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1.
Cureus ; 16(5): e59462, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38826998

RESUMEN

Background The anterior approach for total hip arthroplasty (THA) has gained popularity in recent years. Some surgeons have been hesitant to adopt the approach due to concerns over increased complications such as intraoperative fracture, stem loosening, and stem revision. This study aims to evaluate the all-cause revision rate and survivorship of a collared, triple-tapered stem that was designed specifically for use with the anterior approach in THA to enhance outcomes and reduce adverse events. Methodology A retrospective outcomes review was conducted to assess survivorship and clinical outcomes for a specific proximally coated, medially collared triple-tapered (MCTT) femoral stem. Results In a cohort of 5,264 hips, Kaplan-Meier survivorship estimates (95% confidence interval [CI]; N with further follow-up), with survivorship defined as no revision of any component for any reason at five years after the index procedure, were 98.9% (97.8%-99.4%; 43) under the clinical assumption and 99.6% (99.4%-99.7%; 894) under the registry assumption. With survivorship defined as stem revision for any reason, survivorship estimates at five years postoperatively were 99.6% (99.3%-99.8%; 43) under the clinical assumption and 99.8% (99.7%-99.9%; 894) under the registry assumption. The mean follow-up time was 94.52 days (standard deviation [SD] 2.24, range 90.03-96.02). At five years postoperatively, the mean Harris Hip Score was 95.19, and the mean Hip Disability and Osteoarthritis Outcome Score Junior (HOOS JR) score was 98.66. Conclusions Our evaluation demonstrates excellent construct and stem survivorship and very low complication rates at midterm postoperative follow-up.

2.
Knee ; 49: 52-61, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38848658

RESUMEN

BACKGROUND: There is increasing use of Robotic-Assisted (RA) and personalized alignment techniques in total knee arthroplasty (TKA). The hypothesis of this study was that RA TKA would result in fewer soft-tissue releases, and that fewer soft-tissue releases would be associated with improved clinical outcomes. METHODS: A retrospective review of an internal company registry was conducted for all primary TKAs performed from Jan 1, 2014, through a database extract date of Nov 4, 2022. These were grouped by whether there was an intentional soft-tissue release performed (STR) during the surgery or not (NSTR) and whether RA was utilized. The incidence of STR was compared between RA-TKAs and those performed with manual instrumentation. Knee Society Score (KSS) and Knee Society Function Scores (KSFS) were collected at 6 months, 1 year and 2 years. Kaplan-Meier survivorship was performed. RESULTS: The incidence of STR was significantly lower for RA vs. Manual (43.81% Vs 86.62%, p < 0.0001). The TKAs with NSTR had higher KSFS compared to those with STR at 6 months (84.73 Vs. 77.51, p < 0.0001), 1 year (89.87 Vs. 83.54, p < 0.0001) and 2 years (90.09 Vs. 82.65, p < 0.0001). There was no difference in survivorship, or KSS at any time point. However, the NSTR group had improved KSS pain sub score at 2 years. CONCLUSION: The results of this observational, retrospective analysis found that the incidence of soft-tissue release was lower with RA-TKA. Further, regardless of if RA was used, avoiding releases was associated with improved KSFS and KSS pain scores through 2 years post-operatively.

3.
Environ Sci Technol ; 58(20): 9000-9012, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38710661

RESUMEN

Additive manufacturing (AM) offers a variety of material manufacturing techniques for a wide range of applications across many industries. Most efforts at process optimization and exposure assessment for AM are centered around the manufacturing process. However, identifying the material allocation and potentially harmful exposures in end-of-life (EoL) management is equally crucial to mitigating environmental releases and occupational health impacts within the AM supply chain. This research tracks the allocation and potential releases of AM EoL materials within the US through a material flow analysis. Of the generated AM EoL materials, 58% are incinerated, 33% are landfilled, and 9% are recycled by weight. The generated data set was then used to examine the theoretical occupational hazards during AM EoL material management practices through generic exposure scenario assessment, highlighting the importance of ventilation and personal protective equipment at all stages of AM material management. This research identifies pollution sources, offering policymakers and stakeholders insights to shape pollution prevention and worker safety strategies within the US AM EoL management pathways.


