Background:Uganda's population, though, largely characterized by young people, has seen the number of people aged 60 and over grow from 686,000 twenty years ago, to 1,433,596 in 2014. Effective caring for the well-being of this population requires strategic and deliberate planning that involves Quality Of Life (QoL) assessments. QoL assessments among the elderly are important in evaluating the efficacy of strategies, such as health interventions, welfare programs, health care and well-being of the elderly. However, elderly in Uganda face several challenges, ranging from loneliness, poor housing, lack of social and financial support and poor health. These may negatively affect older persons' quality of life and consequently their perceptions and attitudes towards aging.Methods:The study was carried out in 2019 in the communities of Nansana and Busukuma town councils in Wakiso district, Uganda. The participants were 380 people 60 years and older. To establish the association between perceptions of ageing and QoL, this study utilized a locally adapted version of the Older Person's Quality of Life Questionnaire (OPQOL) and the Brief Ageing Perceptions Questionnaire (B-APQ). The OPQOL assesses three domains of QoL: Health QoL (HQoL); Social economic QoL (SQoL); and Psychosocial QoL (PQoL). The B-APQ assesses perceptions about physical age, participation in social activities, and perceptions about ability to regulate emotions as one ages. Pearson's Chi-square tests were used to characterize the relationship between the perceptions and quality of life.Results:The majority of the respondents, 61% (95%CI 56.7-64.8), had negative perceptions towards ageing. Eighty six percent had poor HQoL, 90% poor SQoL and 83% poor PQoL. There was a significant association between good HQoL and positive perception about participation in social activities (X2 = 7.3670, P = 0.007) as well as with positive perception on regulation of emotions (X2 = 18.1803, P<0.001). There was a significant association between good SQoL and positive perception about participation in social activities (X2 = 5.3472, P = 0.021), as well with positive perception on regulation of emotions (X2 = 10.5128, P<0.001). A significant association between good PQoL and positive perception on regulation of emotions (X2 = 9.2414, P= 0.002).Conclusion:Positive perceptions of ageing are associated with good QoL. Directly addressing perceptions of ageing could be a low cost and effective strategy to improve the QoL of older persons in SSA.

A 48-year-old male with hypertension, uncontrolled type 2 diabetes mellitus, tobacco use, and opioid use disorder presented to a hospital in Baltimore, MD, in September with a right-foot plantar surface wound. He noticed the wound 3 weeks prior and attempted his own wound care and dressings while living in his car. The wound enlarged and developed increasingly purulent drainage, with visible maggots, and his foot became swollen. A review of systems was notable for malaise, fatigue, and anorexia.

Background Men in Sub-Saharan Africa are less engaged than women in accessing HIV testing and treatment and, consequently, experience higher HIV-related mortality. Reaching men with HIV testing services is challenging, thus, increasing the need for innovative ways to engage men with low access and those at higher risk. In this study, we explore men’s perceptions of drivers and barriers of workplace-based HIV self-testing in Uganda. Methods An exploratory study involving men working in private security companies employing more than 50 men in two districts, in central and western Uganda. Focus group discussions and key informant interviews were conducted. Data were analyzed using inductive content analysis. Results Forty-eight (48) men from eight private security companies participated in 5 focus group discussions and 17 key informant interviews. Of the 48 men, 14(29.2%) were ages 26–35 years. The majority 31(64.6%) were security guards. The drivers reported for workplace-based HIV self-testing included convenience, autonomy, positive influence from work colleagues, the need for alternative access for HIV testing services, incentives, and involvement of employers. The barriers reported were the prohibitive cost of HIV tests, stigma, lack of testing support, the fear of discrimination and isolation, and concerns around decreased work productivity in the event of a reactive self-test. Conclusions We recommend the involvement of employers in workplace-based HIV self-testing to encourage participation by employees. There is need for HIV self-testing support both during and after the testing process. Both employers and employees recommend the use of non-monetary incentives, and regular training about HIV self-testing to increase the uptake and acceptability of HIV testing services at the workplace.

Inhibitors of leucine-rich repeat kinase 2 (LRRK2) and mutants, such as G2019S, have potential utility in Parkinson's disease treatment. Fragment hit-derived pyrrolo[2,3-d]pyrimidines underwent optimization using X-ray structures of LRRK2 kinase domain surrogates, based on checkpoint kinase 1 (CHK1) and a CHK1 10-point mutant. (2R)-2-Methylpyrrolidin-1-yl derivative 18 (LRRK2 G2019S cK(i) 0.7 nM, LE 0.66) was identified, with increased potency consistent with an X-ray structure of 18/CHK1 10-pt. mutant showing the 2-methyl substituent proximal to Ala147 (Ala2016 in LRRK2). Further structure-guided elaboration of 18 gave the 2-[(1,3-dimethyl-1H-pyrazol-4-yl)amino] derivative 32. Optimization of 32 afforded diastereomeric oxolan-3-yl derivatives 44 and 45, which demonstrated a favorable in vitro PK profile, although they displayed species disconnects in the in vivo PK profile, and a propensity for P-gp- and/or BCRP-mediated efflux in a mouse model. Compounds 44 and 45 demonstrated high potency and exquisite selectivity for LRRK2 and utility as chemical probes for the study of LRRK2 inhibition.

The serine/threonine kinase DYRK1A has been implicated in regulation of a variety of cellular processes associated with cancer progression, including cell cycle control, DNA damage repair, protection from apoptosis, cell differentiation, and metastasis. In addition, elevated-level DYRK1A activity has been associated with increased severity of symptoms in Down's syndrome. A selective inhibitor of DYRK1A could therefore be of therapeutic benefit. We have used fragment and structure-based discovery methods to identify a highly selective, well-tolerated, brain-penetrant DYRK1A inhibitor which showed in vivo activity in a tumor model. The inhibitor provides a useful tool compound for further exploration of the effect of DYRK1A inhibition in models of disease.

Abstract Hepatitis C virus (HCV) infection occurs in 30–90 per cent of people who inject drugs (PWID). Although cure rates can exceed 95 per cent, treatment access is limited and approximately 400,000 people die each year due to complications of chronic infection. A temporal analysis of cluster networks among PWID can be used to inform strategies to interdict transmission. In Baltimore, PWID have been recruited for The AIDS Linked to the IntraVenous Experience (ALIVE) cohort. A demographic questionnaire was administered and recorded for baseline and recent participants. Viral RNA underwent PCR with primers targeting the core and envelope-1 protein (CE1) and sequenced via Sanger sequencing. Sequences with > 400 bp reads and Q-scores >370 were used for downstream analysis resulting in 322 ALIVE baseline participants (1988–9) and 548 recently diagnosed subjects enrolled approximately two decades later (2005–16). Cluster networks were rendered with a threshold of 4 per cent in MicrobeTRACE, and statistical analyses were performed in R Studio. Of the 1988–9 subjects, the majority (259/317, 81.7%) were a part of cluster. There were nine clusters and fifty-eight singletons, with two large clusters containing most sequences of genotype 1a (73.5%). Two decades later, a minority of recently diagnosed individuals (235/512, 44.1%) were part of a cluster. There were seventeen clusters with 286 singletons with two large clusters containing 1a genotype individuals (21.5%). Additional clustering was done by parsing the two datasets by subtype 1a (n = 714) and 1b (n = 151). The genotype 1a network demonstrates a majority, 65.8 per cent, of participants in clusters. Moreover, two large clusters can be observed with baseline participants towards the center and recent participants on the outskirts indicative of high linkage at baseline. The genotype 1b network produced a single large cluster but subclusters were observed. The sequences between the two time points co-mingled but subclusters were also observed. Interestingly, the two large clusters from 1988 to 1989 were still evident in the 2005–16 viral sequences. We observed greater cluster diversity in more recently diagnosed individuals, indicative of a less connected network of individuals sharing transmission risk, though major viral strains did persist over time in this cohort.

