The mouse dorsal peduncular cortex encodes fear memory.

The rodent medial prefrontal cortex (mPFC) is functionally organized across the dorsoventral axis, where dorsal and ventral subregions promote and suppress fear, respectively. As the ventral-most subregion, the dorsal peduncular cortex (DP) is hypothesized to function in fear suppression. However, this role has not been explicitly tested. Here, we demonstrate that the DP paradoxically functions as a fear-encoding brain region and plays a minimal role in fear suppression. By using multimodal analyses, we demonstrate that DP neurons exhibit fear-learning-related plasticity and acquire cue-associated activity across learning and memory retrieval and that DP neurons activated by fear memory acquisition are preferentially reactivated upon fear memory retrieval. Further, optogenetic activation and silencing of DP fear-related neural ensembles drive the promotion and suppression of freezing, respectively. Overall, our results suggest that the DP plays a role in fear memory encoding. Moreover, our findings redefine our understanding of the functional organization of the rodent mPFC.

The mouse dorsal peduncular cortex encodes fear memory.

The rodent medial prefrontal cortex (mPFC) is a locus for both the promotion and suppression (e.g. extinction) of fear and is composed of four anatomically distinct subregions, including anterior cingulate 1 (Cg1), prelimbic (PL), infralimbic (IL), and the dorsal peduncular (DP) cortex. A vast majority of studies have focused on Cg1, PL, and IL. The Cg1 and PL have been implicated in the promotion of fear, while the IL has been linked to a role in the suppression, or extinction, of fear. Due to its anatomical location ventral to IL, the DP has been hypothesized to function as a fear-suppressing brain region however, no studies have explicitly tested its role in this function or in the regulation of memory generally. Moreover, some studies have pointed towards a dichotomous role for ventral mPFC in the dual suppression and promotion of fear, but the mechanisms underlying these opposing observations remains unclear. Here, we provide evidence that the DP paradoxically functions as a cued fear-encoding brain region and plays little to no role in fear memory extinction. By using a combination of cFos immunohistochemistry, whole-cell brain slice electrophysiology, fiber photometry, and activity-dependent neural tagging, we demonstrate that DP neurons exhibit learning-related plasticity, acquire cue-associated activity across learning and memory retrieval, and that DP neurons activated by learning are preferentially reactivated upon fear memory retrieval. Further, optogenetic activation and silencing of fear learning-related DP neural ensembles drives the promotion and suppression of freezing, respectively. Overall, these data suggest that the DP plays an unexpected role in fear memory encoding. More broadly, our results reveal new principles of organization across the dorsoventral axis of the mPFC.

Effort-related effects of chronic administration of the DA D2 receptor antagonist haloperidol via subcutaneous programmable minipumps: Reversal by co-administration of the adenosine A2A antagonist istradefylline.

RATIONALE: Long-acting antipsychotics such as haloperidol decanoate are becoming more commonly used. Long-acting depot formulations have several advantages, but secondary negative effects of prolonged delivery, including motivational dysfunctions, could have debilitating effects. Assessing the behavioral changes that emerge during chronic antipsychotic administration in rats could provide insight regarding the development of motivational dysfunctions and drug tolerance. OBJECTIVES: Acute administration of dopamine D2 antagonists such as haloperidol induce motivational deficits in rats, as marked by a shift towards a low-effort bias during effort-based choice tasks. In the present studies, programmable subcutaneous infusion pumps provided continuous and controlled drug delivery of haloperidol. Animals were assessed using a fixed ratio (FR) 5 lever pressing schedule and the FR5/chow feeding test of effort-based choice. The adenosine A2A antagonist istradefylline was studied for its ability to reverse the effects of chronic haloperidol. RESULTS: Continuous chronic infusions of haloperidol produced significant reductions in FR5 performance and a shift from lever pressing to chow intake in rats tested on FR5/chow feeding choice, with no evidence of tolerance over the 4-week infusion period. Behavior returned to baseline during the vehicle-infusion washout period. Istradefylline significantly reversed the effects of haloperidol, increasing lever pressing and decreasing chow intake in haloperidol-treated rats. CONCLUSIONS: These studies provide an important behavioral characterization of the effects of chronically infused haloperidol, and demonstrate that A2A antagonism reverses the effects of chronic haloperidol. This research could contribute to the understanding and treatment of motivational dysfunctions seen in schizophrenia, Parkinson's disease, and other disorders involving dopamine.

Analysis of older adult blood pressure readings and hypertension treatment rates among the unsheltered population of Miami-Dade County.

