Therapeutic Indices of Topical Antiseptics in Wound Care: A Systematic Review.

ABSTRACT: Chronic wounds place a heavy burden on healthcare systems and markedly reduce the ability of patients to engage in activities of daily living. One major factor contributing to impaired wound healing is bacterial bioburden. With the rise in antibiotic resistance and the slowdown in antibiotic development pipelines, alternative antimicrobial strategies are important. The objective of this systematic review is to determine the topical antiseptic therapeutic index values for bacterial species commonly isolated from chronic wounds. The therapeutic index is a ratio of the lowest concentration that causes mammalian cell cytotoxicity over the minimum bactericidal concentration. Higher values indicate greater safety and potential clinical benefit. A systematic literature search was performed in Medline and Embase, resulting in the inclusion of 37 articles that reported on the minimum bactericidal concentration in bacterial species commonly isolated from chronic wounds and their cytotoxicity concentrations in mammalian cells. The therapeutic indices for the topical antiseptics included in this study were generally low, with most ranging between 0.5-3.0. The highest therapeutic index values for Escherichia coli (5.49), Staphylococcus aureus (6.31) and Pseudomonas aeruginosa (8.81) were achieved by hypochlorous acid, whereas the highest therapeutic index values for methicillin resistant S aureus (12.1) was achieved by polyhexamethylenebiguanide. Antibiotic stewardship principles may need to be applied to topical antiseptics due to some isolated evidence of topical antiseptic resistance and cross-resistance to antibiotics. The choice of antiseptic should not be made solely based on therapeutic index values, but individualized to the patient, with consideration for the wound healing condition that may include covert infection.

Spectral Background Calibration of Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) Spectrometer Onboard the Perseverance Rover Enables Identification of a Ubiquitous Martian Spectral Component.

The Perseverance rover landed at Jezero crater, Mars, on 18 February 2021, with a payload of scientific instruments to examine Mars' past habitability, look for signs of past life, and process samples for future return to Earth. The instrument payload includes the Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) deep ultraviolet Raman and fluorescence imaging spectrometer designed to detect, characterize, and map the presence of organics and minerals on the Martian surface. Operation and engineering constraints sometimes result in the acquisition of spectra with features near the detection limit. It is therefore important to separate instrumental (background) spectral components and spectral components inherent to Martian surface materials. For SHERLOC, the instrumental background is assessed by collecting spectra in the stowed-arm configuration where the instrument is pointed at the Martian nighttime sky with no surface sample present in its optical path. These measurements reveal weak Raman and fluorescence background spectral signatures as well as charged-coupled device pixels prone to erroneous intensity spikes separate from cosmic rays. We quantitatively describe these features and provide a subtraction procedure to remove the spectral background from surface spectra. By identifying and accounting for the SHERLOC Raman background features within the median Raman spectra of Martian target scans, we find that the undefined silicate spectral feature interpreted to be either amorphous silicate or plagioclase feldspar is ubiquitously found in every Mars target Raman scan collected through Sol 751.

Validation of thoracolumbar injury classification and Severity Score in the management of acute and subacute Osteoporotic vertebral compression fractures - A pilot study and a suggested modification.

Objective: To retrospectively assess the Thoracolumbar Injury Classification and Severity Score (TLICS) in patients with osteoporotic vertebral compression fractures (OVCF) and compare the treatment given with that predicted by the TLICS score. Methods: All medical records of patients presenting from January 2014 to November 2017 for acute atraumatic or low impact OVCF were screened, and eligible patients were retrospectively reviewed. The TLICS score was determined based upon magnetic resonance imaging (MRI) findings and clinical records. Clinical records (including pain score data), imaging data, operative procedures, and stability of neurological examination were tracked over three months for each patient. Results: Of the 56 patients included, 36 patients had a TLICS score of 1, 18 had a TLICS score of 2, and two had a TLICS score of 4. Only one patient with a TLICS score of 4 underwent surgical stabilization, while the rest of the cohort was managed non-operatively, with or without kyphoplasty. TLICS score 1 corresponded to simple compression and TLICS score 2 corresponded to burst morphology with retropulsion and without neurological deficits. Of the patients with a TLICS score of 1 and 2 who underwent kyphoplasty, there was a statistically significant improvement in pain scores in both groups; however no significant difference was observed, between each TLICS score (i.e., 1 or 2). None of the patients developed instability or neurological decline. Conclusion: TLICS score correctly predicted operative versus non-operative management in all patients with OVCF. TLICS may be used in making management decisions, and in the triage of these patients for operative versus non-operative evaluations. Our study suggests that patients with TLICS score of 4 or higher require surgical evaluation, while those with TLICS of 1 or 2 are likely to have satisfactory non-surgical management with augmentation or conservative care. In general, patients with OVCF typically present with low TLICS score. Kyphoplasty appears to be similarly beneficial in patients with a TLICS score of 1 or a TLICS score of 2. A modification of the TLICS score by adding TLICS Zero to include uncompressed OVCF with edema is suggested. The limitations of this study include a small size; a larger study is needed to confirm these findings.