We describe our work to establish structure- and fragment-based drug discovery to identify small molecules that inhibit the anti-apoptotic activity of the proteins Mcl-1 and Bcl-2. This identified hit series of compounds, some of which were subsequently optimized to clinical candidates in trials for treating various cancers. Many protein constructs were designed to identify protein with suitable properties for different biophysical assays and structural methods. Fragment screening using ligand-observed NMR experiments identified several series of compounds for each protein. The series were assessed for their potential for subsequent optimization using 1H and 15N heteronuclear single-quantum correlation NMR, surface plasmon resonance, and isothermal titration calorimetry measurements to characterize and validate binding. Crystal structures could not be determined for the early hits, so NMR methods were developed to provide models of compound binding to guide compound optimization. For Mcl-1, a benzodioxane/benzoxazine series was optimized to a Kd of 40 μM before a thienopyrimidine hit series was identified which subsequently led to the lead series from which the clinical candidate S 64315 (MIK 665) was identified. For Bcl-2, the fragment-derived series were difficult to progress, and a compound derived from a published tetrahydroquinone compound was taken forward as the hit from which the clinical candidate (S 55746) was obtained. For both the proteins, the work to establish a portfolio of assays gave confidence for identification of compounds suitable for optimization.

Abstract On sustaining damage to their DNA, cells employ a sophisticated mechanism of detection and repair, termed the DNA damage response (DDR). As a critical component of the DDR and G2/M checkpoint, Chk1 kinase represents an attractive target for cancer therapy. We have utilized a structure-based drug design approach to identify and develop VER-250840, a novel, orally active inhibitor of the checkpoint kinase, Chk1. VER-250840 exhibited sub-nM potency against Chk1 kinase with exquisite selectivity over an extensive and diverse panel of kinases. In vitro, VER-250840 inhibited Chk1 autophosphorylation with an IC50 of 1.0 nM and increased the number of S-phase tumor cells staining positive for pan-nuclear γH2AX with an EC50 of 7 - 27 nM. Accumulated genomic DNA damage by Chk1 inhibition led to irreversible cell cycle arrest, inhibition of tumor cell proliferation, increased replication stress, and cell death in both 2D culture and multicellular tumor spheroids. In an in vivo A2058 tumor xenograft PD study, VER-250840 demonstrated rapid and sustained inhibition of Chk1 auto-phosphorylation within 30 minutes of oral administration. Doses of 10 mg/kg and higher PO resulted in greater than 90% inhibition of tumor pChk1 (S296) over 24 hours. In SKOV3 in vivo models, VER-250840 inhibited Chk1 auto-phosphorylation, modulated other biomarkers of replication stress and DNA damage, and exhibited moderate antitumor activity with minimal toxicity when administered orally on a 21-day once-daily schedule. Work is ongoing to further optimize in vivo efficacy. In conclusion, VER-250840 demonstrates potent and selective activity as a monotherapy both in vitro and in vivo. From these findings, further evaluation and optimization of this novel kinase inhibitor is justly merited. Citation Format: Joanne Wayne, Stephen Stokes, Nicolas Foloppe, Helen Browne, Teresa Brooks, Karen Benwell, Lisa Baker, Zoe Daniels, Andrea Fiumana, Christopher Graham, Alba Macias, Daniel Maddox, Sean McKenna, Christopher Northfield, Stuart Ray, Heather Simmonite, Emma Stefaniak, Paul Webb, Mike Wood, Andrew Massey. Identification and preclinical characterisation of VER-250840, a potent, selective Chk1 inhibitor with in vivo oral single-agent antitumor activity [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B163.

Perspectives Viewpoints•A key to sustaining impact in academic Departments of Medicine is to develop a diverse, mission-focused leadership structure that capitalizes on faculty strengths to execute the tripartite mission—clinical care, research, and education.•An effective leadership structure should engage the entire department workforce (faculty, nursing, and administration) in a unified mission and vision.•Developing faculty and supporting their highest scholarship achievements is key to success of the academic mission. •A key to sustaining impact in academic Departments of Medicine is to develop a diverse, mission-focused leadership structure that capitalizes on faculty strengths to execute the tripartite mission—clinical care, research, and education.•An effective leadership structure should engage the entire department workforce (faculty, nursing, and administration) in a unified mission and vision.•Developing faculty and supporting their highest scholarship achievements is key to success of the academic mission. Development of an effective, functional leadership structure is critical to the success of any large-scale organization. The department of medicine (DOM) includes over 1800 full- and part-time faculty, 900 nurses, 881 trainees, and more than 1000 employees in nonclinical roles. Like many academic departments, faculty carry out our missions on 2 campuses—Johns Hopkins Hospital (JHH) and Johns Hopkins Bayview Medical Center (JHBMC). These campuses provide complementary strengths, different patient demographics, and serve as program development laboratories for our entire health system. Our overall departmental budget is composed of 3 revenue streams: approximately one-half is from sponsored research, one-quarter from hospital joint agreements, and one-quarter from professional fees. In this unique organizationally and financially integrated model, called a “functional unit,”1Heyssel RM Gaintner JR Kues IW Jones AA Lipstein SH Decentralized management in a teaching hospital.N Engl J Med. 1984; 310: 1477-1480Crossref PubMed Scopus (70) Google Scholar physicians, nurses, and administrators are part of a single financial unit with a shared mission. We have developed a comprehensive vice chair faculty leadership structure that allows efficient execution of our tripartite mission, while at the same time engaging the entire workforce in a unified vision. The vice chair (VC) structure is organized around 4 areas: education, clinical care, research, and people. All VC positions were solicited through an open request for applications process. A detailed job description was disseminated to all department faculty, and applicants underwent comprehensive interviews with the department director and other stakeholders, including division directors, nursing leaders, school of medicine leaders, and health system leadership. The request for applications process enabled us to identify faculty with talent and leadership aspirations, select the strongest candidates with a passion for the academic mission, and create a culture of transparency. Because of the “functional unit” structure of the department, the director has a broader scope of reports and responsibilities than might be present in traditional academic departments. Given the breadth and complexity of these roles, the director created a new executive vice chair (EVC) position. The EVC meets weekly with the department director, advises the director on departmental direction, policy, and operations, and attends various meetings representing the director, serving as departmental leader in the director's absence. The EVC is also responsible for overseeing a monthly VC meeting. To ensure that each VC is meeting his or her goals, the EVC conducts annual reviews with each VC. The EVC aids the director in faculty recruitment and retention, including recruitment and orientation of new division directors and VCs. The EVC provides oversight to division directors and administrators in preparing annual division reviews in collaboration with the VC for faculty development and promotions. Finally, a critical role for the EVC that evolved was to help shape departmental culture and enhance engagement for all employees by 1) leading the development of a unifying mission and vision statement (Table1) and 2) initiating and overseeing the department's new civic engagement initiative.2Golden SH Cudjoe TKM Galiatsatos P et al.A perspective on the Baltimore Freddie Gray riots: turning tragedy into civic engagement and culture change in an academic department of medicine.Acad Med. 2018; 93: 1808-1813Google ScholarTable1Mission, Vision, and Core Values: Department of Medicine, Johns Hopkins University School of MedicineMissionVision and Core ValuesWe are people serving people, to promote health and alleviate suffering locally and globally by:• Delivering exceptional care• Developing and educating future leaders• Driving innovation and discoveryWe want to:• Inspire a culture of respect, integrity, service, equity, and excellence (our core values)• Engage