Scientific Advisory Council Research Articles

Analysis of the admissibility of establishing the circumstances of intentional deprivation of life of the testator by the heir in a civil case through the lens of the presumption of innocence, the practice of the European Court of Human Rights...

The relevance of the subject under study was conditioned by the fact that in Ukrainian judicial practice, both judges and experts who are members of the Scientific Advisory Council of the Supreme Court have differed in their opinions regarding the possibility of disqualifying an heir from inheritance based on the requirements of Article 1224, Part 1 of the Civil Code of Ukraine. The purpose of this study was to clarify such general legal issues as the applicability and extension of the presumption of innocence in civil proceedings, and protection against violation of this principle in the resolution of certain civil law disputes. The methods of analysis, synthesis, comparison, generalisation, and case study were employed to examine the decisions of national courts of general jurisdiction of various instances, the Constitutional Court of Ukraine, and the European Court of Human Rights. It was stated that the deceased heir – the accused, who inflicted serious bodily injuries to his father – the testator, as a result of which the latter died, cannot be considered as having no right to inheritance, based on the analysis of the content of Article 1224, Part 1 of the Civil Code of Ukraine. The study proved that a form of condemnation by public authorities and posthumous conviction outside the scope of due process of law would be establishment by a court in a civil case of the circumstances of intentional deprivation of the testator’s life by an heir, where the former died at the time of the consideration of a civil dispute. It is unacceptable for a civil court to rely on the circumstances of the indictment and the grounds for closing criminal proceedings against a deceased defendant – an heir. Only a guilty verdict establishes a person’s guilt. If it is referred to in other procedural decisions, it is probable that the person will be socially stigmatised. A civil court may not assume the powers of a court that are exercised only in criminal proceedings when resolving a dispute over inheritance. The practical value of the study lies in the development of arguments for the court and participants in the trial

Rapid recognition and optimal management of hemophilia in the emergency department: A quality improvement project.

This study aimed to assess the effectiveness of a continuous quality improvement initiative at the University of Florida Health Physicians practice in reducing the time to administer factor replacement therapy (FRT) for hemophilia patients presenting with bleeding in the emergency department (ED). The study, a quasi-experimental, interventional design, was conducted between January 2020 and January 2023. The intervention, implemented in September 2021, involved training ED physicians, creating a specialized medication order set within the electronic health record (EHR), and a rapid triage system. The effectiveness was measured by comparing the time from ED arrival to factor administration before and after the intervention and benchmarking it against the National Bleeding Disorders Foundation's Medical and Scientific Advisory Council (MASAC)-recommended 1-hour timeline for factor administration. An interrupted time series (ITS) analysis with a generalized least squares model assessed the intervention's impact. A total of 43 ED visits (22 pre-intervention and 21 post-intervention) were recorded. Post-intervention, the average time from ED arrival to factor administration decreased from 5.63 to 3.15hours. There was no significant increase (27%vs. 29%) in the patients receiving factor within 1-hour of ED arrival. The ITS analysis predicted a 20-hour reduction in the average quarterly time to administer factor by the end of the study, an 84% decrease. The quality improvement program decreased the time to administer FRT for patients with hemophilia in the ED. However, the majority of patients did not achieve the 1-hour MASAC-recommended timeline for factor administration after ED arrival.

Constitutional Court of Ukraine - reform in the direction to European integration of Ukraine

It is indicated that a number of issues arising in connection with the activity of the Constitutional Court of Ukraine need to be resolved: 1) the num­ber of judges, 2) the amount of their financial sup­port in the conditions of martial law; 3) the term for which judges are appointed; 4) appointment procedure; 5) issues of the KSU Regulations; 6) issues of the Scientific Advisory Council of the KSU, etc. Since the KSU is the only body of constitution­al jurisdiction in Ukraine, questions regarding the reform of its structure and activity do not interfere with relevance, sometimes gaining great public res­onance. From a practical point of view, the ques­tion of the decisions made by the Court regarding their constitutionality and the possibility of appeal is important, because the mistakes made by judges create an unacceptable situation in the legislation of the country. Illegal dismissal of KSU judges by decree of the President of Ukraine, whose authority is currently not included, also becomes relevant.
 It is proposed to make comprehensive changes to some provisions of current legislation of Ukraine relating to the activities of the CCU (Articles 148, 151-2, 106 of the Constitution of Ukraine, Articles 9, 10, 11, 21, 30, 33, 41 and 75 of the Law of Ukraine "On the Constitutional Court of Ukraine”, to Article 46 of the Law of Ukraine” On the Judicia­ry and the Status of Judges ", to paragraphs 5, 22 and 23 of the Regulations on the Scientific Advisory Board of the CCU) in order to optimize the activities of the CCU.
 І consider it expedient: 1) to allow the President of Ukraine to appoint the Chairman of the CCU to resolve uncertainties and contradictions (to amend Part 4 of Article 33 of the Law of Ukraine "On CCU” and Article 148 of the Constitution of Ukraine), 2) to improve Art. 9, art. 21 of the Law of Ukraine "On CCU” and paragraph 22 of Art. 106 of the Con­stitution of Ukraine and where it is clear that the President of Ukraine appoints to office the entire CCU with the consent of the Verkhovna Rada of Ukraine, and dismisses him by decree "On dismiss­al of judges of the Constitutional Court of Ukraine”. This will determine the full influence of the Presi­dent of Ukraine as the guarantor of the Constitution of the whole state, as well as ensure the proper functioning of the CCU; 3) amend paragraph 22 of the Regulations on the Scientific Advisory Board of the CCU to clarify the costs of its activities, and add paragraph 23 on the termination of the sta­tus of a member of the Council; 4) supported the proposal of V.O. Gergeliynyk to approve the Rules of Procedure of the CCU by the Verkhovna Rada of Ukraine, which is currently approved by the Court itself and thus contradicts Art. 153 of the Constitu­tion of Ukraine, which states that the procedure for organizing and operating the Constitutional Court of Ukraine, the status of judges of the Court, the grounds and procedure for appealing to the Court, the procedure for consideration of cases and exe­cution of decisions are determined by the Consti­tution of Ukraine and law. Deadlines have been set (two months for studying the materials of the con­stitutional petition (appeal) at the preliminary pre­paratory stage), which now begin their countdown from the moment of constitutional proceedings.

