Biotic filtering by species' interactions constrains food-web variability across spatial and abiotic gradients.

Despite intensive research on species dissimilarity patterns across communities (i.e. ß-diversity), we still know little about their implications for variation in food-web structures. Our analyses of 50 lake and 48 forest soil communities show that, while species dissimilarity depends on environmental and spatial gradients, these effects are only weakly propagated to the networks. Moreover, our results show that species and food-web dissimilarities are consistently correlated, but that much of the variation in food-web structure across spatial, environmental, and species gradients remains unexplained. Novel food-web assembly models demonstrate the importance of biotic filtering during community assembly by (1) the availability of resources and (2) limiting similarity in species' interactions to avoid strong niche overlap and thus competitive exclusion. This reveals a strong signature of biotic filtering processes during local community assembly, which constrains the variability in structural food-web patterns across local communities despite substantial turnover in species composition.

Hepatic Pharmacokinetics and Pharmacodynamics With Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir Treatment and Variable Ribavirin Dosage.

Background: It is unknown whether ribavirin (RBV) coadministration modifies the early rate of decline of hepatitis C virus (HCV) RNA in the liver versus plasma compartments, specifically. Methods: This partially randomized, open-label, phase 2 study enrolled treatment-naive, noncirrhotic patients with HCV genotype 1a. Patients were randomized 1:1 into Arms A and B, and then enrolled in Arm C. Patients received ombitasvir/paritaprevir/ritonavir plus dasabuvir for 12 weeks with either: no RBV for the first 2 weeks followed by weight-based dosing thereafter (Arm A), weight-based RBV for all 12 weeks (Arm B), or low-dose RBV (600 mg) once daily for all 12 weeks. Fine needle aspiration (FNA) was used to determine HCV RNA decline within liver. Results: Baseline HCV RNA was higher and declined more rapidly in plasma than liver; however, RBV dosing did not impact either median plasma or liver HCV RNA decline during the first 2 weeks of treatment. Liver-to-plasma drug concentrations were variable over time. The most common adverse event was pain associated with FNA. Conclusions: Coadministration of RBV had minimal visible impact on the plasma or liver kinetics of HCV RNA decline during the first 2 weeks of treatment, regardless of RBV dosing.

The transformation of behavioral healthcare in New Mexico.

Since 1997, public-sector behavioral healthcare in New Mexico has remained under continual transition. We have conducted qualitative research to examine recent efforts in NM to establish a recovery-oriented behavioral healthcare system, focusing on comprehensive community support services, clinical homes, and core service agencies. We examine how decisions made in the outer context (e.g., the system level) shaped the implementation of each initiative within the inner context of service provision (e.g., provider agencies). We also clarify how sociopolitical factors, as exemplified in changes instituted by one gubernatorial administration and undone by its successor, can undermine implementation efforts and create crises within fragile behavioral healthcare systems. Finally, we discuss findings in relation to efforts to promote wraparound service planning and to establish medical home models under national healthcare reform.

Diversity, functional similarity, and top-down control drive synchronization and the reliability of ecosystem function.

The concept that diversity promotes reliability of ecosystem function depends on the pattern that community-level biomass shows lower temporal variability than species-level biomasses. However, this pattern is not universal, as it relies on compensatory or independent species dynamics. When in contrast within-trophic level synchronization occurs, variability of community biomass will approach population-level variability. Current knowledge fails to integrate how species richness, functional distance between species, and the relative importance of predation and competition combine to drive synchronization at different trophic levels. Here we clarify these mechanisms. Intense competition promotes compensatory dynamics in prey, but predators may at the same time increasingly synchronize, under increasing species richness and functional similarity. In contrast, predators and prey both show perfect synchronization under strong top-down control, which is promoted by a combination of low functional distance and high net growth potential of predators. Under such conditions, community-level biomass variability peaks, with major negative consequences for reliability of ecosystem function.

A Toxicokinetic-Toxicodynamic Modeling Workflow Assessing the Quality of Input Mortality Data.

