Recommendations for Responsible Development and Application of Neurotechnologies

Advancements in novel neurotechnologies, such as brain computer interfaces (BCI) and neuromodulatory devices such as deep brain stimulators (DBS), will have profound implications for society and human rights. While these technologies are improving the diagnosis and treatment of mental and neurological diseases, they can also alter individual agency and estrange those using neurotechnologies from their sense of self, challenging basic notions of what it means to be human. As an international coalition of interdisciplinary scholars and practitioners, we examine these challenges and make recommendations to mitigate negative consequences that could arise from the unregulated development or application of novel neurotechnologies. We explore potential ethical challenges in four key areas: identity and agency, privacy, bias, and enhancement. To address them, we propose (1) democratic and inclusive summits to establish globally-coordinated ethical and societal guidelines for neurotechnology development and application, (2) new measures, including “Neurorights,” for data privacy, security, and consent to empower neurotechnology users’ control over their data, (3) new methods of identifying and preventing bias, and (4) the adoption of public guidelines for safe and equitable distribution of neurotechnological devices.

     

Big Brain Data: On the Responsible Use of Brain Data from Clinical and Consumer-Directed Neurotechnological Devices

Neuroethics - The focus of this paper are the ethical, legal and social challenges for ensuring the responsible use of “big brain data”—the recording, collection and analysis of...     

Long-term treatment costs and cost-effectiveness of restoration repair versus replacement

ObjectivesWhen managing partially defective restorations, dentists can choose between repair and replacement. We aimed to assess the long-term treatment costs of repairs and replacements.MethodsPartially defective anterior and posterior composite restorations in permanent teeth had been repaired or replaced in a German university hospital and were retrospectively followed until censoring or one of the following events: (1) Extraction, (2) Major complications including placement of indirect restorations, endodontic treatments and extractions, or (3) Any complications including major complications and further direct restorations. Costs were estimated from a German mixed public-private-payer perspective. Cost-effectiveness differences were described using median-based incremental-cost-effectiveness ratios (ICER_MEDIAN). Statistical analysis was performed using generalized linear mixed modeling (GLM), Chi²-test, and Wilcoxon rank-sum test (p < 0.05).ResultsA total of 616 repairs in 468 patients (follow-up: 4.9 ± 4.1 years) and 264 replacements in 218 patients (follow-up: 4.8 ± 4.3) were included. While replacements were associated with higher initial treatment costs, median annualized treatment costs did not significantly differ between repair (47.58 Euro [IQR: 24.41–107.04]) and replacement (50.64 Euro [IQR: 26.30–118.78]; p > 0.05), but were higher for molars (75.53 Euro [IQR: 24.41–92.18]) than incisors (45.03 Euro [IQR: 28.19–168.50]; p = 0.011). The difference in the % of extractions, major and any complications were minimal between both groups. The mean ICER_MEDIAN of replacement vs. repair was -146.8 Euro/% when extractions were considered as outcomes. Regarding major and any complications, mean ICER_MEDIAN amounted to 67.6 Euro/% and 23.9 Euro/%, respectively.SignificanceRepairs and replacements of partially defective restorations showed similar long-term costs and cost-effectiveness.     

High frequency of MYC gene amplification is a common feature of radiation‐induced sarcomas. Further results from EORTC STBSG TL 01/01

Irradiation is a major causative factor among the small subgroup of sarcomas with a known etiology. The prognosis of radiation‐induced sarcomas (RIS) is significantly worse than that of their spontaneous counterparts. The most frequent histological subtypes include undifferentiated pleomorphic sarcomas, angiosarcomas, and leiomyosarcomas. A high frequency of MYC amplifications in radiation‐induced angiosarcomas, but not in primary angiosarcomas, has recently been described. To investigate whether MYC amplifications are also frequent in RIS other than angiosarcomas, we analyzed the MYC amplification status of 83 RIS and 192 sporadic sarcomas by fluorescence in situ hybridization. We found significantly higher numbers of MYC amplifications in RIS than in sporadic sarcomas (P < 0.0001), especially in angiosarcomas, undifferentiated pleomorphic sarcomas, and leiomyosarcomas. Angiosarcomas were special in that MYC amplifications were particularly frequent and always high level, while other RIS showed low‐level amplifications. We conclude that MYC amplifications are a frequent feature of RIS as a group and may contribute to the biology of these tumors. © 2012 Wiley Periodicals, Inc.     