all Department of Medicine employees in serving our patients• Lead the world in personalized patient care, medical education, and biomedical discovery and innovation Open table in a new tab The vision for the DOM Faculty Development and Promotions Office is to support the highest academic achievements for all faculty across biomedical research, medical education, clinical care, program building, innovation, commercialization, quality, safety, and improving systems of care. At Johns Hopkins School of Medicine, there is a single promotion pathway (ie, only tenure track without a clinician/educator nontenure track) with criteria for national recognition (promotion to Associate Professor) and national leadership or international recognition (promotion to Professor). The DOM Faculty Development Office works with the School of Medicine's Office of Faculty Development to develop guidance on preparation of promotion packages, especially for those outside the traditional physician-scientist pathway. The department supports efforts to maximize recognition by taking an active role in nominating faculty for appropriate awards and maintaining a master directory of awards offered by internal medicine-related professional organizations. Further, a process for recognizing and rewarding clinical excellence was established in the department. The Miller-Coulson Academy for Clinical Excellence3Christmas C Kravet SJ Durso SC Wright SM Clinical excellence in academia: Perspectives from masterful academic clinicians.Mayo Clin Proc. 2008; 83: 989-994Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar began at JHBMC and is now available to all faculty on a competitive basis, and more recently has extended to recognize outstanding advanced practice clinicians and trainees. The VC for Faculty Development and Promotions is supported by 2 associate VCs (AVCs)—the AVC for Women's Academic Careers and the AVC for Diversity and Inclusion (Table2). These AVCs work closely with the VC to ensure that women and faculty underrepresented in medicine (URIM) are successful. Activities include supporting the career development of women and URIM faculty through enhanced mentorship, access to career development opportunities specific to women and minorities, leadership training, and nominating qualified individuals for awards, speaking opportunities, and leadership positions. Regular meetings and exit interviews with women and URIM faculty are used to identify potential barriers that may differentially impact their careers. The office has developed an “equity benchmarking tool” to collect and maintain data on key metrics that reflect the expressed core value of equity and the commitment to departmental transparency.Table2Vice Chair Job Descriptions and ResponsibilitiesExecutive Vice Chair• Directly advise the Director on departmental direction, policy, and operations, attend various meetings representing the Director and serve as the surrogate department leader in the absence of the Director.• Meet weekly with the Department of Medicine executive leadership team.• Work with the Director, Vice Chair for Clinical Operations, and JHM to lay the foundation for interdisciplinary clinical service line agreements for complex disease management and wellness.• Aid the Director in faculty recruitment and retention, including recruitment of new Division Directors, Vice Chairs, and other departmental leaders.• Work with the Director to assess, develop plans, and operationalize effective partnerships between various JHM constituencies.• Serve as Acting Director (meeting attendance, signature authority) in the Director's absence.• Provide leadership and oversight to Division Directors and administrators in preparing annual division reviews, and actively participate in those reviews.• Oversee mission, vision, and departmental culture.Clinical Affairs Vice Chair for Clinical Affairs• Oversee and coordinate efforts to ensure that both inpatient and outpatient care is delivered in an effective, safe, high-quality, and patient-centered manner.• Guide implementation and maintenance of a comprehensive model for continuous quality improvement across all aspects of DOM clinical operations, including process and patient outcomes, patient and provider engagement and satisfaction, and financial performance.• Lead and support strategic planning efforts around the development of interdisciplinary programs that address complex illnesses, enhance efficiency, and improve access to clinical care.• Supervise Associate Vice Chair of Inpatient Operations in Epic implementation and dissemination, length of stay management, readmissions management, and monitoring and improving inpatient throughput.• Supervise Associate Vice Chair of Ambulatory Operations in monitoring primary and specialty clinic performance, access to clinical services, patient satisfaction scores, ambulatory care protocols, and After-Care Clinics and readmission prevention efforts. Associate Vice Chair for Inpatient OperationsCommon responsibilities at JHH and JHBMC• Oversee bed management throughout the DOM (including after-hours calls).• Serve as Hopkins Access Line liaison.• Monitor quality for handoffs and transitions within DOM and between departments.• Oversee quality control for consult services provided by the DOM.• Oversee departmental length of stay management and re-admission reduction efforts including proactive, strategic planning for utilization of alternate care sites.• Lead projects designed to enhance physician professional experience, joy of practice, and top of license work relating to inpatient care.• Monitor and lead improvement in inpatient throughput—emergency department time of decision to admit to discharge; discharge and transfer barriers.• Co-lead efforts in inpatient clinical documentation excellence in collaboration with the Vice Chair for Quality, Safety, and Service• Develop new models of care delivery in collaboration with VC for Clinical Affairs and other partnersResponsibilities specific to JHH:• Oversee inpatient EMR implementation.• Support HCAHPS monitoring and improvement.• Refine and implements collaborative models for inpatient redistribution between academic campuses.Responsibilities specific to JHBMC:• Co-lead DOM efforts on Maryland Hospital Avoidable Condition Reduction. Associate Vice Chair for Ambulatory Operations• Monitor primary and specialty clinic performance such as template and space utilization and access metrics such as time to appointment bump rates using Ambulatory Dashboards and other tools.• Serve as a champion for patient satisfaction and actively monitor CGCAHPS scores and identify best practices and opportunities for improvement.• Monitor documentation standards and open encounters.• Develop new and integrate Ambulatory Care Protocols into DOM clinical practice in collaboration with stakeholders.• Champion JHM Transitions of Care efforts with a specific focus on provider communication;• Serve as the department liaison to After-Care Clinics and other readmission prevention efforts;• Participate in department meetings and committees such as the Clinical Affairs leadership team, safety and quality improvement committees; and,• Represent the DOM at relevant JHM committees such as the Clinical Practice Association (CPA) practice management committee and John Hopkins Outpatient Care Ambulatory Triad. Vice Chair for Patient Safety, Quality, and ServiceSafety/Risk:• Review unexpected deaths and major adverse events with the goal of participating in root cause analysis (RCA) and identifying opportunities for improvement.• Develop and lead risk-reduction teams involving additional DOM leaders, as appropriate, to address problems related to processes and systems.• Review and investigate event reports and participate in and contribute to interdisciplinary case evaluations.• Investigate and report relevant cases to hospital committees (eg, Clinical Quality Improvement, Risk Management Committee)• Work to improve safety culture in the DOM units and ambulatory clinics.Patient Family-Centered Care:• Monitor HCAHPS scores and achieve results consistent with the JHM strategic plan and monitor CGCAHPS scores as needed/as appropriate.• Implement best practice bundle with focus on nurse leader rounding.• Evaluate physician-related complaints and refer for peer review as appropriate.Quality/performance Improvement (in collaboration with Physician Advisor):• Monitor external measures to ensure performance is on track with National Leader strategy (core measures, MHACs, hospital-acquired infections, hand hygiene, Physician Quality Reporting System, Meaningful Use, value-based purchasing/HEDIS, etc.). Actively utilize Department dashboard to measure quality and safety priority metrics and active performance improvement teams to address any measure seriously below performance target.• Coordinate review of deaths and major adverse events with DOM Morbidity & Mortality conference.