Toxicokinetic-toxicodynamic (TKTD) models simulate organismal uptake and elimination of a substance (TK) and its effects on the organism (TD). The Reduced General Unified Threshold model of Survival (GUTS-RED) is a TKTD modeling framework that is well established for aquatic risk assessment to simulate effects on survival. The TKTD models are applied in three steps: parameterization based on experimental data (calibration), comparing predictions with independent data (validation), and prediction of endpoints under environmental scenarios. Despite a clear understanding of the sensitivity of GUTS-RED predictions to the model parameters, the influence of the input data on the quality of GUTS-RED calibration and validation has not been systematically explored. We analyzed the performance of GUTS-RED calibration and validation based on a unique, comprehensive data set, covering different types of substances, exposure patterns, and aquatic animal species taxa that are regularly used for risk assessment of plant protection products. We developed a software code to automatically calibrate and validate GUTS-RED against survival measurements from 59 toxicity tests and to calculate selected model evaluation metrics. To assess whether specific survival data sets were better suited for calibration or validation, we applied a design in which all possible combinations of studies for the same species-substance combination are used for calibration and validation. We found that uncertainty of calibrated parameters was lower when the full range of effects (i.e., from high survival to high mortality) was covered by input data. Increasing the number of toxicity studies used for calibration further decreased parameter uncertainty. Including data from both acute and chronic studies as well as studies under pulsed and constant exposure in model calibrations improved model predictions on different types of validation data. Using our results, we derived a workflow, including recommendations for the sequence of modeling steps from the selection of input data to a final judgment on the suitability of GUTS-RED for the data set. Environ Toxicol Chem 2024;43:197-210. © 2023 Bayer AG and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Reproductive toxicity in birds predicted by physiologically-based kinetics and bioenergetics modelling.

Effects on the growth and reproduction of birds are important endpoints in the environmental risk assessment (ERA) of pesticides. Toxicokinetic-toxicodynamic models based on dynamic energy budget theory (DEB) are promising tools to predict these effects mechanistically and make extrapolations relevant to ERA. However, before DEB-TKTD models are accepted as part of ERA for birds, ecotoxicological case studies are required so that stakeholders can assess their capabilities. We present such a case-study, modelling the effects of the fluopyram metabolite benzamide on the northern bobwhite quail (Colinus virginianus). We parametrised a DEB-TKTD model for the embryo stage on the basis of an egg injection study, designed to provide data for model development. We found that information on various endpoints, such as survival, growth, and yolk utilisation were needed to clearly distinguish between the performance of model variants with different TKTD assumptions. The calibration data were best explained when it was assumed that chemical uptake occurs via the yolk and that benzamide places stress on energy assimilation and mobilisation. To be able to bridge from the in vitro tests to real-life exposure, we developed a physiologically-based toxicokinetic (PBK) model for the quail and used it to predict benzamide exposure inside the eggs based on dietary exposure in a standard reproductive toxicity study. We then combined the standard DEB model with the TKTD module calibrated to the egg injection studies and used it to predict effects on hatchling and 14-day chick weight based on the exposure predicted by the PBK model. Observed weight reductions, relative to controls, were accurately predicted. Thus, we demonstrate that DEB-TKTD models, in combination with suitable experimental data and, if necessary, with an exposure model, can be used in bird ERA to predict chemical effects on reproduction.

N-Cyclo-hexyl-tryptamine: freebase, bromide and fumarate.

The solid-state structures of N-cyclo-hexyl-tryptamine (I) {systematic name: N-[2-(1H-indol-3-yl)eth-yl]cyclo-hexa-namine}, C16H22N2, and two of its salts, N-cyclo-hexyl-tryptammonium bromide (II) {systematic name: N-[2-(1H-indol-3-yl)eth-yl]cyclo-hexa-naminium bromide}, C16H23N2 +·Br-, and N-cyclo-hexyl-tryptammonium fumarate (III) (systematic name: bis-{N-[2-(1H-indol-3-yl)eth-yl]cyclo-hexa-naminium} (2E)-but-2-enedioate), 2C16H23N2 +·C4H2O4 2-, were determined by single-crystal X-ray diffraction. The freebase compound forms infinite chains along [010] through N-H⋯N hydrogen bonds. The bromide salt is held together by N-H⋯Br inter-actions in two-dimensional sheets along (001). The fumarate salt is held together in infinite three-dimensional frameworks by N-H⋯O hydrogen bonds.

The methanol and ethanol solvates of 4-glutarato-N,N-diiso-propyl-tryptamine.

The solid-state structures of two solvated forms of 4-glutarato-N,N-diiso-propyl-tryptamine were determined by single-crystal X-ray diffraction, namely, 5-[(3-{2-[bis(propan-2-yl)azaniumyl]ethyl}-1H-indol-4-yl)oxy]-5-oxopentanoate meth-anol monosolvate, C21H30N2O4·CH3OH, and the analogous ethanol monosolvate, C21H30N2O4·C2H6O. In both compounds, the 4-glutarato-N,N-di-iso--pro-pyl-tryptamine exists as a zwitterion with a protonated tertiary ammonium and a deprotonated glutarato carboxyl-ate. The tryptamine zwitterions and alcohol solvates in both structures combine to produce near identical hydrogen-bonding networks, with N-H⋯O and O-H⋯O hydrogen bonds joining the mol-ecules together in two-dimensional networks parallel to the (100) plane.