Emicizumab Use in Infancy: A Survey of United States Pediatric Hemophilia Treatment Center Medical Directors

Introduction: Emicizumab, a bispecific antibody directed against activated factor IX and factor X, is a subcutaneous non-factor prophylactic option for individuals with hemophilia A (HA). The safety and efficacy of emicizumab has been demonstrated in both adult and pediatric patients. It was approved by the United States (U.S.) Food and Drug Administration for routine prophylaxis to prevent or reduce bleeding episodes in individuals with HA, ages newborn and older, both with (2017) and without (2018) factor VIII (FVIII) inhibitors. Despite this approval, data on emicizumab in infants are limited. The HAVEN 2 pediatric clinical trial had only two infants under 24 months of age, though interim analysis of the HAVEN 7 trial demonstrated emicizumab efficacy and safety in infants. Thus, the optimal use of emicizumab in infants under 12 months of age remains unclear. The objective of this study was to understand the rationale and treatment decisions regarding initiation of emicizumab prophylaxis in children under 12 months of age among pediatric Hemophilia Treatment Center (HTC) Medical Directors in the U.S. Methods: An electronic survey was conducted from April to May 2023 of U.S. HTC Medical Directors via REDCap. Invitations were sent to all individuals listed as HTC Directors at pediatric medical centers on the Center for Disease Control and Prevention database. The survey included two hemophilia patient case scenarios associated with 15 multiple-choice questions and additional free-text options. The first case was of a 9-month-old male with severe HA, without prior bleeding history or exposure to FVIII, who presented for his initial visit to an HTC. The second case was a 3-month-old male with severe HA receiving FVIII replacement therapy for an intracranial hemorrhage. This study was approved by the Baylor College of Medicine Institutional Review Board. Results: Overall, 33 of 97 (34%) pediatric HTC Medical Directors participated in the survey. One survey was minimally completed and excluded for a total of 32 surveys included in the final analysis. The majority of participants had over 15 years of experience caring for patients with HA (n=21, 65.6%) and represented HTCs with over 250 patients (n=22, 68.8%; Table 1). For previously untreated or minimally treated infants (Case 1), 96.9% of responses (n=31) stated they would consider starting emicizumab prophylaxis; 45.2% (n=14) would consider initiating it as young as 1 week of age. The most common reason cited for starting emicizumab in an infant was to prevent an intracranial hemorrhage (n=17, 53.1%) followed by the desire to avoid central line placement (n=7, 21.9%). The majority of respondents did not wait for a minimum number of factor exposure days prior to starting emicizumab (n=31, 96.9%) nor did they report regularly exposing infants to FVIII concentrate until 50 EDs are reached (n=29, 90.6%). After the initial loading phase, the majority of respondents selected an emicizumab dosing regimen of every 2 weeks (n=19, 59.4%). There was a varied approach to monitoring for inhibitor development after starting emicizumab; 40.6% (n=13) reported monitoring at regular intervals between every 6 to 24 months, whereas 46.8% (n=15) did not report following a set schedule and instead obtain FVIII inhibitor testing only after FVIII exposure (Table 2). For infants receiving FVIII replacement for treatment of an intracranial hemorrhage (Case 2), 96.9% (n=31) of participants stated they would transition to emicizumab as a prophylactic agent. Over half (n=16, 51.6%) stated they would initiate emicizumab during the treatment period for the hemorrhage rather than waiting until therapy completion. For providers that use emicizumab in moderate hemophilia, emicizumab was reported to be used routinely by 27.3% (n=6) and on a case-by-case basis in 40.9% (n=9, Table 2) in infants with moderate HA. Conclusion: Pediatric HTC Medical Directors in the U.S. report commonly utilizing emicizumab in infants under 12 months of age despite the lack of robust data in this age group. This practice is consistent with recommendations by the National Hemophilia Foundation's Medical and Scientific Advisory Council. With the completion of clinical trials focused on infants with HA, along with additional long-term outcomes data, more specific guidance around initiation, follow-up and monitoring may be available to inform the optimal management for these patients.