• Develop Departmental/Functional Unit QI priorities and plan in collaboration with the Vice Chair for Clinical Affairs.Value:• Standardize care where appropriate, create algorithms, and implement decision support tools and reduce variation where appropriate.• Utilize clinical analytics to identify areas of opportunity to eliminate harm, improve quality outcomes, and reduce waste.• Utilize value/financial analytics to identify areas to reduce cost: utilization in labs, drugs, imaging, blood, and supplies.• Work to reduce hospital length of stay and reduce readmission.HealthCare IT Safety (in collaboration with Vice Chair for Data Integrity and Analytics):• Identify risks of potential harm related to Health IT systems and develop/implement risk mitigation strategies to prevent potential harm.Trainee and faculty education (in collaboration with Program Directors):• Resident training in the basics of safety, service, and value and communication of safety goals.• Ensure safety leaders within the departments/divisions/units have the appropriate skills and resources to lead quality efforts in their area.• Collaborate with the Residency Director, Vice Chair for Education, and Armstrong Institute Director to promote educational and scholarly opportunities in safety, quality, and service for trainees and faculty.Education Vice Chair for EducationTraining Programs:• Support training program directors in oversight of residency and fellowship education and assist in recruitment efforts.• Meet and exceed accreditation standards for all DOM training programs.Faculty• Support recognition of educator faculty through awards nominations, publicity, and connection to open leadership positions.• Collaborate with VC for Faculty Development with promotions processes and review educational scholarship of educator faculty.Students• Review Departmental letters of recommendation for JHUSOM Internal Medicine (IM) applicants.• Advise JHUSOM IM applicants.Other• Lead educational strategic planning process every 5years minimum and review educational program performance annually.• Oversee educational budget and build innovative funding strategies to support educational programs.• Chair DOM Medical Grand Rounds Committee.• Attend local and national education meetings (eg, Graduate Medical Education Committee, Association of Program Directors in Internal Medicine, AAMC)• Oversee Associate Vice Chair for Education Associate Vice Chair for EducationResponsible for DOM undergraduate medical education• Promote culture to inspire JHUSOM students to pursue IM careers.• Oversee and review basic and sub-internship clerkships and rotation directors at all sites.• Meet and exceed all accreditation standard for student programs.• Review and catalog all DOM teaching in preclinical curriculum.• Coordinate non-JHUSOM medical student observerships.• Oversee IM interest group in JHUSOM.• For IM residency applicants, author all Departmental letters of recommendation and advise all JHUSOM IM and combined program applicants.Other• Co-lead educational strategic planning process every 5years minimum and review educational program performance annually.• Support educational effort for DOM faculty.• Serve as the Co-Chair of DOM Medical Grand Rounds Committee and manage CME accreditation for Medical Grand Rounds.• Attend local and national meetings. Deputy Director of Education at JHBMCShare in some of the vice chair for Education and AVC for Education responsibilities listed above on the Bayview campus for its training programs.Research Vice Chair for Research (duties in partnership)• Build comprehensive strategic efforts to better support our mission of discovery.• Recruit investigators to serve as members of the Department's research committee and oversee the annual Research Retreat Steering Committee.• Develop guidelines for a fiscally sound, transparent, department-wide bridge-funding policy.• Oversee, analyze, and develop recommendations for departmental infrastructure required for pre- and postgrant accounting and administration.• Serve as DOM representative to the School of Medicine Research Council.• Serve on the DOM Emergency Preparedness Committee for Research and maintain the research business continuity plan.• Supervise, in partnership with the Administrator, DOM-sponsored research staff Vice Chair for Basic and Translational Research• Serve as the primary departmental liaison to basic science departments in the Johns Hopkins University School of Medicine.• In collaboration with the VC for Data Integrity and Analytics, maintain data retention policies and provide education and resources to ensure DOM laboratory compliance.• Guide the recruitment and professional development of basic science-oriented faculty.• Provide oversight to DOM Facility Operations to ensure effective use of all research space assigned to the Department, including policy development to guide space assignment.• Facilitate equipment transfers of incoming and departing faculty. Vice Chair for Clinical and Translational Research• Guide the recruitment and professional development of our physician-scientist and clinical and health services research-oriented faculty.• In collaboration with the Vice Chair for Data Integrity and Analytics, maintain data retention policies and provide education and resources to ensure IRB compliance with human subjects research.• Serve as the DOM research lead for LCME accreditation. Vice Chair for Innovation and Commercialization(focus on biomedical technologies aligning JHU with Applied Physics Laboratory and external organizations) Vice Chair for Innovation in Healthcare Implementation(focus on development of business and operational frameworks for faculty to implement and disseminate innovations in healthcare delivery through technology or business solutions)• Partner with other relevant departments across the University to connect with industry in order to understand the needs and wants of our commercial partners and help to develop relationships with industry partners for the projects identified to have the most potential for commercial interest.• Develop and communicate to faculty and staff a succinct description of the process of protection, patent, and commercialization and serve as a resource and advocate for those engaged in these processes.• Increase faculty awareness of opportunities for commercialization through multiple public (eg, Grand Rounds, Division Director Meeting, divisional faculty meeting, special seminar, new faculty orientation) and private (division director, individual faculty) presentations.• Identify patentable ideas and processes.• Ensure an up-to-date database of department faculty patent and commercialization efforts, regularly comparing our efforts with national benchmarks for academic departments of medicine.• Maintain a joint appointment in the Johns Hopkins Carey School of Business to serve as mentor to faculty and students with an interest in the business of biomedical innovation and to participate in relevant lecture series.• Be an active liaison with Johns Hopkins Technology Ventures (JHTV) to help connect DOM faculty with promising research to the appropriate resources provided by JHTV.• Interact with the department's development officers to capitalize on any potential philanthropic partnerships with industry.• Develop an infrastructure for innovation that results in increased licensing revenue, disclosures, patents, and startups in the DOM with an impact on the patient and translational health care. Vice Chair for Data Integrity and Analytics• Serve as DOM representative in facilitating big data issues across the tripartite mission at all campuses.• Collaborate with end users and central resources to innovate and optimize data management and analysis, particularly with large data sets.• Develop and communicate DOM customized solutions for big data issues across the missions.• Serve as the primary departmental liaison to enterprise-wide IT committees, including those focused on enterprise data governance activities to ensure the comparability and consistency of clinical data managed by electronic systems throughout the enterprise.• Facilitate data integrity and accuracy for research and quality improvement purposes from the EMR, including integration of clinical decision support into the EMR that enhances physician workflow and adherence to meaningful use requirements (in collaboration with VC for Patient Safety, Quality, and Service).• Develop a strategic plan to standardize software and IT systems across our campuses.• In collaboration with the Vice Chairs for Research, create and maintain (1) data retention policies and provide education and resources to ensure DOM laboratory compliance and (2) policies guiding best practices for database hygiene and curation.• Lead efforts to ensure electronic security and privacy and develop remediation plans, when necessary.