Facilitating engagement of persons with opioid use disorder in treatment for hepatitis C virus infection via telemedicine: Stories of onsite case managers.

Although hepatitis C virus (HCV) infection has high prevalence and incidence in persons with opioid use disorder (PWOUD), their engagement in HCV care has been limited due to a variety of factors. In an ongoing multisite study at 12 opioid treatment programs (OTPs) throughout New York State (NYS), we have been evaluating telemedicine accompanied by onsite administration of direct acting antiviral (DAA) medications compared with usual care including offsite referral to a liver specialist for HCV management. Each site has a case manager (CM) who is responsible for all study-related activities including participant recruitment, facilitating telemedicine interactions, retention in care, and data collection. Our overall objective is to analyze CM experiences of clients' stories and events to understand how the telemedicine model facilitates HCV treatment. Hermeneutic phenomenology was used to interpret and to explicate common meanings and shared practices of the phenomena of case management, and a focus group with CMs was conducted to reinforce and expand on key themes identified from the CMs' stories. We identified three themes: (1) building trust, (2) identification of multiple competing priorities, and (3) development of personalized care approaches. Our results illustrate that trust is a fundamental pillar on which the telemedicine system can be based. Participants' experiences at the OTP can reinforce trust. Understanding the specific competing priorities and routinizing dedicated personalized approaches to overcome them are key to increasing participation in HCV care among PWOUD.

Effects of nutritional quality during early development on body weight and reproductive maturation of guinea pigs (Cavia aperea f. porcellus).

In many species, somatic and reproductive maturation are sensitive to seasonally-fluctuating environmental conditions such as food quality. The protein content of the diet during early development has been considered to be particularly important, a low-protein diet during gestation and lactation typically delaying growth and reproductive onset. To investigate the effects of maternal and early postnatal diet quality on body weight and puberty of male and female domestic guinea pigs, we fed F0-mothers either a low-protein (14%, LQ-group) or a high-protein diet (23%, HQ-group) during gestation and lactation. Their male and female offspring received the same respective diets until six weeks of age; afterward they were switched to an intermediate control diet. Body weight of F1-subjects was significantly affected by the dietary treatment. Reproductive parameters were only affected in F1-females but not in F1-males. We conclude that in guinea pigs, growth is sensitive to the quality of the maternal and early postnatal diet, and that reproductive maturation is more sensitive in females.

Community participation in New Mexico's behavioral health care reform.

In 2005, New Mexico implemented a unique reform in managed behavioral health services that seeks to ensure delivery of consumer-driven, recovery-oriented care to low-income individuals. Distinguishing features of the reform are the Local Collaboratives (LCs), regionally based community organizations designed by state government to represent behavioral health concerns of New Mexico's diverse cultural populations. We examine community response to the LCs, focusing on two broad sets of themes derived from 18 months of ethnographic fieldwork. The first set--structure and function--encompasses several issues: predominance of provider versus consumer voice; insufficient resources to support internal operations; imposition of state administrative demands; and perceived lack of state response to LC efforts. The second set--participation and collaboration--reveals how problems of information flow and other logistical factors impact involvement in LCs and how the construction of "community" introduced under this initiative exacerbates tensions across localities with varied histories and populations.

The necessity of a holistic approach when managing marine mammal-fisheries interactions: Environment and fisheries impact are stronger than seal predation.

Seal populations are recovering in many regions around the world and, consequently, they are increasingly interacting with fisheries. We used an Ecopath with Ecosim model for the offshore Central Baltic Sea to investigate the interactions between the changes in fish stocks and grey seal (Halichoerus grypus) population under different fishing and environmental scenarios for the twenty-first century. The assumed climate, eutrophication and cod (Gadus morhua) fisheries scenarios modified seal predation impacts on fish. Fish biomass and catches are more affected by fishing mortality and the environment than by seal predation. Our results highlight that the impacts of the increasing seal population on lower trophic levels are complex; thus, we emphasize the need to consider a range of possible ecosystem contexts when evaluating potential impacts of top predators. Finally, we suggest that an increasing seal population is not likely to hinder the preservation of the main Baltic fish stocks.