Scientific advisory councils in the COVID-19 response

Scientific advisory councils in the COVID-19 response

Moral damage and its perception during war: theory, legislation and judicial practice

This article analyzes the scientific works and conclusions of the members of the Scientific Advisory Council of the Supreme Court, devoted to the topical and quite important and debatable issues of compensation for moral damage and the formation of the amount of compensation. The norms of the Civil Code of Ukraine, which regulate moral damage and its compensation, the norms of the Constitution, the judicial practice of consideration of civil cases on the compensation of moral damage to the citizens of Ukraine caused by the armed aggression of the Russian Federation, as well as criminal cases, were analyzed.It was concluded that a particular difficulty in providing evidence in cases of compensation for moral (non-property) damage arises when criminal cases are considered in court, where illegal actions are performed by three or four persons. The complexity of such cases lies in the fact that it is very difficult to establish which individual's actions caused negative consequences for the victim, and the amount of compensation depends on this.In this regard, the author's analysis of court practice is quite important, in particular, the verdict of the Trostyanets District Court of Sumy Oblast dated May 9, 2023, according to which a civil claim for compensation for property damage caused by a criminal offense committed by the invaders during the period of moral damage, in particular the materials of the criminal case, where the actions and events of the committed crime were recorded, gave grounds to conclude that there are three types of evidence in cases regarding the compensation of moral damage: a) direct evidence; b) indirect evidence; c) decisive evidence. Special emphasis is placed on the assistance of the prosecutor's office in protecting the rights of Ukrainian citizens by presenting group lawsuits to the court, the mechanisms of forming such claims, collecting and recording them are revealedcircumstances and evidence needed by the courts when considering this category of cases. Particular attention is paid to the grounds of the lawsuit, in particular, generally known circumstances that do not require proof are identified. But the authors argue that the court should approach the definition of such grounds individually, taking into account the age of the persons who suffered moral damage and the consequences that have come to them. Key words: moral damage, war, compensation for damage, lawsuit, court, amount of moral damage, evidence, expert, arguments, court decisions.

The value of the ‘Science and Economic Development’ Parliamentary Links Day 2023

Potential impact is an important driver in the career choices and journeys of many. There have even been organizations set up to help people make career decisions that can boost their global impact, such as ‘80000hours.org’. Impact has always been an important motivator for me in my decisions; however, I often find myself feeling helpless to make a significant impact through my research. Informing policymaking is an activity where scientists can use their expertise to have a beneficial impact, but how to engage with policymakers can be unclear. This is why I was so excited to have been invited to attend the Royal Society of Biology’s 2023 Parliamentary Links Day on Science and Economic Development. ‘The best way to make an impact is to join scientific advisory councils and panels” was the most important recommendation I took home with me following the event; advice which helped me walk away with more clarity on how I can be impactful.

Correlates of Fluctuations in Moderate-Advanced Dementia with Lewy Bodies (P13-6.007)

<h3>Objective:</h3> To assess correlates of fluctuations in moderate-advanced dementia with Lewy bodies [DLB]. <h3>Background:</h3> Cognitive fluctuations (spontaneous episodic deficits in attention, arousal, cognition, and behavior) are a core DLB feature, but remain poorly understood. <h3>Design/Methods:</h3> The PACE-DLB study collected measures of Lewy body disease, demographics, and patient and caregiver experiences from moderate-advanced DLB individual-caregiver dyads. Fluctuations were assessed via the Mayo Fluctuations Scale (MFS, range 0–4) and Clinician Assessment of Fluctuation (CAF, range 0–16). Concordance was assessed using Spearman correlation for raw scores and Cohen’s Kappa for assessing scores above/below the cut-off. Nonparametric methods including Spearman correlation, two-sample Wilcoxon test, and odds ratios assessed factors associated with fluctuations. The FDR method corrected raw scores for multiple testing. <h3>Results:</h3> Patients (n=137) identified as white non-Hispanic (94.9%) and male (79.6%); mean age 75.0 (SD 8.0), disease duration 3.0 years (SD 2.4). Caregivers were typically wives (72.3%) and daughters (13.1%). On the MFS, 116 participants (84.7%) had fluctuations (score ≥3) (mean 3.3, SD 0.8) versus 116 (84.7%) on the CAF (score &gt;0) (correlation: 0.2, p&lt;0.001; fluctuations absent/present: 0.3, p=0.002). The mean CAF score was 8.8 (SD 6.6). Variables associated with a positive MFS included higher sleepiness scores (p=0.02), lower QoL-AD scores (p=0.02), and parkinsonism (p=0.02). No variables associated with a positive CAF. Higher MFS scores associated with higher sleepiness scores (p&lt;0.001), lower QoL-AD, and more autonomic symptoms (p=0.03). Higher CAF scores associated with higher Neuropsychiatric Inventory severity scores (p&lt;0.0001), hallucinations (p=0.045), orthostatic hypotension (p=0.02), more comorbidities (p=0.04), and higher sleepiness scores (p=0.045). Fluctuations associated with worse patient and caregiver quality of life and higher caregiver burden and depression. <h3>Conclusions:</h3> The MFS and CAF correlated weakly. Fluctuations associated with sleepiness, autonomic symptoms, parkinsonism, and neuropsychiatric symptoms. Given the impact of fluctuations on quality of life and caregiver burden and depression, fluctuations are an important target for future pharmacologic therapies. <b>Disclosure:</b> Dr. Tholanikunnel has nothing to disclose. Mr. LaBarre has nothing to disclose. Ms. Sovich has nothing to disclose. Li Zhigang has nothing to disclose. James Galvin has nothing to disclose. Dr. Paulson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Exicure. The institution of Dr. Paulson has received research support from National Institutes of Health. Dr. Paulson has a non-compensated relationship as a Member, Nominating committee with American Neurological Association that is relevant to AAN interests or activities. An immediate family member of Dr. Maixner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Law office . The institution of Dr. Manning has received research support from Department of Defense. The institution of Dr. Fields has received research support from National Institutes of Health. The institution of Dr. Fields has received research support from Patient-Centered Outcomes Research Institute. Ms. Lunde has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Mayo Clinic . Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care. Ms. Forsberg has nothing to disclose. Angela Taylor has received personal compensation for serving as an employee of Lewy Body Dementia Association . The institution of Dr. Armstrong has received research support from National Institute of Aging. The institution of Dr. Armstrong has received research support from Florida Department of Health. The institution of Dr. Armstrong has received research support from Lewy Body Dementia Association. Dr. Armstrong has received research support from Parkinson Foundation. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Clinical Trials Consortium. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Disease Cooperative Study. Dr. Armstrong has a non-compensated relationship as a Member, Scientific Advisory Council with Lewy Body Dementia Association that is relevant to AAN interests or activities.