Asunto(s)
Exposición Profesional , Humanos , Reciclaje
4.
Foods ; 12(20)2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37893677

RESUMEN

Cruciferous vegetable consumption is associated with numerous health benefits attributed to the phytochemical sulforaphane (SFN) that exerts antioxidant and chemopreventive properties, among other bioactive compounds. Broccoli sprouts, rich in SFN precursor glucoraphanin (GRN), have been investigated in numerous clinical trials. Broccoli microgreens are similarly rich in GRN but have remained largely unexplored. The goal of this study was to examine SFN bioavailability and the microbiome profile in subjects fed a single serving of fresh broccoli microgreens. Eleven subjects participated in a broccoli microgreens feeding study. Broccoli microgreens GRN and SFN contents and stability were measured. Urine and stool SFN metabolite profiles and microbiome composition were examined. Broccoli microgreens had similar GRN content to values previously reported for broccoli sprouts, which was stable over time. Urine SFN metabolite profiles in broccoli microgreens-fed subjects were similar to those reported previously in broccoli sprouts-fed subjects, including the detection of SFN-nitriles. We also reported the detection of SFN metabolites in stool samples for the first time. A single serving of broccoli microgreens did not significantly alter microbiome composition. We showed in this study that broccoli microgreens are a significant source of SFN. Our work provides the foundation for future studies to establish the health benefits of broccoli microgreens consumption.

5.
J Occup Environ Hyg ; 20(11): 545-562, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37526475

RESUMEN

Under the Toxic Substances Control Act (TSCA), the United States Environmental Protection Agency (USEPA) is required to determine whether a new chemical substance poses an unreasonable risk to human health or the environment before the chemical is manufactured in or imported into the United States. This manuscript provides a review of the process used to evaluate the risk associated with a chemical based on the scenarios and models used in the evaluation. Specifically, the Generic Scenarios and Emission Scenario Documents developed by the USEPA were reviewed, along with background documentation prepared by USEPA to identify the core elements of the environmental release and occupational exposure scenarios used to assess the risk of the chemical being evaluated. Additionally, this contribution provides an overview of methods used to model occupational exposures and environmental releases as part of the chemical evaluation process used in other jurisdictions, along with work being performed to improve these models. Finally, the alternative methods to evaluate occupational exposures and environmental releases that may be used as part of the decision-making process regarding a chemical are identified. The contribution provides a path forward for reducing the time required and improving the chemical evaluation of the unreasonable risk determination regarding the manufacture or import of a chemical.


Asunto(s)
Exposición Profesional , Estados Unidos , Humanos , Exposición Profesional/prevención & control , Medición de Riesgo/métodos , Factores de Riesgo , Exposición a Riesgos Ambientales
6.
ACS Sustain Chem Eng ; 11: 7986-7996, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37476647

RESUMEN

One type of firefighting foam, referred to as aqueous filmforming foams (AFFF), is known to contain per- and polyfluoroalkyl substances (PFAS). The concerns raised with PFAS, and their potential environmental and health impacts, have led to a surge in research on fluorine-free alternatives both in the United States and globally. Particularly, in January 2023, a new military specification (MIL-PRF-32725) for fluorine-free foam was released in accordance with Congressional requirements for the U.S. Department of Defense. This paper provides a critical analysis of the present state of the various fluorine-free options that have been developed to date. A nuanced perspective of the challenges and opportunities of more sustainable replacements is explored by examining the performance, cost, and regulatory considerations associated with these fluorine-free alternatives. Ultimately, this evaluation shows that the transition to fluorine-free replacements is likely to be complex and multifaceted, requiring careful consideration of the trade-offs involved. Yet, the ongoing work will provide valuable insights for future research on alternatives to AFFF and enhancing the safety and sustainability of fire suppression systems.

