Liability Risk Research Articles

PD42-11 MALPRACTICE LITIGATION IN PENILE AUGMENTATION SURGERY: A LEGAL DATABASE REVIEW

You have accessJournal of UrologyCME1 Apr 2023PD42-11 MALPRACTICE LITIGATION IN PENILE AUGMENTATION SURGERY: A LEGAL DATABASE REVIEW Shanice Cox, Nicolas Seranio, Wade Muncey, and Michael Eisenberg Shanice CoxShanice Cox More articles by this author , Nicolas SeranioNicolas Seranio More articles by this author , Wade MunceyWade Muncey More articles by this author , and Michael EisenbergMichael Eisenberg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003352.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Surgical penile augmentation for aesthetic purposes is an invasive procedure that carries with it an increased risk of medicolegal liability. The purpose of this study is to investigate the factors associated with malpractice litigation surrounding penile augmentation surgery. METHODS: We reviewed the Nexis Uni legal database for state and federal cases using the terms "penile” or “penis” and “enlargement" or "augmentation" or "enhancement”. Variables extracted included trial date, demographic information, procedure performed, alleged breach of duty, alleged damages, and legal outcome. Data were analyzed using descriptive statistics. RESULTS: The initial database search yielded 48 cases that were narrowed to six after exclusions. The original surgeries took place between 1993 and 2004 while the cases were between the years of 2001 to 2008. Most cases were processed in state court systems (83%) with the majority taking place in New York (66.67%). Half of the physician defendants were urologists and half were plastic surgeons. The alleged breaches of duty included lack of informed consent (44.44%), negligence (33.33%), and deceptive business practices (22.22%). The verdict in 60% of the cases favored the defendant. Suspensory ligament release accounted for the most common (44.4%) type of augmentation surgery performed with the remaining being unspecified (33.3%), autologous fat injection (11.10%), and autologous fat grafting (11.10%). The most commonly alleged damages were equal amongst erectile dysfunction, decreased sensation, and need for additional corrective surgeries at 23.1% each. CONCLUSIONS: The relatively few cases since the 2000’s likely reflects a trend towards nonsurgical methods of penile augmentation. The main issues involved in malpractice litigation in penile augmentation surgery included lack of informed consent, negligence, and deceptive business practices. Additionally patients complained of a number of damages including sexual dysfunction and the need for corrective surgeries. Given that that total number of penile augmentation is not known, the prevalence of postoperative litigation cannot be estimated. Nevertheless, penile augmentation surgery remains investigational and providers should be aware of its medicolegal implications. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1115 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shanice Cox More articles by this author Nicolas Seranio More articles by this author Wade Muncey More articles by this author Michael Eisenberg More articles by this author Expand All Advertisement PDF downloadLoading ...

Chronic inflammatory pain promotes place preference for fentanyl in male rats but does not change fentanyl self-administration in male and female rats

The current opioid epidemic is a national health crisis marked by skyrocketing reports of opioid misuse and overdose deaths. Despite the risks involved, prescription opioid analgesics are the most powerful and effective medications for treating pain. There is a clear need to investigate the risk of opioid misuse liability in male and female adults experiencing chronic pain. In the present study, we tested the hypothesis that chronic inflammatory pain would increase fentanyl intake, motivation to acquire fentanyl, and drug seeking in the absence of fentanyl in rats. Fentanyl intake, motivation for fentanyl, and drug seeking were tested under limited and extended access conditions using intravenous fentanyl self-administration. Fos activity in ventral tegmental area (VTA) dopamine neurons following intravenous fentanyl challenge (35 μg/kg) was examined using immunohistochemistry. Finally, we tested whether low-dose fentanyl supports development of conditioned place preference under an inflammatory pain state in rats. Contrary to our hypothesis, fentanyl self-administration and VTA Fos activity were unaffected by inflammatory pain status. During acquisition, males exhibited increased fentanyl intake compared to females. Animals given extended access to fentanyl escalated fentanyl intake over time, while animals given limited access did not. Males given extended access to fentanyl demonstrated a greater increase in fentanyl intake over time compared to females. During the dose-response test, females given limited access to fentanyl demonstrated increased motivation to acquire fentanyl compared to males. Both sexes displayed significant increases in responding for fentanyl as unit fentanyl doses were lowered. Following fentanyl challenge, females exhibited higher numbers of Fos-positive non-dopaminergic VTA neurons compared to males. Using conditioned place preference, we found that chronic inflammatory pain promotes fentanyl preference in males, but not females. These findings suggest that established fentanyl self-administration is resistant to change by inflammatory pain manipulation in both sexes, but chronic inflammatory pain increases the rewarding properties of low-dose fentanyl in males.