Perspectives on Parkinson’s Disease Medications: A Qualitative Study of People with Parkinson’s Disease (P14-11.015)

<h3>Objective:</h3> To explore the thoughts, beliefs, and expectations of people with Parkinson’s disease (PwPD) regarding their Parkinson’s disease (PD) medications. <h3>Background:</h3> Few studies investigate the factors that inform the impact of PD medications on individuals’ lives. This qualitative study aims to better understand PwPD’s experiences with and perspectives on their medications. <h3>Design/Methods:</h3> PwPD treated with PD medications at five movement disorder clinics in five states across the United States were recruited to participate in semi-structured interviews (SSIs) and focus groups (FGs). Interview and moderator guides developed to explore participants’ experiences with PD medication were utilized. Inclusion criteria consisted of confirmed PD diagnosis, history of taking medications for PD, aged ≥18 years, and ability to consent and participate. SSI and FG transcripts were analyzed via grounded theory methodology to identify primary themes and subthemes. <h3>Results:</h3> Twenty PwPD (8 females/12 males; aged 48–80 years) participated in one-hour telephone SSIs and 32 (16 females/16 males; aged 57–86 years) participated in one-hour online FGs. Four primary themes (subthemes in parentheses) emerged regarding medications for PD: (1) effectiveness (effectiveness uncertainty, expectation realignment), (2) side effects (tolerating side effects, discerning side effects vs disease progression), (3) timing challenges (dosage timing, off-times), and (4) desires (more options, therapy advancement). Participants were uncertain whether they were experiencing the full benefits of their medications and unsure of whether their symptoms were medication side effects or signs of disease progression. High dosing frequency is especially taxing on PwPD, and participants expressed a desire for longer-lasting medications and more therapeutic options. <h3>Conclusions:</h3> This study identified four core dimensions of PD medications from the perspective of PwPD. Results indicate the need for enhanced communication between providers and patients regarding PD medication to reduce uncertainties around symptom burden, and continued efforts to develop and advance PD treatments. <b>Disclosure:</b> Dr. Richards has received research support from Cerevel Therapeutics. Dr. Brown has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Taiho. Dr. Brown has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Patient Centered Outcomes Research Institute (PCORI). The institution of Dr. Brown has received research support from National Comprehensive Cancer Network/Pfizer. The institution of Dr. Brown has received research support from American Society of Clinical Oncology/Pfizer. The institution of Dr. Brown has received research support from Cerevel Therapeutics . Dr. Johnsrud has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Atlas Clarity. Dr. Johnsrud has stock in NuCara Management Group. The institution of Dr. Johnsrud has received research support from Cerevel Therapeutics. Dr. Arcona has received personal compensation for serving as an employee of Cerevel. Dr. Arcona has stock in Cerevel. Dr. Sasane has nothing to disclose. The institution of Dr. Armstrong has received research support from National Institute of Aging. The institution of Dr. Armstrong has received research support from Florida Department of Health. The institution of Dr. Armstrong has received research support from Lewy Body Dementia Association. Dr. Armstrong has received research support from Parkinson Foundation. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Clinical Trials Consortium. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Disease Cooperative Study. Dr. Armstrong has a non-compensated relationship as a Member, Scientific Advisory Council with Lewy Body Dementia Association that is relevant to AAN interests or activities. Dr. Feuerstein has nothing to disclose. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal Pharmaceuticals. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbive. Dr. Talman has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Oregon Federal Public Defenders Office. Dr. Talman has received personal compensation in the range of $500-$4,999 for serving as a panelist with HDSA. Dr. Mantri has received personal compensation in the range of $0-$499 for serving as a Consultant for Deep Brain Innovations, LLC. Dr. Mantri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grey Matter Technology. The institution of Dr. Mantri has received research support from The Michael J Fox Foundation for Parkinson Research.

Longitudinal free-water changes in dementia with Lewy bodies (P8-11.007)