Health assessment of nesting loggerhead sea turtles (Caretta caretta) in one of their largest rookeries (central eastern Florida coast, USA).

Reproduction is a physiologically demanding process for sea turtles. Health indicators, including morphometric indices and blood analytes, provide insight into overall health, physiology and organ function for breeding sea turtles as a way to assess population-level effects. The Archie Carr National Wildlife Refuge (ACNWR) on Florida's central eastern coast is critical nesting habitat for loggerhead sea turtles (Caretta caretta), but health variables from this location have not been documented. Objectives of the study were to (1) assess morphometrics and blood analyte data (including haematology, plasma biochemistry, protein electrophoresis, ß-hydroxybutyrate, trace nutrients, vitamins and fatty acid profiles) from loggerheads nesting on or near the beaches of the ACNWR, (2) investigate correlations of body condition index (BCI) with blood analytes and (3) analyse temporal trends in morphometric and blood analyte data throughout the nesting season. Morphometric and/or blood analyte data are reported for 57 nesting loggerheads encountered between 2016 and 2019. Plasma copper and iron positively correlated with BCI. Mass tended to decline across nesting season, whereas BCI did not. Many blood analytes significantly increased or decreased across nesting season, reflecting the catabolic state and haemodynamic variations of nesting turtles. Twenty-three of 34 fatty acids declined across nesting season, which demonstrates the physiological demands of nesting turtles for vitellogenesis and reproductive activities, thus suggesting potential utility of fatty acids for the assessment of foraging status and phases of reproduction. The findings herein are relevant for future spatiotemporal and interspecies comparisons, investigating stressor effects and understanding the physiological demands in nesting sea turtles. This information provides comparative data for individual animals in rescue or managed care settings and for assessment of conservation strategies.

Comparing efficiencies of population control methods for responding to introductions of transboundary animal diseases in wild pigs.

Introductions of transboundary animal diseases (TADs) into free-ranging wildlife can be difficult to control and devastating for domestic livestock trade. Combating a new TAD introduction in wildlife with an emergency response requires quickly limiting spread of the disease by intensely removing wild animals within a contiguous area. In the case of African swine fever virus (ASFv) in wild pigs (Sus scrofa), which has been spreading in many regions of the world, there is little information on the time- and cost-efficiency of methods for intensively and consistently culling wild pigs and recovering carcasses in an emergency response scenario. We compared the efficiencies of aerial operations, trapping, experimental toxic baiting, and ground shooting in northcentral Texas, USA during two months in 2023. Culling and recovering carcasses of wild pigs averaged a rate of 0.15 wild pigs/person hour and cost an average of $233.04/wild pig ($USD 2023) across all four methods. Aerial operations required the greatest initial investment but subsequently was the most time- and cost-efficient, costing an average of $7266 to reduce the population by a standard measure of 10 %, including recovering carcasses. Aerial operations required a ground crew of ∼7 people/helicopter to recover carcasses. Costs for reducing the population of wild pigs using trapping were similar, although took 13.5 times longer to accomplish. In cases where carcass recovery and disposal are needed (e.g., response to ASFv), a benefit of trapping was immediate carcass recovery. Toxic baiting was less efficient because both culling and carcass recovery required substantial time. We culled very few wild pigs with ground shooting in this landscape. Our results provide insight on the efficiencies of each removal method. Strategically combining removal methods may increase overall efficiency. Overall, our findings inform the preparation of resources, personnel needs, and deployment readiness for TAD responses involving wild pigs.

Compressed sensing reconstruction for high-SNR, rapid dissolved 129Xe gas exchange MRI.