8.
Laryngoscope Investig Otolaryngol ; 7(2): 437-443, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35434343

RESUMEN

Objectives: Cisplatin-based chemoradiation is an established organ-preserving strategy for locally advanced laryngeal cancer, but long-term survival remains suboptimal. Immunotherapy has been studied in the metastatic and unresectable recurrent settings. However, additional data are needed to assess its role in organ preservation for locally advanced laryngeal cancer. Methods: This trial was an open-label, single-arm, multi-institutional study with a Phase I run-in portion followed by a planned Phase II component, which closed early due to low accrual. Study patients had Stage III or IV (T2-3; N0-3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given 2-3 weeks prior to chemoradiation and then, q21 days concurrently with high-dose cisplatin and radiation prescribed to a total dose of 70 Gy. The primary endpoint of the trial was organ-preservation rate (OPR) at 18 months. Results: A total of nine patients were enrolled with a median follow-up of 30.1 months. No patient required laryngectomy, resulting in 100% OPR at 18 months. The 12-month overall survival (OS) rate was 77.8% and the median duration of OS was not reached. All acute Grade 4 (n = 3) toxicities occurred in a single patient with poorly controlled diabetes at baseline. One patient had late Grade 4 laryngeal edema requiring tracheostomy 8 months after chemoradiation, which self-resolved. Conclusion: UCCI-HN-15-02 demonstrated the safety of the addition of immunotherapy to definitive chemoradiation and the patient outcomes suggest the potential for improving long-term survival while minimizing negative impact from treatment. While results from this trial were promising, a randomized study with a larger number of patients and longer follow-up is warranted to verify this treatment approach prior to wider adoption. NCT #: NCT02759575.Level of evidence: 2b.

9.
Int J Part Ther ; 8(2): 1-16, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34722807

RESUMEN

Proton therapy is a promising but controversial treatment in the management of prostate cancer. Despite its dosimetric advantages when compared with photon radiation therapy, its increased cost to patients and insurers has raised questions regarding its value. Multiple prospective and retrospective studies have been published documenting the efficacy and safety of proton therapy for patients with localized prostate cancer and for patients requiring adjuvant or salvage pelvic radiation after surgery. The Particle Therapy Co-Operative Group (PTCOG) Genitourinary Subcommittee intends to address current proton therapy indications, advantages, disadvantages, and cost effectiveness. We will also discuss the current landscape of clinical trials. This consensus report can be used to guide clinical practice and research directions.

10.
Brachytherapy ; 20(3): 595-600, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33750644

RESUMEN

PURPOSE: The true long-term toxicity associated with most radiation treatments is unknown. Prostate cancer patients survive decades after prostate cancer brachytherapy, with unclear long-term toxicity profiles. We therefore evaluated prostate cancer patients who had received I-125 brachytherapy treatment (14,400 cGy) 14-24 years prior and assessed their long-term quality of life based on urinary, bowel, and sexual function. METHODS AND MATERIALS: We performed a single-institutional, retrospective analysis of 39 men who received brachytherapy between 1996 and 2005. Analysis was based on physician evaluations, laboratory values, and International Prostate Symptom Score (IPSS) results. RESULTS: At last followup, the mean patient age was 80 years (median 81 years), with a mean of 17.8 years posttreatment followup. Fifteen percent of patients had experienced recurrence. Urinary symptoms were limited, with 0% of patients reporting dysuria, 13% reporting incontinence, and 33% on medication for urinary symptoms. Average times nocturia was 1.7 with mean IPSS of 6.4. With regard to bowel symptoms, 3% of patients reported incontinence, 8% noted diarrhea, 3% had rectal bleeding, 8% noted constipation, and no patients required prescription medication for bowel function. Thirty-nine percent of patients potent before treatment reported being potent with or without medication. CONCLUSIONS: Prostate cancer survivors, postbrachytherapy treatment, have an overall good quality of life for many years to come. Urinary and bowel symptoms are limited, IPSS scores are generally low, and patients who consider sexual function important at their stage in life are frequently found to be potent. Overall, the long-term side effects of brachytherapy are limited at 14-24 years posttreatment.


Asunto(s)
Braquiterapia , Neoplasias de la Próstata , Anciano de 80 o más Años , Braquiterapia/métodos , Humanos , Radioisótopos de Yodo , Masculino , Recurrencia Local de Neoplasia , Próstata , Neoplasias de la Próstata/radioterapia , Calidad de Vida , Estudios Retrospectivos
11.
Nat Plants ; 7(2): 198-208, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33574576

RESUMEN

Late blight caused by Phytophthora infestans greatly constrains potato production. Many Resistance (R) genes were cloned from wild Solanum species and/or introduced into potato cultivars by breeding. However, individual R genes have been overcome by P. infestans evolution; durable resistance remains elusive. We positionally cloned a new R gene, Rpi-amr1, from Solanum americanum, that encodes an NRC helper-dependent CC-NLR protein. Rpi-amr1 confers resistance in potato to all 19 P. infestans isolates tested. Using association genomics and long-read RenSeq, we defined eight additional Rpi-amr1 alleles from different S. americanum and related species. Despite only ~90% identity between Rpi-amr1 proteins, all confer late blight resistance but differentially recognize Avramr1 orthologues and paralogues. We propose that Rpi-amr1 gene family diversity assists detection of diverse paralogues and alleles of the recognized effector, facilitating durable resistance against P. infestans.