<h3>Objective:</h3> To characterize longitudinal diffusion microstructural changes in individuals with dementia with Lewy bodies (DLB). <h3>Background:</h3> Diffusion-weighted MRI (dMRI) examines tissue microstructure integrity and white matter pathways in vivo. Prior DLB studies focused on white matter or voxel-based techniques. Less is known about longitudinal white and grey matter microstructural changes in DLB. <h3>Design/Methods:</h3> dMRI scans were collected on individuals with DLB from the Mayo Clinic Longitudinal Imaging Biomarkers of DLB Program. Demographics, clinical evaluations and MRI were collected at baseline, and 12 or 24 months. Free-water (FW) and FW-corrected fractional anisotropy (FA_T) were analyzed in grey and white matter using 122 bilateral template regions and tracts of interest in Montreal Neurological Institute space. Primary outcomes were differences in FW and FA_T between baseline and 12 or 24 months. <h3>Results:</h3> We identified 23 individuals with DLB from baseline to 12 months [mean age 69.3 years (SD 9.5); 95.8% male], and 16 individuals from baseline to 24 months [mean age 67.5 years (SD 9.3); 100% male]. Participants at both time-points showed worsening in Montreal Cognitive Assessment and Movement Disorders Society Unified Parkinson’s Disease Rating Scale motor scores (<i>p</i>&lt;0.05). We found significant differences in FW, but not FA_T, from baseline to 12 months. Significant increases in FW at both time-points compared to baseline were observed in the insula, putamen, parahippocampal, and rolandic operculum regions (p&lt;0.05). We found more widespread microstructural changes from baseline to 24 months, with increased FW in the amygdala, entorhinal, mid and posterior cingulum, inferior frontal, hippocampal, pallidum, precuneus and retrosplenial regions (p&lt;0.05). We found decreased FA_T from baseline to 24 months in the cerebellar and superior occipital regions (<i>p</i>&lt;0.01). <h3>Conclusions:</h3> Longer follow-up at 24 months identified broader networks of free-water changes in individuals with DLB. More investigation is needed to evaluate the relationship of microstructural changes with clinical progression in DLB. <b>Disclosure:</b> Dr. Chiu has received research support from NIH/NIA. Mr. Chen has nothing to disclose. Dr. Wang has nothing to disclose. The institution of Dr. Armstrong has received research support from National Institute of Aging. The institution of Dr. Armstrong has received research support from Florida Department of Health. The institution of Dr. Armstrong has received research support from Lewy Body Dementia Association. Dr. Armstrong has received research support from Parkinson Foundation. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Clinical Trials Consortium. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Disease Cooperative Study. Dr. Armstrong has a non-compensated relationship as a Member, Scientific Advisory Council with Lewy Body Dementia Association that is relevant to AAN interests or activities. Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care. The institution of Dr. Kantarci has received research support from Eli Lilly. The institution of Dr. Kantarci has received research support from NIH. The institution of Dr. Kantarci has received research support from ADDF. David Vaillancourt has received personal compensation for serving as an employee of Automated Imaging Diagnostics. David Vaillancourt has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. The institution of David Vaillancourt has received research support from NIH. David Vaillancourt has received intellectual property interests from a discovery or technology relating to health care.

Recommendations of the Scientific Advisory Council at the Intellectual Property Rights Court on issues arising when establishing one economic goal and the unity of intentions of the offender (paragraphs 56 and 65 of the Resolution of the Plenum of the Supreme Court of the Russian Federation dated 23.04.2019 No. 10 "On the application of Part Four of the Civil Code

Recommendations of the Scientific Advisory Council at the Intellectual Property Rights Court on issues arising when establishing one economic goal and the unity of intentions of the offender (paragraphs 56 and 65 of the Resolution of the Plenum of the Supreme Court of the Russian Federation dated 23.04.2019 No. 10 "On the application of Part Four of the Civil Code

Scientific Advisory Council at the Constitutional Court of Ukraine as a subject of scientific support of its activity

The article examines the issue of determining the legal status of the Scientific Advisory Council at the Constitutional Court of Ukraine, the mechanisms and directions of its functioning, and reveals the uniqueness of this institution of scientific support for the Court's activities.The peculiarities of the legal status of the Scientific Advisory Council, which determine its uniqueness, are revealed. It was determined that the powers of the Scientific Advisory Council, the areas of activity of its members are derived from the powers of the Constitutional Court of Ukraine and are regulated at the level of a state by-law. It is emphasized that the activities of the Scientific Advisory Council are open and transparent.

Criminal and legal protection of the activity of a legal expert

The analysis of the norms of the Criminal Code of Ukraine allowed to establish the availability of only two articles (Articles 343, 386) that provide responsibility for illegal actions against an expert. It has been stated that among the victims of such criminal offenses, the theory of law defines exactly judicial experts. In the article, an attempt is made to investigate the question of whether legal experts belong to the category of judicial specialists (experts), and to evaluate the legal significance of the scientific and legal conclusions they prepare.&#x0D; It was affirmed that the relevant legislation does not provide the recognition by a judicial expert of such a specialist as an expert on legal issues. It has been established that certain procedural (civil, economic and administrative justice) codes divide the categories of legal expert” and “judicial expert”, which are significantly different; however, the criminal procedural code of Ukraine does not contain such a concept at all, but uses the term expert as a participant in the criminal process, that is a judicial expert. The analysis of judicial practice and scientific literature allowed us to assume that the conclusions of scientific and legal expertise are used in the criminal process.&#x0D; It has been proven that the Supreme Court and the Constitutional Court of Ukraine use in their practice the conclusions of the members of the scientific advisory councils, i.e. experts in the field of law. A certain injustice was noted regarding the possibilityof using conclusions on legal issues in court proceedings at different levelsof the judicial system.&#x0D; The considered provisions of the regulatory legal acts allowed to classify expert conclusions on legal issues depending on certain criteria: by legal meaning (prohibited for use and permitted for use); by compensatory nature (paid and unpaid); according to the procedure of involving an expert (on the initiative of the participants in the process and on the initiative of the court).&#x0D; The article suggests the characteristics of an expert conclusion on legal issues: it has a recommendatory character; has local legal significance (refers to a specific court case); is not evidence in the case; does not entail legal responsibility for the expert; can be prepared by both an individual and a legal entity.&#x0D; The conducted research allowed to draw certain conclusions: a legal specialist (expert) does not belong to the category of judicial experts; the legal status of a legal specialist (expert) and a judicial expert have significant differences; the victim in the commission of criminal offenses provided in Articles 343 and 386 of the Criminal Code of Ukraine cannot be a legal specialist (expert); based on the study of foreign experience, law-making activity, current legislation and national law enforcement practice, it is proposed to extend such a legal institution to the Criminal Procedure Code of Ukraine and the Code of Ukraine on Administrative Offenses; in the legislation, it is recommended to provide a mechanism of criminal legal protection of the activity of a legal specialist (expert) by making appropriate changes to Articles 343 and 386 of the Criminal Code of Ukraine.

