"Politics Versus Policy": Qualitative Insights on Stigma and Overdose Prevention Center Policymaking in the United States.

BACKGROUND: Federal, state, and municipal governments in the United States have been reluctant to authorize overdose prevention centers (OPCs), which are evidence-based approaches for preventing overdose deaths and blood-borne pathogen transmission. METHODS: From July 2022 to February 2023, we explored how stigma manifests in OPC policymaking by conducting in-depth interviews with 17 advocates, legislators, service providers, and researchers involved with OPC advocacy and policymaking in Rhode Island, California, Pennsylvania, and New York. RESULTS: We found that although jurisdictions differed in their OPC policymaking experiences, stigma manifested throughout the process, from planning to authorization. Participants described OPCs as a tool for destigmatizing overdose and substance use, yet confronted institutionalized stigma and discriminatory attitudes toward people who use drugs (PWUD) and harm reduction from multiple sources (eg, politicians, media, and members of the public). Opposition toward OPCs and harm reduction approaches more broadly intersected with public discourse on crime, homelessness, and public disorder. Employed stigma-mitigation strategies included humanizing PWUD, publicizing the benefits of OPCs to the wider community, and strategically engaging media. CONCLUSION: These findings illustrate the importance of understanding stigma at different stages of the policymaking process to better facilitate authorization and eventual implementation of OPCs in the United States.

The information, control, and value models of mobile health-driven empowerment.

Mobile health tools are often said to empower users by providing them with the information they need to exercise control over their health. We aim to bring clarity to this claim, and in doing so explore the relationship between empowerment and autonomy. We have identified three distinct models embedded in the empowerment rhetoric: empowerment as information, empowerment as control, and empowerment as values. Each distinct model of empowerment gives rise to an associated problem. These problems, the Problem of Interpretation, the Value Alignment Problem, and the Priority Problem, show that mobile health tools in their current form are either insufficient for empowerment or are self-defeating. These digital health technologies encourage users to adopt an individualized conception of autonomy, one that may weaken the doctor-patient relationship and undermine practices in shared decision making, and ultimately may not deliver on improving the health outcomes for those that need it the most.

π-Conjugated redox-active two-dimensional polymers as organic cathode materials.

Redox-active two-dimensional polymers (RA-2DPs) are promising lithium battery organic cathode materials due to their regular porosities and high chemical stabilities. However, weak electrical conductivities inherent to the non-conjugated molecular motifs used thus far limit device performance and the practical relevance of these materials. We herein address this problem by developing a modular approach to construct π-conjugated RA-2DPs with a new polycyclic aromatic redox-active building block PDI-DA. Efficient imine-condensation between PDI-DA and two polyfunctional amine nodes followed by quantitative alkyl chain removal produced RA-2DPs TAPPy-PDI and TAPB-PDI as conjugated, porous, polycrystalline networks. In-plane conjugation and permanent porosity endow these materials with high electrical conductivity and high ion diffusion rates. As such, both RA-2DPs function as organic cathode materials with good rate performance and excellent cycling stability. Importantly, the improved design enables higher areal mass-loadings than were previously available, which drives a practical demonstration of TAPPy-PDI as the power source for a series of LED lights. Collectively, this investigation discloses viable synthetic methodologies and design principles for the realization of high-performance organic cathode materials.

Is mechanical bowel preparation necessary in bariatric surgery?

BACKGROUND: Historically, mechanical bowel preparation (MBP) is performed prior to bariatric procedures; but our counter parts in colorectal surgery have shown that no-MBP is non-inferior to MBP, in regard to post-operative complications. The purpose of our study was to show that no-MBP prior to bariatric surgery is also non-inferior to MBP. METHODS: A prospective, randomized, controlled trial was conducted on patients undergoing bariatric surgical procedures (Roux-en-Y Gastric Bypass, or Sleeve Gastrectomy). We randomized patients to MBP and no-MBP. Number of post-operative complications (intraabdominal abscess, anastomotic leak, acute kidney injury, dehydration), readmission, and wound infection for 30 days post-procedure was recorded. RESULTS: A total of 139 patients were enrolled with 71 in the MBP group and 68 in the no-MBP group. Complication rates were similar between the MBP and no-MBP (12.7% vs. 10.2%, respectively; p = 0.660). Median hospital length of stay was similar for MBP and no-MBP (1 vs. 1 day, respectively; p = 0.782). Hospital readmissions for MBP vs. no-MBP was, 4.4% vs. 5.6%, respectively (p = 1.000). CONCLUSION: Mechanical bowel preparation is likely not necessary prior to bariatric procedures.

