Detecting national human enteric disease outbreaks linked to animal contact in the United States of America.

Enteric pathogens, such as non-typhoidal Salmonella, Campylobacter and Escherichia coli, can reside in the intestinal tract of many animals, including livestock, companion animals, small mammals and reptiles. Often, these animals can appear healthy; nonetheless, humans can become infected after direct or indirect contact, resulting in a substantial illness burden. An estimated 14% of the 3.2 million illnesses that occur in the United States of America (USA) each year from such enteric pathogens are attributable to animal contact. Surveillance for enteric pathogens in the USA includes the compilation and interpretation of both laboratory and epidemiologic data. However, the authors feel that a collaborative, multisectoral and transdisciplinary - or One Health - approach is needed for data collection and analysis, at every level. In addition, they suggest that the future of enteric illness surveillance lies in the development of improved technologies for pathogen detection and characterisation, such as genomic sequencing and metagenomics. In particular, using whole-genome sequencing to compare genetic sequences of enteric pathogens from humans, food, animals and the environment, can help to predict antimicrobial resistance among these pathogens, determine their genetic relatedness and identify outbreaks linked to a common source. In this paper, the authors describe three recent, multi-state human enteric illness outbreaks linked to animal contact in the USA and discuss how integrated disease surveillance was essential to outbreak detection and response. Additional datasharing between public health and animal health laboratories and epidemiologists at the local, national, regional and international level may help to improve surveillance for emerging animal and human health threats and lead to new opportunities for prevention.

Les agents pathogènes entériques tels que les Salmonella non typhiques, Campylobacter et Escherichia coli peuvent coloniser le tractus intestinal d'un grand nombre d'animaux y compris les espèces d'élevage, les animaux de compagnie, les petits mammifères et les reptiles. Les animaux porteurs sont souvent sains en apparence ; néanmoins, les humains peuvent contracter l'infection après un contact direct ou indirect avec un animal atteint, ce qui induit un fardeau significatif associé à ces maladies. D'après les estimations, environ 14 % des 3,2 millions de cas annuels d'infections par des agents pathogènes entériques aux États-Unis d'Amérique ont pour origine un contact avec des animaux. Aux États-Unis, la surveillance des agents pathogènes entériques est basée sur la collecte et l'interprétation des résultats de laboratoire et des données épidémiologiques. Les auteurs sont néanmoins convaincus de la nécessité de recourir à une approche collaborative, multisectorielle et transdisciplinaire (en d'autres termes, une approche Une seule santé) pour la collecte et l'analyse des données, à tous les niveaux. Ils considèrent également que la surveillance des infections entériques reposera à l'avenir sur le développement de technologies avancées dans le domaine de la détection et de la caractérisation des agents pathogènes, notamment le séquençage génomique et la métagénomique. En particulier, le recours au séquençage du génome entier afin de comparer les séquences d'agents pathogènes d'origine humaine, alimentaire, animale et environnementale permettra d'anticiper l'apparition d'antibiorésistances, de déterminer le degré de parenté génétique de ces agents et d'identifier les foyers provenant d'une même source. Les auteurs décrivent trois foyers récents d'infections entériques humaines survenus dans plusieurs états des États-Unis et soulignent à quel point l'exercice d'une surveillance sanitaire intégrée a été déterminant pour la détection de ces foyers et la mise en œuvre d'une réponse appropriée. Un partage accru d'informations entre les laboratoires et les épidémiologistes de santé publique et animale aux niveaux local, national, régional et international pourrait contribuer à améliorer la surveillance des menaces émergentes pesant sur la santé animale et humaine et à mettre en œuvre de nouvelles modalités de prévention.

En el tracto intestinal de muchos animales, entre ellos ganado, mascotas, pequeños mamíferos o reptiles, puede haber patógenos intestinales como salmonelas no tifoideas, Campylobacter o Escherichia coli. A menudo los animales parecen sanos, pese a lo cual las personas pueden infectarse por contacto directo o indirecto con ellos, lo que da lugar a una considerable carga de morbilidad. Se calcula que, de los 3,2 millones de casos de enfermedad que estos patógenos intestinales causan al año en los EE. UU., un 14% es atribuible al contacto con animales. La vigilancia de patógenos intestinales que se practica en los EE. UU. incluye la compilación e interpretación de datos tanto epidemiológicos como de laboratorio. En opinión de los autores, sin embargo, es preciso que la obtención y el análisis de datos respondan a un planteamiento de colaboración multisectorial y transdisciplinar ­ esto es, a la lógica de Una sola salud ­ que abarque todos los niveles. Los autores apuntan además que el futuro de la vigilancia de las enfermedades intestinales pasa por el desarrollo de tecnologías más eficaces de detección y caracterización de patógenos, como la secuenciación genómica o la metagenómica. En particular, el uso de la secuenciación de genomas completos para comparar entre sí las secuencias genéticas de patógenos intestinales presentes en personas, alimentos, animales y el medio ambiente puede ayudar a predecir la aparición de resistencias a los antimicrobianos en estos patógenos, determinar su parentesco genético e identificar brotes vinculados con un origen común. Los autores, tras describir tres recientes brotes de enfermedad intestinal humana ligados al contacto con animales que afectaron a varios estados de los EE. UU., explican la función esencial que cumplió la vigilancia integrada de enfermedades para detectar esos brotes y responder a ellos. El intercambio de más datos entre los laboratorios de salud pública y sanidad animal y los epidemiólogos a escala local, nacional, regional e internacional puede ser de ayuda para mejorar la vigilancia de amenazas sanitarias y zoosanitarias emergentes y abrir nuevas posibilidades de prevención.

Development of a battery of tests to measure attitudes and intended behaviours of dental students towards people with disability or those in marginalised groups.

INTRODUCTION: Recommended curricula in Special Care Dentistry (SCD) outline learning objectives that include the domain of attitudes and behaviours, but these are notoriously difficult to measure. The aims of this study were (i) to develop a test battery comprising adapted and new scales to evaluate values, attitudes and intentions of dental students towards people with disability and people in marginalised groups and (ii) to determine reliability (interitem consistency) and validity of the scales within the test battery. MATERIALS AND METHODS: A literature search identified pre-existing measures and models for the assessment of attitudes in healthcare students. Adaptation of three pre-existing scales was undertaken, and a new scale was developed based upon the Theory of Planned Behaviour (TPB) using an elicitation survey. These scales underwent a process of content validation. The three adapted scales and the TPB scale were piloted by 130 students at 5 different professional stages, from 4 different countries. RESULTS: The scales were adjusted to ensure good internal reliability, variance, distribution, and face and content validity. In addition, the different scales showed good divergent validity. DISCUSSION: These results are positive, and the scales now need to be validated in the field. CONCLUSIONS: It is hoped that these tools will be useful to educators in SCD to evaluate the impact of teaching and clinical exposure on their students.

Toward an Information Infrastructure for Global Health Improvement.

Profound global challenges to individual and population health, alongside the opportunities to benefit from digital technology, have spawned the concept of the Learning Health System. Learning Health Systems (LHSs)--which can function at organizational, network, regional, and national levels of scale--have the capability of continuous data-driven self-study that promotes change and improvement. The LHS concept, which originated in the U.S. in 2007, is rapidly gaining attention around the world. LHSs require, but also transcend, the secondary use of health data. This paper describes the key features of LHSs, argues that effective and sustainable LHSs must be supported by infrastructures that allow them to function with economies of scale and scope, and describes the services that such infrastructures must provide. While it is relatively straightforward to describe LHSs, achieving them at the high level of capability necessary to promote significant health benefits will require advancements in science and engineering, engaging the field of informatics among a wider range of disciplines. It also follows from this vision that LHSs cannot be built from an imposed blueprint; LHSs will more likely evolve from efforts at smaller scales that compose into larger systems.

Patient-Centered Network of Learning Health Systems: Developing a resource for clinical translational research.

INTRODUCTION: The Learning Health System Network clinical data research network includes academic medical centers, health-care systems, public health departments, and health plans, and is designed to facilitate outcomes research, pragmatic trials, comparative effectiveness research, and evaluation of population health interventions. METHODS: The Learning Health System Network is 1 of 13 clinical data research networks assembled to create, in partnership with 20 patient-powered research networks, a National Patient-Centered Clinical Research Network. RESULTS AND CONCLUSIONS: Herein, we describe the Learning Health System Network as an emerging resource for translational research, providing details on the governance and organizational structure of the network, the key milestones of the current funding period, and challenges and opportunities for collaborative science leveraging the network.