100-OR: Association of Recent Myocardial Infarction with Insulin Resistance and Fatty Liver Disease in Type 2 Diabetes

Insulin resistance and nonalcoholic fatty liver disease (NAFLD) frequently associate with type 2 diabetes (T2D) and cardiovascular disease and worsen their prognosis. We hypothesized that people with recent myocardial infarction (MI) have lower left ventricular ejection fraction (EF) and higher degree of insulin resistance (IR) , hepatocellular lipid content (HCL) and risk of hepatic fibrosis than matched people without MI. Thus, participants of the “DIabetes and ST-Elevation MI (DISTEMI) Study” were examined 6-12 weeks after MI (MI+; n=53, 28% T2D) and compared to age-, sex-, BMI-matched people without MI (MI-; n=48, 31% T2D) . Insulin sensitivity was assessed during fasting (Homeostasis Model Assessment (HOMA) 2-IR) and hyperinsulinemic-euglycemic clamps (M-value) . EF, HCL and liver stiffness, associated with fibrosis stages, were quantified by 1H-magnetic resonance imaging, spectroscopy and elastography, respectively. MI+ had a lower EF (47±2 vs. 58±1 %, p&amp;lt;0.0001) and M-value (7.3±0.4 vs. 8.2±0.4 mg*kg-1*min-1, p&amp;lt;0.05) compared to MI-, which was mainly due to a difference between the T2D groups (EF: 39±6 vs. 52±2 %, p&amp;lt;0.001; M-value: 4.2±0.5 vs. 6.1±0.6 mg*kg-1*min-1, p&amp;lt;0.05) . HCL (3.4±0.8 vs. 5.8±0.9 %) and liver stiffness (2.2±0.1 vs. 2.3±0.1 kPa) were comparable between MI+ and MI-. HCL correlated negatively with M-value (r=-0.95, p&amp;lt;0.05) and positively with systolic blood pressure (r=0.91, p&amp;lt;0.05) in MI+ with T2D. In MI+ without T2D, HCL correlated positively with HOMA2-IR (r=0.58, p&amp;lt;0.01) and BMI (r=0.53, p&amp;lt;0.01) . In conclusion, recent myocardial infarction in people with type 2 diabetes associates with decreased ejection fraction and increased insulin resistance. The correlation between insulin resistance and liver fat content suggests that HCL can serve as a non-invasive cardiovascular marker and may identify persons with a worse outcome after myocardial infarction. Disclosure C.Möser: None. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. O.P.Zaharia: n/a. F.C.Michlotti: None. Y.Kupriyanova: None. V.Schrauwen-hinderling: None. P.Bobrov: None. V.Burkart: None. M.Kelm: Board Member; DGIM-Deutsche Geselleschaft für Innere Medizin, DGK-Deutsche Gesellschaft für Kardiologie, DSHF-Deutsche Stiftung für Herzforschung, ESC- European Society of Cardiology, Other Relationship; Abiomed , Bayer AG, diaplan, Kel Con GmbH, Research Support; Abiomed Europe GmbH, B.Braun, Edwards Lifesciences Corporation, European Union, IPP Med GmbH - Institut für Pharmakologie u. präventive Medizin GmbH, Mars Scientific Advisory Council (MSAC) , Medicure Inc., Microvision Medical. J.M.Szendroedi: Consultant; Boehringer Ingelheim International GmbH. Funding Research Network SFB 1116 of the German Research Foundation

Effects of Bypassing Hemostatic Agents in the Co-Presence of NXT007, Emicizumab-Based Engineered Bispecific Antibody to Fixa/Fx, Using in Vitro Global Assays: Rough Indicators for Their Concomitant Use

