From scaling up to sustainability in HIV: potential lessons for moving forward

Background: In 30 years of experience in responding to the HIV epidemic, critical decisions and program characteristics for successful scale-up have been studied. Now leaders face a new challenge: sustaining large-scale HIV prevention programs. Implementers, funders, and the communities served need to assess what strategies and practices of scaling up are also relevant for sustaining delivery at scale. Methods: We reviewed white and gray literature to identify domains central to scaling-up programs and reviewed HIV case studies to identify how these domains might relate to sustaining delivery at scale. Results: We found 10 domains identified as important for successfully scaling up programs that have potential relevance for sustaining delivery at scale: fiscal support; political support; community involvement, integration, buy-in, and depth; partnerships; balancing flexibility/adaptability and standardization; supportive policy, regulatory, and legal environment; building and sustaining strong organizational capacity; transferring ownership; decentralization; and ongoing focus on sustainability. We identified one additional potential domain important for programs sustaining delivery at scale: emphasizing equity. Conclusions: Today, the public and private sector are examining their ability to generate value for populations. All stakeholders are aiming to stem the tide of the HIV epidemic. Implementers need a framework to guide the evolution of their strategies and management practices. Greater research is needed to refine the domains for policy and program implementers working to sustain HIV program delivery at scale

The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort.

ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01).InterpretationPPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials

The Enigmatic Young Low-Mass Variable TWA 30

TWA 30 is a remarkable young (7+/-3 Myr), low-mass (0.12+/-0.04 Msun), late-type star (M5+/-1) residing 42+/-2 pc away from the sun in the TW Hydrae Association. It shows strong outflow spectral signatures such as [S II], [O I], [O II], [O III], and Mg I], while exhibiting weak Halpha emission (-6.8+/-1.2 Angstroms). Emission lines of [S II] and [O I] are common to T Tauri stars still residing in their natal molecular clouds, while [O III] and Mg I] emission lines are incredibly rare in this same population; in the case of TWA 30, these latter lines may arise from new outflow material colliding into older outflow fronts. The weak Halpha emission and small radial velocity shifts of line emission relative to the stellar frame of rest (generally <=10 km/s) suggest that the disk is viewed close to edge-on and that the stellar axis may be inclined to the disk, similar to the AA Tau system, based on its temporal changes in emission/absorption line strengths/profiles and variable reddening (A_V=1.5-9.0). The strong Li absorption (0.61+/-0.13 Angstroms) and common kinematics with members of the TWA confirm its age and membership to the association. Given the properties of this system such as its proximity, low mass, remarkable outflow signatures, variability, and edge-on configuration, this system is a unique case study at a critical time in disk evolution and planet-building processes.Comment: ApJ in press, 51 pages, 8 tables, 12 figures; converted to preprint style since emulateapj version cut off Tables 4-

The Fontan epidemic: population projections from the Australia and New Zealand Fontan registry

Background: The number and age demographic of the future Fontan population is unknown

Guiding phosphorus stewardship for multiple ecosystem services

The essential role of phosphorus (P) for agriculture and its impact on water quality has received decades of research attention. However, the benefits of sustainable P use and management for society due to its downstream impacts on multiple ecosystem services are rarely acknowledged. We propose a conceptual framework—the “phosphorus-ecosystem services cascade” (PESC)—to integrate the key ecosystem processes and functions that moderate the relationship between P released to the environment from human actions and ecosystem services at distinct spatial and temporal scales. Indirect pathways in the cascade via soil and aquatic processes link anthropogenic P to biodiversity and multiple services, including recreation, drinking water provision, and fisheries. As anthropogenic P cascades through catchments, it often shifts from a subsidy to a stressor of ecosystem services. Phosphorus stewardship can have emergent ecosystem service co-benefits due to synergies with other societal or management goals (e.g., recycling of livestock manures and organic wastes could impact soil carbon storage). Applying the PESC framework, we identify key research priorities to align P stewardship with the management of multiple ecosystem services, such as incorporating additional services into agri-environmental P indices, assessing how widespread recycling of organic P sources could differentially impact agricultural yields and water quality, and accounting for shifting baselines in P stewardship due to climate change. Ultimately, P impacts depend on site-specific agricultural and biogeophysical contexts, so greater precision in targeting stewardship strategies to specific locations would help to optimize for ecosystem services and to more effectively internalize the downstream costs of farm nutrient management

Establishing a Pragmatic Framework to Optimise Health Outcomes in Heart Failure and Multimorbidity (ARISE-HF): A Multidisciplinary Position Statement

Background Multimorbidity in heart failure (HF), defined as HF of any aetiology and multiple concurrent conditions that require active management, represents an emerging problem within the ageing HF patient population worldwide. Methods To inform this position paper, we performed: 1) an initial review of the literature identifying the ten most common conditions, other than hypertension and ischaemic heart disease, complicating the management of HF (anaemia, arrhythmias, cognitive dysfunction, depression, diabetes, musculoskeletal disorders, renal dysfunction, respiratory disease, sleep disorders and thyroid disease) and then 2) a review of the published literature describing the association between HF with each of the ten conditions. From these data we describe a clinical framework, comprising five key steps, to potentially improve historically poor health outcomes in this patient population. Results We identified five key steps (ARISE-HF) that could potentially improve clinical outcomes if applied in a systematic manner: 1) Acknowledge multimorbidity as a clinical syndrome that is associated with poor health outcomes, 2) Routinely profile (using a standardised protocol — adapted to the local health care system) all patients hospitalised with HF to determine the extent of concurrent multimorbidity, 3) Identify individualised priorities and person-centred goals based on the extent and nature of multimorbidity, 4) Support individualised, home-based, multidisciplinary, case management to supplement standard HF management, and 5) Evaluate health outcomes well beyond acute hospitalisation and encompass all-cause events and a person-centred perspective in affected individuals. Conclusions We propose ARISE-HF as a framework for improving typically poor health outcomes in those affected by multimorbidity in HF