High-performance organic pseudocapacitors via molecular contortion.

Pseudocapacitors harness unique charge-storage mechanisms to enable high-capacity, rapidly cycling devices. Here we describe an organic system composed of perylene diimide and hexaazatrinaphthylene exhibiting a specific capacitance of 689 F g-1 at a rate of 0.5 A g-1, stability over 50,000 cycles, and unprecedented performance at rates as high as 75 A g-1. We incorporate the material into two-electrode devices for a practical demonstration of its potential in next-generation energy-storage systems. We identify the source of this exceptionally high rate charge storage as surface-mediated pseudocapacitance, through a combination of spectroscopic, computational and electrochemical measurements. By underscoring the importance of molecular contortion and complementary electronic attributes in the selection of molecular components, these results provide a general strategy for the creation of organic high-performance energy-storage materials.

Defining codominance in plant communities.

Species dominance and biodiversity in plant communities have received considerable attention and characterisation. However, species codominance, while often alleged, is seldom defined or quantified. Codominance is a common phenomenon and is likely to be an important driver of community structure, ecosystem function and the stability of both. Here we review the use of the term 'codominance' and find inconsistencies in its use, suggesting that the scientific community currently lacks a universal understanding of codominance. We address this issue by: (1) qualitatively defining codominance as mostly shared abundance that is distinctively isolated within a subset of a community, and (2) presenting a novel metric for quantifying the degree to which relative abundances are shared among a codominant subset of plant species, while also accounting for the remaining species within a plant community. Using both simulated and real-world data, we then demonstrate the process of applying the codominance metric to compare communities and to generate a quantitatively defensible subset of species to consider codominant within a community. We show that our metric effectively distinguishes the degree of codominance between four types of grassland ecosystems as well as simulated ecosystems with varying degrees of abundance sharing among community members. Overall, we make the case that increased research focusses on the conditions under which codominance occurs and the consequences for species coexistence, community structure and ecosystem function that would considerably advance the fields of community and ecosystem ecology.

Is a drought a drought in grasslands? Productivity responses to different types of drought.

Drought, defined as a marked deficiency of precipitation relative to normal, occurs as periods of below-average precipitation or complete failure of precipitation inputs, and can be limited to a single season or prolonged over multiple years. Grasslands are typically quite sensitive to drought, but there can be substantial variability in the magnitude of loss of ecosystem function. We hypothesized that differences in how drought occurs may contribute to this variability. In four native Great Plains grasslands (three C4- and one C3-dominated) spanning a ~ 500-mm precipitation gradient, we imposed drought for four consecutive years by (1) reducing each rainfall event by 66% during the growing season (chronic drought) or (2) completely excluding rainfall during a shorter portion of the growing season (intense drought). The drought treatments were similar in magnitude but differed in the following characteristics: event number, event size and length of dry periods. We observed consistent drought-induced reductions (28-37%) in aboveground net primary production (ANPP) only in the C4-dominated grasslands. In general, intense drought reduced ANPP more than chronic drought, with little evidence that drought duration altered this pattern. Conversely, belowground net primary production (BNPP) was reduced by drought in all grasslands (32-64%), with BNPP reductions greater in intense vs. chronic drought treatments in the most mesic grassland. We conclude that grassland productivity responses to drought did not strongly differ between these two types of drought, but when differences existed, intense drought consistently reduced function more than chronic drought.

Resolving the Dust Bowl paradox of grassland responses to extreme drought.