PURPOSE: Three-dimensional hyperpolarized 129Xe gas exchange imaging suffers from low SNR and long breath-holds, which could be improved using compressed sensing (CS). The purpose of this work was to assess whether gas exchange ratio maps are quantitatively preserved in CS-accelerated dissolved-phase 129Xe imaging and to investigate the feasibility of CS-dissolved 129Xe imaging with reduced-cost natural abundance (NA) xenon. METHODS: 129Xe gas exchange imaging was performed at 1.5 T with a multi-echo spectroscopic imaging sequence. A CS reconstruction with an acceleration factor of 2 was compared retrospectively with conventional gridding reconstruction in a cohort of 16 healthy volunteers, 5 chronic obstructive pulmonary disease patients, and 23 patients who were hospitalized following COVID-19 infection. Metrics of comparison included normalized mean absolute error, mean gas exchange ratio, and red blood cell (RBC) image SNR. Dissolved 129Xe CS imaging with NA xenon was assessed in 4 healthy volunteers. RESULTS: CS reconstruction enabled acquisition time to be halved, and it reduced background noise. Median RBC SNR increased from 6 (2-18) to 11 (2-100) with CS, and there was strong agreement between CS and gridding mean ratio map values (R2 = 0.99). Image fidelity was maintained for gridding RBC SNR > 5, but below this, normalized mean absolute error increased nonlinearly with decreasing SNR. CS increased the mean SNR of NA 129Xe images 3-fold. CONCLUSION: CS reconstruction of dissolved 129Xe imaging improved image quality with decreased scan time, while preserving key gas exchange metrics. This will benefit patients with breathlessness and/or low gas transfer and shows promise for NA-dissolved 129Xe imaging.

Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort.

INTRODUCTION: Hearing loss is identified as one of the largest modifiable risk factors for cognitive impairment and dementia. Studies evaluating this relationship have yielded mixed results. METHODS: We investigated the longitudinal relationship between self-reported hearing loss and cognitive/functional performance in 695 cognitively normal (CN) and 941 participants with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative. RESULTS: Within CN participants with hearing loss, there was a significantly greater rate of cognitive decline per modified preclinical Alzheimer's cognitive composite. Within both CN and MCI participants with hearing loss, there was a significantly greater rate of functional decline per the functional activities questionnaire (FAQ). In CN and MCI participants, hearing loss did not significantly contribute to the risk of progression to a more impaired diagnosis. DISCUSSION: These results confirm previous studies demonstrating a significant longitudinal association between self-reported hearing loss and cognition/function but do not demonstrate an increased risk of conversion to a more impaired diagnosis. CLINICAL TRIAL REGISTRATION INFORMATION: NCT00106899 (ADNI: Alzheimer's Disease Neuroimaging Initiative, clinicaltrials.gov), NCT01078636 (ADNI-GO: Alzheimer's Disease Neuroimaging Initiative Grand Opportunity, clinicaltrials.gov), NCT01231971 (ADNI2: Alzheimer's Disease Neuroimaging Initiative 2, clinicaltrials.gov), NCT02854033 (ADNI3: Alzheimer's Disease Neuroimaging Initiative 3, clinicaltrials.gov). HIGHLIGHTS: Hearing loss is a potential modifiable risk factor for dementia. We assessed the effect of self-reported hearing loss on cognition and function in the ADNI cohort. Hearing loss contributes to significantly faster cognitive and functional decline. Hearing loss was not associated with conversion to a more impaired diagnosis.

Automated High-Throughput Biological Sex Identification from Archeological Human Dental Enamel Using Targeted Proteomics.

Biological sex is key information for archeological and forensic studies, which can be determined by proteomics. However, the lack of a standardized approach for fast and accurate sex identification currently limits the reach of proteomics applications. Here, we introduce a streamlined mass spectrometry (MS)-based workflow for the determination of biological sex using human dental enamel. Our approach builds on a minimally invasive sampling strategy by acid etching, a rapid online liquid chromatography (LC) gradient coupled to a high-resolution parallel reaction monitoring (PRM) assay allowing for a throughput of 200 samples per day (SPD) with high quantitative performance enabling confident identification of both males and females. Additionally, we developed a streamlined data analysis pipeline and integrated it into a Shiny interface for ease of use. The method was first developed and optimized using modern teeth and then validated in an independent set of deciduous teeth of known sex. Finally, the assay was successfully applied to archeological material, enabling the analysis of over 300 individuals. We demonstrate unprecedented performance and scalability, speeding up MS analysis by 10-fold compared to conventional proteomics-based sex identification methods. This work paves the way for large-scale archeological or forensic studies enabling the investigation of entire populations rather than focusing on individual high-profile specimens. Data are available via ProteomeXchange with the identifier PXD049326.

