Gradient (United States)

Objectives: There is a critical need for effective focal therapies for patients with inoperable or anatomically complex tumors where conventional ablation techniques pose high risk or are ineffective. Integrated Nanosecond Pulsed Irreversible Electroporation (INSPIRE) is a novel non-thermal ablation modality which uses real time temperature feedback during pulse delivery to safely treat tumors near critical structures. This study evaluated the impact of exposed electrode length on ablation zone size, reproducibility, and cardiac safety in a large animal model. Methods: INSPIRE treatments were performed in an in vivo healthy porcine liver model. All treatments administered 6000 V 1000 ns pulses with a 45 °C temperature set point. Treatments were administered percutaneously via an electrode and grounding pad approach using an internally cooled electrode applicator. The exposed electrode region at the distal end of the applicator was set to either 0.5, 1.0, 1.5, or 2.0 cm. Ablation zones were assessed via ultrasound, contrast-enhanced CT, and gross pathology one week post-treatment. Cardiac safety was evaluated by measuring pre- and post-treatment serum Troponin levels. Results: All treatments were completed without adverse events. Troponin levels remained stable (pre: 0.249 ng/mL; post: 0.224 ng/mL), indicating no measurable cardiac injury. The 1.5 cm exposure length produced the largest and most consistent ablation volumes, with a mean volume of 12.8 ± 2.6 cm3 and average dimensions of 3.7 × 2.7 cm in under 6 min. Increasing exposure length beyond 1.5 cm introduced greater variability and reduced treatment volumes. Conclusions: INSPIRE enables safe, large-volume, single-applicator ablation without a need for electrical pulse synchronization with R wave in cardiac rhythm. The 1.5 cm exposure length offers optimal balance between energy delivery and treatment consistency. These findings support further clinical investigation of INSPIRE for non-thermal ablation of inoperable tumors.

This paper summarizes several presentations in the Thresholds in Epidemiology and Risk Assessment session at the Monticello III conference. These presentations described evidence regarding thresholds for particles, including asbestos and silica, and cancer (e.g., mesothelioma) and noncancer (e.g., silicosis) endpoints. In the case of exposure to various types of particles and malignancy, it is clear that even though a linear non-threshold model has often been assumed, experimental and theoretical support for thresholds exist (e.g., through particle clearance, repair mechanisms, and various other aspects of the carcinogenic process). For mesothelioma and exposure to elongate mineral particles (EMPs), there remains controversy concerning the epidemiological demonstration of thresholds. However, using data from the Québec mining cohort studies, it was shown that a "practical" threshold exists for chrysotile exposure and mesothelioma. It was also noted that, in such evaluations, measurement error in diagnosis and exposure assessment needs to be incorporated into risk analyses. Researchers were also encouraged to use biobanks that collect specimens and data on mesothelioma to more precisely define cases of mesothelioma and possible variants for cases of all ages, and trends that may help define background rates and distinguish those mesotheliomas related to EMP exposures from those that are not, as well as other factors that support or define thresholds. New statistical approaches have been developed for identifying and quantifying exposure thresholds, an example of which is described for respirable crystalline silica (RCS) exposure and silicosis risk. Finally, the application of Artificial Intelligence (AI) to considering the multiple factors influencing risk and thresholds may prove useful.

Annex G of ISO 10993-11:2017 lists 24 substances that are allegedly material-mediated pyrogens (MMPs) in medical devices and recommends using the rabbit pyrogen test (RPT) for MMP evaluation. We aimed to establish whether medical devices contain MMPs; determine if MMPs are pyrogens or uncouplers of oxidative phosphorylation (UOPs); complete a survey of RPT failures; and develop a UOP screening list. A literature search was conducted to identify MMPs associated with medical devices. Concurrently, data mining was conducted to search for MMPs in medical device extractables databases and collect RPT data from industry and contract research labs. The literature search produced the conclusions: (1) Annex G’s endogenous biological compounds are pyrogenic; (2) Annex G’s drugs and UOP substances are not pyrogenic but thermogenic; (3) numerous other UOPs were identified; and (4) nearly all UOPs are poorly soluble in saline (the RPT’s injection solvent). The data mining found two Annex G MMPs in medical device extracts that were not pyrogenic and confirmed that the RPT failure rate was low, with investigated failures caused by endotoxin or test incompatibilities, not by Annex G MMPs. Since no pyrogenic Annex G MMPs or saline soluble UOPs were found in medical device extracts, the RPT is unnecessary. If UOPs are detected during chemical characterization studies, an ISO 10993-17:2023 toxicological risk assessment can be used to determine their hazard potential. Residual biological contamination can be evaluated with the human monocyte activation test, which detects all biological pyrogens. The term “MMP” is inaccurate and obsolete. Plain language summary Pyrogens cause fevers in mammals. Medical devices contaminated with bacterial components or chemicals generate a material-mediated pyrogenic (MMP) response. The rabbit pyrogen test (RPT) is used to detect MMPs even though its accuracy is questionable. An international standard lists 24 chemicals that are alleged to be medical device MMPs. To evaluate this belief, a search of the scientific literature was conducted to identify MMPs associated with medical devices along with a data mining effort that searched for MMPs found by chemistry laboratories that test medical devices. Failure rates for the RPT were also studied. Only two of the 24 chemicals were found in medical devices, and they were not pyrogens, plus the RPT failures were not due to MMPs. It was concluded that MMPs do not exist and therefore the RPT could be replaced with a human blood cell test that detects all types of biological pyrogens.