During the 1930s Dust Bowl drought in the central United States, species with the C3 photosynthetic pathway expanded throughout C4-dominated grasslands. This widespread increase in C3 grasses during a decade of low rainfall and high temperatures is inconsistent with well-known traits of C3 vs. C4 pathways. Indeed, water use efficiency is generally lower, and photosynthesis is more sensitive to high temperatures in C3 than C4 species, consistent with the predominant distribution of C3 grasslands in cooler environments and at higher latitudes globally. We experimentally imposed extreme drought for 4 y in mixed C3/C4 grasslands in Kansas and Wyoming and, similar to Dust Bowl observations, also documented three- to fivefold increases in C3/C4 biomass ratios. To explain these paradoxical responses, we first analyzed long-term climate records to show that under nominal conditions in the central United States, C4 grasses dominate where precipitation and air temperature are strongly related (warmest months are wettest months). In contrast, C3 grasses flourish where precipitation inputs are less strongly coupled to warm temperatures. We then show that during extreme drought years, precipitation-temperature relationships weaken, and the proportion of precipitation falling during cooler months increases. This shift in precipitation seasonality provides a mechanism for C3 grasses to respond positively to multiyear drought, resolving the Dust Bowl paradox. Grasslands are globally important biomes and increasingly vulnerable to direct effects of climate extremes. Our findings highlight how extreme drought can indirectly alter precipitation seasonality and shift ecosystem phenology, affecting function in ways not predictable from key traits of C3 and C4 species.

Radical enhancement as a moral status de-enhancer.

Nicholas Agar, Jeff McMahan and Allen Buchanan have all expressed concerns about enhancing humans far outside the species-typical range. They argue radically enhanced beings will be entitled to greater and more beneficial treatment through an enhanced moral status, or a stronger claim to basic rights. I challenge these claims by first arguing that emerging technologies will likely give the enhanced direct control over their mental states. The lack of control we currently exhibit over our mental lives greatly contributes to our sense of vulnerability. I then argue moral status should be viewed in terms of vulnerability. The enhanced will slowly gain the ability to command their mental states, reducing their vulnerability. These radically enhanced beings will have greater capacities, and possibly an inner life more valuable than our own. They will also be less vulnerable, and as a result, their moral status will be subordinate to our own.

Firing Rate Homeostasis Can Occur in the Absence of Neuronal Activity-Regulated Transcription.

Despite dynamic inputs, neuronal circuits maintain relatively stable firing rates over long periods. This maintenance of firing rate, or firing rate homeostasis, is likely mediated by homeostatic mechanisms such as synaptic scaling and regulation of intrinsic excitability. Because some of these homeostatic mechanisms depend on transcription of activity-regulated genes, including Arc and Homer1a, we hypothesized that activity-regulated transcription would be required for firing rate homeostasis. Surprisingly, however, we found that cultured mouse cortical neurons from both sexes grown on multi-electrode arrays homeostatically adapt their firing rates to persistent pharmacological stimulation even when activity-regulated transcription is disrupted. Specifically, we observed firing rate homeostasis in Arc knock-out neurons, as well as knock-out neurons lacking the activity-regulated transcription factors AP1 and SRF. Firing rate homeostasis also occurred normally during acute pharmacological blockade of transcription. Thus, firing rate homeostasis in response to increased neuronal activity can occur in the absence of neuronal-activity-regulated transcription.SIGNIFICANCE STATEMENT Neuronal circuits maintain relatively stable firing rates even in the face of dynamic circuit inputs. Understanding the molecular mechanisms that enable this firing rate homeostasis could potentially provide insight into neuronal diseases that present with an imbalance of excitation and inhibition. It has long been proposed that activity-regulated transcription could underlie firing rate homeostasis because activity-regulated genes turn on when neurons are above their target firing rates and include many genes that could regulate firing rate. Surprisingly, despite this prediction, we found that cortical neurons can undergo firing rate homeostasis in the absence of activity-regulated transcription, indicating that firing rate homeostasis can be controlled by non-transcriptional mechanisms.

Blue Light Increases Neuronal Activity-Regulated Gene Expression in the Absence of Optogenetic Proteins.

Optogenetics is widely used to control diverse cellular functions with light, requiring experimenters to expose cells to bright light. Because extended exposure to visible light can be toxic to cells, it is important to characterize the effects of light stimulation on cellular function in the absence of optogenetic proteins. Here we exposed mouse cortical cultures with no exogenous optogenetic proteins to several hours of flashing blue, red, or green light. We found that exposing these cultures to as short as 1 h of blue light, but not red or green light, results in an increase in the expression of neuronal activity-regulated genes. Our findings suggest that blue light stimulation is ill suited to long-term optogenetic experiments, especially those that measure transcription, and they emphasize the importance of performing light-only control experiments in samples without optogenetic proteins.

The neuronal stimulation-transcription coupling map.