• Work with the Director and Communications Director to develop efficient and effective department electronic communication strategies utilizing various electronic modalities.• Supervise, in partnership with the Academic Administrator, DOM MNet, IT, and Analytics staff.People Vice Chair for Faculty Development and Promotion• In partnership with the Chair of the Departmental Promotions Committee, determine faculty readiness for promotion and review.• Assemble a mentoring committee to review faculty at rank for extended time (>6 years).• Update and oversee the division review process in collaboration with the Director and Executive Vice Chair.• Review faculty annual review materials.• Maintain a calendar of standing award deadlines to facilitate timely nomination of faculty for research, clinical, and education awards; assist nominated faculty with the application process, and connect faculty to former DOM or institutional award recipients.• Recommend and support DOM faculty applying for departmental and institutional awards and local and national leadership development programs in the domains of clinical care, research and education.• Serve as a resource for institutional faculty mentoring programs and as an advisor to faculty in need of objective career mentoring advice outside of his or her division.• Support and collaborate with mentoring programs established by the Diversity Council and the Task Force on Women's Careers in Academic Medicine.• Oversee, with the administrative support of the DOM credentialing manager, the Reappointment Review Committee. Associate Vice Chair for Women's Careers in Academic Medicine• Chair the DOM Task Force on Women's Careers in Academic Medicine (TF) and advisory board, which may include: leading recruitment efforts to ensure a diverse and robust membership; leading monthly meetings; preparing an annual budget; developing a schedule of annual events; planning the TF Annual Dinner; guiding TF members to develop activities and projects that address the mission and priorities of the membership and department.• Meet regularly with the Vice President for Diversity and Inclusion for Johns Hopkins Medicine.• Serve on the DOM compensation model steering committee.• Participate in recruitment visits for incoming faculty and leaders.• Participate in the divisional annual review process. Associate Vice Chair for Diversity and Inclusion• Chair the DOM Diversity Council (DC) and advisory board to the DC, which may include: leading recruitment efforts to ensure a diverse and robust membership; leading monthly meetings; preparing an annual budget; developing a schedule of events; overseeing the planning of the annual visiting professorship program; and guiding DC members in projects and activities that address the mission and priorities of the council and department.• Partner with the residency directors at the Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center to conduct targeted recruitment activities for groups under-represented in medicine (URIM).• Oversee the DOM URIM visiting clerkship program.• Meet regularly with the Vice President for Diversity and Inclusion for Johns Hopkins Medicine;• Serve on the DOM compensation model steering committee.• Participate in faculty recruitment visits for incoming faculty and leaders.• Participate in the divisional annual review process.AAMC = Association of American Medical Colleges; AVC = Associate Vice Chair; CGCAHPS = Clinician and Group Consumer Assessment of Healthcare Providers and Systems; CME = continuing medical education; CPA = Clinical Practice Association; DOM = Department of Medicine; EMR = electronic medical record; HCAHPS = Hospital Consumer Assessment of Healthcare Providers and Systems; HEDIS = Healthcare Effectiveness Data and Information Set; IRB = institutional review board; IT = information technology; JHBMC = Johns Hopkins Bayview Medical Center; JHH = Johns Hopkins Hospital; JHM = Johns Hopkins Medicine; JHUSOM = Johns Hopkins University School of Medicine; LCME = Liaison Committee for Medical Education; MHAC = Maryland Hospital Acquired Condition; QI = Quality Improvement. Open table in a new tab AAMC = Association of American Medical Colleges; AVC = Associate Vice Chair; CGCAHPS = Clinician and Group Consumer Assessment of Healthcare Providers and Systems; CME = continuing medical education; CPA = Clinical Practice Association; DOM = Department of Medicine; EMR = electronic medical record; HCAHPS = Hospital Consumer Assessment of Healthcare Providers and Systems; HEDIS = Healthcare Effectiveness Data and Information Set; IRB = institutional review board; IT = information technology; JHBMC = Johns Hopkins Bayview Medical Center; JHH = Johns Hopkins Hospital; JHM = Johns Hopkins Medicine; JHUSOM = Johns Hopkins University School of Medicine; LCME = Liaison Committee for Medical Education; MHAC = Maryland Hospital Acquired Condition; QI = Quality Improvement. The vision of the Clinical Affairs Office is to deliver the highest-quality patient- and family-centered care and foster an environment that educates trainees in core principles of safe, patient-centered care; to develop innovations in clinical care delivery utilizing financial models that generate a margin for mission-based programs and address areas of immediate departmental clinical safety and financial risk; and to lead clinical integration efforts within the department and across the health system by interfacing with partners to share best practices and to use rigorous analytic methodology to assess their impact on clinical and economic outcomes. The department clinical leadership team consists of 2 VCs–one for overall clinical affairs and one for quality, safety, and service—and 3 AVCs—2 focused on inpatient operations at each of the academic sites and one focused on ambulatory operations (Table2). Each of the VCs collaborates closely with nursing and administrative leadership in a triad or dyad to lead the daily clinical mission activities of the department. The VC for Clinical Affairs is directly responsible for clinical issues that cross inpatient and outpatient settings, including professionalism, professional satisfaction, and credentialing, and interfaces with divisional clinical directors. The VC for Clinical Affairs also represents the department on various hospital and school committees with significant clinical influence. The inpatient operations group focuses on hospital throughput, interhospital transfer processes, length of stay, readmissions, and inpatient care policies and procedures. The ambulatory operations group oversees clinical practices on both academic campuses as well as more than 30 satellite locations. This team focuses on practice improvement, compliance with access goals and metrics, and integration and standardization of best practices across the department's multiple practice sites. The ambulatory group also represents the department to the Clinical Practice Association for key strategic initiatives. The triad team that focuses on quality, safety, and service (“quality”) efforts within the department is composed of the VC for Quality, Safety, and Service; representatives from nursing and administrative operations; and a senior faculty member department physician advisor. The quality team organizes its work around 4 domains4Mathews SC Pronovost PJ Daugherty Biddison EL et al.A Department of Medicine infrastructure for patient safety and clinical quality improvement.Am J Med Qual. 2018; 33: 989-994Google Scholar—patient safety, defined as internally recognized risk, detected by monitoring events reported through an electronic safety event reporting system; externally reported quality metrics such as risk-adjusted inpatient mortality, hospital-acquired condition rates, and core measure performance; patient experience, measured by the Hospital Consumer Assessment of Healthcare Providers and Systems survey; and value, identified as activities that focus on reducing the cost of care while maintaining quality. The key roles of the VC of Research are to connect individuals with specialized expertise, strengthen shared resources, improve faculty research funding success, and remove barriers to conducting research. The department has divided this responsibility between 2 individuals with complementary expertise in basic and clinical research, with translation as a common emphasis (Table2). They work synergistically on problems common to all types of research (eg, grants administration, infrastructure, core research services, communication, and collaboration), while also addressing issues unique to basic or clinical research. The primary objectives focus on supporting faculty to excel in scientific discovery by enhancing faculty competitiveness; fostering communication and collaboration; bolstering the research infrastructure; fostering the pipeline of physician-scientists; and expanding opportunities to develop and commercialize discoveries (in collaboration with the VCs for Innovation and Commercialization). To