Background:NXT007, emicizumab (Emi)-based engineered therapeutic bispecific antibody which increases tissue factor (TF)-triggered thrombin generation (TG) potential of factor(F) VIII-deficient plasma to non-hemophiliac ranges at around 5-30 μg/mL (Yamaguchi, ASH 2020), is currently in a phase 1/2 clinical study. In the clinical settings under NXT007-prophylaxis, bypassing hemostatic agents (BPAs), such as activated prothrombin complex concentrates (aPCC) and recombinant(r) FVIIa, may be concomitantly administered. Under Emi-prophylaxis, repeated doses of aPCC impose a thrombotic risk. Against the risk, NHF's Medical and Scientific Advisory Council (MASAC) recommends ≤50 U/kg and ≤100 U/kg of aPCC as initial dose and one day dosage, respectively. In case of NXT007-prophylaxis, concomitant-use with BPAs should be also carefully managed and thus basic non-clinical combination data are needed.Objectives:To examine in vitro effects of BPAs in the co-presence of NXT007 for providing rough indicators for determining their safe doses.Methods:First, TF-triggered TG assay was performed using commercial FVIII-deficient plasma. rFVIII, rFVIIa or aPCC was spiked in the co-presence of NXT007 or Emi (0.1-50 μg/mL). Second, the TG assay and whole blood clot viscosity test (ROTEM) using Ca 2+-trigger was performed using healthy volunteer's blood incubated with anti-FVIII antibodies (HA model), where aPCC or rFVIIa was spiked in the co-presence of NXT007. Third, ROTEM was performed as above using whole blood from persons with hemophilia A (PwHA) under Emi- or FVIII-prophylaxis.Results:Peak height of TF-triggered TG assay using FVIII-deficient plasma was increased by spiking each of the agents (rFVIII, rFVIIa or aPCC) in the co-presence of NXT007 (0.1-50 μg/mL). Peak height increase by rFVIII under NXT007 was roughly additive. Peak height increase by each BPA under NXT007 was synergistic. Synergistic effect by aPCC was more intensive than that by rFVIIa. The combination effect of 0.1 U/mL aPCC and 0.1-50 μg/mL NXT007 on peak height did not exceed that of 0.5 U/mL aPCC and 50 μg/mL Emi. Peak height at 2 μg/mL NXT007 alone was comparable to that at 50 μg/mL Emi alone. When adding BPAs to these two settings, similar synergistic effects were observed. It suggested that NXT007's combination actions with BPAs were qualitatively similar to Emi's.In the TG assay using the HA model plasma (n=2), the combined effect of aPCC and NXT007 was similarly confirmed. In ROTEM using the same HA model whole blood (n=2), clotting time (ROTEM-CT, 7380±605 sec) was shortened by spiking 5 μg/mL NXT007 (791±148 sec) to yield normal levels (1521±110 sec). Spiked aPCC (0.13, 0.65 U/mL in whole blood, equivalent to ~10, ~50 U/kg infusion) shortened ROTEM-CT (1228±549, 435±54 sec) and further shortened it in the co-presence of 5 or 15 μg/mL NXT007 (171±11, 113±1* or 143±4, 90±5* sec [* significantly ( p<0.05) shorter than that of the Emi-treated PwHA blood spiking 0.65 U/mL aPCC, 162±21 sec)].In PwHA without Emi-prophylaxis (n=2), ROTEM-CT (5148±1290 sec) was shortened by spiking 5 or 15 μg/mL NXT007 (1598±482 or 1116±14 sec) to non-hemophiliac levels (20 IU/dL rFVIII, 1569±222 sec). Spiked aPCC (0.13, 0.65 U/mL) shortened ROTEM-CT (1383±322, 680±84 sec) and further shortened it in the co-presence of 5 or 15 μg/mL NXT007 (230±35, 144±4 or 193±11, 121±0* sec). Spiked rFVIIa also shortened ROTEM-CT in the co-presence of NXT007, but the intensity was less than spiked aPCC.ROTEM using blood from PwHA under Emi-prophylaxis (n=3) were also performed and demonstrated that the effects by co-spiking BPAs and NXT007 were roughly consistent with those using PwHA blood without Emi-prophylaxis. These ROTEM data indicated that the combined effect of 0.13 U/mL aPCC and 5-15 μg/mL NXT007 was less intensive than that of 0.65 U/mL aPCC spiked to the Emi-treated PwHA blood, while that of 0.65 U/mL aPCC and 5-15 μg/mL NXT007 had more intensive effect (Table).Conclusion:In considering concomitant use of BPA under NXT007-prophylaxis, dose of aPCC should be more carefully determined than that of rFVIIa. In this non-clinical study, the combined effect of ~0.13 U/mL aPCC (equivalent to ~10 U/kg infusion) and ~15 μg/mL NXT007 did not exceed that of 0.65 U/mL aPCC (50 U/kg infusion) under Emi-prophylaxis situation corresponding to the upper limit of initial concomitant dose recommended by MASAC, which might be rough indicators in future clinical settings. [Display omitted] DisclosuresOgiwara: Chugai Pharmaceutical Co., Ltd.: Consultancy, Research Funding. Furukawa: Chugai Pharmaceutical Co., Ltd.: Research Funding. Sasai: Chugai Pharmaceutical Co., Ltd.: Research Funding. Inaba: Chugai Pharmaceutical Co., Ltd.: Current Employment. Kitazawa: Chugai Pharmaceutical Co., Ltd.: Current Employment, Current equity holder in publicly-traded company. Nogami: Chugai Pharmaceutical Co., Ltd.: Consultancy, Research Funding.

Editorial introductions

Editorial introductions

Ethical Decision Making Framework in Previously Untreated Severe Hemophilia A Patients