Tumor–microenvironment interactions studied by zonal transcriptional profiling of squamous cell lung carcinoma

Invasion is a critical step in lung tumor progression. The interaction between tumor cells and their surroundings may play an important role in tumor invasion and metastasis. To better understand the mechanisms of tumor invasion and tumor–microenvironment interactions in lung tumors, total RNA was isolated from the inner tumor, tumor invasion front, adjacent lung, and distant normal lung tissue from 17 patients with primary squamous cell lung carcinoma using punch‐aided laser capture microdissection. Messenger RNA expression profiles were obtained by microarray analysis, and microRNA profiles were generated from eight of these samples using TaqMan Low Density Arrays. Statistical analysis of the expression data showed extensive changes in gene expression in the inner tumor and tumor front compared with the normal lung and adjacent lung tissue. Only a few genes were differentially expressed between tumor front and the inner tumor. Several genes were validated by immunohistochemistry. Evaluation of the microRNA data revealed zonal expression differences in nearly a fourth of the microRNAs analyzed. Validation of selected microRNAs by in situ hybridization demonstrated strong expression of hsa‐miR‐196a in the inner tumor; moderate expression of hsa‐miR‐224 in the inner tumor and tumor front, and strong expression of hsa‐miR‐650 in the adjacent lung tissue. Pathway analysis placed the majority of genes differentially expressed between tumor and nontumor cells in intrinsic processes associated with inflammation and extrinsic processes related to lymphocyte physiology. Genes differentially expressed between the inner tumor and the adjacent lung/normal lung tissue affected pathways of arachidonic acid metabolism and eicosanoid signaling. © 2012 Wiley Periodicals, Inc.     

Comparative study of the corrosion behavior of peripheral stents in an accelerated corrosion model: experimental in vitro study of 28 metallic vascular endoprostheses

PURPOSE

Clinical cases of stent-fractures show that corrosion behavior might play a role in these fractures. Implanted in vivo, especially in combination with other implanted foreign materials, these metallic products are exposed to special conditions, which can cause a process of corrosion. Here, we aimed to test the corrosion potential of stents made of different materials in an in vitro setting.

METHODS

A total of 28 peripheral stents of different materials (nitinol, cobalt-chromium-nickel, tantalum, V4A) and surface treatments (electropolish, mechanical polish, no polish) were tested in vitro. Corrosion was accelerated by applying a constant voltage of 3.5 V and amperage of 1.16 mA in 0.9% NaCl.

RESULTS

Nitinol stents showed the lowest susceptibility to corrosion and the longest period without damage. The Memotherm II^® (BARD Angiomed^®) was the only stent that showed neither macroscopic nor microscopic damages. The worst performing material was cobalt-chromium-nickel, which showed corrosion damages about ten times earlier compared to nitinol. Considering the reasons for termination of the test, nitinol stents primarily showed length deficits, while V4A and tantalum stents showed fractures. Cobalt-chromium-nickel stents had multiple fractures or a complete lysis in equal proportions. When placed in direct contact, nitinol stents showed best corrosion resistance, regardless of what material they were combined with. In terms of polishing treatments, electropolished stents performed the best, mechanical-polished stents and those without polishing treatment followed.

CONCLUSION

The analysis of corrosion behavior may be useful to select the right stent fulfilling the individual needs of the patient within a large number of different stents.Congenital stenosis or volume decreasing processes due to accumulation of tissues or by outside pressures are the most common indications for vascular interventional therapies. After the initial “cardiac catheterization” by Forssmann et al. (1) in 1929, percutaneous interventional techniques for treatment of vasoconstricting processes was continued constantly, whereby the use of permanent mechanical stents has gained an increasingly important role.Stents used in clinical practice should fulfill certain conditions to achieve an un-problematic application as well as an optimal result. The following properties apply to this ideal: good biocompatibility, low shortening, high-density in X-ray, high patency rates, low thrombogenicity, rapid endothelialization without excessive intimal hyperplasia, high flexibility and longitudinal elasticity, sufficient pressure stability at high centrifugal force, technical ability to secure application and exact positioning, and good expansion ratio for safe percutaneous application also with larger prostheses (2, 3). With the approval of stents for clinical use in 1986, the use of stents in peripheral vessels was also practiced on human patients. Palmaz et al. (4) published the first results of the clinical use in 1988 in one of the first multicenter trials on the use of stents in stenosed atherosclerotic iliac arteries. After the successful development of Palmaz^® stents and Wallstents^® as prototypes of balloon-expandable and self-expanding stents, a variety of new stents have been developed.The stents used today are made of different materials. These include nickel titanium alloys (nitinol), surgical stainless steel (V4A), tantalum, and cobalt compounds. Implanted in the human body, especially in combination with other implanted foreign materials, these metallic products are exposed to special conditions causing a process of corrosion. The higher the ionic conductivity of a liquid is, the faster the reaction. For this reason, liquids that contain a high proportion of electrolytes, such as blood with its high proportion of NaCl, cause much faster corrosion of materials (5).We aimed to perform a comparative study regarding the corrosion behavior of peripheral stents, to reffect the behavior of implanted stents in patients and contribute to find a safer indication in the selection of vascular prostheses. Likewise, we tested the hypothesis that the polishing process influences their corrosion behavior.     