Food web and fisheries in the future Baltic Sea.

We developed numerical simulations of potential future ecological states of the Baltic Sea ecosystem at the end of century under five scenarios. We used a spatial food web (Ecospace) model, forced by a physical-biogeochemical model. The scenarios are built on consistent storylines that describe plausible developments of climatic and socioeconomic factors in the Baltic Sea region. Modelled species diversity and fish catches are driven by climate- and nutrient load-related changes in habitat quality and by fisheries management strategies. Our results suggest that a scenario including low greenhouse gas concentrations and nutrient pollution and ecologically focused fisheries management results in high biodiversity and catch value. On the other hand, scenarios envisioning increasing societal inequality or economic growth based on fossil fuels, high greenhouse gas emissions and high nutrient loads result in decreased habitat quality and diminished biodiversity. Under the latter scenarios catches are high but they predominantly consist of lower-valued fish.

Model uncertainty and simulated multispecies fisheries management advice in the Baltic Sea.

Different ecosystem models often provide contrasting predictions (model uncertainty), which is perceived to be a major challenge impeding their use to support ecosystem-based fisheries management (EBFM). The focus of this manuscript is to examine the extent of model disagreements which could impact management advice for EBFM in the central Baltic Sea. We compare how much three models (EwE, Gadget and a multispecies stock production model) differ in 1) their estimates of fishing mortality rates (Fs) satisfying alternative hypothetical management scenario objectives and 2) the outcomes of those scenarios in terms of performance indicators (spawning stock biomasses, catches, profits). Uncertainty in future environmental conditions affecting fish was taken into account by considering two seal population growth scenarios and two nutrient load scenarios. Differences in the development of the stocks, yields and profits exist among the models but the general patterns are also sufficiently similar to appear promising in the context of strategic fishery advice. Thus, we suggest that disagreements among the ecosystem models will not impede their use for providing strategic advice on how to reach management objectives that go beyond the traditional maximum yield targets and for informing on the potential consequences of pursuing such objectives. This is especially true for scenarios aiming at exploiting forage fish sprat and herring, for which the agreement was the largest among our models. However, the quantitative response to altering fishing pressure differed among models. This was due to the diverse environmental covariates and the different number of trophic relationships and their functional forms considered in the models. This suggests that ecosystem models can be used to provide quantitative advice only after more targeted research is conducted to gain a deeper understanding into the relationship between trophic links and fish population dynamics in the Baltic Sea.

Extensive Recruitment of Plasma Blasts to the Cerebrospinal Fluid in Toscana Virus Encephalitis.

An unexpectedly extensive recruitment of B cells and plasma blasts to the cerebrospinal fluid (CSF) in a patient with Toscana virus (TOSV) encephalitis is described. Acute infection by TOSV was demonstrated by serological methods and by detection of TOSV-specific nucleic acid in the CSF by real-time polymerase chain reaction and sequencing.

Latent and active transforming growth factor beta1 released from genetically modified keratinocytes modulates extracellular matrix expression by dermal fibroblasts in a coculture system.

Transforming growth factor beta1 is a multifunctional cytokine involved in many aspects of wound healing. Here we report the effects of both latent and active transforming growth factor beta1 released from genetically modified keratinocytes on extracellular matrix expression by dermal fibroblasts in a coculture system. Human keratinocytes were genetically modified with adenovirus containing cDNA for latent transforming growth factor beta1 (AdTGF-beta1) or active transforming growth factor beta1 (AdTGF-beta1(223/225)) or LacZ and cultured with human dermal fibroblasts. Northern blotting for mRNA confirmed that keratinocytes were successfully transduced with the adenoviruses as the cDNA transcripts are smaller than native transforming growth factor beta1 mRNA. An enzyme-linked immunosorbent assay specific for transforming growth factor beta1 demonstrated that the transforming growth factor beta1 produced by the genetically modified keratinocytes was able to pass through the membrane separating the two cell layers. Levels of transforming growth factor beta1 were significantly higher for both latent (p < 0.0001) and active (p < 0.0001) transforming growth factor beta1 compared to the LacZ control. Without acid activation of samples, keratinocytes transduced with the active transforming growth factor beta1 construct exhibited significantly higher levels of transforming growth factor beta1 than either the latent construct or the LacZ control (p < 0.0001). The transforming growth factor beta1 produced was biologically active, as shown by the plasminogen activator inhibitor assay (p < 0.0001). To demonstrate that transforming growth factor beta1 had an effect on underlying fibroblasts, mRNA was extracted and analyzed using Northern analysis. Latent transforming growth factor beta1 significantly increased the expression of type I collagen mRNA (p < 0.05) but did not significantly affect collagenase mRNA. Active transforming growth factor beta1 significantly increased type I collagen mRNA (p < 0.005) while also decreasing collagenase mRNA (p < 0.05). These results illustrate the ability of increased levels of transforming growth factor beta1 to override the effects of normal keratinocytes on the behavior of dermal fibroblasts.