Asunto(s)
Mapeo Cromosómico , Clonación Molecular/métodos , Resistencia a la Enfermedad/genética , Phytophthora infestans/patogenicidad , Enfermedades de las Plantas/genética , Inmunidad de la Planta/genética , Solanum/genética , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Genómica , Fitomejoramiento/métodos
12.
Curr Opin Anaesthesiol ; 33(5): 633-638, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32826629

RESUMEN

PURPOSE OF REVIEW: Ketamine has been used for decades for a variety of indications. Beyond the historical benefits and effects of ketamine, newer developments have occurred worthy of an update. This review will discuss common uses and indications for ketamine in the perioperative setting, as well as highlight newer indications in recent years. RECENT FINDINGS: Multiple studies have examined the use of ketamine in a variety of environments, as ketamine has become more popular in emergency rooms and ICUs. Ketamine may be particularly beneficial in management of burn patients, who often require multiple procedures over the course of their treatment. Ketamine's role in the ongoing opioid crisis has been of particular interest, with multiple studies evaluating its potential role in managing both acute and chronic pain conditions. Ongoing studies examining the role of ketamine in treatment of depressions show promise as well. SUMMARY: Ketamine is regaining popularity in the field of anesthesia and beyond. New studies provide insight on the many indications and use that anesthesia providers may encounter during their perioperative care of patients. Ongoing research is needed to further elucidate ketamine's effects on the management of psychiatric conditions and potential indications for ketamine metabolites.


Asunto(s)
Analgesia , Analgésicos/farmacología , Anestesia , Anestésicos Disociativos/farmacología , Quemaduras/tratamiento farmacológico , Depresión/tratamiento farmacológico , Ketamina/farmacología , Dolor/tratamiento farmacológico , Humanos , Manejo del Dolor , Periodo Perioperatorio
13.
Methods Mol Biol ; 2149: 297-313, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32617941

RESUMEN

Attenuated total reflectance Fourier transform mid-infrared (ATR-FTIR) spectroscopy is widely applicable for the chemical analysis of biological materials, relatively inexpensive, requires only simple sample preparation, and is of comparatively high-throughput compared to traditional wet chemical or chromatographic methods. It is particularly well suited for the nondestructive analysis of dried and finely ground plant samples for the subsequent prediction of cell wall and other compositional or processing parameters using chemometric regression models. Furthermore, analysis of mid IR spectra by nonregression methods (e.g., principal component analysis) provides a straightforward approach for multivariate comparison of the effects of experimental, processing, and environmental treatments, and genotypic and temporal differences on chemical composition including changes in cell wall composition. There is thus great potential for using ATR-FTIR in the lignocellulosic biomass industry at a number of levels. Here we describe methods for cell wall sample preparation and generation of ATR-FTIR spectra, and suggest techniques for the statistical analysis and/or chemometric pattern recognition between the analyzed samples.


Asunto(s)
Pared Celular/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Análisis de los Mínimos Cuadrados , Metaboloma , Compuestos Orgánicos/química , Hojas de la Planta/química , Análisis de Componente Principal , Solubilidad , Solventes , Almidón/aislamiento & purificación
14.
Int J Radiat Oncol Biol Phys ; 108(4): 886-890, 2020 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-32592833

RESUMEN

PURPOSE: The majority of oncologic care is provided in the outpatient setting, yet at many medical schools, the dominant means of exposure to oncology occurs during inpatient rotations. Given the multidisciplinary nature of the specialty, radiation oncology departments are well positioned to lead outpatient oncology rotations within medical schools. Since 1992, the University of Cincinnati's Department of Radiation Oncology has administered a 2-week, third-year clinical oncology elective. This report characterizes the rotation and evaluates the impact of the rotation on students' oncology exposure and career choices over the past 10 years. METHODS AND MATERIALS: A list of medical students who participated in the MS3 clinical oncology elective rotation from 2008 to 2018 was reviewed. A search engine was used to locate the physicians and identify their specialty choices. A survey of 7 questions was distributed to the oncologists to evaluate how the rotation influenced their oncology exposure and career choice. RESULTS: Two hundred sixty-eight medical students participated in the MS3 Clinical Oncology Specialty Clerkship from 2008 to 2018. Thirty-nine students (15%) ultimately pursued a career in oncology. Seventy-four percent of the oncologists are radiation oncologists. Eighty-eight percent of the physicians surveyed had a positive to very positive experience with the rotation. The rotation was the first clinical exposure to the field of oncology for 48% of the respondents and the first exposure to the field of radiation oncology for 69% of the physicians. Seventy-two percent of the oncologists attributed the MS3 rotation as providing a moderate or great deal of early exposure to the field of oncology. CONCLUSIONS: Radiation oncology departments are well positioned to lead multidisciplinary, ambulatory oncology electives within US medical schools. A majority of participating oncologists viewed the rotation positively and attributed the rotation with their entrance into oncology.