accommodate variation in the size and research portfolios of the divisions, a mixed model of grants administration has evolved, with some large divisions operating semi-autonomously while smaller divisions rely on central departmental personnel for pre- and post-award services. Coordination of all grants administrators at the departmental and divisional levels occur through an enhanced research administration and support team. New hires now participate in a common onboarding/training process to become familiar with the grants administration systems and procedures. A “float” research analyst is maintained to rapidly provide competent, trained staff to fill vacancies. Finally, standardized reporting formats are being used for post-award management with real-time information on budget balances, burn rates, and personnel. An intranet-based peer review portal was implemented to facilitate secure document sharing for researchers to engage grant pre-reviewers to read specific aims or complete grant proposals prior to submission. The committees are typically composed of seasoned faculty with experience on National Institutes of Health study sections. The research VCs, with support from the director, engaged and provide funding to the biostatistics epidemiology and data management core to offer up to 20hours of free research consultative services to all department faculty. This core provides customer-oriented, one-stop research support services that can help faculty navigate other existing institutional resources as well as provide hands-on assistance with research studies, grants, or manuscripts. The annual DOM Research Retreat is an excellent venue to update faculty and trainees on department research, stimulate interdisciplinary communication among clinical and basic scientists, recognize outstanding achievements, and introduce VC initiatives to the faculty. The department has led the way at the institution in bringing the process of innovation to market into the academic mainstream by creating a first-of-its-kind program called Innovation and Commercialization in Medicine (InCMed), led by 2 VCs in collaboration with Johns Hopkins Carey School of Business. The vision of InCMed is to make the department a nation-leading engine for innovation in health care that can translate discoveries in biomedical science and clinical care delivery into marketable products that add value to the lives of patients. Major goals include helping plan department-wide projects that can lead to clear commercialization pathways; providing networking across the medical campus and with other Johns Hopkins Medicine organizations, such as the Applied Physics Laboratory; providing support for faculty-led projects through teams of entrepreneurial students and postdoctoral trainees to encourage future generations to embrace innovation for health care improvement; and providing guidance for entrepreneurial faculty, including plans to formalize an additional track for academic advancement. The VC for Innovation and Commercialization (Table2) is responsible for the overall conduct and success of InCMed and works closely with the VC for Innovation in Healthcare Implementation. In addition, the VC focuses on developing educational programs and the infrastructure required to support biotech and medtech solutions for patient care. The VC for Innovation in Healthcare Implementation focuses on department innovations that improve the implementation and delivery of medicine, including commercializable process improvements, educational products and programs, and other faculty-driven initiatives that aim to improve health care delivery. Some of these critical improvements involve nonpatented intellectual property or new business models for which commercialization pathways can be complex. The vision for the VC for Data Integrity and Analytics is to innovate, harmonize, and maintain best practices spanning the life cycle of data from acquisition, storage, and analysis to reporting and retention in a manner that fosters excellence in patient care, research, and education. This VC develops tools to protect the privacy of patients and the integrity of science, fosters innovative uses of information technology (IT) infrastructure by all faculty and staff, and infuses data integrity into training at all levels. The VC for Data Integrity and Analytics engages in IT-related governance by disseminating policy messages, facilitating faculty access to analytics resources while also guiding their responsible use, and serving as a member of multiple policy-setting committees at the departmental and enterprise levels. This mission area is overseen by a VC for Education, an AVC for Education, a Deputy Director of Education at the JHBMC, and many other education program leads (Table2). The VC has oversight over all educational programs in the department. The AVC oversees all student and continuing medical education-related activities in the department. The department houses 2 residency programs: Osler Medical Housestaff Training Program at Johns Hopkins Hospital and Johns Hopkins Bayview Internal Medicine Residency Program. While these programs have different structures and separate leadership, their relationship is highly collaborative. There are several education priorities. First, we ensure that learners (eg, medical students, housestaff, and faculty) in the department have outstanding clinical skills, which includes optimizing ambulatory and inpatient clinical learning experiences with an emphasis on bedside rounding to best promote patient-centered care. Second, we created educational pathways to access the diverse spectrum of careers in health care, ensuring that residents with interest in specific career paths receive accelerated training by experts and thought leaders. Our first 3 implemented pathways in the Osler Program include:•The Global Health Pathway includes a portfolio of structured opportunities for motivated residents to conduct clinical and research-based global health rotations in low- and middle-income countries.•The Patient Safety and Quality Pathway provides residents with unique, guided opportunities to improve patient safety, quality of medical care, and high value care.•The Scientific Discovery Pathway is composed of a funded physician-scientist pathway (Molina Scholars) in which selected postgraduate year one housestaff receive a commitment from the department for fellowship training, research development, discretionary research funds, and mentored career development. Our third educational priority is to support faculty to participate in the teaching mission. Effective faculty teaching rewards include compensation model incentive, promotional credit, and enhanced faculty development. Our fourth goal is to develop leaders in ambulatory medicine by enhancing the curriculum, precepting models, IT systems, and engagement of ambulatory subspecialists. Finally, we train residents and students to know the patient as a person, facilitated by the Aliki curriculum.5Hanyok LA Record JD Christmas C Hellmann DB Rand CS Ziegelstein RC Update on the Aliki Initiative at year 10: changing the culture of medicine to know our patients as individuals.The Pharos. 2018; : 29-34Google Scholar Departments of Medicine are often the largest departments in schools of medicine, resulting in impactful contributions to the tripartite mission. A key to sustaining our impact is to develop a diverse, mission-focused leadership structure that capitalizes on the strengths of faculty and enables us to accomplish all aspects of the academic mission simultaneously. Over the 4years that this structure has been in place, we have seen tremendous growth in transparency, accountability, and progress. It is our hope that lessons learned from our journey will serve other academic departments of medicine as they seek to optimize efforts across the tripartite mission.

Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of developing Parkinson's disease. Surrogates for the LRRK2 kinase domain based on checkpoint kinase 1 (CHK1) mutants were designed, expressed in insect cells infected with baculovirus, purified, and crystallized. X-ray structures of the surrogates complexed with known LRRK2 inhibitors rationalized compound potency and selectivity. The CHK1 10-point mutant was preferred, following assessment of surrogate binding affinity with LRRK2 inhibitors. Fragment hit-derived arylpyrrolo[2,3-b]pyridine LRRK2 inhibitors underwent structure-guided optimization using this crystallographic surrogate. LRRK2-pSer935 HEK293 IC50 data for 22 were consistent with binding to Ala2016 in LRRK2 (equivalent to Ala147 in CHK1 10-point mutant structure). Compound 22 was shown to be potent, moderately selective, orally available, and brain-penetrant in wild-type mice, and confirmation of target engagement was demonstrated, with LRRK2-pSer935 IC50 values for 22 in mouse brain and kidney being 1.3 and 5 nM, respectively.