Inorganic interpretation of luminescent materials encountered by the Perseverance rover on Mars.

A major objective of the Mars 2020 mission is to sample rocks in Jezero crater that may preserve organic matter for later return to Earth. Using an ultraviolet Raman and luminescence spectrometer, the Perseverance rover detected luminescence signals with maximal intensities at 330 to 350 nanometers and 270 to 290 nanometers that were initially reported as consistent with organics. Here, we test the alternative hypothesis that the 330- to 350-nanometer and 270- to 290-nanometer luminescence signals trace Ce3+ in phosphate and silicate defects, respectively. By comparing the distributions of luminescence signals with the rover detections of x-ray fluorescence from P2O5 and Si-bearing materials, we show that, while an organic origin is not excluded, the observed luminescence can be explained by purely inorganic materials. These findings highlight the importance of eventual laboratory analyses to detect and characterize organic compounds in the returned samples.

Phase I pilot safety and feasibility of a novel restraint device for critically ill patients requiring mechanical ventilation.

Background: Mechanically ventilated Intensive Care Unit (ICU) patients often require wrist restraints, contributing to immobility and agitation, over-sedation, and delirium. The Exersides® Refraint® (Healthy Design, LLC), a novel restraint alternative, may be safe and facilitate greater mobility than traditional restraints. Objective: This National Institutes of Health Small Business Technology Transfer (STTR) Program Grant-funded single-site Phase I feasibility study evaluated Exersides® safety and feasibility in anticipation of a multi-site Phase II randomized controlled trial (RCT). Methods: In two academic ICUs, mechanically ventilated adults ⩾25 years old who were non-comatose, required restraints and had an expected stay of ⩾2 days were enrolled to wear Exersides® and traditional wrist restraints for 4 h on day 1, in a randomized order, and in the reverse order on day 2. Main outcomes were Exersides® safety (i.e., patient/clinician lacerations/injuries), feasibility (i.e., ⩾90% of required data collected), and patient/family/clinician feedback. Results: Eight patients were enrolled; one no longer required restraints at initiation, yielding seven subjects (median [interquartile range (IQR)] age 65 [55, 70] years, 86% men). All seven wore Exersides®, averaging (SD) 2.5 (1.0) hours per session, with no safety events reported. Across restraint time periods, 92% and 100% of Richmond Agitation-Sedation Scale (RASS) and wrist actigraphy data, respectively, were collected. Feedback was positive (more movement and comfortable than traditional restraints) and constructive (bulky, intimidating to apply). Conclusions: This pilot study provided key safety and feasibility data for a Phase II RCT evaluating Exersides® versus traditional wrist restraints. Feedback motivated minor device modifications before RCT initiation.

Bioaerosols downwind from animal feeding operations: A comprehensive review.

Bioaerosols originating from animal feeding operations (AFOs) may carry pathogens, allergens, and other hazardous biocomponents, such as endotoxins, posing a potential risk to community health and the environment when dispersed downwind. This review summarizes and synthesizes existing literature data on bioaerosols downwind from three major types of AFOs (swine, poultry, and cattle), covering their composition, concentration, dispersion patterns, measurement methodologies, potential health effects, and mitigation strategies. While many of these bioaerosols are typically detected only near AFOs, evidence indicates that certain bioaerosols, particularly viruses, can travel up to tens of kilometers downwind and remain infectious. Despite the critical importance of these bioaerosols, a refined modeling framework to simulate their transport and fate in downwind air has not yet been developed, nor have source attribution methods been established to track their origins in complex agricultural environments where multiple bioaerosols could co-exist. Therefore, it is imperative to further research downwind bioaerosols from AFOs, including their assessment, modeling, source attribution, and mitigation, to address the public health and environmental challenges associated with animal agriculture.

Popliteal sinus venipuncture in anurans.