Discussion of "Combining Health Data Uses to Ignite Health System Learning".

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Combining Health Data Uses to Ignite Health System Learning" written by John D. Ainsworth and Iain E. Buchan [1]. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the paper of Ainsworth and Buchan. In subsequent issues the discussion can continue through letters to the editor. With these comments on the paper "Combining Health Data Uses to Ignite Health System Learning", written by John D. Ainsworth and Iain E. Buchan [1], the journal seeks to stimulate a broad discussion on new ways for combining data sources for the reuse of health data in order to identify new opportunities for health system learning. An international group of experts has been invited by the editor of Methods to comment on this paper. Each of the invited commentaries forms one section of this paper.

The kinematics of the California sea lion foreflipper during forward swimming.

To determine the two-dimensional kinematics of the California sea lion foreflipper during thrust generation, a digital, high-definition video is obtained using a non-research female sea lion at the Smithsonian National Zoological Park in Washington, DC. The observational videos are used to extract maneuvers of interest--forward acceleration from rest using the foreflippers and banked turns. Single camera videos are analyzed to digitize the flipper during the motions using 10 points spanning root to tip in each frame. Digitized shapes were then fitted with an empirical function that quantitatively allows for both comparison between different claps, and for extracting kinematic data. The resulting function shows a high degree of curvature (with a camber of up to 32%). Analysis of sea lion acceleration from rest shows thrust production in the range of 150-680 N and maximum flipper angular velocity (for rotation about the shoulder joint) as high as 20 rad s⁻¹. Analysis of turning maneuvers indicate extreme agility and precision of movement driven by the foreflipper surfaces.

Similarity-based modeling applied to signal detection in pharmacovigilance.

One of the main objectives in pharmacovigilance is the detection of adverse drug events (ADEs) through mining of healthcare databases, such as electronic health records or administrative claims data. Although different approaches have been shown to be of great value, research is still focusing on the enhancement of signal detection to gain efficiency in further assessment and follow-up. We applied similarity-based modeling techniques, using 2D and 3D molecular structure, ADE, target, and ATC (anatomical therapeutic chemical) similarity measures, to the candidate associations selected previously in a medication-wide association study for four ADE outcomes. Our results showed an improvement in the precision when we ranked the subset of ADE candidates using similarity scorings. This method is simple, useful to strengthen or prioritize signals generated from healthcare databases, and facilitates ADE detection through the identification of the most similar drugs for which ADE information is available.

Assessing the influence of secondary organic versus primary carbonaceous aerosols on long-range atmospheric polycyclic aromatic hydrocarbon transport.

We use the chemical transport model GEOS-Chem to evaluate the hypothesis that atmospheric polycyclic aromatic hydrocarbons (PAHs) are trapped in secondary organic aerosol (SOA) as it forms. We test the ability of three different partitioning configurations within the model to reproduce observed total concentrations in the midlatitudes and the Arctic as well as midlatitude gas-particle phase distributions. The configurations tested are (1) the GEOS-Chem default configuration, which uses instantaneous equilibrium partitioning to divide PAHs among the gas phase, a primary organic matter (OM) phase (absorptive), and a black carbon (BC) phase (adsorptive), (2) an SOA configuration in which PAHs are trapped in SOA when emitted and slowly evaporate from SOA thereafter, and (3) a configuration in which PAHs are trapped in primary OM/BC upon emission and subsequently slowly evaporate. We also test the influence of changing the fraction of PAHs available for particle-phase oxidation. Trapping PAHs in SOA particles upon formation and protecting against particle-phase oxidation (2) better simulates observed remote concentrations compared to our default configuration (1). However, simulating adsorptive partitioning to BC is required to reproduce the magnitude and seasonal pattern of gas-particle phase distributions. Thus, the last configuration (3) results in the best agreement between observed and simulated concentration/phase distribution data. The importance of BC rather than SOA to PAH transport is consistent with strong observational evidence that PAHs and BC are coemitted.