Beyond the Glass Ceiling: Panes of Equity Partnership

This Article, prepared for a “micro-symposium” on Professor Kerri Stone’s monograph Panes of the Glass Ceiling (2022), explores the partnership pay gap in large law firms and the role of high-profile litigation in facilitating pay equity. There is a rich literature and extensive data on the gender attainment gap in elite law firms, particularly with regard to women’s attrition from practice and poor representation within the partnership ranks. Less attention has been paid to the way in which the exceptional women who achieve equity partner status continue to lag behind their male peers. This Article explores “Women v. BigLaw,” a cluster of equal pay cases brought by women partners in the late 2010s against elite firms. Using Stone’s work as a lens, it reveals how the same unspoken beliefs that underlie the law firm glass ceiling operate above it, placing women partners at the bottom of a new compensation hierarchy centered on origination credit. Due to historical allocations, a culture of deference toward male rainmakers, and implicitly biased attorney development and evaluation practices, origination operates as a form of “legacy credit” that locks in preexisting entitlements favoring male partners. Despite this, gender equity in law practice has been framed principally as a professional value, not a legal imperative. Women v. BigLaw and the unprecedented use of the court system by women lawyers reveals, however, that partnership pay practices pose a liability risk to firms. This new reality may incentivize structural change in ways that attention to gender equity as a managerial and professional goal could not.

Assessor liability DGOU

The legal liability risks in assessments are often overestimated, but also sometimes underestimated. In fact, lawsuits for incorrect assessment are rarely successful, but they are nevertheless annoying and require considerable time for those affected as defendants. In the following, the legal principles of expert opinion liability within and outside of formal court proceedings are presented.

해제로 인한 원상회복에서의 원물반환 불능의 효과

In social life, it is not uncommon for contracts of sale to be canceled. This includes contract cancellation, such as contract cancellation or cancellation pursuant to Article 565, or statutory cancellation due to delay in performance or inability to perform. At this time, the prevailing view and the Supreme Court regard the relationship of restoration to original state due to cancellation as the relationship of return of unjust enrichment, which is related to legal claims, and apply the provisions on the return of unjust enrichment unless there are special provisions such as Article 548 regarding restoration to original state. However, there are still many issues that remain unresolved here. One of such issues is the issue of liability for damages and risk bearing due to the impossibility of returning the original goods in the restoration of the original state due to cancellation, and the rightt of vicarious compensation Through this article, we will discuss the subject and scope of the obligation to return the original property and value in restoration of the original condition due to the cancellation of the sales contract, the right to make a claim for damages and the right to claim compensation for damages (Article 390) due to the impossibility of returning the original property, and the risk bearing problem. I looked. In particular, although there is no express provision in the Civil Act, the dominant view and the right to claim the subject recognized by the Supreme Court are not only recognized in the case of inability to pay (impossibility to perform), etc. I knew that it could be accepted in any case. And apart from the liability for damages caused by default on the basis of the default that caused the statutory release, if the recipient's intention or negligence is recognized for the impossibility of returning the original state due to the release, the recipient also claims to the beneficiary at this time. It was also confirmed that it could bear the liability for damages under Article 390. For example, if the buyer, who is the recipient who is to deliver (return) the object to its original condition after the contract is canceled due to the buyer's delay in paying the price, loses the object by negligence, Since the recipient, obligated to return the object, violated the duty of care of a good manager in keeping the object and destroyed the object, he is liable for damages caused by the non-fulfillment of obligations. Compensation is caused by non-fulfillment of contractual obligations, and compensation for damages due to inability to return original goods in restoration to original state due to cancellation is caused by non-fulfillment of statutory obligations, which is the obligation to restore the original state. In addition, regarding Article 553, which stipulates the special cause of extinction of the right of rescission, the prevailing opinion affirms the application of Article 553 even before the right of rescission occurs, but it is difficult to agree with the above view because the extinguishment can only be discussed after the right of rescission has occurred. It is hoped that this article will be of some help in understanding the nature and effect of the obligation to restore the original state due to cancellation.