OBJECTIVE: To demonstrate an underutilized, reliable, and technically simple anuran venipuncture technique by use of the popliteal sinus. ANIMALS: Medium to large (> 30 g) anuran species. METHODS: The animal is manually restrained using an encircling grip around the pelvic girdle. With the ventrum facing the phlebotomist, the phlebotomist grasps the distal hind limb and gently extends it. If necessary, the medial stifle can be rinsed with sterile water or saline to remove gross debris. Using a caudomedial approach, a 25- to 27-G, 0.5-inch (1.27-cm) needle and attached syringe is advanced toward the stifle at an approximately 45° angle while maintaining negative pressure. If lymphatic fluid or a visibly lymphatic fluid-contaminated blood sample is obtained, the sample is discarded and the attempt is repeated with a new needle and syringe. Collection volume should not exceed 1% of body weight in systemically healthy animals. In compromised animals, a reduction in collection volume should be considered (eg, ≤ 0.5% of body weight). While the phlebotomist may have an ergonomic preference, either hind limb can be used for blood collection. RESULTS: Popliteal sinus venipuncture in anurans can be safely and easily performed with only manual restraint. CLINICAL RELEVANCE: Commonly utilized anuran blood collection techniques include venipuncture of the ventral abdominal vein and lingual venous plexus and cardiocentesis. These techniques can be technically difficult and may pose risks to the patient, particularly if attempted without chemical restraint. Popliteal sinus venipuncture is a reliable, technically simple alternative blood collection technique that can be safely performed in anurans with only manual restraint.

Identification and characterization of human GDF15 knockouts.

Growth differentiation factor 15 (GDF15) is a secreted protein that regulates food intake, body weight and stress responses in pre-clinical models1. The physiological function of GDF15 in humans remains unclear. Pharmacologically, GDF15 agonism in humans causes nausea without accompanying weight loss2, and GDF15 antagonism is being tested in clinical trials to treat cachexia and anorexia. Human genetics point to a role for GDF15 in hyperemesis gravidarum, but the safety or impact of complete GDF15 loss, particularly during pregnancy, is unknown3-7. Here we show the absence of an overt phenotype in human GDF15 loss-of-function carriers, including stop gains, frameshifts and the fully inactivating missense variant C211G3. These individuals were identified from 75,018 whole-exome/genome-sequenced participants in the Pakistan Genomic Resource8,9 and recall-by-genotype studies with family-based recruitment of variant carrier probands. We describe 8 homozygous ('knockouts') and 227 heterozygous carriers of loss-of-function alleles, including C211G. GDF15 knockouts range in age from 31 to 75 years, are fertile, have multiple children and show no consistent overt phenotypes, including metabolic dysfunction. Our data support the hypothesis that GDF15 is not required for fertility, healthy pregnancy, foetal development or survival into adulthood. These observations support the safety of therapeutics that block GDF15.

Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis.

Identification of disease and therapeutic biomarkers remains a significant challenge in the early diagnosis and effective treatment of juvenile idiopathic arthritis (JIA). In this study, plasma metabolomic profiling was conducted to identify disease-related metabolic biomarkers associated with JIA. Plasma samples from treatment-naïve JIA patients and non-JIA reference patients underwent global metabolomic profiling across discovery (60 JIA, 60 non-JIA) and replication (49 JIA, 38 non-JIA) cohorts. Univariate analysis identified significant metabolites (q-value ≤ 0.05), followed by enrichment analysis using ChemRICH and metabolic network mapping with MetaMapp and Cytoscape. Receiver operating characteristic (ROC) analysis determined the top discriminating biomarkers based on area under the curve (AUC) values. A total of over 800 metabolites were measured, consisting of 714 known and 155 unknown compounds. In the discovery cohort, 587 metabolites were significantly altered in JIA patients compared with the reference population (q < 0.05). In the replication cohort, 288 metabolites were significantly altered, with 78 overlapping metabolites demonstrating the same directional change in both cohorts. JIA was associated with a notable increase in plasma levels of sphingosine metabolites and fatty acid ethanolamides and decreased plasma levels of sarcosine, iminodiacetate, and the unknown metabolite X-12462. Chemical enrichment analysis identified cycloparaffins in the form of naproxen and its metabolites, unsaturated lysophospholipids, saturated phosphatidylcholines, sphingomyelins, ethanolamines, and saturated ceramides as the top discriminating biochemical clusters. ROC curve analysis identified 11 metabolites classified as highly discriminatory based on an AUC > 0.90, with the top discriminating metabolite being sphinganine-1-phosphate (AUC = 0.98). This study identifies specific metabolic changes in JIA, particularly within sphingosine metabolism, through both discovery and replication cohorts. Plasma metabolomic profiling shows promise in pinpointing JIA-specific biomarkers, differentiating them from those in healthy controls and Crohn's disease, which may improve diagnosis and treatment.