Asunto(s)
Atención Ambulatoria , Selección de Profesión , Prácticas Clínicas/estadística & datos numéricos , Oncología Médica/educación , Estudiantes de Medicina/estadística & datos numéricos , Atención Ambulatoria/estadística & datos numéricos , Curriculum , Humanos , Oncología Médica/estadística & datos numéricos , Ohio , Oncología por Radiación/educación , Oncología por Radiación/estadística & datos numéricos , Facultades de Medicina , Encuestas y Cuestionarios/estadística & datos numéricos
15.
Glob J Qual Saf Healthc ; 3(3): 87-88, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37275598
16.
J Arthroplasty ; 34(6): 1139-1142, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30885407

RESUMEN

BACKGROUND: Interest in direct anterior approach (DAA) has increased over the last decade. In our previously published study comparing DAA to posterolateral approach (PA), early 3-month benefits were noted in terms of pain and function. There was no difference noted at 6 or 12 months. This study reports average 5-year follow-up of our original study. METHODS: Originally there were 43 DAA patients and 44 PA patients. At an average 5-year follow-up, patients were evaluated clinically with a University of California at Los Angeles activity score, Harris hip score, and Hip Disability and Osteoarthritis Outcome Score Jr Survivorship analysis was calculated. Radiographs were evaluated for loosening and evidence of radiolucent lines. RESULTS: There were 2 deaths 1 in each group, neither was related to the implant or procedure. Four patients were lost to follow-up: 2 in the DAA group and 2 in the PA group. There was no statistical difference between surgical approaches in terms of Harris hip score, University of California at Los Angeles activity score, and Hip Disability and Osteoarthritis Outcome Score Jr. The 7-year survivorship was not significantly different. There were no loose implants at average 5-year follow-up. CONCLUSION: Both DAA and PA yield good results at an average 5-year follow-up in terms of survivorship, function, rate of complications, and radiographic analysis.


Asunto(s)
Artroplastia de Reemplazo de Cadera/métodos , Prótesis de Cadera , Diseño de Prótesis , Adulto , Anciano , Artroplastia de Reemplazo de Cadera/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
17.
Cancer ; 125(12): 2027-2038, 2019 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-30913305

RESUMEN

BACKGROUND: Radiation Therapy Oncology Group (RTOG)-0129 recursive partitioning analysis was the basis for risk-based therapeutic intensification trials for oropharyngeal cancer (OPC). To the authors' knowledge, the question of whether RTOG-0129 overall survival (OS) estimates for low-risk, intermediate-risk, and high-risk groups are similar in other data sets or applicable to progression-free survival (PFS) is unknown. Therefore, the authors evaluated whether survival differences between RTOG-0129 risk groups persist at 5 years, are reproducible in an independent clinical trial, and are applicable to PFS, and whether toxicities differ across risk groups. METHODS: Prospective randomized clinical trials were analyzed retrospectively. RTOG-0129 evaluated standard versus accelerated fractionation radiotherapy concurrent with cisplatin. RTOG-0522 compared the combination of cisplatin and accelerated fractionation with or without cetuximab. Patients with OPC with available p16 status and tobacco history were eligible. RESULTS: There was a total of 260 patients and 287 patients, respectively, from RTOG-0129 and RTOG-0522, with median follow-ups for surviving patients of 7.9 years (range, 1.7-9.9 years) and 4.7 years (range, 0.1-7.0 years), respectively. Previous OS differences in RTOG-0129 persisted at 5 years. In RTOG-0522, the 5-year OS rates for the low-risk, intermediate-risk, and high-risk groups were 88.1%, 69.9%, and 45.1%, respectively (P for trend, <.001). The 5-year PFS rates for the same 3 groups were 72.9%, 56.1%, and 42.2%, respectively. In RTOG-0522 among a subgroup of patients considered to be at very good risk (p16-positive disease, smoking history of ≤10 pack-years, and classified with T1-T2 disease with ipsilateral lymph nodes measuring ≤6 cm or T3 disease without contralateral or >6 cm lymph nodes), the 5-year OS and PFS rates were 93.8% and 82.2%, respectively. Overall rates of acute and late toxicities were similar by risk group. CONCLUSIONS: RTOG-0129 risk groups persisted at 5 years and were reproducible in RTOG-0522. However, there was variability in the estimates. These data underscore the importance of long-term follow-up and appropriate patient selection in therapeutic deintensification trials.


Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Quimioradioterapia/mortalidad , Ensayos Clínicos como Asunto/normas , Neoplasias Orofaríngeas/mortalidad , Infecciones por Papillomavirus/complicaciones , Selección de Paciente , Medición de Riesgo/métodos , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia
18.
ACS Sustain Chem Eng ; 7: 1260-1270, 2019 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-30881772

RESUMEN

A framework is presented to address the toolbox of chemical release estimation methods available for manufacturing processes. Although scientists and engineers often strive for increased accuracy, the development of fit-for-purpose release estimates can speed results that could otherwise delay decisions important to protecting human health and the environment. A number of release estimation approaches are presented, with the newest using decision trees for regression and prediction. Each method is evaluated in a case study for cumene production to study the reconciliation of data quality concerns and requirements for time, resources, training, and knowledge. The evaluation of these decision support criteria and the lessons learned are used to develop a purpose-driven framework for estimating chemical releases.

19.
Oncotarget ; 10(8): 856-868, 2019 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-30783515

RESUMEN

Normal living cells exhibit phosphatidylserine (PS) primarily within the intracellular leaflet of the plasma membrane. In contrast, viable cancer cells have high levels of PS on the external surface, and exhibit a broad range of surface PS, even within specific types of cancer. Agents that target surface PS have recently been developed to treat tumors and are expected to be more effective with higher surface PS levels. In this context, we examined whether surface PS is increased with irradiation. In vitro irradiation of cancer cell lines selected surviving cells that had higher surface PS in a dose- and time-dependent manner. This was more pronounced if surface PS was initially in the lower range for cancer cells. Radiation also increased the surface PS of tumor cells in subcutaneous xenografts in nude mice. We found an inverse relationship between steady state surface PS level of cancer cell lines and their sensitivity to radiation-induced cell death. In addition, serial irradiation, which selected surviving cells with higher surface PS, also increased resistance to radiation and to some chemotherapeutic drugs, suggesting a PS-dependent mechanism for development of resistance to therapy. On the other hand, fractionated radiation enhanced the effect of a novel anti-cancer, PS-targeting drug, SapC-DOPS, in some cancer cell lines. Our data suggest that we can group cancer cells into cells with low surface PS, which are sensitive to radiation, and high surface PS, which are sensitive to SapC-DOPS. Combination of these interventions may provide a potential new combination therapy.

20.
ACS Sustain Chem Eng ; 7(8): 7630-7641, 2019 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33123418

RESUMEN

The evaluation of potential alternatives for chemicals of concern (CoC) requires an understanding of their potential human health and environmental impacts during the manufacture, use, recycle and disposal life stages. During the manufacturing phase, the processes used to produce a desired chemical are defined based on the sequence of chemical reactions and unit operations required to produce the molecule and separate it from other materials used or produced during its manufacture. This paper introduces and demonstrates a tool that links a chemical's structure to information about its synthesis route and the manufacturing process for that chemical. The structure of the chemical is entered using either a SMILES string or the molecule MOL file, and the molecule is searched to identify functional groups present. Based on those functional groups present, the respective named reactions that can be used in its synthesis routes are identified. This information can be used to identify input and output materials for each named reaction, along with reaction conditions, solvents, and catalysts that participate in the reaction. Additionally, the reaction database contains links to internet references and appropriate reaction-specific keywords, further increasing its comprehensiveness. The tool is designed to facilitate the cataloging and use of the chemical literature in a way that allows user to identify and evaluate information about the reactions, such as alternative solvents, catalysts, reaction conditions and other reaction products which enable the comparison of various reaction pathways for the manufacture of the subject chemical. The chemical manufacturing processing steps can be linked to a chemical process ontology to estimate releases and exposures occurring during the manufacturing phase of a chemical.

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