Objective: To assess prevalence of elevated blood pressure readings, rates of established hypertension diagnosis, and blood pressure control medication prescription rates in a cohort of older people experiencing unsheltered homelessness presenting to a Street Medicine clinic in Miami-Dade County, Florida. In addition, we will compare outcomes found in the study cohort to that of the general population. Methods: Demographic information, clinical history, blood pressure control medication prescription, and blood pressure measurements were taken by a Street Medicine team of medical providers. The team routinely provides medical evaluations and care for people experiencing unsheltered homelessness who reside in rough sleeper tent encampments located on the street. Clinical information and vitals were recorded in REDCap. De-identified data from patients 65 years and above were downloaded and compared to a general population data set-the Centers for Disease Control National Health and Nutrition Examination Survey (CDC NHANES) 2017-2020 Pre-pandemic cohort. Data analysis was performed using R Studio version 4.3.2. Results: Blood pressure was reported in 120 distinct interactions with older people experiencing homelessness. Compared to the age-matched NHANES data, older people experiencing unsheltered homelessness were at significantly increased relative risk for elevated blood pressure within the range of Stage 1 Hypertension (RR: 3.914, 95% CI: 2.560-5.892, P < 0.001), and within range of Stage 2 Hypertension (RR: 5.550, 95% CI: 4.272-7.210, P < 0.001). According to NHANES, 49.6% of adults over 60 with diagnosed hypertension receive treatment. Of study participants, 69% of those with elevated blood pressure had previously received a diagnosis of hypertension and 15.9% on medication to control blood pressure. Conclusion: Our cohort of older people experiencing unsheltered homelessness had higher rates of elevated blood pressure and reduced rates of hypertension diagnosis and treatment as compared to the general population. Older people experiencing unsheltered homelessness are a growing population, and future research should seek to evaluate and understand older adult care vulnerabilities, including chronic disease management, to improve health outcomes for those who are aging, hypertensive, and unhoused.

Cutaneous Manifestation of Diabetes Mellitus in an Unsheltered Male Leading to Emergent Hospitalization.

Diabetes mellitus (DM) is one of the most common chronic diseases in the United States. It is characterized by increased patient morbidity and mortality due to the many complications that can arise. Certain dermatological findings can be indicative of poorly controlled DM and can be a useful clue to further management. Persons experiencing homelessness (PEH) with DM often have higher rates of diabetic complications than the general diabetic population. Medical providers caring for PEH in the setting of limited resources should carefully evaluate cutaneous disease as a potential indicator of underlying illness. This physical manifestation of illness can serve to guide the next appropriate steps in management. A 41-year-old unsheltered male with an extensive medical history of hypertension, seizures, chronic diarrhea, and cocaine use was seen at a "foot-washing" medical outreach event. He presented with fevers, chills, and multiple painless right lower extremity ulcerated lesions of unspecified origin. A finger-stick glucose measurement was found to be 650 mg/dL. After immediate administration of 10 units of insulin, he was transported immediately to the emergency department and admitted. His month-long hospital course was complicated and involved the amputation of multiple toes. Preemptive outreach and management could have prevented the marked deterioration of his disease and represents the importance of outreach and regular follow-up with the PEH community.

A framework for allocating conservation resources among multiple threats and actions.

Land managers decide how to allocate resources among multiple threats that can be addressed through multiple possible actions. Additionally, these actions vary in feasibility, effectiveness, and cost. We sought to provide a way to optimize resource allocation to address multiple threats when multiple management options are available, including mutually exclusive options. Formulating the decision as a combinatorial optimization problem, our framework takes as inputs the expected impact and cost of each threat for each action (including do nothing) and for each overall budget identifies the optimal action to take for each threat. We compared the optimal solution to an easy to calculate greedy algorithm approximation and a variety of plausible ranking schemes. We applied the framework to management of multiple introduced plant species in Australian alpine areas. We developed a model of invasion to predict the expected impact in 50 years for each species-action combination that accounted for each species' current invasion state (absent, localized, widespread); arrival probability; spread rate; impact, if present, of each species; and management effectiveness of each species-action combination. We found that the recommended action for a threat changed with budget; there was no single optimal management action for each species; and considering more than one candidate action can substantially increase the management plan's overall efficiency. The approximate solution (solution ranked by marginal cost-effectiveness) performed well when the budget matched the cost of the prioritized actions, indicating that this approach would be effective if the budget was set as part of the prioritization process. The ranking schemes varied in performance, and achieving a close to optimal solution was not guaranteed. Global sensitivity analysis revealed a threat's expected impact and, to a lesser extent, management effectiveness were the most influential parameters, emphasizing the need to focus research and monitoring efforts on their quantification.