Strategy and business model disclosures in annual reports: The role of legal regime

We examine the role of legal regime in the use and usefulness of management disclosures relating to firm strategy and the business model (SBM disclosures). We conduct our analysis in the bijural Canadian setting, where firms operate under either common law (CL) or French Civil law (FCL), depending on where they are headquartered. We find that SBM disclosures vary in length and usefulness across legal regimes. Quebec firms operating under a FCL legal regime produce less extensive SBM disclosures, but such disclosures have a more pronounced information asymmetry-reducing effect, as compared to those of firms operating in CL jurisdictions. Our analysis introduces legal liability risk related to the legal regime as an additional factor that shapes SBM disclosures in the annual reports. Our findings can be of interest to the IASB and the national accounting standard setters as they develop SBM disclosure-related implementation guidance across various jurisdictions.

Analysis of the Reasons for Medical Malpractice Litigation Due to Facet Injections.

Introduction As the use of facet joint injections (FJI) increases, practitioners performing FJI may be at increased risk of legal liability.Malpractice claim analysis is performed by several specialties as it provides valuable insight into patient values and methods to mitigate the risk of malpractice litigation pertaining to a specific procedure or treatment. Malpractice analysis regarding FJI may provide clinicians with a better understanding of the reasons that lead to malpractice due to FJI, thereby allowing practitioners to improve the quality of care delivered to patients whilst mitigating the incidence of malpractice. The aim of our study was to analyze the reasons for malpractice litigation due to FJI by querying Westlaw and VerdictSearch, two well-established legal databases widely used in medicolegal research. Methods We queried the Westlaw Edge and VerdictSearchlegal databases utilizing the terms "facet injection" and "spine". Our database queries yielded 1026 results on Westlaw Edge and 545 results on VerdictSearch. Cases were reviewed and categorized by two independent reviewers based on the grievance(s) levied by the plaintiff. Discrepancies between reviewers were resolved by a third reviewer. Inclusion criteria for case relevance were defined as a basis of litigation resting on malpractice claims filed between the years 2000-2022 directly pertaining to FJI. Additional data collected included the date of the case hearing, verdict ruling, location of filed claim, payment or settlement amount, and sustained injuries. Results Of all 1571 cases reviewed, 1568 cases were excluded due to a basis of litigation unrelated to FJI. Of the three cases pertaining to FJI, the first case involved an alleged procedural error on the part of the anesthesiologist, whereby the anesthesiologist misplaced the needle during FJI, resulting in quadriplegia due to a cervical spine infarction. The plaintiff also contended that the pre-procedural timeout was improperly conducted as the practitioner utilized iohexol as the injected contrast material despite the patient's well-documented allergy to iohexol. The jury deemed both the practitioner and hospital negligent, and a plaintiff verdict was issued. The second case was filed under a basis of litigation alleging delayed diagnosis and treatment on the part of an emergency medicine physician. The court acquitted the physician, and a defense verdict was issued.The third case was filed under a basis of litigation of alleged deviation from the standard of care on the part of the anesthesiologist, whereby the anesthesiologist performing the FJI did not use fluoroscopy.The court affirmed fluoroscopy is not dictated as the standard of care for FJI and issued a defendant verdict. Conclusion This study provides insight into the risk of medical malpractice suits brought on by facet joint injection. Our findings suggest that despite the high prevalence of facet joint injections performed annually, there is limited legal liability associated with the procedure. Nevertheless, there are certain reasons a malpractice claim may be filed due to facet injection, including gross procedural error resulting in patient paralysis, delay in treatment or diagnosis, and deviation from the established standard of care.As such, treatment decisions regarding facet joint injection should not be influenced by medicolegal concerns and remain predicated on patient care needs and standard of care.

A Novel Puff Recording Electronic Nicotine Delivery System for Assessing Naturalistic Puff Topography and Nicotine Consumption During Ad Libitum Use: Ancillary Study.

