STATE RESEARCH, OUTREACH AND TECHNICAL ASSISTANCE TO IMPROVE THE NATION’S TRANSMISSION AND DISTRIBUTION SYSTEMS

The goal of the project 'State Research, Outreach and Technical Assistance to Improve the Nation's Transmission and Distribution Systems' was for the National Association of State Energy Officials (NASEO) to partner with the National Governors Association (NGA) Center for Best Practices, the National Conference of State Legislators (NCSL), and the National Association of Regulatory Utility Commissioners (NARUC) to assist DOE's Office of Electricity Delivery and Energy Reliability (OE) in its effort to modernize and expand America's electric delivery system. NASEO focused on key transmission and distribution issues where coordination between the federal and state governments was critical. Throughout the duration of this program, NASEO engaged in monthly coordination - occasionally more often - with NGA, NCSL and NARUC. NASEO staff and General Counsel Jeff Genzer also had regular face-to-face meetings, phone calls and emails with OE staff to learn from DOE and share information and feedback from the state energy offices on transmission and distribution. To commence work on this project, NASEO met with OE, NGA, NCSL and NARUC in January 2005 and remained committed to regular communications with all involved entities throughout the duration of this project. NASEO provided comments and analysis to the other partners on deliverable reports under this award. This award provided support to NASEO's Energy Production Committee (chaired by Dub Taylor of Texas, followed by Tom Fuller of Wyoming) to plan and host sessions at NASEO's Annual Meeting and Energy Outlook Conferences. Sessions included presentations from state, DOE, national laboratory and private sector experts on transmission, distribution, distributed energy resources, integrating renewable resources into the electricity grid. NASEO disseminated information to its members through emails and its website on transmission and distribution technology and policy. NASEO was an active member of the National Council on Electricity Policy as part of its transmission and distribution work. The National Council on Electricity Policy (National Council) is a venture between NASEO, NARUC, NCSL, National Association of Clean Air Agencies (NACAA) and the National Governors Association (NGA). The National Council also includes several federal members including FERC, DOE, and the U.S. Environment Protection Agency (EPA). NASEO members serve on the policy committee and NASEO General Council Jeff Genzer is a member of the National Council's Executive Committee. NASEO staff participated on regularly scheduled policy committee and executive committee calls and helped to plan agendas and publications for various state decision-makers. Specifically, NASEO organized state energy officials and participating in formulating the agenda for meetings, including the Mid-Atlantic Distributed Generation Workshop in New Jersey in September 2007. NASEO shared the results of these meetings through its website, email communications and direct conversations with state energy officials. NASEO participated as a member of the National Action Plan for Energy Efficiency (NAPEE) Leadership Committee, representing the interests and expertise of the state energy offices. In addition, NASEO was part of the Long-Term Vision Committee. NASEO members also participated in these activities and NASEO has encouraged further efforts of its membership with regards to NAPEE. NASEO has worked to ensure that its membership has the most timely and accurate information about transmission and distribution technology and policy. Its work with other associations has facilitated greater partnerships to enhance activities across the nation and encourage state energy offices to collaborate with public utility commissions, legislatures and executives to improve modern transmission and distribution. NASEO has identified transmission and distribution as a key area for further action

Methotrexate Decreases Tenofovir Exposure in Antiretroviral-Suppressed Individuals Living With HIV.

BackgroundTo mitigate increased risk of premature cardiovascular disease in antiretroviral therapy (ART) suppressed adults living with HIV (PWH), low-dose methotrexate (LDMTX) was evaluated in a multicenter randomized placebo controlled clinical trial of 176 PWH taking various ART regimens (ACTG A5314). Given shared methotrexate (MTX) and tenofovir (TFV) pharmacokinetic (PK) pathways, a substudy was conducted to investigate whether LDMTX alters TFV exposure.MethodsAdults virally suppressed on ART for >24 weeks were randomized to LDMTX or placebo. The first 66 participants taking a tenofovir disoproxil fumarate-containing regimen underwent intensive PK sampling over 24 hours after the second dose of LDMTX 10 mg or placebo. TFV and MTX levels were quantified using validated mass spectrometry methods. TFV PK between LDMTX and placebo groups were compared and MTX PK was characterized.ResultsForty-eight participants completed this substudy (n = 20 on LDMTX and 28 on placebo). Baseline characteristics were balanced except for protease inhibitor (PI)-use (25% in LDMTX and 43% in placebo groups). For TFV, AUC6 (primary endpoint), and AUC24,imputed, Cmax, and Cmin (secondary endpoints) were on average 22%, and 24%, 27%, and 31% less in the LDMTX versus placebo groups, with reductions in secondary endpoints reaching statistical significance. Additional analyses suggested a greater reduction in the absence of PI although not significant.ConclusionLower TFV AUC24,imputed and Cmax indicates that LDMTX reduces TFV exposure in PWH. However, this change was modest, not warranting a change in TFV dosing at this time. Further studies of TFV PK with LDMTX, especially without PI co-administration, are warranted

Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative.

Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19. Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings. Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies