Harnessing Raman spectroscopy for the analysis of plant diversity.

Here, we explore the application of Raman spectroscopy for the assessment of plant biodiversity. Raman spectra from 11 vascular plant species commonly found in forest ecosystems, specifically angiosperms (both monocots and eudicots) and pteridophytes (ferns), were acquired in vivo and in situ using a Raman leaf-clip. We achieved an overall accuracy of 91% for correct classification of a species within a plant group and identified lignin Raman spectral features as a useful discriminator for classification. The results demonstrate the potential of Raman spectroscopy in contributing to plant biodiversity assessment.

Current Patterns of Treatment and Outcomes in Advanced Melanoma at a Single Institution.

INTRODUCTION: Treatment of advanced melanoma has been transformed by novel systemic therapies. The purpose of this study is to describe the current utilization patterns of immunotherapies with respect to survival outcomes in advanced melanoma. METHODS: We performed a retrospective cohort study of patients with Stage 3 and 4 melanoma at our institution (2009-2019). Primary outcomes included overall survival (OS) and progression free survival (PFS). Kaplan-Meier survival analysis and Cox proportional hazards regression analysis evaluated associations between covariates and survival outcomes. RESULTS: Of 244 patients, 5-y OS was 62.4%. Lymphovascular invasion (hazard ratio [HR] = 2.462, P = 0.030) was associated with shorter PFS whereas female gender (HR = 0.324, P = 0.010) was associated with longer PFS. Residual tumor (HR = 146, P = 0.006) and Stage 4 disease (HR = 3.349, P = 0.011) were associated with shorter OS. Use of immunotherapy increased from 2% to 23% over the study period, and use of neoadjuvant immunotherapy also increased up to 2016. Timing of immunotherapy administration was not significantly associated with survival. Of the 193 patients who received 2 or more treatment types, the most common treatment sequence was surgery followed by immunotherapy (n = 117, 60.6%). CONCLUSIONS: Immunotherapy is increasingly used for treatment of advanced melanoma. In this heterogeneous cohort, there was no significant association between timing of immunotherapy and survival outcomes.

Non-targeted hepatitis C virus screening in acute care healthcare settings in the Southern Appalachian region.

Objectives: The objective of this study was to evaluate the performance of non-targeted hepatitis C virus (HCV) screening in emergency departments (EDs) and other healthcare settings in terms of patients identified with HCV infection and linked to HCV care. Methods: In the Southern Appalachian region of the United States, we developed non-targeted HCV screening and linkage-to-care programs in 10 institutions at different healthcare settings, including EDs, outpatient clinics, and inpatient units. Serum samples were tested for HCV antibodies, and if positive, reflexed to HCV ribonucleic acid (RNA) testing as a confirmatory test for active infection. Patients with positive RNA tests were contacted to link them to HCV care. Results: Between 2017 and 2019, among 195,152 patients screened for HCV infection, 16,529 (8.5%) were positive by antibody testing, 10,139 (5.2% of screened patients and 61.3% of patients positive by antibody test) were positive by RNA testing, and 5778 (3.0% of screened patients and 57.0% of patients positive by RNA test) were successfully linked to HCV care. Among 83,645 patients screened in EDs, 9060 (10.8%) were positive by HCV antibody, and 5243 (6.3%) were positive by RNA test. Among patients positive by RNA testing, linkage to care was lower for patients screened in the ED (44.1%) compared with outpatient clinics (67.6%) (P < 0.01) and inpatient units (50.9%) (P < 0.01). Conclusions: Non-targeted HCV screening in acute care settings can identify large numbers of people with HCV infection. To optimize the utility of these screening programs, future work is needed to develop best practices that consistently link these patients to HCV care.

Adsorption of Individual and Mixtures of ß-Blockers and Copper in Soils and Sediments.

The (bio)availability of pharmaceuticals at solid/water interfaces is governed by their sorption, which determines their concentrations in groundwaters and surface waters in contact with biota, and can be affected by the presence of other contaminants such as metallic trace elements likely to compete for adsorption sites and form complexes with pharmaceuticals. We studied the adsorption of the pharmaceuticals propranolol and sotalol-two ß-blockers-on one soil and one sediment using batch experiments to assess their (bio)availability. The influence of contact time, pH, and concentration was studied. As in the real environment these contaminants are not alone but in mixtures, and they were studied alone, simultaneously added, and in the presence of Cu2+ , which is known to form coordination complexes with propranolol and sotalol, but their presence in mixtures did not alter their adsorption properties. Sotalol was more mobile in water and thus more bioavailable for organisms than propranolol. The mobility in surface waters of both ß-blockers and thus their bioavailabity for organisms is more important than their risk of transfer to groundwater during rainwater infiltration and to surface water due to runoff. Environ Toxicol Chem 2022;41:2700-2707. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Amplifying the Student Voice: Medical Student Perceptions of AΩA.

BACKGROUND: Recent literature has suggested racial disparities in Alpha Omega Alpha Honor Medical Society (AΩA) selection and raised concerns about its effects on the learning environment. Internal reviews at multiple institutions have led to changes in selection practices or suspension of student chapters; in October 2020, the national AΩA organization provided guidance to address these concerns. OBJECTIVE: This study aimed to better understand student opinions of AΩA. DESIGN: An anonymous survey using both multiple response option and free response questions. PARTICIPANTS: Medical students at the Perelman School of Medicine at the University of Pennsylvania. MAIN MEASURES: Descriptive statistics and logistic regressions were used to examine predictors of student opinion towards AΩA. Free responses were analyzed by two independent coders to identify key themes. KEY RESULTS: In total, 70% of the student body (n = 547) completed the survey. Sixty-three percent had a negative opinion of AΩA, and 57% felt AΩA should not exist at the student level. Thirteen percent believed AΩA membership appropriately reflects the student body; 8% thought selection processes were fair. On multivariate analysis, negative predictors of a student's preference to continue AΩA at the student level included belief that AΩA membership does not currently mirror class composition (OR: 0.45, [95% CI: 0.23-0.89]) and that AΩA selection processes were unfair (OR: 0.20 [0.08-0.47]). Self-perception as not competitive for AΩA selection was also a negative predictor (OR: 0.44 [0.22-0.88]). Major qualitative themes included equity, impact on the learning environment, transparency, and positive aspects of AΩA. CONCLUSIONS: This single-institution survey demonstrated significant student concerns regarding AΩA selection fairness and effects on the learning environment. Many critiques extended beyond AΩA itself, instead focusing on the perceived magnification of existing disparities in the learning environment. As the national conversation about AΩA continues, engaging student voices in the discussion is critical.

Acceptability of a HIV self-testing program among people who use illicit drugs.

BACKGROUND: People who use illicit drugs (PWUD) remain at significantly elevated risk for HIV infection and continue to have very low testing rates. HIV self-testing (HIVST) has been shown to be acceptable among many high-risk populations, but less is known about PWUD. METHODS: From May-June 2021, a HIVST program was implemented at a syringe services program (SSP) in Louisville, Kentucky. PWUD were given the option to privately self-test at the SSP or take the test home and follow-up with study staff. Primary outcomes were acceptability, ease of use, usability, reasons for self-testing, testing location, frequency of future testing, and preference for future testing location. RESULTS: Among 230 study participants, 77% reported high acceptability (i.e., the HIVST kits made them feel much more able to keep track of their HIV status compared to standard testing methods). Virtually all (97.4%) reported the test kits were very easy to use. Problems while using the HIVST kits were rare (range 1.3-3.0%). The most common reasons for testing were a desire to know their status (85.2%), the test was free (37%), and the short duration for results (30.9%). Testing primarily occurred onsite (87.8%). The majority (83%) reported they would use the HIVST kits at least every six months if made available through the health department and would prefer to test at home (71.7%). Multivariate analyses found that awareness of and intention to use pre-exposure prophylaxis (PrEP) were significantly associated with high acceptability and testing onsite. CONCLUSION: Study participants found HIVST to be acceptable and very easy to use. The multivariate findings suggest HIVST interventions should be packaged with PrEP interventions and harm reduction programs.

Technologies Enabling Situational Awareness During Disaster Response: A Systematic Review.

Situational awareness (SA) is critical to mobilizing a rapid, efficient, and effective response to disasters. Limited by time and resources, response agencies must make decisions about rapidly evolving situations, which requires the collection, analysis, and sharing of actionable information across a complex landscape. Emerging technologies, if appropriately applied, can enhance SA and enable responders to make quicker, more accurate decisions. The aim of this systematic review is to identify technologies that can improve SA and assist decision-making across the United States Government and the domestic and international agencies they support during disaster response operations. A total of 1459 articles and 36 after-action reports were identified during literature searches. Following the removal of duplicates and application of inclusion/exclusion criteria, 302 articles and after-action reports were included in the review. Our findings suggest SA is constrained primarily due to unreliable and significantly delayed communications, time-intensive data analysis and visualization, and a lack of interoperable sensor networks and other capabilities providing data to shared platforms. Many of these challenges could be addressed by existing technologies. Bridging the divide between research and development efforts and the operational needs of response agencies should be prioritized.

COVID-19 response by the Hopi Tribe: impact of systems improvement during the first wave on the second wave of the pandemic.

The Hopi Tribe is a sovereign nation home to ~7500 Hopi persons living primarily in 12 remote villages. The Hopi Tribe, like many other American Indian nations, has been disproportionately affected by COVID-19. On 18 May 2020, a team from the US Centers for Disease Control and Prevention (CDC) was deployed on the request of the tribe in response to increases in COVID-19 cases. Collaborating with Hopi Health Care Center (the reservation's federally run Indian Health Service health facility) and CDC, the Hopi strengthened public health systems and response capacity from May to August including: (1) implementing routine COVID-19 surveillance reporting; (2) establishing the Hopi Incident Management Authority for rapid coordination and implementation of response activities across partners; (3) implementing a community surveillance programme to facilitate early case detection and educate communities on COVID-19 prevention; and (4) applying innovative communication strategies to encourage mask wearing, hand hygiene and physical distancing. These efforts, as well as community adherence to mitigation measures, helped to drive down cases in August. As cases increased in September-November, the improved capacity gained during the first wave of the pandemic enabled the Hopi leadership to have real-time awareness of the changing epidemiological landscape. This prompted rapid response coordination, swift scale up of health communications and redeployment of the community surveillance programme. The Hopi experience in strengthening their public health systems to better confront COVID-19 may be informative to other indigenous peoples as they also respond to COVID-19 within the context of disproportionate burden.

Trends in Use of Telehealth Among Health Centers During the COVID-19 Pandemic - United States, June 26-November 6, 2020.

Telehealth can facilitate access to care, reduce risk for transmission of SARS-CoV-2 (the virus that causes coronavirus disease 2019 [COVID-19]), conserve scarce medical supplies, and reduce strain on health care capacity and facilities while supporting continuity of care. Health Resources and Services Administration (HRSA)-funded health centers* expanded telehealth† services during the COVID-19 pandemic (1). The Centers for Medicare & Medicaid Services eliminated geographic restrictions and enhanced reimbursement so that telehealth services-enabled health centers could expand telehealth services and continue providing care during the pandemic (2,3). CDC and HRSA analyzed data from 245 health centers that completed a voluntary weekly HRSA Health Center COVID-19 Survey§ for 20 consecutive weeks to describe trends in telehealth use. During the weeks ending June 26-November 6, 2020, the overall percentage of weekly health care visits conducted via telehealth (telehealth visits) decreased by 25%, from 35.8% during the week ending June 26 to 26.9% for the week ending November 6, averaging 30.2% over the study period. Weekly telehealth visits declined when COVID-19 cases were decreasing and plateaued as cases were increasing. Health centers in the South and in rural areas consistently reported the lowest average percentage of weekly telehealth visits over the 20 weeks, compared with health centers in other regions and urban areas. As the COVID-19 pandemic continues, maintaining and expanding telehealth services will be critical to ensuring access to care while limiting exposure to SARS-CoV-2.

Telehealth Practice Among Health Centers During the COVID-19 Pandemic - United States, July 11-17, 2020.

Early in the coronavirus disease 2019 (COVID-19) pandemic, in-person ambulatory health care visits declined by 60% across the United States, while telehealth* visits increased, accounting for up to 30% of total care provided in some locations (1,2). In March 2020, the Centers for Medicare & Medicaid Services (CMS) released updated regulations and guidance changing telehealth provisions during the COVID-19 Public Health Emergency, including the elimination of geographic barriers and enhanced reimbursement for telehealth services† (3-6). The Health Resources and Services Administration (HRSA) administers a voluntary weekly Health Center COVID-19 Survey§ to track health centers' COVID-19 testing capacity and the impact of COVID-19 on operations, patients, and staff. CDC and HRSA analyzed data from the weekly COVID-19 survey completed by 1,009 HRSA-funded health centers (health centers¶) for the week of July 11-17, 2020, to describe telehealth service use in the United States by U.S. Census region,** urbanicity,†† staffing capacity, change in visit volume, and personal protective equipment (PPE) supply. Among the 1,009 health center respondents, 963 (95.4%) reported providing telehealth services. Health centers in urban areas were more likely to provide >30% of health care visits virtually (i.e., via telehealth) than were health centers in rural areas. Telehealth is a promising approach to promoting access to care and can facilitate public health mitigation strategies and help prevent transmission of SARS-CoV-2 and other respiratory illnesses, while supporting continuity of care. Although CMS's change of its telehealth provisions enabled health centers to expand telehealth by aligning guidance and leveraging federal resources, sustaining expanded use of telehealth services might require additional policies and resources.

Health Center Testing for SARS-CoV-2 During the COVID-19 Pandemic - United States, June 5-October 2, 2020.

Long-standing social inequities and health disparities have resulted in increased risk for coronavirus disease 2019 (COVID-19) infection, severe illness, and death among racial and ethnic minority populations. The Health Resources and Services Administration (HRSA) Health Center Program supports nearly 1,400 health centers that provide comprehensive primary health care* to approximately 30 million patients in 13,000 service sites across the United States.† In 2019, 63% of HRSA health center patients who reported race and ethnicity identified as members of racial ethnic minority populations (1). Historically underserved communities and populations served by health centers have a need for access to important information and resources for preventing exposure to SARS-CoV-2, the virus that causes COVID-19, to testing for those at risk, and to follow-up services for those with positive test results.§ During the COVID-19 public health emergency, health centers¶ have provided and continue to provide testing and follow-up care to medically underserved populations**; these centers are capable of reaching areas disproportionately affected by the pandemic.†† HRSA administers a weekly, voluntary Health Center COVID-19 Survey§§ to track health center COVID-19 testing capacity and the impact of COVID-19 on operations, patients, and personnel. Potential respondents can include up to 1,382 HRSA-funded health centers.¶¶ To assess health centers' capacity to reach racial and ethnic minority groups at increased risk for COVID-19 and to provide access to testing, CDC and HRSA analyzed survey data for the weeks June 5-October 2, 2020*** to describe all patients tested (3,194,838) and those who received positive SARS-CoV-2 test results (308,780) by race/ethnicity and state of residence. Among persons with known race/ethnicity who received testing (2,506,935), 36% were Hispanic/Latino (Hispanic), 38% were non-Hispanic White (White), and 20% were non-Hispanic Black (Black); among those with known race/ethnicity with positive test results, 56% were Hispanic, 24% were White, and 15% were Black. Improving health centers' ability to reach groups at increased risk for COVID-19 might reduce transmission by identifying cases and supporting contact tracing and isolation. Efforts to improve coordination of COVID-19 response-related activities between state and local public health departments and HRSA-funded health centers can increase access to testing and follow-up care for populations at increased risk for COVID-19.

Evaluation of vitreous degeneration as a potential risk factor for retinal detachment after phacoemulsification in dogs.

PURPOSE: To evaluate vitreous degeneration as a potential risk factor for retinal detachment in dogs after phacoemulsification. METHODS: Medical records for dogs with preoperative ocular ultrasound and phacoemulsification between September 28, 2006, and August 2, 2016, were reviewed. Ultrasound images were reviewed by two observers independently, and vitreous echogenicity was graded using an established scale. The following factors were compared between eyes with and without retinal detachment: signalment, operated eye, cataract stage at the time of surgery, and presence or absence of the following: lens-induced uveitis (LIU), glaucoma, anterior vitreous presentation, lens subluxation, history of prophylactic retinopexy, diabetes mellitus, operating surgeon, concurrent prophylactic retinopexy, posterior capsular tear, phacoemulsification duration, use of automated anterior vitrectomy, placement of an artificial intraocular lens, and intraocular lens type (polymethyl methacrylate or acrylic foldable). Total follow-up time was recorded. Presence and time from surgery to onset of complications were recorded. Retinal detachment was diagnosed based on observation via indirect ophthalmoscopy or ocular ultrasound. RESULTS: Evaluation for association between vitreous degeneration and retinal detachment included 290 eyes of 180 dogs. There was no statistically significant correlation between vitreous degeneration and postoperative retinal detachment. Retinal detachment was observed in 17 of 290 eyes (5.9%). Vitreous degeneration was marked as present by at least one observer in 189 of 290 eyes (65%). CONCLUSIONS: Ultrasonically identifiable vitreous degeneration does not correlate with increased risk of retinal detachment following phacoemulsification.

Spatial control of oxygen delivery to three-dimensional cultures alters cancer cell growth and gene expression.

Commonly used monolayer cancer cell cultures fail to provide a physiologically relevant environment in terms of oxygen delivery. Here, we describe a three-dimensional (3D) bioreactor system where cancer cells are grown in Matrigel in modified six-well plates. Oxygen is delivered to the cultures through a polydimethylsiloxane (PDMS) membrane at the bottom of the wells, with microfabricated PDMS pillars to control oxygen delivery. The plates receive 3% oxygen from below and 0% oxygen at the top surface of the media, providing a gradient of 3-0% oxygen. We compared growth and transcriptional profiles for cancer cells grown in Matrigel in the bioreactor, 3D cultures grown in 21% oxygen, and cells grown in a standard hypoxia chamber at 3% oxygen. Additionally, we compared gene expression of conventional two-dimensional monolayer culture and 3D Matrigel culture in 21% oxygen. We conclude that controlled oxygen delivery may provide a more physiologically relevant 3D system.

Combining sorption experiments and Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to study the adsorption of propranolol onto environmental solid matrices - Influence of copper(II).

The bioavailability of pharmaceuticals is governed by their sorption in soils/sediments, as the retention processes determine their concentration in surface- and ground-water. The adsorption of these contaminants can involve various solid components such as organic matter, clays and metallic oxides, and their distribution among these solid components depends on contaminant and solid properties. In this paper we studied the adsorption of the pharmaceutical propranolol - a beta-blocker - on eight different solids (six soils, one sediment and one kaolinite-based sample) by batch experiments. The influence of contact time, propranolol concentration and pH was considered, as well as the presence of copper(II). The investigated solids displayed a wide variability in terms of CEC (cationic exchange capacity) and organic carbon and carbonates contents. The influence of pH was negligible in the pH range from 5.5 to 8.6. The adsorbed amounts were greatly dependent on the solid and two groups of solids were evidenced: three soils of high CEC and organic carbon contents which retained high amounts of propranolol, and three soils, the sediment and the kaolinite-based sample (low CEC and organic carbon content) displaying a low adsorption capacity for the beta-blocker. A linear model enabling the determination of the sorption parameters Kd and Koc was pertinent to describe the adsorption isotherms but the Koc values showed a great variability. It was shown that organic carbon content alone could not explain propranolol adsorption. The CEC value was identified as influent parameter and a simple empirical model was proposed to describe propranolol adsorption. At microscopic and molecular scales, ToF-SIMS experiments indicated (i) a decrease of potassium on the surface upon propranolol adsorption with a distribution of the beta-blocker similarly to alumino-silicates, iron and organic carbon on the surface confirming a cation exchange mechanism and (ii) the absence of degradation products and copper-propranolol complexes.

Animal-Assisted Therapies and Dementia: A Systematic Mapping Review Using the Lived Environment Life Quality (LELQ) Model.

OBJECTIVE: The authors mapped the literature on animal-assisted therapies (AATs) and institutionalized adults with dementia onto the Lived Environment Life Quality (LELQ) Model as a guide for future services and research. METHOD: Refereed literature addressing AATs and institutionalized people with dementia was comprehensively gathered, described, categorized, and synthesized in this systematic mapping review. RESULTS: From 1,342 screened records, the authors included 10 research articles that incorporated dogs in therapy for institutionalized adults with dementia. These canine-assisted therapies offered occupational opportunities and environmental supports conducive to experiences of relative well-being, occupational engagement, and optimal functioning. CONCLUSION: The findings offer proof of the concept that canine-assisted therapies are feasible and can elicit positive quality-of-life experiences in institutionalized people with dementia. Researchers and practitioners need to elucidate the theoretical foundations of AATs. The LELQ Model may serve as a guide for client-centered, occupation-focused, and ecologically valid approaches to animal-assisted occupational therapy.

Diagnosis of Retrobulbar Round Cell Neoplasia in a Macaroni Penguin ( Eudyptes chrysolophus ) Through Use of Computed Tomography.

A 25-year-old female macaroni penguin (Eudyptes chrysolophus) was diagnosed with exophthalmos secondary to retrobulbar neoplasia through use of computed tomography (CT). Histopathologic examination of the mass supported a diagnosis of malignant round cell neoplasia. Immunohistochemical (IHC) labeling was applied to determine cell origin; the neoplastic cells did not label with T-cell marker CD3 or B-cell marker BLA.36 and could not be further characterized. The scleral ossicles precluded evaluation of the retrobulbar space by ultrasonography; therefore, CT scanning is recommended for examination of intraorbital structures in penguin and other avian species.

The efficacy and pharmacokinetics of brincidofovir for the treatment of lethal rabbitpox virus infection: a model of smallpox disease.

Brincidofovir (BCV) has broad-spectrum in vitro activity against dsDNA viruses, including smallpox, and is being developed as a treatment for smallpox as well as infections caused by other dsDNA viruses. BCV has previously been shown to be active in multiple animal models of smallpox. Here we present the results of a randomized, blinded, placebo-controlled study of the efficacy and pharmacokinetics of a novel, "humanized" regimen of BCV for treatment of New Zealand White rabbits infected with a highly lethal inoculum of rabbitpox virus, a well characterized model of smallpox. Compared with placebo, a dose-dependent increase in survival was observed in all BCV-treatment groups. Concentrations of cidofovir diphosphate (CDV-PP), the active antiviral, in rabbit peripheral blood mononuclear cells (PBMCs) were determined for comparison to those produced in humans at the dose proposed for treatment of smallpox. CDV-PP exposure in PBMCs from rabbits given BCV scaled to human exposures at the dose proposed for treatment of smallpox, which is also currently under evaluation for other indications. The results of this study demonstrate the activity of BCV in the rabbitpox model of smallpox and the feasibility of scaling doses efficacious in the model to a proposed human dose and regimen for treatment of smallpox.

Social determinants of HIV/AIDS and sexually transmitted diseases among black women: implications for health equity.

Recent epidemiologic reports show that black women are at risk for HIV infection and other sexually transmitted diseases (STDs). In this report, we go beyond race and consider a number of social and economic trends that have changed the way many black women experience life. We discuss poverty, loss of status and support linked to declining marriage participation, and female-headed single-parent household structure-all of which influence sexual risks. We also discuss the Centers for Disease Control and Prevention-led national efforts to advance consideration of social determinants of health (SDH) and promotion of health equity in public health activities that may have impact on black and other women.

Development of CMX001 for the Treatment of Poxvirus Infections.

CMX001 (phosphonic acid, [[(S)-2-(4-amino-2-oxo-1(2H)-pyrimidinyl)-1-(hydroxymethyl)ethoxy]methyl]mono[3-(hexadecyloxy)propyl] ester) is a lipid conjugate of the acyclic nucleotide phosphonate, cidofovir (CDV). CMX001 is currently in Phase II clinical trials for the prophylaxis of human cytomegalovirus infection and under development using the Animal Rule for smallpox infection. It has proven effective in reduction of morbidity and mortality in animal models of human smallpox, even after the onset of lesions and other clinical signs of disease. CMX001 and CDV are active against all five families of double-stranded DNA (dsDNA) viruses that cause human morbidity and mortality, including orthopoxviruses such as variola virus, the cause of human smallpox. However, the clinical utility of CDV is limited by the requirement for intravenous dosing and a high incidence of acute kidney toxicity. The risk of nephrotoxicity necessitates pre-hydration and probenecid administration in a health care facility, further complicating high volume CDV use in an emergency situation. Compared with CDV, CMX001 has a number of advantages for treatment of smallpox in an emergency including greater potency in vitro against all dsDNA viruses that cause human disease, a high genetic barrier to resistance, convenient oral administration as a tablet or liquid, and no evidence to date of nephrotoxicity in either animals or humans. The apparent lack of nephrotoxicity observed with CMX001 in vivo is because it is not a substrate for the human organic anion transporters that actively secrete CDV into kidney cells. The ability to test the safety and efficacy of CMX001 in patients with life-threatening dsDNA virus infections which share many basic traits with variola is a major advantage in the development of this antiviral for a smallpox indication.