Over the past several decades, there have been many epidemiology studies on talc and cancer published in the scientific literature, and several reviews and meta-analyses of talc and respiratory, female reproductive, and stomach cancers, specifically. To help provide a resource for the evaluation of talc as a potential human carcinogen, we applied a consistent set of examination methods and criteria for all epidemiology studies that examined the association between talc exposure (by various routes) and cancers (of various types). We identified 30 cohort, 35 case-control, and 12 pooled studies that evaluated occupational, medicinal, and personal-care product talc exposure and cancers of the respiratory system, the female reproductive tract, the gastrointestinal tract, the urinary system, the lymphohematopoietic system, the prostate, male genital organs, and the central nervous system, as well as skin, eye, bone, connective tissue, peritoneal, and breast cancers. We tabulated study characteristics, quality, and results in a systematic manner, and evaluated all cancer types for which studies of at least three unique populations were available in a narrative review. We focused on study quality aspects most likely to impact the interpretation of results. We found that only one study, of medicinal talc use, evaluated direct exposure measurements for any individuals, though some used semi-quantitative exposure metrics, and few studies adequately assessed potential confounders. The only consistent associations were with ovarian cancer in case-control studies and these associations were likely impacted by recall and potentially other biases. This systematic review indicates that epidemiology studies do not support a causal association between occupational, medicinal, or personal talc exposure and any cancer in humans.

This study is not limited to the Cooperative-Style Group Homes found in Toyama and Miyagi prefectures, but also covers GHs that do not have common facilities and are symbiotic regardless of the building type or system. We conducted questionnaire and interview surveys after revealing the locations of the survey targets. The purpose of the survey was to clarify the factors required for the establishment and management of GHs with integrated services for the elderly and disabled by organizing the outline of the corporation, the building, and the situations of the establishment and management.

A diversidade fenotípica em sistemas biológicos frequentemente estrutura-se em padrões que, uma vez identificados, permitem a elaboração de modelos explicativos com predições derivadas. Exemplos desses incluem relações entre o tamanho corpóreo e parâmetros ambientais, como regimes pluviométricos, incidência solar, temperaturas ambientais e sazonalidade do clima, que podem limitar ou acentuar taxas de crescimento e o tamanho corpóreo em adultos de diferentes linhagens de organismos. O estudo da evolução do tamanho corpóreo em lagartos, em particular, é um tópico que tem recebido bastante atenção por parte de diferentes grupos de pesquisa mas ainda carece de abordagens utilizando bases de dados com grande abrangência taxonômica que implementem análises integrativas com diversas camadas ambientais. O presente trabalho compilou uma base de dados com informações de tamanho corpóreo disponíveis na literatura para 1309 espécies de 23 famílias de lagartos e dados de valores médios e amplitudes referentes a 6 variáveis climáticas relacionadas com a área de distribuição estimada para cada espécie, e avaliou diferentes modelos preditivos dos padrões de tamanho corpóreo nesses animais. Os modelos implementados consideraram as diferentes variáveis climáticas isoladas e também as interações entre elas. O modelo com melhor ajuste selecionado sugere uma associação negativa entre o tamanho corpóreo e a sazonalidade da precipitação, influenciada por sinal filogenético, e as análises não excluem a possibilidade de associações linhagem-especificas do tamanho corpóreo. Esse trabalho inova ao identificar associações entre tamanho corpóreo e a sazonalidade de uma variável climática (\\"precipitação sazonal\\"), um resultado discutido no contexto de relações entre crescimento e produção primária relacionada à disponibilidade de água e alimentos.

From 2019 through 2022, Gradient Technology conducted five demonstrations of its cut and capture system technology for the underwater demilitarization of unexploded ordnance or munitions and explosives of concern. The goal of these demonstrations was to validate its underwater suite of tools. The proprietary technology for underwater demilitarization of munitions utilizes a suite of tools that accomplish the following: 1) clean a munition of external bioencrustations using a high-pressure waterjet cleaning tool, 2) position a cut and capture apparatus on the munition, 3) cut an access hole in the side of the munition using a high-pressure entrainment-style abrasive waterjet cutting head, 4) remove the resulting plug, 5) wash out the internal contents of the munition using a high-pressure washout head, and 6) capture the effluent generated during operations without leakage to the environment. These demonstrations have shown that the cut and capture system can reliably operate underwater at depths less than 100 feet of sea water in which the supporting equipment is located above water on the deck of a vessel, barge, or pier.