The Empirical Foundations of Telemedicine Interventions in Primary Care

Introduction: This article presents the scientific evidence for the merits of telemedicine interventions in primary care. Although there is no uniform and consistent definition of primary care, most agree that it occupies a central role in the healthcare system as first contact for patients seeking care, as well as gatekeeper and coordinator of care. It enables and supports patient-centered care, the medical home, managed care, accountable care, and population health. Increasing concerns about sustainability and the anticipated shortages of primary care physicians have sparked interest in exploring the potential of telemedicine in addressing many of the challenges facing primary care in the United States and the world. Materials and Methods: The findings are based on a systematic review of scientific studies published from 2005 through 2015. The initial search yielded 2,308 articles, with 86 meeting the inclusion criteria. Evidence is organized and evaluated according to feasibility/acceptance, intermediate outcomes, health outcomes, and cost. Results: The majority of studies support the feasibility/acceptance of telemedicine for use in primary care, although it varies significantly by demographic variables, such as gender, age, and socioeconomic status, and telemedicine has often been found more acceptable by patients than healthcare providers. Outcomes data are limited but overall suggest that telemedicine interventions are generally at least as effective as traditional care. Cost analyses vary, but telemedicine in primary care is increasingly demonstrated to be cost-effective. Conclusions: Telemedicine has significant potential to address many of the challenges facing primary care in today's healthcare environment. Challenges still remain in validating its impact on clinical outcomes with scientific rigor, as well as in standardizing methods to assess cost, but patient and provider acceptance is increasingly making telemedicine a viable and integral component of primary care around the world.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140293/1/tmj.2016.0045.pd

Warming of the Indian Ocean Threatens Eastern and Southern Africa, but could be Mitigated by Agricultural Development

Since 1980, the number of undernourished people in eastern and southern Africa has more than doubled. Rural development stalled and rural poverty expanded during the 1990s. Population growth remains very high and declining per capita agricultural capacity retards progress towards Millennium Development goals. Analyses of in situ station data and satellite observations of precipitation identify another problematic trend. Main growing season rainfall receipts have diminished by approximately 15% in food insecure countries clustered along the western rim of the Indian Ocean. Occurring during the main growing seasons in poor countries dependent on rain fed agriculture, these declines are societally dangerous. Will they persist or intensify? Tracing moisture deficits upstream to an anthropogenically warming Indian Ocean leads us to conclude that further rainfall declines are likely. We present analyses suggesting that warming in the central Indian Ocean disrupts onshore moisture transports, reducing continental rainfall. Thus late 20th century anthropogenic Indian Ocean warming has probably already produced societally dangerous climate change by creating drought and social disruption in some of the world's most fragile food economies. We quantify the potential impacts of the observed precipitation and agricultural capacity trends by modeling millions of undernourished people as a function of rainfall, population, cultivated area, seed and fertilizer use. Persistence of current tendencies may result in a 50% increase in undernourished people. On the other hand, modest increases in per capita agricultural productivity could more than offset the observed precipitation declines. Investing in agricultural development can help mitigate climate change while decreasing rural poverty and vulnerability

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma.

The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy

<i>Pseudomonas aeruginosa</i> AlgF is a protein-protein interaction mediator required for acetylation of the alginate exopolysaccharide

Enzymatic modifications of bacterial exopolysaccharides enhance immune evasion and persistence during infection. In the Gram-negative opportunistic pathogen Pseudomonas aeruginosa, acetylation of alginate reduces opsonic killing by phagocytes and improves reactive oxygen species scavenging. Although it is well-known that alginate acetylation in P. aeruginosa requires AlgI, AlgJ, AlgF, and AlgX, how these proteins coordinate polymer modification at a molecular level remains unclear. Here, we describe the structural characterization of AlgF and its protein interaction network. We characterize direct interactions between AlgF and both AlgJ and AlgX in vitro, and demonstrate an association between AlgF and AlgX, as well as AlgJ and AlgI, in P. aeruginosa. We determine that AlgF does not exhibit acetylesterase activity and is unable to bind to polymannuronate in vitro. Therefore, we propose that AlgF functions to mediate protein-protein interactions between alginate acetylation enzymes, forming the periplasmic AlgJFXK (AlgJ-AlgF-AlgX-AlgK) acetylation and export complex required for robust biofilm formation.</p

P. aeruginosa SGNH Hydrolase-Like Proteins AlgJ and AlgX Have Similar Topology but Separate and Distinct Roles in Alginate Acetylation

The O-acetylation of polysaccharides is a common modification used by pathogenic organisms to protect against external forces. Pseudomonas aeruginosa secretes the anionic, O-acetylated exopolysaccharide alginate during chronic infection in the lungs of cystic fibrosis patients to form the major constituent of a protective biofilm matrix. Four proteins have been implicated in the O-acetylation of alginate, AlgIJF and AlgX. To probe the biological function of AlgJ, we determined its structure to 1.83 Å resolution. AlgJ is a SGNH hydrolase-like protein, which while structurally similar to the N-terminal domain of AlgX exhibits a distinctly different electrostatic surface potential. Consistent with other SGNH hydrolases, we identified a conserved catalytic triad composed of D190, H192 and S288 and demonstrated that AlgJ exhibits acetylesterase activity in vitro. Residues in the AlgJ signature motifs were found to form an extensive network of interactions that are critical for O-acetylation of alginate in vivo. Using two different electrospray ionization mass spectrometry (ESI-MS) assays we compared the abilities of AlgJ and AlgX to bind and acetylate alginate. Binding studies using defined length polymannuronic acid revealed that AlgJ exhibits either weak or no detectable polymer binding while AlgX binds polymannuronic acid specifically in a length-dependent manner. Additionally, AlgX was capable of utilizing the surrogate acetyl-donor 4-nitrophenyl acetate to catalyze the O-acetylation of polymannuronic acid. Our results, combined with previously published in vivo data, suggest that the annotated O-acetyltransferases AlgJ and AlgX have separate and distinct roles in O-acetylation. Our refined model for alginate acetylation places AlgX as the terminal acetlytransferase and provides a rationale for the variability in the number of proteins required for polysaccharide O-acetylation

Over 500 Days in the Life of the Photosphere of the Type Iax Supernova SN 2014dt

Type Iax supernovae (SN Iax) are the largest known class of peculiar white dwarf supernovae, distinct from normal Type Ia supernovae (SN Ia). The unique properties of SN Iax, especially their strong photospheric lines out to extremely late times, allow us to model their optical spectra and derive physical parameters for the long-lasting photosphere. We present an extensive spectral timeseries, including 21 new spectra, of SN Iax 2014dt from +11 to +562 days after maximum light. We are able to reproduce the entire timeseries with a self-consistent, nearly unaltered deflagration explosion model from Fink et al. (2014) using TARDIS, an open-source radiative transfer code (Kerzendorf & Sim 2014; Kerzendorf et al. 2023). We find that the photospheric velocity of SN 2014dt slows its evolution between +64 and +148 days, which closely overlaps the phase when we see SN 2014dt diverge from the normal spectral evolution of SN Ia (+90 to +150 days). The photospheric velocity at these epochs, ~400$-$1000 km s$^{-1}$, may demarcate a boundary within the ejecta below which the physics of SN Iax and normal SN Ia differ. Our results suggest that SN 2014dt is consistent with a weak deflagration explosion model that leaves behind a bound remnant and drives an optically thick, quasi-steady-state wind creating the photospheric lines at late times. The data also suggest that this wind may weaken at epochs past +450 days, perhaps indicating a radioactive power source that has decayed away.Comment: Accepted to ApJ, 22 pages, 8 figures, 3 table