Nationally Representative Rates of Incident Prescription Opioid Use Among United States Adults and Selected Subpopulations: Longitudinal Cohort Study From the National Health Interview Survey, 2019 to 2020.

Nationally representative rates of incident prescription opioid use in the United States adult population and selected subpopulations are unknown. Using the National Health Interview Survey (2019-2020) longitudinal cohort, a cohort with 1-year follow-up created using random cluster probability sampling of noninstitutionalized civilian U.S. adults, we estimated rates and predictors of incident opioid use. Of 21,161 baseline (2019) participants randomly chosen for follow-up, the final analytic sample included 10,415 who also participated in 2020. Exposure variables were selected per the socio-behavioral model of health care utilization: predisposing characteristics (sex, age, race, etc), enabling characteristics (socioeconomic status, insurance status), health status (pain, disability, comorbidities, etc), and health care use (office visits, emergency room visits, and hospitalizations). Among adults who did not use prescription opioids in 2019, a 1-year cumulative incidence of 4.1% (95% confidence interval [CI]: 3.5-4.6) was seen in 2020, with an incidence rate (IR) of 32.6 cases of new prescription opioid use per 1,000 person-years (PYs). Cumulative incidence, IR, and adjusted relative risk (RR) varied by participant characteristics. We observed the highest IR in those with ineffective pain treatment (81.6 cases per 1,000 PY) and those who visited the emergency room ≥3 times (93.8 cases per 1,000 PY). Participants reporting ≥4 painful conditions had an adjusted RR of 2.9 (95% CI: 2.0-4.1), while the RR for those with sleep problems was 2.3 (95% CI: 1.7-3.1). Overall, this study presents nationally representative rates of incident prescription opioid use and suggests that some participants are using prescription opioids as an early-resort analgesic contrary to best-practice guidelines. PERSPECTIVE: This longitudinal cohort study presents nationally representative rates of incident prescription opioid use in U.S. adults and selected subpopulations. Our data suggest that some participants are using prescription opioids as a first-line or early-resort analgesic, contrary to best-practice guidelines.

Agricultural and Ecological Resources Safeguarded by the Prevention of Wild Pig Population Expansion.

Wild pigs (Sus scrofa) are one of the most destructive invasive species in the US, known for causing extensive damage to agricultural commodities, natural resources, and property, and for transmitting diseases to livestock. Following the establishment of the National Feral Swine Damage Management Program (NFSDMP) in 2014, the expansion of wild pig populations has been successfully slowed. This paper combines two modeling approaches across eight separate models to characterize the expansion of wild pig populations in the absence of intervention by the NFSDMP and forecasts the value of a subset of resources safeguarded from the threat of wild pigs. The results indicate that if wild pigs had continued spreading at pre-program levels, they would have spread extensively across the US, with significant geographic variation across modeling scenarios. Further, by averting the threat of wild pigs, a substantial amount of crops, land, property, and livestock was safeguarded by the NFSDMP. Cumulatively, between 2014 and 2021, wild pig populations were prevented from spreading to an average of 724 counties and an average of USD 40.2 billion in field crops, pasture, grasses, and hay was safeguarded. The results demonstrate that intervention by the NFSDMP has delivered significant ecological and economic benefits that were not previously known.

A framework for developing a real-time lake phytoplankton forecasting system to support water quality management in the face of global change.

Phytoplankton blooms create harmful toxins, scums, and taste and odor compounds and thus pose a major risk to drinking water safety. Climate and land use change are increasing the frequency and severity of blooms, motivating the development of new approaches for preemptive, rather than reactive, water management. While several real-time phytoplankton forecasts have been developed to date, none are both automated and quantify uncertainty in their predictions, which is critical for manager use. In response to this need, we outline a framework for developing the first automated, real-time lake phytoplankton forecasting system that quantifies uncertainty, thereby enabling managers to adapt operations and mitigate blooms. Implementation of this system calls for new, integrated ecosystem and statistical models; automated cyberinfrastructure; effective decision support tools; and training for forecasters and decision makers. We provide a research agenda for the creation of this system, as well as recommendations for developing real-time phytoplankton forecasts to support management.