HomeCirculation ResearchVol. 120, No. 10It's 10 pm; Do You Know Where Your Data Are? Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBIt's 10 pm; Do You Know Where Your Data Are?Data Provenance, Curation, and Storage Mark E. Anderson and Stuart C. Ray Mark E. AndersonMark E. Anderson From the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (M.E.A., S.C.R.); and Department of Physiology and the Program in Cellular and Molecular Medicine, The Johns Hopkins School of Medicine, Baltimore, MD (M.E.A.). and Stuart C. RayStuart C. Ray From the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (M.E.A., S.C.R.); and Department of Physiology and the Program in Cellular and Molecular Medicine, The Johns Hopkins School of Medicine, Baltimore, MD (M.E.A.). Originally published12 May 2017https://doi.org/10.1161/CIRCRESAHA.116.310424Circulation Research. 2017;120:1551–1554is corrected byCorrection to: It's 10 pm; Do You Know Where Your Data Are?High integrity data retention and curation are critical for preserving the scientific record and informing future discovery.1 However, these steps are often neglected or inadequate because of lack of a tractable, easily operated approach. We offer general guidelines and an exemplar method that is applicable to many, but by no means all, laboratories.Data Retention and ProvenanceData generated from National Institutes of Health funding should be stored for 3 years after the end of the last competitive renewal. In some cases, data related to patients and patents has longer storage obligations. Data storage rules are in evolution and may differ among various funding agencies, institutions, and journals. The data belong to the host institution, but the responsibility for storage (ie, stewardship) is typically transferred to individual investigators, many of whom have insufficient understanding of or infrastructure for this important role.2 While authors are routinely asked to affirm their accountability for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved,3 there is no standard infrastructure for sharing all primary data among all authors concurrently during drafting of an article, much less after publication.If you have worked in a laboratory for much time, you will know it is sometimes difficult to locate original data. Some of these challenges are magnified by moving laboratory locations, storing data on proprietary and outmoded platforms, lack of a clear paper trail after laboratory personnel move on, or multiple collaborators generating data at various sites. In general, older data are harder to follow compared with newer data. These truths became starkly evident to me (M.E. Anderson) after a former laboratory member was discovered to have engaged in scientific misconduct. While there was no doubt about his transgressions involving manipulated and repurposed example tracings, published work by us and others, independent of this individual, indicated that his represented findings most likely reflected actual biology. However, the trail of data was incomplete, and most of the publications were over 10 years old. The laboratory notebooks were in hand, but his computer, left behind in a laboratory move, was lost. During the investigation, we repeated many of the key experiments and obtained results similar to those published, but these were unsuitable for replacing the vitiated data because of modern concepts of peer review. These wrenching events led me (M.E. Anderson) and our laboratory to consider improved ways of retaining data, with a focus on a method that was durable and where retrieval of original data used to build published tables and figures did not impose an undue burden and was reliable. In discussions with many scientific leaders, I (M.E. Anderson) learned that few laboratories had clear approaches to storing data, much less ones that would allow data sets immediately supporting publications to be readily located and safely protected. Our laboratory implemented the following simple policy on data storage, sharing, and curation.Anderson Laboratory Data Sharing and Storage PolicyAll data and laboratory records need to be accessible for all laboratory members. Records should be detailed enough for others to recreate an experiment.Each laboratory member is required to keep the following:A bound notebook describing daily laboratory activities and referencing associated electronic files for each experiment. Records should be written with indelible ink, and errors marked, but not erased. An equivalent electronic notebook is also acceptable.All raw data acquired, either physical (ie, printouts, films, etc) or electronic (ie, images, patch clamp recordings, etc).Backups of all electronic data files. All data should be stored on the laboratory's shared server drive or backed up on an equivalent secure server (ie, cold storage).For each published article, the lead author is required to provide the following:The final accepted article file/s.All figures (regular and supplementary) published.All raw data files and calculated data files associated with each figure. The data should be organized into folders by figure.A Word document (or similar) describing the files associated with each figure, indicating any special software necessary for viewing files and any additional data that are not electronic (ie, notebooks, films, etc). Other laboratory members should be able to identify the data used to create each figure.These files should be saved in a folder with the author name, journal, and year published. The folder is to be stored on the laboratory shared server drive.On leaving the laboratory, all notebooks, data backups, and raw data are to remain in the laboratory with the laboratory manager.This policy, once adopted, changed practice but did not substantially increase workload because these data had been recently aggregated to prepare the article for publication. At the time data are acquired, proper storage is a matter of practice—like putting away pipettes or wiping down a biosafety cabinet. Data stewardship must be taught and reinforced, but the burden of this practice is reduced if proper IT infrastructure and support is available.Different Situations Require Different SolutionsThese guidelines were relatively simple, easy to implement, and provided an approach for data storage in a format purposed for retrieving published data. When a network-attached server (NAS) used to store the data has backups that are retained for years, particularly if logging is enabled, it is feasible to recover the sequence of data changes (additions/deletions/edits) that may have occurred. Given the plummeting cost of deep or cold storage, it seems likely that data so stored will outlast its authors. However, our method did not aim to save for all time the universe of data generated in all studies, did not provide a clear framework for protecting data obtained from humans, nor consider the cost of storing large data sets, such as those generated by imaging studies. After I (M.E. Anderson) moved to Johns Hopkins, I began meeting with data experts to learn more about what our institution was planning and how these plans might align with resources and best practices to serve our faculty and the larger scientific community.Recruiting a Departmental LeaderOur department is research intensive, so approaches to data storage and curation were of broad interest, but a key opinion leader was needed to craft departmental language and speak to faculty at multiple levels. Because institutional policies were changing rapidly to keep in pace with an increasingly complex data security landscape, these changes needed to be communicated to and influenced by our department. Because of this, we established a new Vice Chair for Data Integrity and Analytics and recruited S.C. Ray to lead these efforts and to represent our interests to the School of Medicine and the University. Alignment of departmental efforts with those of the institution is facilitated by participation at the university level in governance of institutional data and clinical applications/analytics.What Is Good Enough?MinimumCompliance with sponsor (eg, National Institutes of Health) requirements for laboratory documentation1Authorship is clear (who wrote what)Timing is clear (when they wrote it)Completeness (no complete deletion, only strikethrough or equivalent)Data/records must remain on campus (removal only with institutional permission)If personal health information are included, then data privacy and security rules must be followed4Only members of the Institutional Review Board–approved study team may have access to personal health informationProtections against data loss—backups, etc5Working With the FacultyEducation and communication are essential. Individuals learn painfully that hard drives fail; this knowledge must be disseminated so that hard drive failure is anticipated. Similarly, electronic devices get lost and stolen; ransomware attacks are now commonplace. Use of commercial storage of sensitive/precious data, without an institutional contract, is not permissible—contracts provide for protection from data loss, breach, and secondary use of data. Most importantly, shared awareness of institutional resources will accelerate adoption of best practices. Threats to data security are constantly evolving, requiring changes that can be frustrating if not clearly justified. Communication between faculty and IT leadership must be bidirectional and collegial; addressing faculty needs and opportunities with respect to data storage can advance science and improve productivity.What Assets Are Available to Help Investigators Comply?Currently, data storage approaches are highly heterogeneous and many are poorly aligned with risk and regulation (Figure). NAS is readily available, flexible, and powerful. Most institutions secure their networks with lightweight directory access protocols that maintain a database of user credentials, enabling authentication (and loss of credentials on employment termination, etc). Federated authentication or sponsored accounts can give trusted collaborators at other institutions access to shared data. Also prevalent are tools like Active Directory that