Assessing the naturalistic puff topography and associated nicotine consumption during e-cigarette use is important as such information will not only unveil how these products are being consumed in real-world conditions, but also enable investigators and regulatory bodies to conduct quantitative, accurate, and realistic harmful exposure and nicotine abuse liability risk assessments based on actual e-cigarette use. Conventional approaches cannot accurately, conveniently, and noninvasively determine e-cigarette puff topography in a natural use environment. Thus, novel technology-enabled systems that do not primarily rely on self-report mechanisms or intrusive measurements to monitor e-cigarette product use behaviors are highly desired. This study aimed to explore and demonstrate the feasibility of a novel puff recording electronic nicotine delivery system (PR-ENDS) device for measuring naturalistic puff topography and estimating nicotine consumption during the ad libitum use of products among smokers and vapers. An ancillary data analysis based on a completed parent study was conducted. The parent study was a 1-way randomized controlled open-label puff topography and nicotine pharmacokinetic assessment carried out in 24 healthy adults (12 smokers and 12 vapers). Participants were assigned a randomized product use sequence of a PR-ENDS device within 5 site visits for both controlled and ad libitum product use sessions. Blood samples were obtained for plasma nicotine analysis, and questionnaires were administered at various time points. During the ad libitum use session, puff topography was measured using a Clinical Research Support System (CReSS) device as a benchmark, as well as the PR-ENDS device with a built-in puff recording feature. There were no significant differences in representative puff topography parameters (number of puffs, total puff duration, and average puff duration) between the PR-ENDS and CReSS devices at the populational level across different device powers, e-liquid nicotine strengths, and flavors. The nicotine consumption estimated by the PR-ENDS device suggested that this device can be employed as a convenient monitoring tool for estimating nicotine use without measuring e-liquid weight loss between puffs. The linear relationship between nicotine consumption estimated by the PR-ENDS device and the pharmacokinetic parameter AUCad lib (plasma concentration-time curve for 1-hour ad libitum use) substantiated the potential of using this device as a pragmatic, noninvasive, and convenient means for estimating nicotine intake in the human body without blood collection. The novel PR-ENDS device was feasible for assessing naturalistic puff topography and estimating nicotine consumption and intake in the human body during ad libitum use. Several key factors can influence users' puff topography, including device power levels, e-liquid nicotine strengths, and flavors. The study results pave the way for further research in the real-time measurement of naturalistic puff topography and puffing behaviors in the real world.

Off-label use of reverse total shoulder arthroplasty: the American Academy of Orthopedic Surgeons Shoulder and Elbow Registry

HypothesisAfter the popularity of reverse total shoulder arthroplasty (rTSA) in Europe, the United States Food and Drug Administration (FDA) cleared the Delta rTSA system (DePuy Inc., Warsaw, IN, USA) for use in late 2003. The original FDA approved indications for rTSA in the United States were limited to a “Grossly rotator cuff deficient joint with severe arthropathy or a previous failed joint replacement with a grossly rotator cuff deficient joint.” Surgeons began to use rTSA for many off-label indications: osteoarthritis (OA) without rotator cuff tear (RCT), massive RCT without OA, proximal humerus fractures (PHFx), inflammatory arthritis (IA), and chronic glenohumeral joint dislocation (GHJD). Since 2006, The FDA has approved PHFx as an indication for some but not all reverse implants. The purpose of this study is to evaluate the trends in off-label rTSA use in the American Academy of Orthopaedic Surgeons Shoulder and Elbow Registry (AAOS-SER). MethodsAll rTSA procedures reported to the AAOS-SER from January 2015 to March 2021 were analyzed. Diagnoses associated with the use of rTSA including RCT arthropathy, OA without RCT, RCT without OA, PHFx, IA, and GHJD were evaluated, and trends were assessed over the data collection period. ResultsAt the time of data analysis the AAOS-SER contained 3850 cases of rTSA. Only 24.4% of rTSA surgeries were performed for original on-label use (RCT arthropathy). Off-label use of rTSA was seen in 75.6% of cases. When reviewing those rTSA done off-label, the majority (41.4%) were done for OA without RCT. Other off-label rTSA use included 15.1% for RCT without OA, 13% potentially off-label for PHFx, 4.6% for IA, and 1.6% for GHJD. Proportionally, off-label use is increasing over time while on-label use is decreasing. ConclusionIn the AAOS-SER, the majority of rTSA were performed for indications originally considered off-label by the FDA-a trend increasing over time. Some implant manufacturers have expanded indications for rTSA without providing clinical data to support changing FDA approved indications for use. The incremental expansion of indications for use without supportive data, a practice known as predicate creep, is occurring with rTSA. Performing rTSA for off-label indications may create liability risk for surgeons and implant manufacturers. Device manufacturers should formally expand indications of use for rTSA with the FDA to be consistent with published literature and trends.