Adverse effects of irreversible electroporation of malignant liver tumors under CT fluoroscopic guidance: a single-center experience

PURPOSE

We aimed to describe the frequency of adverse events after computed tomography (CT) fluoroscopy-guided irreversible electroporation (IRE) of malignant hepatic tumors and their risk factors.

METHODS

We retrospectively analyzed 85 IRE ablation procedures of 114 malignant liver tumors (52 primary and 62 secondary) not suitable for resection or thermal ablation in 56 patients (42 men and 14 women; median age, 61 years) with regard to mortality and treatment-related complications. Complications were evaluated according to the standardized grading system of the Society of Interventional Radiology. Factors influencing the occurrence of major and minor complications were investigated.

RESULTS

No IRE-related death occurred. Major complications occurred in 7.1% of IRE procedures (6/85), while minor complications occurred in 18.8% (16/85). The most frequent major complication was postablative abscess (4.7%, 4/85) which affected patients with bilioenteric anastomosis significantly more often than patients without this condition (43% vs. 1.3%, P = 0.010). Bilioenteric anastomosis was additionally identified as a risk factor for major complications in general (P = 0.002). Minor complications mainly consisted of hemorrhage and portal vein branch thrombosis.

CONCLUSION

The current study suggests that CT fluoroscopy-guided IRE ablation of malignant liver tumors may be a relatively low-risk procedure. However, patients with bilioenteric anastomosis seem to have an increased risk of postablative abscess formation.About 70% of hepatic metastases are nonresectable because of their anatomic location, the presence of comorbidities, or limited hepatic functional reserve (1). In these patients and in case of nonresectable primary liver tumors, percutaneous thermal ablation procedures, such as radiofrequency (RF) and microwave ablation, have become effective tools for treating hepatic malignancies (2–4). However, the effectiveness of RF and microwave treatment may be limited, either because of thermal damage to temperature-sensitive structures located in close proximity to the target tissue (5) or because of incomplete ablation of tumors adjacent to major hepatic vessels due to a phenomenon commonly termed “heat-sink effect” (6–10) which describes the loss of the applied thermal energy through the blood flow in those major vessels, whereby the effective energy application remains inadequate to ablate the target lesion.Irreversible electroporation (IRE) is a theoretically nonthermal ablation technique that delivers a series of high-voltage millisecond electrical pulses to the surrounding tissue, thus leading to irreversible disruption of the integrity of cell membranes and subsequent cell death by apoptosis (11–14). IRE may overcome the problems raised with thermal ablation: previous animal studies reported that bile ducts, blood vessels, nerves, and connective tissues are affected by IRE; however, regeneration is possible to some extent due to preservation of the tissue architecture (12, 13, 15–19). Moreover the feasibility of inducing cell death up to a vessel wall without any perivascular sparing was shown with IRE (12, 13, 18). The safety of IRE in the treatment of humans has been described (20). First reports have described potential complications after IRE, such as hemorrhage requiring blood transfusion (1.2%, two of 167 ablation procedures), portal vein thrombosis (3.2%, one of 31 ablation procedures), injury to bile ducts (1.8%, three of 167 ablation procedures), and infection (3.6%, six of 167 ablation procedures) (21, 22). However, few data are available for evaluating the potential risk factors associated with the occurrence of post-IRE complications.The purpose of this study was to review the frequency of mortality and morbidity after computed tomography (CT) fluoroscopy-guided liver IRE conducted at a single center and assess the factors influencing the occurrence of major complications.