Neurons transcribe different genes in response to different extracellular stimuli, and these genes regulate neuronal plasticity. Thus, understanding how different stimuli regulate different stimulus-dependent gene modules would deepen our understanding of plasticity. To systematically dissect the coupling between stimulation and transcription, we propose creating a 'stimulation-transcription coupling map' that describes the transcription response to each possible extracellular stimulus. While we are currently far from having a complete map, recent genomic experiments have begun to facilitate its creation. Here, we describe the current state of the stimulation-transcription coupling map as well as the transcriptional regulation that enables this coupling.

Cell-type-specific programs for activity-regulated gene expression.

Experience leaves a lasting mark on neural circuit function in part through activity-regulated gene (ARG) expression. New genome wide approaches have revealed that ARG programs are highly cell-type-specific, raising the possibility that they mediate different forms of experience-dependent plasticity in different cell types. The cell-type specificity of these gene programs is achieved by a combination of cell-intrinsic mechanisms that determine the transcriptional response of each neuronal subtype to a given stimulus and by cell-extrinsic mechanisms that influence the nature of the stimulus a cell receives. A better understanding of these mechanisms could usher in an era of molecular systems neuroscience in which genetic perturbations of cell-type-specific plasticities are assessed using electrophysiology and in vivo imaging to reveal the neural basis of adaptive behaviors.

A reality check for climate change experiments: Do they reflect the real world?

Experiments are widely used in ecology, particularly for assessing global change impacts on ecosystem function. However, results from experiments often are inconsistent with observations made under natural conditions, suggesting the need for rigorous comparisons of experimental and observational studies. We conducted such a "reality check" for a grassland ecosystem by compiling results from nine independently conducted climate change experiments. Each experiment manipulated growing season precipitation (GSP) and measured responses in aboveground net primary production (ANPP). We compared results from experiments with long-term (33-yr) annual precipitation and ANPP records to ask if collectively (n = 44 experiment-years) experiments yielded estimates of ANPP, rain-use efficiency (RUE, grams per square meter ANPP per mm precipitation), and the relationship between GSP and ANPP comparable to observations. We found that mean ANPP and RUE from experiments did not deviate from observations. Experiments and observational data also yielded similar functional relationships between ANPP and GSP, but only within the range of historically observed GSP. Fewer experiments imposed extreme levels of GSP (outside the observed 33-yr record), but when these were included, they altered the GSP-ANPP relationship. This result underscores the need for more experiments imposing extreme precipitation levels to resolve how forecast changes in climate regimes will affect ecosystem function in the future.

Different Neuronal Activity Patterns Induce Different Gene Expression Programs.

A vast number of different neuronal activity patterns could each induce a different set of activity-regulated genes. Mapping this coupling between activity pattern and gene induction would allow inference of a neuron's activity-pattern history from its gene expression and improve our understanding of activity-pattern-dependent synaptic plasticity. In genome-scale experiments comparing brief and sustained activity patterns, we reveal that activity-duration history can be inferred from gene expression profiles. Brief activity selectively induces a small subset of the activity-regulated gene program that corresponds to the first of three temporal waves of genes induced by sustained activity. Induction of these first-wave genes is mechanistically distinct from that of the later waves because it requires MAPK/ERK signaling but does not require de novo translation. Thus, the same mechanisms that establish the multi-wave temporal structure of gene induction also enable different gene sets to be induced by different activity durations.

Brain-wide maps of Fos expression during fear learning and recall.

Fos induction during learning labels neuronal ensembles in the hippocampus that encode a specific physical environment, revealing a memory trace. In the cortex and other regions, the extent to which Fos induction during learning reveals specific sensory representations is unknown. Here we generate high-quality brain-wide maps of Fos mRNA expression during auditory fear conditioning and recall in the setting of the home cage. These maps reveal a brain-wide pattern of Fos induction that is remarkably similar among fear conditioning, shock-only, tone-only, and fear recall conditions, casting doubt on the idea that Fos reveals auditory-specific sensory representations. Indeed, novel auditory tones lead to as much gene induction in visual as in auditory cortex, while familiar (nonconditioned) tones do not appreciably induce Fos anywhere in the brain. Fos expression levels do not correlate with physical activity, suggesting that they are not determined by behavioral activity-driven alterations in sensory experience. In the thalamus, Fos is induced more prominently in limbic than in sensory relay nuclei, suggesting that Fos may be most sensitive to emotional state. Thus, our data suggest that Fos expression during simple associative learning labels ensembles activated generally by arousal rather than specifically by a particular sensory cue.