Treatment recommendations and decision making for severe hemophilia A previously untreated patients (PUPs) have recently become a significant debate with an ethical valence. Primary prophylaxis, initiation of factor replacement prior to the second joint bleed and before the age of three, has been the recommended standard of care in resource rich countries for the last two decades. Since the widespread availability of recombinant factor VIII (rFVIII) products, the choice has been fairly straightforward for PUPs, whereby transmission of blood borne pathogens associated with plasma-derived FVIII (pdFVIII) products were avoided. The Survey of Inhibitors in Plasma-Products Exposed Toddlers (SIPPET) randomized controlled trial demonstrated a higher incidence of FVIII alloantibody inhibitors in PUPs started on rFVIII products compared to pdFVIII products (Peyvandi F, et al., 2016). This finding has had a tremendous controversial impact on the decision making of product choice for PUPs despite the supportive Medical and Scientific Advisory Council recommendations to consider starting a PUP on a pdFVIII product (MASAC, 2016).For this patient population, we developed a modified utilitarian framework of decision making that employs clinical, public health, and research ethics. The framework recognizes that there are many stakeholders involved in the provision of FVIII products and health care of those with severe hemophilia A and provides guidance when there is concern for bias. Utilizing the premise of shared decision making, the framework takes a patient and family centered rather than a paternalistic approach. In discussions about care, it is recommended that the provider learn about relevant patient and family values. Doing so would better enable providers to inform the patient and family about the available treatments (including the risks, benefits and alternatives) and disclose any conflicts of interest and biases. Using shared decision making would serve to maximize understanding, minimize bias, respect informed consent or dissent, and provide care that aligns with patient values when medically and practically feasible.The framework has three tiers. First, it evaluates whether resources are scarce or abundant, which is important in equitably allocating resources. Where life-saving FVIII products are scarce, there could be a direct impact on patient care and clinical research. Healthcare providers would be at risk of compromising not only standard of care but also their fiduciary responsibilities to patient care in bedside rationing. If FVIII products are scarce, we recommend developing a central supply for emergency use and then evaluating the needs of the severe hemophilia A patients. Prioritization of who receives the factor products would be decided by a designated team based on the availability of the factor products and clinical scenarios, with no preference given to those on research trials. However, if resources are abundant, treatment for acute bleeding and standard of care prophylaxis measures, including primary prophylaxis, could continue.The second tier takes into account whether there is a new infectious epidemic or concern where the pathogen cannot be eliminated. If not, pdFVIII and rFVIII products are to be equally presented. If there is an epidemic, healthcare and public health workers may limit the use of pdFVIII products.The third tier evaluates the clinical scenario and if there is an acute bleeding emergency or not. If there is an acute bleeding event, the immediately available resource should be recommended, along with bypassing and/or adjuvant resources as needed until the bleeding has resolved or improved. To align with patient and family preferences, attempts to have both pdFVIII and rFVIII products available at similar costs in institutions would be ideal.The ethical framework we developed endeavors to balance autonomy, beneficence, nonmaleficence and justice. As treatment decisions are complex, the framework may help guide discussions among providers, PUPs with severe hemophilia A, and their families.Disclaimer:The findings and conclusions in this abstract are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention, Emory University, or Children's Healthcare of Atlanta. DisclosuresSidonio:Bioverativ: Consultancy; CSL Behring: Consultancy; Grifols: Research Funding; Bioverativ: Research Funding; Shire: Consultancy, Research Funding; Novo Nordisk: Consultancy; Bayer: Consultancy.

Development and psychometric properties of surveys to assess provider perspectives on the barriers and facilitators of effective care transitions

BackgroundThe quality of the discharge process and effective care transitions between settings of care are critical to minimize gaps in patient care and reduce hospital readmissions. Few studies have explored which care transition components and strategies are most valuable to patients and providers. This study describes the development, pilot testing, and psychometric analysis of surveys designed to gain providers’ perspectives on current practices in delivering transitional care services.MethodsWe underwent a comprehensive process to develop items measuring unique aspects of care transitions from the perspectives of the three types of providers (downstream, ambulatory, and hospital providers). The process involved 1) an environmental scan, 2) provider interviews, 3) survey cognitive testing, 4) pilot testing, 5) a Stakeholder Advisory Group, 6) a Scientific Advisory Council, and 7) a collaborative Project ACHIEVE (Achieving Patient-Centered Care and Optimized Health in Care Transitions by Evaluating the Value of Evidence) research team. Three surveys were developed and fielded to providers affiliated with 43 hospitals participating in Project ACHIEVE. Web-based survey administration resulted in 948 provider respondents. We assessed response variability and response missingness. To evaluate the composites’ psychometric properties, we examined intercorrelations of survey items, item factor loadings, model fit indices, internal consistency reliability, and intercorrelations between the composite measures and overall rating items.ResultsResults from psychometric analyses of the three surveys provided support for five composite measures: 1) Effort in Coordinating Patient Care, 2) Quality of Patient Information Received, 3) Organizational Support for Transitional Care, 4) Access to Community Resources, and 5) Strength of Relationships Among Community Providers. All factor loadings and reliability estimates were acceptable (loadings ≥ 0.40, α ≥ 0.70), and the fit indices showed a good model fit. All composite measures positively and significantly correlated with the overall ratings (0.13 ≤ r ≤ 0.71).ConclusionsWe determined that the items and composite measures assessing the barriers and facilitators to care transitions within this survey are reliable and demonstrate satisfactory psychometric properties. The instruments may be useful to healthcare organizations and researchers to assess the quality of care transitions and target areas of improvement across different provider settings.

Peter John Bell Clarricoats. 6 April 1932—17 January 2020

Peter Clarricoats made fundamental contributions as a microwave engineer in the fields of applied electromagnetics for microwave and optical waveguides, and microwave antenna feeds. Peter was also a pioneer of optical fibres, and established the theory of electromagnetic propagation on dielectric and ferrite structures. In the course of this, he discovered that such structures can, under some conditions, support ‘backward waves’ and that guides can propagate complex modes. Over 40 years of his academic career, Peter Clarricoats had numerous notable achievements, including pioneering designs for shaped reflectors, reconfigurable reflectors and especially corrugated horns for microwave antennas. The latter are now universally used in satellite ground stations and in spacecraft. He published what became standard reference texts on corrugated horns for microwave antennas, microwave horns and feeds. He served as vice-president of both the Institution of Engineering and Technology and the International Union of Radio Science, and from 1998 to 2000 was chairman of the Defence Scientific Advisory Council. He was appointed a CBE in 1996. He is the recipient of the 2001 Distinguished Achievement Award of the Institute of Electrical and Electronics Engineers Antennas and Propagation Society, and in 2015 he received the Sir Frank Whittle Gold Medal from the Royal Academy of Engineering.

The State of Melanoma: Emergent Challenges and Opportunities.

Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence, and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike, prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for patients with melanoma and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome, and offer recommendations for the best path forward.