Ichthyophonus-infected walleye pollock Theragra chalcogramma (Pallas) in the eastern Bering Sea: a potential reservoir of infections in the North Pacific.

In 2003, the Alaska walleye pollock industry reported product quality issues attributed to an unspecified parasite in fish muscle. Using molecular and histological methods, we identified the parasite in Bering Sea pollock as Ichthyophonus. Infected pollock were identified throughout the study area, and prevalence was greater in adults than in juveniles. This study not only provides the first documented report of Ichthyophonus in any fish species captured in the Bering Sea, but also reveals that the parasite has been present in this region for nearly 20 years and is not a recent introduction. Sequence analysis of 18S rDNA from Ichthyophonus in pollock revealed that consensus sequences were identical to published parasite sequences from Pacific herring and Yukon River Chinook salmon. Results from this study suggest potential for Ichthyophonus exposures from infected pollock via two trophic pathways; feeding on whole fish as prey and scavenging on industry-discharged offal. Considering the notable Ichthyophonus levels in pollock, the low host specificity of the parasite and the role of this host as a central prey item in the Bering Sea, pollock likely serve as a key Ichthyophonus reservoir for other susceptible hosts in the North Pacific.

Pharmacologic evidence to support clinical decision making for peripartum methadone treatment.

RATIONALE: Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum. OBJECTIVES: Study goals were to (1) characterize changes in methadone dose across childbearing, (2) determine enantiomer-specific methadone withdrawal kinetics from steady state during late pregnancy, (3) assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and (4) explore relationships between CYP2B6, CYP2C19, and CYP3A4 single-nucleotide polymorphisms and maternal dose, plasma concentration, and L/D. METHODS: Methadone dose changes and timed plasma samples were obtained for women on methadone (n = 25) followed prospectively from third trimester of pregnancy to 3 months postpartum. RESULTS: Participants were primarily white, Medicaid insured, and multiparous. All women increased their dose from first to end of second trimester (mean peak increase = 23 mg/day); 71 % of women increased from second trimester to delivery (mean peak increase = 19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7-24.9 h; S-methadone, 8.02-18.9 h) were about half of those reported in non-pregnant populations. In three women with weekly 24-h methadone levels after delivery, L/D increased within 1-2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum. CONCLUSIONS: Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery.

Detection of pharmacovigilance-related adverse events using electronic health records and automated methods.

Electronic health records (EHRs) are an important source of data for detection of adverse drug reactions (ADRs). However, adverse events are frequently due not to medications but to the patients' underlying conditions. Mining to detect ADRs from EHR data must account for confounders. We developed an automated method using natural-language processing (NLP) and a knowledge source to differentiate cases in which the patient's disease is responsible for the event rather than a drug. Our method was applied to 199,920 hospitalization records, concentrating on two serious ADRs: rhabdomyolysis (n = 687) and agranulocytosis (n = 772). Our method automatically identified 75% of the cases, those with disease etiology. The sensitivity and specificity were 93.8% (confidence interval: 88.9-96.7%) and 91.8% (confidence interval: 84.0-96.2%), respectively. The method resulted in considerable saving of time: for every 1 h spent in development, there was a saving of at least 20 h in manual review. The review of the remaining 25% of the cases therefore became more feasible, allowing us to identify the medications that had caused the ADRs.

Inability to demonstrate fish-to-fish transmission of Ichthyophonus from laboratory infected Pacific herring Clupea pallasii to naïve conspecifics.

The parasite Ichthyophonus is enzootic in many marine fish populations of the northern Atlantic and Pacific Oceans. Forage fishes are a likely source of infection for higher trophic level predators; however, the processes that maintain Ichthyophonus in forage fish populations (primarily clupeids) are not well understood. Lack of an identified intermediate host has led to the convenient hypothesis that the parasite can be maintained within populations of schooling fishes by waterborne fish-to-fish transmission. To test this hypothesis we established Ichthyophonus infections in Age-1 and young-of-the-year (YOY) Pacific herring Clupea pallasii (Valenciennes) via intraperitoneal (IP) injection and cohabitated these donors with naïve conspecifics (sentinels) in the laboratory. IP injections established infection in 75 to 84% of donor herring, and this exposure led to clinical disease and mortality in the YOY cohort. However, after cohabitation for 113 d no infections were detected in naïve sentinels. These data do not preclude the possibility of fish-to-fish transmission, but they do suggest that other transmission processes are necessary to maintain Ichthyophonus in wild Pacific herring populations.

