Phase separation methods for protein purification: A meta-analysis of purification performance and cost-effectiveness.

Protein purifications based on phase separations (e.g., precipitation and liquid-liquid extraction) have seen little adoption in commercial protein drug production. To identify barriers, we analyzed the purification performance and economics of 290 phase separation purifications from 168 publications. First, we found that studies using Design of Experiments for optimization achieved significantly greater mean yield and host cell protein log10 removal values than those optimizing one factor at a time (11.5% and 53% increases, respectively). Second, by modeling each reported purification at scales from 10 to 10,000 kg product/year and comparing its cost-effectiveness versus chromatography, we found that cost-effectiveness depends strongly on scale: the fraction of phase separations predicted to be cost-effective at the 10, 100, and 1000 kg/year scales was 8%, 15%, and 43%, respectively. Total cost per unit product depends inversely on input purity, with phase separation being cheaper than chromatography at the 100 kg/year scale in 100% of cases where input purity was ≤ 1%, compared to about 25% of cases in the dataset as a whole. Finally, we identified a simple factor that strongly predicts phase separation process costs: the mass ratio of reagents versus purified product (the "direct materials usage rate"), which explains up to 58% of variation in cost per unit of purified product among all 290 reports, and up to 98% of variation within particular types of phase separation.

A telemedicine bridge clinic improves access and reduces cost for opioid use disorder care.

Objective: We evaluated the impact of a telemedicine bridge clinic on treatment outcomes and cost for patients with opioid use disorder. Telemedicine bridge clinics deliver low-barrier rapid assessment of patients with opioid use disorder via audio-only and audiovisual telemedicine to facilitate induction on medication therapy and connection to ongoing care. Methods: A pre-post analysis of UPMC Health Plan member claims was performed to evaluate the impact of this intervention on the trajectory of care for patients with continuous coverage before and after bridge clinic visit(s). Results: Analysis included 150 UPMC Health Plan members evaluated at the bridge clinic between April 2020 and October 2021. At least one buprenorphine prescription was filled within 30 days by 91% of patients; median proportion of days covered by buprenorphine was 73.3%, 54.4%, and 50.6% at 30, 90, and 180 days after an initial visit compared to median of no buprenorphine claims 30 days prior among the same patients. Patients had an 18% decline in unplanned care utilization 30 days after initial Bridge Clinic visit, with a 62% reduction in unplanned care cost per member per month (PMPM), 38% reduction in medical cost PMPM, and 10% reduction in total PMPM (medical + pharmacy cost) at 180 days. Primary care, outpatient behavioral health, and laboratory costs increased while emergency department, urgent care, and inpatient costs declined. Conclusion: Utilization of a telemedicine bridge clinic was associated with buprenorphine initiation, linkage to ongoing care with retention including medication treatment, reduced unplanned care cost, and overall savings.

A qualitative assessment of emergency physicians' experiences with robust emergency department buprenorphine bridge programs.

OBJECTIVES: Emergency departments (EDs) are a critical point of entry into treatment for patients struggling with opioid use disorder (OUD). When initiated in the ED, buprenorphine is associated with increased addiction treatment engagement at 30 days when initiated. Despite this association, it has had slow adoption. The barriers to ED buprenorphine utilization are well documented; however, the benefits of prescribing buprenorphine for emergency physicians (EPs) have not been explored. This study utilized semistructured interviews to explore and understand how EPs perceive their experiences working in EDs that have successfully implemented ED bridge programs (EDBPs) for patients with OUD. METHODS: Semistructured interviews were conducted with EPs from four geographically diverse academic hospitals with established EDBPs. Interviews were recorded and transcribed, and emergent themes were identified using codebook thematic analysis. Analysis credibility and transparency were confirmed with peer debriefing. RESULTS: Twenty-two interviews were conducted across the four sites. Three key themes were constructed during the analyses: (1) provided EPs agency; (2) transformed EPs' emotions, attitudes, and behaviors related to treating patients with OUD; and (3) improved EPs' professional quality of life. CONCLUSIONS: Participants in this study reported several common themes related to participation in their hospital's BP. Overall our results suggest that physicians who participate in EDBPs may feel a renewed sense of fulfillment and purpose in their personal and professional lives. These positive changes may lead to increased job satisfaction in hospitals that have successfully launched EDBP.

Precipitation and Extraction Methods for Protein Purification: A Meta-Analysis of Purification Performance and Cost-Effectiveness.