Liability Risk Sharing Framework for Commercial Launch Industry in India

ABSTRACT There is an appreciable body of research addressing the liability issues in space launch activities. Yet, the accommodation of these principles into the legal frameworks governing commercial space launch industry in developing states, like India, is not adequately addressed. Despite being a spacefaring state since 1963, India’s commercial launching industry is in its nascent stage primarily due to statutory restrictions. Although the Indian government has allowed private participation, the liability sharing framework under the proposed laws, as reflected from drafts, is not fit to accommodate non-governmental launchings. To mend this, the paper posits that India devise a liability risk sharing framework to ensure legal certainty with a balance between industrial goals and exchequer’s interests. As such, this paper considers, comparatively and analytically, a tailored regulatory environment for first, second, and third-party liabilities in India along with damage assessment standards and insurance requirements.

The risk of personal liability for money damages under the South African Companies Act, 2008 and the possible impact on nonexecutive directors

This article considers, critically, the risks associated with imposing personal liability for money damages under the South African Companies Act and the risks of willingness by non-executive directors to serve on the board of companies due to risks associated thereto. The article considers the legal position relating to liability as it is known under common law and as it was applied by the South African courts over the years. Further consideration is given to the legal positions of similar provisions in other jurisdictions practicing similar company law practices. The introduction of the provisions requiring imposition of monetary damages on directors in South Africa followed on a comparable practice globally, specifically, on those countries which share company law practices. However, it will be discussed what South African policymakers may possibly have not considered following the deliberations during the drafting stage – as was advised by the advisors who were appointed to carry out the drafting exercise. The impact of imposing money damages will be discussed and the use of other mechanisms to mitigate against the potential effect of the statutory provisions will be discussed. Through a detailed analysis of the rights associated with money damages, recommendations will be made on how to best deal with the effects of these provisions.

Czas trwania samopomocy legalnej w rozumieniu art. 343 § 2 Kodeksu cywilnego

The article is devoted to the issue of the time in which the owner of an object can take the so-called legal self-help in order to restore the previous state of ownership pursuant to Article 343 § 2 of the Civil Code, as a result of infringement or loss of possession. In the first place the author discusses the essence of the institution itself, its place among the so-called countertypes, i.e. circumstances excluding criminal liability and the reasons for introducing this institution to the Civil Code, which has remained unchanged since the entry into force of the Act of 23 April 1964 Civil Code. Subsequently, the attention is focused on the analysis of the most important, from the perspective of the title issue, the terms “immediately after” and “instantly after”, which mark the beginning and end of the holder’s authorized action. According to the prevailing position of jurisprudence and doctrine, the possessor may do so only immediately after the infringement or loss of possession of the thing, and in the event of taking action at a later time, he runs the risk of criminal liability. The analysis carried out in the article aims to show that the literal wording of Article 343 § 2 of the Civil Code does not at all mean that self-help has to be undertaken immediately after the violation of possession or instantly after its loss, but only that it may be undertaken at such time, which would mean that both of the above-mentioned concepts determine the starting point of self-help, and not the final one, which is supported by the contextual and teleological interpretation of Article 343 § 2 of the Civil Code. The dominant interpretation of the terms “immediately after” and “instantly after” also raises doubts from the perspective of equal treatment of citizens in the same legal situation, for example as a result of loss of possession as a result of theft of possessions within the meaning of Article 278 § 1 of the Penal Code, or violation of possession as a result of violation of home privacy pursuant to Article 193 of the Penal Code, because it makes the possibility of restoring the previous state conditional only whether the holder has caught the perpetrator in the act or not. This leads to the conclusion that the possibility of exercising this right is determined, according to the currently dominant interpretation, by the time the crime was committed, and not the subjective knowledge of the holder about this fact, who for various reasons may not know about it. The article therefore attempts to show that a different interpretation of Article 343 § 2 of the Civil Code, giving the possessor the opportunity to undertake self-help throughout the period in which the perpetrator unlawfully violates possession or unlawfully possesses a given object. This position is supported in the study with examples that illustrate the advantages and disadvantages of the currently adopted, narrow interpretation of the terms “immediately after” and “instantly after”. The final part of the paper is a proposal to amend Article 343 § 2 of the Civil Code, which would leave no doubt to the interpretation of duration period of permitted self-help.