Development of a polymerase chain reaction for the detection of abalone herpesvirus infection based on the DNA polymerase gene.

A 5781-base pair (bp) fragment of genomic DNA from the Taiwanese abalone herpesvirus was obtained and showed 99% (5767/5779) homology in the nucleotide sequence and 99% (1923/1926) in the amino acid sequence with the DNA polymerase gene of the abalone herpesvirus strain Victoria/AUS/2007. Homology of the amino acid sequence with the DNA polymerase of ostreid herpesvirus 1 was 30% (563/1856). In this study, a PCR-based procedure for detecting herpesvirus infection of abalone, Haliotis diversicolor supertexta, in Taiwan was developed. The method employed primer sets targeting the viral DNA polymerase gene, and was able to amplify DNA fragments of the expected size from infected samples. Primer sets of 40f and 146r were designed for amplification of an expected PCR product of 606 bp. Combining the new PCR protocol with histopathology, this assay can serve as a reliable diagnostic for herpesvirus infections in abalone.

Novel data-mining methodologies for adverse drug event discovery and analysis.

An important goal of the health system is to identify new adverse drug events (ADEs) in the postapproval period. Datamining methods that can transform data into meaningful knowledge to inform patient safety have proven essential for this purpose. New opportunities have emerged to harness data sources that have not been used within the traditional framework. This article provides an overview of recent methodological innovations and data sources used to support ADE discovery and analysis.

Methods for identifying suicide or suicidal ideation in EHRs.

Electronic health records contain important data elements for detection of novel adverse drug reactions, genotype/phenotype identification and psychosocial factor analysis, and the role of each of these as risk factors for suicidality warrants further investigation. Suicide and suicidal ideation are documented in clinical narratives. The specific purpose of this study was to define an algorithm for automated detection of this serious event. We found that ICD-9 E-Codes had the lowest positive predictive value: 0.55 (90% CI: 0.42-0.67), while combining ICD-9 and NLP had the best PPV: 0.97 (90% CI: 0.92-0.99). A qualitative analysis and classification of the types of errors by ICD-9 and NLP automated coding compared to manual review are also discussed.

von Willebrand factor/factor VIII concentrate (Humate-P) for management of elective surgery in adults and children with von Willebrand disease.

von Willebrand disease (VWD) is the most common inherited bleeding disorder. Treatment guidelines recommend the use of von Willebrand factor/factor VIII (VWF/FVIII) concentrate for VWD patients with type 2 or 3 VWD undergoing surgery, and type 1 patients undergoing surgery who are unresponsive, or for whom desmopressin acetate is contraindicated. This prospective, open-label, multinational study evaluated the safety, efficacy and optimal dosing of a VWF/FVIII concentrate (Humate-P) in subjects with VWD undergoing elective surgery. Dosing was based on VWF ristocetin cofactor (VWF:RCo) and FVIII pharmacokinetic assessments performed before surgery. Pharmacokinetic assessments were completed in 33 adults and 9 children. Haemostatic efficacy was assessed on a 4-point scale (excellent, good, moderate/poor or none). Overall effective haemostasis was achieved in 32/35 subjects. Median terminal VWF:RCo half-life was 11.7 h, and median incremental in vivo recovery was 2.4 IU dL(-1) per IU kg(-1) infused. Major haemorrhage occurred after surgery in 3/35 cases despite achieving target VWF and FVIII levels. Median VWF/FVIII concentrate loading doses ranged from 42.6 IU VWF:RCo kg(-1) (oral surgery) to 61.2 IU VWF:RCo kg(-1) (major surgery), with a median of 10 (range, 2-55) doses administered per subject. Adverse events considered possibly treatment-related (n = 6) were generally mild and of short duration. The results indicate that this VWF/FVIII concentrate is safe and effective in the prevention of excessive bleeding during and after surgery in individuals with VWD.