For protein drug purification, packed-bed chromatography often remains both the predominant method and a bottleneck for cost and scalability. Accordingly, extensive efforts have been made to develop alternatives, such as precipitation and liquid-liquid extraction. Despite decades of development, such methods have been slow to see adoption in commercial processes. To diagnose the key barriers to implementation and guide future work, we have systematically reviewed studies of protein precipitation and liquid-liquid extraction. We classify the products, methods, and results of 168 publications representing 290 unique purification operations and analyze these operations in terms of both process economics and purification performance. Whereas it is generally assumed that precipitation and extraction methods will have lower costs than chromatography, we find that this is only the case under specific process conditions such as at a large manufacturing scale and low initial sample purity. Furthermore, we find that only a small number of the many precipitation and extraction methods reported to date have shown readiness for implementation in protein drug purification processes. Finally, we identify key factors governing both the economic and purification performance of this class of methods: first, that operating costs are almost entirely predictable by the ratio between the mass of phase-forming materials used and the mass of product protein yielded; second, that use of modern optimization techniques such as Design of Experiments is associated with significantly better purification performance and cost-effectiveness. Highlights: Alternative separation purification methods are not always cheaper than chromatographyThe use of a combination of phase separating agents remains largely underexplored/underutilizedLower initial purity and increasing production scale favor phase-separation over chromatographyThe direct material usage rate is an important predictor of alternative separation cost-effectivenessCurrent alternative separation method development has largely ignored optimization of direct material usage rate.

Flagellar energy costs across the tree of life.

Flagellar-driven motility grants unicellular organisms the ability to gather more food and avoid predators, but the energetic costs of construction and operation of flagella are considerable. Paths of flagellar evolution depend on the deviations between fitness gains and energy costs. Using structural data available for all three major flagellar types (bacterial, archaeal, and eukaryotic), flagellar construction costs were determined for Escherichia coli, Pyrococcus furiosus, and Chlamydomonas reinhardtii. Estimates of cell volumes, flagella numbers, and flagellum lengths from the literature yield flagellar costs for another ~200 species. The benefits of flagellar investment were analysed in terms of swimming speed, nutrient collection, and growth rate; showing, among other things, that the cost-effectiveness of bacterial and eukaryotic flagella follows a common trend. However, a comparison of whole-cell costs and flagellum costs across the Tree of Life reveals that only cells with larger cell volumes than the typical bacterium could evolve the more expensive eukaryotic flagellum. These findings provide insight into the unsolved evolutionary question of why the three domains of life each carry their own type of flagellum.

Most creatures on Earth are single cell organisms. The tree of life comprises three domains, two of which ­ bacteria and archaea ­ are formed exclusively of creatures that spend their existence as independent cells. Yet even eukaryotes, the domain which include animals and plants, feature single cell species such as yeasts and algae. Regardless of which group they belong to, all single-celled organisms must find food in their environment. For this, many are equipped with flagella, whip-like structures that protrude from the cell and allow it to swim. In fact, archaea, bacteria and eukaryotes have all independently evolved these structures. However, flagella are also expensive for an organism to build, maintain and operate. They are only worth having if the advantages they bring to the cell compensate for their cost; many single-cell species do not carry flagella and obtain their food without having to swim. To explore this trade-off, Schavemaker and Lynch calculated the cost of building and using flagella for about 200 species across the tree of life. The analysis show that the amount of energy spent on flagella varied between 0.1% and 40% of the entire cell budget. This investment is only worthwhile if the cell is above a certain size. Smaller than this, and the organism is better off obtaining its food passively. The results also show that while eukaryotic flagella are much bigger and quite different than their bacterial counterpart, both appendages share the same patterns of cost effectiveness. However only eukaryotic cells, which are on average larger than bacteria, can afford to evolve such sizable and complex structures; making just one would cost more than the entire energy budget of a bacterial cell. Many single-cell species which are critical for the health of the planet are equipped with flagella, such as the microorganisms which recycle matter in the oceans and release carbon dioxide. Understanding the costs and benefits of flagella could explain more about this aspect of the carbon cycle, and therefore global warming.

A heutagogical approach for the assessment of Internet Communication Technology (ICT) assignments in higher education.

