The aim of this study was to demonstrate feasibility of low-dose glucarpidase to facilitate MTX clearance in patients with CNS lymphoma (CNSL).

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Background And Objectives: High-dose melphalan is an integral part of conditioning chemotherapy prior to both autologous and allogeneic hematopoietic cell transplantation. While underexposure may lead to relapse, overexposure may lead to toxicities include mucositis, diarrhea, bone marrow suppression, and rarely sinusoidal obstruction syndrome. In this study, we describe the population pharmacokinetics of high-dose melphalan as a first step towards individualized dosing.

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Background: Public policy measures and clinical risk assessments relevant to COVID-19 need to be aided by risk prediction models that are rigorously developed and validated. We aimed to externally validate a risk prediction algorithm (QCovid) to estimate mortality outcomes from COVID-19 in adults in England.

Methods: We did a population-based cohort study using the UK Office for National Statistics Public Health Linked Data Asset, a cohort of individuals aged 19-100 years, based on the 2011 census and linked to Hospital Episode Statistics, the General Practice Extraction Service data for pandemic planning and research, and radiotherapy and systemic chemotherapy records.

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Busulfan and melphalan are cytotoxic DNA alkylating agents that are used in many hematopoietic stem cell transplantation (HCT) conditioning regimens. We report the development of an assay using turbulent flow liquid chromatography (TFLC) and tandem mass spectrometry to simultaneously measure the concentration of busulfan (Bu) and melphalan (Mel) in human plasma. The method involves precipitating proteins in the plasma specimen with an organic solvent containing deuterated internal standards of both compounds.

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A very sensitive LC-MS/MS assay was developed implementing a liquid-liquid extraction step followed by mass spectrometry which was operated in both positive and negative ion modes. The assay was calibrated with readily available commercial calibrators and compared with international reference standards. This data is also presented in "Sensitive Simultaneous Quantitation of Testosterone and Estradiol in Serum by LC-MS/MS without Derivatization and Comparison with the CDC HoSt Program" (Schofield et al.

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Polymerization induced self-assembly (PISA) using methacrylate-based macromonomers as RAFT agents is an unexplored, attractive route to make self-assembled colloidal objects. The use of this class of RAFT-agents in heterogeneous polymerizations is however not trivial, because of their inherent low reactivity. In this work we demonstrate that two obstacles need to be overcome, one being control of chain-growth (propagation), the other monomer partitioning.

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Background: Very sensitive measurements of serum estrogens and testosterone are important in adult and pediatric endocrinology and immunoassays are known to lack the required performance at very low levels. Our aim was to develop a sensitive HPLC-MS/MS assay for both estradiol (E) and testosterone (Te) in serum without the need for chemical derivatization and using commercially available calibrators.

Methods: Serum samples were prepared by the addition of internal standards followed by extraction using hexane:ethyl acetate.

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Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis.

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Methotrexate (MTX) is a folic acid antagonist that is widely used as an immunosuppressant and chemotherapeutic agent. After high-dose administration of MTX serum levels must be monitored to determine when to administer leucovorin, a folic acid analog that bypasses the enzyme inhibition caused by MTX and reverses its toxicity. We describe a rapid and simple turbulent flow liquid chromatography (TFLC) method implementing positive heated electrospray ionization (HESI) for the accurate and precise determination of MTX, 7-hydroxymethotrexate (7-OH MTX), and 4-amino-4-deoxy-N(10)-methylpteroic acid (DAMPA) concentrations in serum.

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Antiepileptic drugs (AEDs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Over the past several decades some new AEDs, including lamotrigine (LTG), levetiracetam (LVA), oxcarbazepine (OXC), topiramate (TOP), and zonisamide (ZNS), have become widely used. This chapter describes a very simple and rapid liquid chromatography-tandem mass spectrometry method for simultaneous quantitation of LVA, ZNS, LTG, TOP, and MHD in human serum.

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Patients with significant proteinuria represent a unique population with respect to vitamin D status due to the urinary losses of vitamin D-binding protein (DBP) to which >99 % of circulating 25-hydroxy vitamin D (25(OH)D) is bound. Low serum concentrations of 25(OH)D have been found in children and adults with nephrotic syndrome (NS). However, previously described assays developed to quantify the magnitude of urinary loss are technically challenging.

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A rapid and simple turbulent flow liquid chromatography (TFC-LC) method implementing positive heated electrospray ionization (HESI) for the accurate and precise determination of methotrexate (MTX), 7-hydroxy methotrexate (7-OH MTX), and 4-amino-4-deoxy-N(10)-methylpteroic acid (DAMPA) concentrations in serum was developed. MTX was isolated from serum samples (100μL) after protein precipitation with methanol containing formic acid and internal standard (MTX-D3) followed by centrifugation. The supernatant was injected into the turbulent flow liquid chromatography which is followed by electrospray positive ionization tandem mass spectrometry (TFC-LC-MS/MS) and quantified using a six-point calibration curve.

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Fluorescent retrograde tracers were used to identify the cells in auditory cortex that project directly to the cochlear nucleus (CN). Following injection of a tracer into the CN, cells were labeled bilaterally in primary auditory cortex and the dorsocaudal auditory field as well as several surrounding fields. On both sides, the cells were limited to layer V.

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