Biclustering of adverse drug events in the FDA's spontaneous reporting system.

In this article, we present a new pharmacovigilance data mining technique based on the biclustering paradigm, which is designed to identify drug groups that share a common set of adverse events (AEs) in the spontaneous reporting system (SRS) of the US Food and Drug Administration (FDA). A taxonomy of biclusters is developed, revealing that a significant number of bona fide adverse drug event (ADE) biclusters have been identified. Statistical tests indicate that it is extremely unlikely that the bicluster structures thus discovered, as well as their content, could have arisen by mere chance. Some of the biclusters classified as indeterminate provide support for previously unrecognized and potentially novel ADEs. In addition, we demonstrate the potential importance of the proposed methodology in several important aspects of pharmacovigilance such as providing insight into the etiology of ADEs, facilitating the identification of novel ADEs, suggesting methods and a rationale for aggregating terminologies, highlighting areas of focus, and providing an exploratory tool for data mining.

Antibodies raised against tobacco aquaporins of the PIP2 class label viscin tissue of the explosive dwarf mistletoe fruit.

Dwarf mistletoes, genus Arceuthobium, are parasitic flowering plants and forest pests. In western North America, Arceuthobium americanum (lodgepole pine dwarf mistletoe) is principally found on Pinus contorta var. latifolia (lodgepole pine). Dwarf mistletoes disperse their seeds by an explosive process that involves the buildup of hydrostatic pressure within a mucilaginous fruit tissue called the 'viscin'. Living viscin tissue envelops the discharged seeds. This study examined the possibility that aquaporins, critical in plant water relations, might be found in the dwarf mistletoe fruit, specifically the viscin cells. An antibody raised against a tobacco plasma membrane intrinsic 2 (PIP2) aquaporin was used with a gold-labeled secondary antibody to probe dwarf mistletoe fruit at various developmental stages. Viscin cell plasma membranes were successfully labeled with the anti-tobacco probe, and the validity of the immunolabeling was supported by Western blot analysis, showing a strong signal at about 30 kDa, which is at the expected size of a PIP2. A definitive immunolabeling pattern, supported by quantification of gold signal per membrane length, was observed: viscin cells sampled early in development had abundant gold label at their plasma membranes (1.93 +/- 0.13 to 2.13 +/- 0.33 gold particles per microm membrane), while other areas of the cells had no discernible label. Viscin cells sampled near the time of explosive discharge had significantly less label at the plasma membrane (0.21 gold particles +/- 0.11 per microm membrane, P < 0.05), and label was seen at vesicular membranes. Aquaporins likely have a role in directing water to the viscin mucilage early in development, but are retrieved via endocytosis to prevent excess water loss from viscin cells when discharge is imminent.

Biological nomenclatures: a source of lexical knowledge and ambiguity.

There has been increased work in developing automated systems that involve natural language processing (NLP) to recognize and extract genomic information from the literature. Recognition and identification of biological entities is a critical step in this process. NLP systems generally rely on nomenclatures and ontological specifications as resources for determining the names of the entities, assigning semantic categories that are consistent with the corresponding ontology, and assignment of identifiers that map to well-defined entities within a particular nomenclature. Although nomenclatures and ontologies are valuable for text processing systems, they were developed to aid researchers and are heterogeneous in structure and semantics. A uniform resource that is automatically generated from diverse resources, and that is designed for NLP purposes would be a useful tool for the field, and would further database interoperability. This paper presents work towards this goal. We have automatically created lexical resources from four model organism nomenclature systems (mouse, fly, worm, and yeast), and have studied performance of the resources within an existing NLP system, GENIES. Using nomenclatures is not straightforward because issues concerning ambiguity, synonymy, and name variations are quite challenging. In this paper we focus mainly on ambiguity. We determined that the number of ambiguous gene names within the individual nomenclatures, across the four nomenclatures, and with general English ranged from 0%-10.18%, 1.187%-20.30%, and 0%-2.49% respectively. When actually processing text, we found the rate of ambiguous occurrences (not counting ambiguities stemming from English words) to range from 2.4%-32.9% depending on the organisms considered.