Pedagogical foundations exist for incorporating technology in instruction; however, these foundations have not kept pace with technology's evolution. Through the use of Information Communication Technologies (ICTs), students now can share content directed at external audiences, i.e., audiences other than the instructor. These audiences are referred to as authentic audiences as they are public-facing and exist outside of the classroom. The existing literature offers evidence of student satisfaction with assignments directed at appealing to external audiences, however, the literature provides no comprehensive pedagogical rationale for assignments directed at authentic audiences wherein the goals are self-determined. The authors discuss the theory of heutagogy, the study of self-determined learning, as an approach for assessing assignments that utilize ICTs and are directed at authentic audiences. Finally, the authors offer an approach for the assessment of these assignments, including a rubric.

Physical bioenergetics: Energy fluxes, budgets, and constraints in cells.

Cells are the basic units of all living matter which harness the flow of energy to drive the processes of life. While the biochemical networks involved in energy transduction are well-characterized, the energetic costs and constraints for specific cellular processes remain largely unknown. In particular, what are the energy budgets of cells? What are the constraints and limits energy flows impose on cellular processes? Do cells operate near these limits, and if so how do energetic constraints impact cellular functions? Physics has provided many tools to study nonequilibrium systems and to define physical limits, but applying these tools to cell biology remains a challenge. Physical bioenergetics, which resides at the interface of nonequilibrium physics, energy metabolism, and cell biology, seeks to understand how much energy cells are using, how they partition this energy between different cellular processes, and the associated energetic constraints. Here we review recent advances and discuss open questions and challenges in physical bioenergetics.

BioSamplr: An open source, low cost automated sampling system for bioreactors.

Autosampling from bioreactors reduces error, increases reproducibility and offers improved aseptic handling when compared to manual sampling. Additionally, autosampling greatly decreases the hands-on time required for a bioreactor experiment and enables sampling 24 h a day. We have designed, built and tested a low cost, open source, automated bioreactor sampling system, the BioSamplr. The BioSamplr can take up to ten samples from a bioreactor at a desired sample interval and cools them to a desired temperature. The device, assembled from low cost and 3D printed components, is controlled wirelessly by a Raspberry Pi, and records all sampling data to a log file. The cost and accessibility of the BioSamplr make it useful for laboratories without access to more expensive and complex autosampling systems.

Science and Risked-Based Stability Testing Strategies-a Test Case on the Global Implementation and Regulatory Reception.

The global regulatory implementation and acceptance of a science and risk-based stability (SRB) strategies for a stable drug product is reviewed. This stability strategy may also be referred to as "lean stability" since it includes a stability protocol reduction in the number of tests and time points than might normally be applied. A product line extension (new solid dosage form) for a well-understood product was used as a test case for this stability strategy. The drug product line extension was filed globally with a proposed reduction to analytical stability tests and frequency. This stability protocol is aligned with the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q1A (R2) stability guidelines (ICH: Guideline Q1A(R2), 2003), the World Health Organization (WHO) (WHO INT. [Online], 2020), and most country regulatory guidelines. Although this strategy was not accepted universally, the strategy enabled opportunities to engage in productive dialogs with regulatory authorities in several countries on how the case leveraged product understanding and development knowledge to develop a fit for purpose stability protocol. A persistent and consistent effort from industry to move toward product-specific protocols based on product knowledge and stability risk assessments should lead to further acceptance of science and risk-based stability strategies in all regions.

Low-Cost, Large-Scale Production of the Anti-viral Lectin Griffithsin.

Griffithsin, a broad-spectrum antiviral lectin, has potential to prevent and treat numerous viruses including HIV, HCV, HSV, SARS-CoV, and SARS-CoV-2. For these indications, the annual demand for Griffithsin could reach billions of doses and affordability is paramount. We report the lab-scale validation of a bioprocess that supports production volumes of >20 tons per year at a cost of goods sold below $3,500/kg. Recombinant expression in engineered E. coli enables Griffithsin titers ∼2.5 g/L. A single rapid precipitation step provides > 90% yield with 2-, 3-, and 4-log reductions in host cell proteins, endotoxin, and nucleic acids, respectively. Two polishing chromatography steps remove residual contaminants leading to pure, active Griffithsin. Compared to a conventional one this process shows lower costs and improved economies of scale. These results support the potential of biologics in very large-scale, cost-sensitive applications such as antivirals, and highlight the importance of bioprocess innovations in enabling these applications.

Trajectories of prescription opioids filled over time.

We performed a retrospective cohort study that aimed to identify one or more groups that followed a pattern of chronic, high prescription use and quantify individuals' time-dependent probabilities of belonging to a high-utilizer group. We analyzed data from 52,456 adults age 18-45 who enrolled in Medicaid from 2009-2017 in Allegheny County, Pennsylvania who filled at least one prescription for an opioid analgesic. We used group-based trajectory modeling to identify groups of individuals with distinct patterns of prescription opioid use over time. We found the population to be comprised of three distinct trajectory groups. The first group comprised 83% of the population and filled few, if any, opioid prescriptions after their index prescription. The second group (12%) initially filled an average of one prescription per month, but declined over two years to near-zero. The third group (6%) demonstrated sustained high opioid prescriptions utilization. Using individual patients' posterior probability of membership in the high utilization group, which can be updated iteratively over time as new information become available, we defined a sensitive threshold predictive of sustained future opioid utilization. We conclude that individuals at risk of sustained opioid utilization can be identified early in their clinical course from limited observational data.

Evolution of protein interfaces in multimers and fibrils.

A majority of cellular proteins function as part of multimeric complexes of two or more subunits. Multimer formation requires interactions between protein surfaces that lead to closed structures, such as dimers and tetramers. If proteins interact in an open-ended way, uncontrolled growth of fibrils can occur, which is likely to be detrimental in most cases. We present a statistical physics model that allows aggregation of proteins as either closed dimers or open fibrils of all lengths. We use pairwise amino-acid contact energies to calculate the energies of interacting protein surfaces. The probabilities of all possible aggregate configurations can be calculated for any given sequence of surface amino acids. We link the statistical physics model to a population genetics model that describes the evolution of the surface residues. When proteins evolve neutrally, without selection for or against multimer formation, we find that a majority of proteins remain as monomers at moderate concentrations, but strong dimer-forming or fibril-forming sequences are also possible. If selection is applied in favor of dimers or in favor of fibrils, then it is easy to select either dimer-forming or fibril-forming sequences. It is also possible to select for oriented fibrils with protein subunits all aligned in the same direction. We measure the propensities of amino acids to occur at interfaces relative to noninteracting surfaces and show that the propensities in our model are strongly correlated with those that have been measured in real protein structures. We also show that there are significant differences between amino acid frequencies at isologous and heterologous interfaces in our model, and we observe that similar effects occur in real protein structures.

The Effect of a Medical Toxicology Inpatient Service in an Academic Tertiary Care Referral Center.

INTRODUCTION: Morbidity and mortality from poison- and drug-related illness continue to rise in the USA. Medical toxicologists are specifically trained to diagnose and manage these patients. Inpatient medical toxicology services exist but their value-based economic benefits are not well established. METHODS: This was a retrospective study where length of stay (LOS) and payments received between a hospital with an inpatient medical toxicology service (TOX) and a similar hospital in close geographic proximity that does not have an inpatient toxicology service (NONTOX) were compared. Controlling for zip code, demographics and distance patients lived from each hospital, we used a fitted multivariate linear regression model to identify factors associated with changes in LOS and payment. RESULTS: Patients admitted to the TOX center had 0.87 days shorter LOS per encounter and the hospital received an average of $1800 more per patient encounter. CONCLUSION: In this study, the presence of an inpatient medical toxicology service was associated with decreased patient LOS and increased reimbursement for admitted patients. Differences may be attributable to improved direct patient care provided by medical toxicologists, but future prospective studies are needed.

The Effect of a Statewide Mandatory Prescription Drug Monitoring Program on Opioid Prescribing by Emergency Medicine Providers Across 15 Hospitals in a Single Health System.

Prescription drug monitoring programs (PDMPs) enable registered prescribers to obtain real-time information on patients' prescription history of controlled medications. We sought to describe the effect of a state-mandated PDMP on opioid prescribing by emergency medicine providers. We retrospectively analyzed electronic medical records of 122,732 adult patients discharged with an opioid prescription from 15 emergency departments in a single health system in Pennsylvania from July 2015 to March, 2017. We used an interrupted time series design to evaluate the percentage of patients discharged each month with an opioid prescription before and after state law-mandated PDMP use on August 25, 2016. From August (pre-PDMP) to September, 2016 (post-PDMP), the opioid prescribing rate decreased from 12.4% (95% confidence interval [CI], 10.8%-14.1%) to 10.2% (95% CI, 8.8%-11.8%). For each month between September 2016 to March 2017, there was a mean decline of .46% (95% CI, -.38% to -.53%) in the percentage of patients discharged with an opioid prescription. There was heterogeneity in opioid prescribing across hospitals as well as according to patient diagnosis. PERSPECTIVE: This study examined the effect of a state-mandated PDMP on opioid prescribing among emergency medicine providers from 15 different hospitals in a single health system. Findings support current PDMP mandates in reducing opioid prescriptions, which could curb the prescription opioid epidemic and may ultimately reduce abuse, misuse, and overdose death.