Un Marco de Referencia para Asignar Recursos para la Conservación entre Múltiples Amenazas y Acciones Resumen Los administradores de tierras deciden cómo asignar recursos entre múltiples amenazas que pueden abordarse por medio de múltiples acciones. Adicionalmente, estas acciones varían en viabilidad, efectividad y costo. Buscamos proporcionar una manera para optimizar la asignación de recursos para abordar varias amenazas cuando están disponibles muchas opciones de manejo, incluyendo opciones mutuamente excluyentes. Con una formulación de la decisión como un problema combinatorio de optimización, nuestro marco de referencia toma como entradas el impacto esperado y el costo de cada amenaza para cada acción (incluyendo hacer nada) y para cada presupuesto generalizado identifica la acción óptima a realizar ante cada amenaza. Comparamos la solución óptima con una aproximación de un algoritmo avaricioso fácil de calcular y una variedad de esquemas plausibles de clasificación. Aplicamos el marco de trabajo al manejo de múltiples especies de plantas introducidas en las áreas alpinas de Australia. Desarrollamos un modelo de invasión para predecir el impacto esperado en 50 años para cada combinación de especie-acción que consideró el estado actual de invasión para cada especie (ausente, localizada, ampliamente distribuida), la probabilidad de invasión, la tasa de esparcimiento, el impacto, cuando abundante, de cada especie y la efectividad de manejo de cada combinación especie-acción. Descubrimos que la acción recomendada para una amenaza cambia con el presupuesto, que no existe una acción única de manejo óptimo para cada especie y que considerar más de una acción candidata puede incrementar sustancialmente la eficiencia general del plan de manejo. La solución aproximada (solución clasificada por rentabilidad) tuvo un buen desempeño cuando el presupuesto fue igual al costo de las acciones prioritarias, lo que indica que esta estrategia sería efectiva si el presupuesto está fijado como parte del proceso de priorización. Los esquemas de clasificación variaron en cuanto a desempeño, y lograr una solución cercana a lo óptimo no estuvo garantizado. El análisis de sensibilidad global reveló que el impacto esperado de una amenaza y, a menor grado, la efectividad del manejo no fueron los parámetros con mayor influencia, lo que enfatiza la necesidad de enfocar la investigación y los esfuerzos de monitoreo en la cuantificación del impacto esperado y la efectividad del manejo.

Two-step adaptive management for choosing between two management actions.

Adaptive management is widely advocated to improve environmental management. Derivations of optimal strategies for adaptive management, however, tend to be case specific and time consuming. In contrast, managers might seek relatively simple guidance, such as insight into when a new potential management action should be considered, and how much effort should be expended on trialing such an action. We constructed a two-time-step scenario where a manager is choosing between two possible management actions. The manager has a total budget that can be split between a learning phase and an implementation phase. We use this scenario to investigate when and how much a manager should invest in learning about the management actions available. The optimal investment in learning can be understood intuitively by accounting for the expected value of sample information, the benefits that accrue during learning, the direct costs of learning, and the opportunity costs of learning. We find that the optimal proportion of the budget to spend on learning is characterized by several critical thresholds that mark a jump from spending a large proportion of the budget on learning to spending nothing. For example, as sampling variance increases, it is optimal to spend a larger proportion of the budget on learning, up to a point: if the sampling variance passes a critical threshold, it is no longer beneficial to invest in learning. Similar thresholds are observed as a function of the total budget and the difference in the expected performance of the two actions. We illustrate how this model can be applied using a case study of choosing between alternative rearing diets for hihi, an endangered New Zealand passerine. Although the model presented is a simplified scenario, we believe it is relevant to many management situations. Managers often have relatively short time horizons for management, and might be reluctant to consider further investment in learning and monitoring beyond collecting data from a single time period.

Communication of scientific uncertainty: international case studies on the development of folate and vitamin D Dietary Reference Values.