Managed care or managed inequality? A call for critiques of market-based medicine.

This review article critiques the growing dominance of market-based medicine in the United States against the background of existing problems with quality of care, rising costs, devaluation of doctor-patient relationships, and, especially, persistent inequalities of access and outcomes. It summarizes the present state of health care delivery by focusing on the concurrent trends of growth in managed care, expanding profits, increasing proportion of those uninsured, and widening racial, ethnic, and class disparities in access to care. Allowing market forces to dictate the shape of health care delivery in this country ensures that inequalities will continue to grow and modern medicine will become increasingly adept at managing inequality rather than managing (providing) care. The article challenges anthropology to become more involved in critiquing these developments and suggests how anthropologists can expand on and contextualize debates surrounding the market's role in medicine, here and abroad.

BIM is the primary mediator of MYC-induced apoptosis in multiple solid tissues.

MYC is one of the most frequently overexpressed oncogenes in human cancer, and even modestly deregulated MYC can initiate ectopic proliferation in many postmitotic cell types in vivo. Sensitization of cells to apoptosis limits MYC's oncogenic potential. However, the mechanism through which MYC induces apoptosis is controversial. Some studies implicate p19ARF-mediated stabilization of p53, followed by induction of proapoptotic BH3 proteins NOXA and PUMA, whereas others argue for direct regulation of BH3 proteins, especially BIM. Here, we use a single experimental system to systematically evaluate the roles of p19ARF and BIM during MYC-induced apoptosis, in vitro, in vivo, and in combination with a widely used chemotherapeutic, doxorubicin. We find a common specific requirement for BIM during MYC-induced apoptosis in multiple settings, which does not extend to the p53-responsive BH3 family member PUMA, and find no evidence of a role for p19ARF during MYC-induced apoptosis in the tissues examined.

Lost in the rush to national reform: recommendations to improve impact on behavioral health providers in rural areas.

As the United States embarks on the most ambitious national health reform since the 1960s, this article highlights the challenges faced by behavioral health agencies, providers, and clients in rural areas and presents recommendations to improve access to and quality of services. Lessons learned from five years of research on a major systems-change initiative in New Mexico illuminate potential problem areas for rural agencies under national health reform, including insufficient financial resources, shortages of trained staff, particularly clinicians with advanced credentials, and delays in adopting the latest information technology. We recommend that rural states: (1) undertake careful planning for smooth transitions; (2) provide financial resources and technical assistance to expand rural safety-net services and capacity; (3) modify the health home model for the rural context; and (4) engage in ongoing evaluation, which can help ensure the early identification and rectification of unanticipated implementation issues.

Predator-prey dynamics driven by feedback between functionally diverse trophic levels.

Neglecting the naturally existing functional diversity of communities and the resulting potential to respond to altered conditions may strongly reduce the realism and predictive power of ecological models. We therefore propose and study a predator-prey model that describes mutual feedback via species shifts in both predator and prey, using a dynamic trait approach. Species compositions of the two trophic levels were described by mean functional traits--prey edibility and predator food-selectivity--and functional diversities by the variances. Altered edibility triggered shifts in food-selectivity so that consumers continuously respond to the present prey composition, and vice versa. This trait-mediated feedback mechanism resulted in a complex dynamic behavior with ongoing oscillations in the mean trait values, reflecting continuous reorganization of the trophic levels. The feedback was only possible if sufficient functional diversity was present in both trophic levels. Functional diversity was internally maintained on the prey level as no niche existed in our system, which was ideal under any composition of the predator level due to the trade-offs between edibility, growth and carrying capacity. The predators were only subject to one trade-off between food-selectivity and grazing ability and in the absence of immigration, one predator type became abundant, i.e., functional diversity declined to zero. In the lack of functional diversity the system showed the same dynamics as conventional models of predator-prey interactions ignoring the potential for shifts in species composition. This way, our study identified the crucial role of trade-offs and their shape in physiological and ecological traits for preserving diversity.