Framework for Evaluating the Health Impact of the Scale-Up of Malaria Control Interventions on All-Cause Child Mortality in Sub-Saharan Africa.

Concerted efforts from national and international partners have scaled up malaria control interventions, including insecticide-treated nets, indoor residual spraying, diagnostics, prompt and effective treatment of malaria cases, and intermittent preventive treatment during pregnancy in sub-Saharan Africa (SSA). This scale-up warrants an assessment of its health impact to guide future efforts and investments; however, measuring malaria-specific mortality and the overall impact of malaria control interventions remains challenging. In 2007, Roll Back Malaria's Monitoring and Evaluation Reference Group proposed a theoretical framework for evaluating the impact of full-coverage malaria control interventions on morbidity and mortality in high-burden SSA countries. Recently, several evaluations have contributed new ideas and lessons to strengthen this plausibility design. This paper harnesses that new evaluation experience to expand the framework, with additional features, such as stratification, to examine subgroups most likely to experience improvement if control programs are working; the use of a national platform framework; and analysis of complete birth histories from national household surveys. The refined framework has shown that, despite persisting data challenges, combining multiple sources of data, considering potential contributions from both fundamental and proximate contextual factors, and conducting subnational analyses allows identification of the plausible contributions of malaria control interventions on malaria morbidity and mortality.

Production, characterization, and assessment of a stable analog of the response regulator CheY-phosphate from Thermotoga maritima.

Phosphorylation of CheY promotes association with the flagellar motor and ultimately controls the directional bias of the motor. However, biochemical studies of activated CheY-phosphate have been challenging due to the rapid hydrolysis of the aspartyl-phosphate in vitro. An inert analog of Tm CheY-phosphate, phosphono-CheY, was synthesized by chemical modification and purified by cation-exchange chromatography. Changes in HPLC retention times, chemical assays for phosphate and free thiol, and mass spectrometry experiments demonstrate modification of Cys54 with a phosphonomethyl group. Additionally, a crystal structure showed electron density for the phosphonomethyl group at Cys54, consistent with a modification at that position. Subsequent biochemical experiments confirmed that protein crystals were phosphono-CheY. Isothermal titration calorimetry and fluorescence polarization binding assays demonstrated that phosphono-CheY bound a peptide derived from FliM, a native partner of CheY-phosphate, with a dissociation constant of ∼29 µM, at least sixfold more tightly than unmodified CheY. Taken together these results suggest that Tm phosphono-CheY is a useful and unique analog of Tm CheY-phosphate.

Malaria: Global progress 2000 - 2015 and future challenges.

BACKGROUND: 2015 was the target year for malaria goals set by the World Health Assembly and other international institutions to reduce malaria incidence and mortality. A review of progress indicates that malaria programme financing and coverage have been transformed since the beginning of the millennium, and have contributed to substantial reductions in the burden of disease. FINDINGS: Investments in malaria programmes increased by more than 2.5 times between 2005 and 2014 from US$ 960 million to US$ 2.5 billion, allowing an expansion in malaria prevention, diagnostic testing and treatment programmes. In 2015 more than half of the population of sub-Saharan Africa slept under insecticide-treated mosquito nets, compared to just 2 % in 2000. Increased availability of rapid diagnostic tests and antimalarial medicines has allowed many more people to access timely and appropriate treatment. Malaria incidence rates have decreased by 37 % globally and mortality rates by 60 % since 2000. It is estimated that 70 % of the reductions in numbers of cases in sub-Saharan Africa can be attributed to malaria interventions. CONCLUSIONS: Reductions in malaria incidence and mortality rates have been made in every WHO region and almost every country. However, decreases in malaria case incidence and mortality rates were slowest in countries that had the largest numbers of malaria cases and deaths in 2000; reductions in incidence need to be greatly accelerated in these countries to achieve future malaria targets. Progress is made challenging because malaria is concentrated in countries and areas with the least resourced health systems and the least ability to pay for system improvements. Malaria interventions are nevertheless highly cost-effective and have not only led to significant reductions in the incidence of the disease but are estimated to have saved about US$ 900 million in malaria case management costs to public providers in sub-Saharan Africa between 2000 and 2014. Investments in malaria programmes can not only reduce malaria morbidity and mortality, thereby contributing to the health targets of the Sustainable Development Goals, but they can also transform the well-being and livelihood of some of the poorest communities across the globe.

Assessing the availability of LLINs for continuous distribution through routine antenatal care and the Expanded Programme on Immunizations in sub-Saharan Africa.

BACKGROUND: In addition to mass distribution campaigns, the World Health Organization (WHO) recommends the continuous distribution of long-lasting insecticidal nets (LLINs) to all pregnant women attending antenatal care (ANC) and all infants attending the Expanded Programme on Immunization (EPI) services in countries implementing mosquito nets for malaria control. Countries report LLIN distribution data to the WHO annually. For this analysis, these data were used to assess policy and practice in implementing these recommendations and to compare the numbers of LLINs available through ANC and EPI services with the numbers of women and children attending these services. METHODS: For each reporting country in sub-Saharan Africa, the presence of a reported policy for LLIN distribution through ANC and EPI was reviewed. Prior to inclusion in the analysis the completeness of data was assessed in terms of the numbers of LLINs distributed through all channels (campaigns, EPI, ANC, other). For each country with adequate data, the numbers of LLINs reportedly distributed by national programmes to ANC was compared to the number of women reportedly attending ANC at least once; the ratio between these two numbers was used as an indicator of LLIN availability at ANC services. The same calculations were repeated for LLINs distributed through EPI to produce the corresponding LLIN availability through this distribution channel. RESULTS: Among 48 malaria-endemic countries in Africa, 33 malaria programmes reported adopting policies of ANC-based continuous distribution of LLINs, and 25 reported adopting policies of EPI-based distribution. Over a 3-year period through 2012, distribution through ANC accounted for 9 % of LLINs distributed, and LLINs distributed through EPI accounted for 4 %. The LLIN availability ratios achieved were 55 % through ANC and 34 % through EPI. For 38 country programmes reporting on LLIN distribution, data to calculate LLIN availability through ANC and EPI was available for 17 and 16, respectively. CONCLUSIONS: These continuous LLIN distribution channels appear to be under-utilized, especially EPI-based distribution. However, quality data from more countries are needed for consistent and reliable programme performance monitoring. A greater focus on routine data collection, monitoring and reporting on LLINs distributed through both ANC and EPI can provide insight into both strengths and weaknesses of continuous distribution, and improve the effectiveness of these delivery channels.

The bioenergetic costs of a gene.

An enduring mystery of evolutionary genomics concerns the mechanisms responsible for lineage-specific expansions of genome size in eukaryotes, especially in multicellular species. One idea is that all excess DNA is mutationally hazardous, but weakly enough so that genome-size expansion passively emerges in species experiencing relatively low efficiency of selection owing to small effective population sizes. Another idea is that substantial gene additions were impossible without the energetic boost provided by the colonizing mitochondrion in the eukaryotic lineage. Contrary to this latter view, analysis of cellular energetics and genomics data from a wide variety of species indicates that, relative to the lifetime ATP requirements of a cell, the costs of a gene at the DNA, RNA, and protein levels decline with cell volume in both bacteria and eukaryotes. Moreover, these costs are usually sufficiently large to be perceived by natural selection in bacterial populations, but not in eukaryotes experiencing high levels of random genetic drift. Thus, for scaling reasons that are not yet understood, by virtue of their large size alone, eukaryotic cells are subject to a broader set of opportunities for the colonization of novel genes manifesting weakly advantageous or even transiently disadvantageous phenotypic effects. These results indicate that the origin of the mitochondrion was not a prerequisite for genome-size expansion.

A lexicon of assessment and outcome measures for telemental health.

BACKGROUND: The purpose of this document is to provide initial recommendations to telemental health (TMH) professionals for the selection of assessment and outcome measures that best reflect the impacts of mental health treatments delivered via live interactive videoconferencing. MATERIALS AND METHODS: The guidance provided here was created through an expert consensus process and is in the form of a lexicon focused on identified key TMH outcomes. RESULTS: Each lexical item is elucidated by a definition, recommendations for assessment/measurement, and additional commentary on important considerations. The lexicon is not intended as a current literature review of the field, but rather as a resource to foster increased dialogue, critical analysis, and the development of the science of TMH assessment and evaluation. The intent of this lexicon is to better unify the TMH field by providing a resource to researchers, program managers, funders, regulators and others for assessing outcomes. CONCLUSIONS: This document provides overall context for the key aspects of the lexicon.