OBJECTIVE: Transparent evidence-based decision making has been promoted worldwide to engender trust in science and policy making. Yet, little attention has been given to transparency implementation. The degree of transparency (focused on how uncertain evidence was handled) during the development of folate and vitamin D Dietary Reference Values was explored in three a priori defined areas: (i) value request; (ii) evidence evaluation; and (iii) final values. DESIGN: Qualitative case studies (semi-structured interviews and desk research). A common protocol was used for data collection, interview thematic analysis and reporting. Results were coordinated via cross-case synthesis. SETTING: Australia and New Zealand, Netherlands, Nordic countries, Poland, Spain and UK. SUBJECTS: Twenty-one interviews were conducted in six case studies. RESULTS: Transparency of process was not universally observed across countries or areas of the recommendation setting process. Transparency practices were most commonly seen surrounding the request to develop reference values (e.g. access to risk manager/assessor problem formulation discussions) and evidence evaluation (e.g. disclosure of risk assessor data sourcing/evaluation protocols). Fewer transparency practices were observed to assist with handling uncertainty in the evidence base during the development of quantitative reference values. CONCLUSIONS: Implementation of transparency policies may be limited by a lack of dedicated resources and best practice procedures, particularly to assist with the latter stages of reference value development. Challenges remain regarding the best practice for transparently communicating the influence of uncertain evidence on the final reference values. Resolving this issue may assist the evolution of nutrition risk assessment and better inform the recommendation setting process.

The optimal number of surveys when detectability varies.

The survey of plant and animal populations is central to undertaking field ecology. However, detection is imperfect, so the absence of a species cannot be determined with certainty. Methods developed to account for imperfect detectability during surveys do not yet account for stochastic variation in detectability over time or space. When each survey entails a fixed cost that is not spent searching (e.g., time required to travel to the site), stochastic detection rates result in a trade-off between the number of surveys and the length of each survey when surveying a single site. We present a model that addresses this trade-off and use it to determine the number of surveys that: 1) maximizes the expected probability of detection over the entire survey period; and 2) is most likely to achieve a minimally-acceptable probability of detection. We illustrate the applicability of our approach using three practical examples (minimum survey effort protocols, number of frog surveys per season, and number of quadrats per site to detect a plant species) and test our model's predictions using data from experimental plant surveys. We find that when maximizing the expected probability of detection, the optimal survey design is most sensitive to the coefficient of variation in the rate of detection and the ratio of the search budget to the travel cost. When maximizing the likelihood of achieving a particular probability of detection, the optimal survey design is most sensitive to the required probability of detection, the expected number of detections if the budget were spent only on searching, and the expected number of detections that are missed due to travel costs. We find that accounting for stochasticity in detection rates is likely to be particularly important for designing surveys when detection rates are low. Our model provides a framework to do this.

Linking indices for biodiversity monitoring to extinction risk theory.

Biodiversity indices often combine data from different species when used in monitoring programs. Heuristic properties can suggest preferred indices, but we lack objective ways to discriminate between indices with similar heuristics. Biodiversity indices can be evaluated by determining how well they reflect management objectives that a monitoring program aims to support. For example, the Convention on Biological Diversity requires reporting about extinction rates, so simple indices that reflect extinction risk would be valuable. We developed 3 biodiversity indices that are based on simple models of population viability that relate extinction risk to abundance. We based the first index on the geometric mean abundance of species and the second on a more general power mean. In a third index, we integrated the geometric mean abundance and trend. These indices require the same data as previous indices, but they also relate directly to extinction risk. Field data for butterflies and woodland plants and experimental studies of protozoan communities show that the indices correlate with local extinction rates. Applying the index based on the geometric mean to global data on changes in avian abundance suggested that the average extinction probability of birds has increased approximately 1% from 1970 to 2009.

When should we save the most endangered species?

At the heart of our efforts to protect threatened species, there is a controversial debate about whether to give priority to cost-effective actions or whether focusing solely on the most endangered species will ultimately lead to preservation of the greatest number of species. By framing this debate within a decision-analytic framework, we show that allocating resources solely to the most endangered species will typically not minimise the number of extinctions in the long-term, as this does not account for the risk of less endangered species going extinct in the future. It is only favoured when our planning timeframe is short or we have a long-term view and we are optimistic about future conditions. Conservation funding tends to be short-term in nature, which biases allocations to more endangered species. Our work highlights the need to consider resource allocation for biodiversity over the long-term; 'preventive conservation', rather than just short-term fire-fighting.

Designing nature reserves in the face of uncertainty.

Conservation reserves are a fundamental tool for managing biodiversity. The so-called SLOSS debate--should we have a Single Large Or Several Small reserves - is central to conservation theory. Population dynamic models suggest that the design that minimizes the risk of extinction of a species is case-specific, with the optimal number of reserves ranging between one and very many. Uncertainty is pervasive in ecology, but, the previous analyses of the SLOSS debate have not considered how uncertainty in the model of extinction risk might influence the optimal design. Herein, we show that when uncertainty is considered, the SLOSS problem is simplified and driven more by the aspirations of the manager than the population dynamics of the species. In this case, the optimal solution is to have in the order of twenty or fewer reserves for any species. This result shows counter-intuitively that considering uncertainty actually simplifies rather than complicates decisions about designing nature reserves.