Prescribed burning on private land: reflections on recent law reform in Australia and California

Background Prescribed fire is a critical tool for building resilience to changing fire regimes. Policymakers can accelerate the development of effective, adaptation-oriented fire governance by learning from other jurisdictions. Aims We analyse reforms to prescribed fire governance to highlight improvements for fire hazard reduction and resilience. Methods We searched legislative registers in New South Wales (NSW), Australia and California, United States, identifying Bills tabled between 2011 and 2022 that mention the terms ‘prescribed (fire or burn)’ or ‘controlled (fire or burn)’. We reviewed the eight relevant Bills from NSW and 67 Bills from California to identify and thematically code reforms relevant to private landowners. Key results We found three primary themes across relevant legislative proposals: (1) reforms to simplify permitting and regulatory approval processes (primarily in Australia); (2) efforts to mitigate the risk of legal liability for escaped burns (primarily in California); and (3) recent recognition of and support for cultural burns (primarily in California). Conclusions Expanding prescribed burning on private land remains an ongoing challenge in NSW and California but recent reforms indicate greater attention, and jurisdiction-specific approaches, to this challenge. Implications Despite differing governance arrangements, California and NSW offer important insights for improving climate-adaptive governance of prescribed fire.

General Medical Practitioners Acting as Geneticists, a Risky Business?

The availability of precision medicine tools and approaches has increased considerably over the past decades, propelled by rapid scientific advances in genomics and the popularity of direct-to-consumer genetic testing. Genetic specialists working within public healthcare systems are struggling to meet the growing demand for clinical genetic services. Some experts have suggested that doctors who are not specialized in genetics could take on some of the tasks performed by genetic specialists since they are regularly the first point of contact for people with a genetic predisposition to cancer. However, expanding doctors’ roles may heighten their standard of practice and concomitant medical liability risk to that of genetic specialists. This paper reviews the medical liability regime applicable to this situation through the lens of Canada’s unique bijural legal system. We then compare the state of the law in Canada to that of the United States. According to our findings, unless there is an improvement in the quality of genetic services provided by general practitioners, we could see a growing number of successful liability suits in clinical genetics and precision medicine in the coming years. To prevent this unsatisfactory outcome, additional professional training in core genetic tasks should be made increasingly available to general practitioners and the creation of communities of practice in genetics encouraged. Furthermore, courses introducing medical students to genetics, including its ethical and legal challenges, should be made available and actively promoted within medical curricula.

The Role of Multi-Family Properties in Hedging Pension Liability Risk: Long-Run Evidence

The Role of Multi-Family Properties in Hedging Pension Liability Risk: Long-Run Evidence

External Consulting in Corporate Crisis and Insolvency: Consulting Risks and Liability Risks for Consultants in Germany

External Consulting in Corporate Crisis and Insolvency: Consulting Risks and Liability Risks for Consultants in Germany

Consulting and Liability Risks for Consultants in Corporate Crisis and Insolvency

Consulting and Liability Risks for Consultants in Corporate Crisis and Insolvency

합성생물학 위험에 대한 민사책임법적 대응

This paper deals with issues related to the concept and characteristics of synthetic biology(engineering biology), its usefulness and risks, the regulation and management of risks, and the relief of damages caused by the manifestation of risks. In particular, civil liability issues that may arise in the course of synthetic biology research and its industrialization were reviewed.
 Due to the nature of synthetic biology, it is realistically impossible to prevent all damages incurred in the process even if the operator of the technology fulfills the duty of care in operation. Damage relief through the application of the general illegal liability provisions and the Product Liability Act based on the principle of negligence liability cannot be an effective means due to the difficulty of proof, the limited scope of application, and the possibility of exemption through defense of development risks. It may also be considered to reduce the victim's burden of proof through interpretative theories such as presumption of negligence and shifting the burden of proof.
 However, in the field of high-level science and technology, it can harm legal stability because there are considerable difficulties in proving fault and making judgments.
 Damages caused by risks inherent in synthetic biology technology should be compensated through laws of risk liability. In the course of research and technical operation of synthetic biology, a person who controls and manages a risk source (Gefahrquelle) is liable for damages even if he or she is not at fault in the event that the risk materializes and infringes on the legal interests of others, which is consistent with the idea of fairness. Due to the nature of synthetic biology and genetic engineering, unlike product liability, the defense of development risk is excluded, but the assumption of causal relationship must be acknowledged. Regarding the establishment of the maximum amount of liability, considering the structure of the Damages Compensation Act, which takes the principle of limited compensation, it is judged that it is right not to limit it.
 No legislation has been enacted on risk management and regulation related to synthetic biology. In the LMO Act, there is no provision for liability for damages. Right now, it can be said that it is realistic to establish new regulations in the LMO. In addition to enhancing global industrial competitiveness through the use of synthetic biology technology, it is also a challenge to respond to legislation related to risk management, regulation, and damage relief.

Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes

Age-related macular degeneration (AMD) has been implicated as a risk factor for severe consequences from COVID-19. We evaluated the genetic architecture shared between AMD and COVID-19 (critical illness, hospitalization, and infections) using analyses of genetic correlations and pleiotropy (i.e., cross-phenotype meta-analysis) of AMD (n = 33,976) and COVID-19 (n ≥ 1,388,342) and subsequent analyses including expression quantitative trait locus (eQTL), differential gene expression, and Mendelian randomization (MR). We observed a significant genetic correlation between AMD and COVID-19 infection (rG = 0.10, p = 0.02) and identified novel genome-wide significant associations near PDGFB (best SNP: rs130651; p = 2.4 × 10-8) in the pleiotropy analysis of the two diseases. The disease-risk allele of rs130651 was significantly associated with increased gene expression levels of PDGFB in multiple tissues (best eQTL p = 1.8 × 10-11 in whole blood) and immune cells (best eQTL p = 7.1 × 10-20 in T-cells). PDGFB expression was observed to be higher in AMD cases than AMD controls {fold change (FC) = 1.02; p = 0.067}, as well as in the peak COVID-19 symptom stage (11-20 days after the symptom onset) compared to early/progressive stage (0-10 days) among COVID-19 patients over age 40 (FC = 2.17; p = 0.03) and age 50 (FC = 2.15; p = 0.04). Our MR analysis found that the liability of AMD risk derived from complement system dysfunction {OR (95% CI); hospitalization = 1.02 (1.01-1.03), infection = 1.02 (1.01-1.03) and increased levels of serum cytokine PDGF-BB {β (95% CI); critical illness = 0.07 (0.02-0.11)} are significantly associated with COVID-19 outcomes. Our study demonstrated that the liability of AMD is associated with an increased risk of COVID-19, and PDGFB may be responsible for the severe COVID-19 outcomes among AMD patients.

Role of Hepatocyte Transporters in Drug-Induced Liver Injury (DILI)-In Vitro Testing.

Bile acids and bile salts (BA/BS) are substrates of both influx and efflux transporters on hepatocytes. Canalicular efflux transporters, such as BSEP and MRP2, are crucial for the removal of BA/BS to the bile. Basolateral influx transporters, such as NTCP, OATP1B1/1B3, and OSTα/β, cooperate with canalicular transporters in the transcellular vectorial flux of BA/BS from the sinusoids to the bile. The blockage of canalicular transporters not only impairs the bile flow but also causes the intracellular accumulation of BA/BS in hepatocytes that contributes to, or even triggers, liver injury. In the case of BA/BS overload, the efflux of these toxic substances back to the blood via MRP3, MRP4, and OST α/β is considered a relief function. FXR, a key regulator of defense against BA/BS toxicity suppresses de novo bile acid synthesis and bile acid uptake, and promotes bile acid removal via increased efflux. In drug development, the early testing of the inhibition of these transporters, BSEP in particular, is important to flag compounds that could potentially inflict drug-induced liver injury (DILI). In vitro test systems for efflux transporters employ membrane vesicles, whereas those for influx transporters employ whole cells. Additional in vitro pharmaceutical testing panels usually include cellular toxicity tests using hepatocytes, as well as assessments of the mitochondrial toxicity and accumulation of reactive oxygen species (ROS). Primary hepatocytes are the cells of choice for toxicity testing, with HepaRG cells emerging as an alternative. Inhibition of the FXR function is also included in some testing panels. The molecular weight and hydrophobicity of the drug, as well as the steady-state total plasma levels, may positively correlate with the DILI potential. Depending on the phase of drug development, the physicochemical properties, dosing, and cut-off values of BSEP IC50 ≤ 25-50 µM or total Css,plasma/BSEP IC50 ≥ 0.1 may be an indication for further testing to minimize the risk of DILI liability.