support creation of groups of users, thereby supporting authorization (eg, study team membership) that can manage shared access. Virtual environments can be augmented to support analytics, at the same time making NAS storage more convenient (by mapping NAS drives to virtual desktops and sharing NAS drives among study team members); in this way, data and tools can be combined without leaving the data center, while still be available to investigators anywhere in the world that has an Internet connection.Download figureDownload PowerPointFigure. Comparison chart of user features and solutions for storing biomedical research data, based on generalities; specific implementations and institutions will vary, but suggested preference is indicated by color ranging from green (prefer) to red (avoid). aLaptops, if institutionally managed/secured, may be suitable for carrying a copy of research data, but the primary/essential data should reside in a more secure location. bRemote desktop access tools can create vulnerabilities unless managed by IT personnel. cIf primary/essential data are stored, removal from campus would violate policy on location of institutional data (must remain on-site). dRemote access to cloud data requires network access or synchronization (when network access is intermittent); latter may be disabled at some institutions for IT security reasons. eRemote access to network-attached server (NAS) requires network connection and cloud desktop, VPN with drive mapping, or other solution (now becoming routine). fHard drives have high failure rate; laptops increase failure rate and add risk of device loss/theft/damage. gProper authentication and authorization generally depend on device management by institutional IT team. hPrimary/essential research data must remain on campus (or in institutionally contracted storage) and accessible to authorized institutional authorities for compliance reasons. iWhile laboratory data often do not include personal health information (PHI), many laboratories handle clinical specimens with some PHI (medical record numbers, dates of clinical events, date of birth, etc); in addition, clinician scientists tend to have some PHI wherever they work. jUnder special circumstances when there is not suitable alternative, desktop (locked office server) storage of PHI-containing data may be approved by some institutions. kAffordability of NAS depends on data footprint, economies of scale, institutional investment, Moore's Law, planning. lIn the event of concern raised (eg, to the National Institutes of Health [NIH] Office of Research Integrity), it is essential that the host institution have access to primary data and methods to support the publication or grant proposal in question.Moving Beyond Minimum Requirements to Best PracticesA best-practice solution will maximize data integrity at each step in data generation. It is difficult and error-prone to recreate data records post hoc. Moving data to secure storage as early as possible (ideally on acquisition) reduces risk of loss because of storage failure or omission and minimizes additional effort when it becomes routine practice.What Will Happen and What Won't Happen?We anticipate an institutional system that will support investigator-initiated creation of publication/proposal-specific folders similar to that described above for the Anderson Laboratory. These folders would be accessible to all study team members during the creation of figures and draft documents; once published, these resources could be made immutable so that additional files could be added but none removed. The ideal system, like a robust database, would keep a traceable record of all changes—an immutable record providing data provenance. Such a record would be maintained by the corresponding author or their designee and remain available to collaborators in accordance with data retention guidelines.In a best practice scenario, the primary data associated with a scientific work product will be retrievable, and the contributions of the study team members would be discoverable in the event of an inquiry. The work will be more reproducible because key data and methods will be included. Currently, these elements can be hard to locate with confidence, and such gaps create challenges for future scientific inquiry and for investigating potential scientific misconduct. In our opinion, optimized data storage creates an important obstacle against scientific misconduct, but will not prevent it. Importantly, future discoveries may shed new light on older work, providing an opportunity for additional discovery when the data can be assessed accurately.Not addressed above are topics that require more specialized solutions. Massive data storage and high-performance computing require specialized hardware, domain-specific design, and decisions with regard to primary and intermediate data that might be retained. Data sharing is an important component of validation and reproducibility of research, with its own set of considerations.6 Multiinstitution collaborations can be supported by the solutions described above, but may have special requirements. A substantial challenge in maintenance of reproducibility is software/version dependency and proprietary data formats (binary, especially)—considerations that can be mitigated by detailed methods (including software versions), scripted analysis, and colocation of software when feasible.SidebarNAS is file-level storage attached to a computing network, routinely available in research settings. With support from network experts, NAS can offer scalable storage with user-level authentication (who is logging in, and are they using valid credentials), authorization (is this user authorized to access this file/folder), event logging (who did what, when), and automated backup.AcknowledgmentsWe thank Dr Elizabeth Luczak for her help in developing and implementing the Anderson laboratory data storage policy.Sources of FundingThis work was supported in part by National Institutes of Health (NIH) awards U19 A1088791, HL079031, HL096652, HL070250, and HL071140.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Mark E. Anderson, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD. E-mail [email protected]; or Stuart C. Ray, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD. E-mail [email protected]References1. ORI. Guidelines for responsible data management in research.2006. https://ori.hhs.gov/education/products/clinicaltools/data.pdf.Google Scholar2. DuBois JM, Chibnall JT, Tait R, Vander Wal J. Misconduct: Lessons from researcher rehab.Nature. 2016; 534:173–175. doi: 10.1038/534173a.CrossrefMedlineGoogle Scholar3. ICMJE. Recommendations for the conduct, reporting, editing, and publication of scholarly work in medical journals2015. http://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-authors-and-contributors.html.Google Scholar4. DHHS. Hipaa privacy rule – research.2013. https://www.hhs.gov/hipaa/for-professionals/special-topics/research.Google Scholar5. NIH. Grants policy statement.Application and Information Processes. 2016. https://grants.nih.gov/grants/policy/nihgps/html5/section_2/2.3_application_information_and_processes.htm#Protecti.Google Scholar6. NIH. NIH data sharing policy.2007. https://grants.nih.gov/grants/policy/data_sharing/.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesCorrection to: It's 10 pm; Do You Know Where Your Data Are?Circulation Research. 2017;121:e1-e1 May 12, 2017Vol 120, Issue 10 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCRESAHA.116.310424PMID: 28495991 Originally publishedMay 12, 2017 PDF download Advertisement

Over the past decade, landmark collaboration between regulatory agencies, pharmaceutical companies, academia, and patient community representatives has enabled the development and approval of new hepatitis C virus (HCV) treatment regimens with unprecedented speed. By providing a neutral platform for cross-sector engagement, the Forum for Collaborative HIV Research's(1) HCV Drug Development Advisory Group played a critical role in fostering this collaboration and expediting drug development. The applicability of this model to other therapeutic areas should be explored.

Die mikrobielle Translokation aus dem Darmlumen mit resultierender Endotoxinämie kann zu hepatischer Enzephalopathie und Infektionen führen und stellt daher ein Problem in der Behandlung der Leberzirrhose dar, insbesondere nach Anlage eines TIPS. Um die hepatische „Clearance“ von Endotoxinen in Patienten mit Leberzirrhose zu untersuchen, wurden die Konzentrationen von bakteriellem Lipopolysaccharid (LPS), LPS-bindendem Protein (LBP), L-Arginin und asymmetrischem Dimethylarginin (ADMA) in einer Kohorte von 8 Patienten mit dekompensierter Leberzirrhose vor und nach elektiver Anlage eines TIPS gemessen. Dabei wurden zentral-venöse, portal-venöse sowie Proben aus der Vena hepatica gewonnen. Mittels eines adaptierten LPS-Assays wurden hohe portal-venöse LPS-Konzentrationen gemessen (1743±819 pg/mL). Auch im zentral-venösen Blut wurden –passend zur zugrunde liegenden dekompensierten Zirrhose– hohe LPS-Konzentrationen gefunden (931±551 pg/mL). Der transhepatische LPS-Gradient lag bei 438±287 pg/mL; somit betrug die Clearance der zirrhotischen Leber 25±12% des portal-venös eingeströmten LPS. Nach Einbringen des TIPS stieg die LPS-Konzentration in der V. hepatica sowie zentral-venös an, passend zum Shunting von LPS mit dem portal-venösen Blut durch den Stent. Gleichzeitig kam es zu einem Anstieg der systemischen L-Arginin Konzentration, während der NO-Synthasehemmer ADMA unverändert blieb, passend zur Rolle der bakteriellen Translokation in der Kreislaufdysfunktion nach TIPS-Anlage. Schlussfolgerung: In dieser Pilotstudie konnten quantitative Daten über die Rolle der Leber bei der bakteriellen Translokation gewonnen werden. Während die zirrhotische Leber offensichtlich eine relativ stabile Clearance für bakterielle Endotoxine aus dem Darmlumen behält, wird diese Clearance durch eine TIPS Anlage signifikant vermindert. Die erhöhten systemischen LPS-Konzentrationen könnten somit zur gesteigerten Rate hepatischer Enzephalopathien bei Patienten nach TIPS Anlage beitragen.