Bentho-pelagic divergence of cichlid feeding architecture was prodigious and consistent during multiple adaptive radiations within African rift-lakes.

BACKGROUND: How particular changes in functional morphology can repeatedly promote ecological diversification is an active area of evolutionary investigation. The African rift-lake cichlids offer a calibrated time series of the most dramatic adaptive radiations of vertebrate trophic morphology yet described, and the replicate nature of these events provides a unique opportunity to test whether common changes in functional morphology have repeatedly facilitated their ecological success. METHODOLOGY/PRINCIPAL FINDINGS: Specimens from 87 genera of cichlid fishes endemic to Lakes Tanganyka, Malawi and Victoria were dissected in order to examine the functional morphology of cichlid feeding. We quantified shape using geometric morphometrics and compared patterns of morphological diversity using a series of analytical tests. The primary axes of divergence were conserved among all three radiations, and the most prevalent changes involved the size of the preorbital region of the skull. Even the fishes from the youngest of these lakes (Victoria), which exhibit the lowest amount of skull shape disparity, have undergone extensive preorbital evolution relative to other craniofacial traits. Such changes have large effects on feeding biomechanics, and can promote expansion into a wide array of niches along a bentho-pelagic ecomorphological axis. CONCLUSIONS/SIGNIFICANCE: Here we show that specific changes in trophic anatomy have evolved repeatedly in the African rift lakes, and our results suggest that simple morphological alterations that have large ecological consequences are likely to constitute critical components of adaptive radiations in functional morphology. Such shifts may precede more complex shape changes as lineages diversify into unoccupied niches. The data presented here, combined with observations of other fish lineages, suggest that the preorbital region represents an evolutionary module that can respond quickly to natural selection when fishes colonize new lakes. Characterizing the changes in cichlid trophic morphology that have contributed to their extraordinary adaptive radiations has broad evolutionary implications, and such studies are necessary for directing future investigations into the proximate mechanisms that have shaped these spectacular phenomena.

On valuing information in adaptive-management models.

Active adaptive management looks at the benefit of using strategies that may be suboptimal in the near term but may provide additional information that will facilitate better management in the future. In many adaptive-management problems that have been studied, the optimal active and passive policies (accounting for learning when designing policies and designing policy on the basis of current best information, respectively) are very similar. This seems paradoxical; when faced with uncertainty about the best course of action, managers should spend very little effort on actively designing programs to learn about the system they are managing. We considered two possible reasons why active and passive adaptive solutions are often similar. First, the benefits of learning are often confined to the particular case study in the modeled scenario, whereas in reality information gained from local studies is often applied more broadly. Second, management objectives that incorporate the variance of an estimate may place greater emphasis on learning than more commonly used objectives that aim to maximize an expected value. We explored these issues in a case study of Merri Creek, Melbourne, Australia, in which the aim was to choose between two options for revegetation. We explicitly incorporated monitoring costs in the model. The value of the terminal rewards and the choice of objective both influenced the difference between active and passive adaptive solutions. Explicitly considering the cost of monitoring provided a different perspective on how the terminal reward and management objective affected learning. The states for which it was optimal to monitor did not always coincide with the states in which active and passive adaptive management differed. Our results emphasize that spending resources on monitoring is only optimal when the expected benefits of the options being considered are similar and when the pay-off for learning about their benefits is large.

How we value the future affects our desire to learn.

Active adaptive management is increasingly advocated in natural resource management and conservation biology. Active adaptive management looks at the benefit of employing strategies that may be suboptimal in the near term but which may provide additional information that will facilitate better management in future years. However, when comparing management policies it is traditional to weigh future rewards geometrically (at a constant discount rate) which results in far-distant rewards making a negligible contribution to the total benefit. Under such a discounting scheme active adaptive management is rarely of much benefit, especially if learning is slow. A growing number of authors advocate the use of alternative forms of discounting when evaluating optimal strategies for long-term decisions which have a social component. We consider a theoretical harvested population for which the recovery rate from an unharvestably small population size is unknown and look at the effects on the benefit of experimental management when three different forms of discounting are employed. Under geometric discounting, with a discount rate of 5% per annum, managing to learn actively had little benefit. This study demonstrates that discount functions which weigh future rewards more heavily result in more conservative harvesting strategies, but do not necessarily encourage active learning. Furthermore, the optimal management strategy is not equivalent to employing geometric discounting at a lower rate. If alternative discount functions are made mandatory in calculating optimal management strategies for environmental management then this will affect the structure of optimal management regimes and change when and how much we are willing to invest in learning.