Background: Deep brain stimulation (DBS) in Parkinson’s disease (PD) requires extensive trial-and-error programming, often taking over a year to optimize. An objective, rapid biomarker of stimulation success is needed. Our team developed a functional magnetic resonance imaging (fMRI)-based algorithm to identify optimal DBS settings. This study prospectively compared fMRI-guided programming with standard-of-care (SoC) clinical programming in a double-blind, crossover, non-inferiority trial. Methods: Twenty-two PD-DBS patients were prospectively enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. Optimal settings were identified using our published classification algorithm. Subjects then underwent >1 year of SoC programming. Clinical improvement was assessed under SoC and fMRI-determined stimulation conditions. Results: fMRI optimization significantly reduced the time required to determine optimal settings (1.6 vs. 5.6 months, p<0.001). Unified Parkinson’s Disease Rating Scale (UPDRSIII) improved comparably with both approaches (23.8 vs. 23.6, p=0.9). Non-inferiority was demonstrated within a predefined margin of 5 points (p=0.0018). SoC led to greater tremor improvement (p=0.019), while fMRI showed greater bradykinesia improvement (p=0.040). Conclusions: This is the first prospective evaluation of an algorithm able to suggest stimulation parameters solely from the fMRI response to stimulation. It suggests that fMRI-based programming may achieve equivalent outcomes in less time than SoC, reducing patient burden while potentially enhancing bradykinesia response.

The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA’s blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.

Working equids support the livelihoods of millions of low-income households worldwide and face several welfare challenges. Although equipment-related wounds are common, little is known about specific risk factors. This cross-sectional study surveyed equids used for cart-work in three Ethiopian towns. Number, size, severity and location of wounds were recorded for each animal, as well as work equipment characteristics and indicators of equipment fit and assembly. Questionnaires were conducted with each cart-driver focusing on equipment practices and attitudes. Logistic regression models were generated to investigate associations between equipment-related wounds (outcome) and equipment, work, driver and animal-related factors (predictors). In total, 369 equids and cart-drivers were surveyed. The prevalence of equipment-related wounds was 72.6% (268/369) with girth wounds being the predominant wound type in horses (50%; 122/244) while donkeys had predominantly shaft-related wounds (59%; 72/122). Donkeys were two times more likely to have equipment-related wounds than horses. The presence of equipment-related wounds was associated with factors such as previously having wounds, inadequate collar positioning and using purchased equipment compared to partly home-made equipment. Characteristics of specific equipment components were also associated with certain wound types, such as narrow saddle pressure points and saddle wounds. Equipment-related wounds are highly prevalent in working equids, representing a serious welfare concern. Factors relating to equipment design, fit and assembly were associated with the presence of wounds. Importantly, species differences require tailoring of preventive approaches amongst working equids. A better understanding of work equipment should therefore be promoted as part of wound prevention and animal welfare strategies.

Certified organic farming is a suite of regulated practices that can support social, economic, and ecological sustainability in agriculture. Despite the standardization and regulation of certifying bodies, practices adopted by organic farmers vary with potential heterogeneous effects on environmental outcomes. While it is accepted that beliefs can enable or constrain the adoption of farming practices, it remains unclear if variation in organic farmer beliefs mediates observed heterogeneity in practices and the ecology of farms. Communities of soil microorganisms that induce plant resistance and regulate insect herbivores offer a lens to explore the relationship between beliefs and practice adoption. Variation in insect herbivores across organic farms is common but none have studied the role of farmer beliefs in regulating pests through the soil microbiome. Herein, we hypothesized that variation in adoption of microbiome-supportive practices by organic farmers is driven by heterogeneity in their microbiome beliefs. We also investigate the importance of demographic variables and farm characteristics, compared to farmer beliefs, for adoption of practices that support the microbiome. To test our hypothesis, we surveyed the microbiome beliefs, farming practices, and motivations of 85 organic farmers in New York State, USA. We used affinity propagation to cluster farmers by their beliefs, and statistical models to evaluate variation in farming practice adoption and farmer motivations. Our survey received a 30.5% response rate, most organic farmers (≈96%) believed the soil microbiome was important for supporting plant defenses and reducing pests, and <16% believed their farming practices were unimportant for promoting beneficial microbiomes. Seven clusters of farmers were identified that varied in their microbiome beliefs. Among the clusters ≈42% of farmers believed on-farm management and external factors (e.g., climate change) were important for promoting the microbiome. These farmers used fewer pesticides and synthetic mulches, more pre-planting practices (e.g., solarization), and were more motivated to adopt new practices to support the microbiome than their peers. The most important factors motivating adoption were reductions in pests, increased yields, and biodiversity benefits. Beliefs, demographics, and farm characteristics (e.g., time in organic management) were correlated with similar suites of farming practices, but only beliefs predicted farmer motivations. Our study suggests beliefs are key to understanding farmer motivations and promoting organic farming system sustainability via the pest-suppressive microbiome. More broadly, we suggest the need for socio-ecological approaches that account for farmer beliefs when studying the adoption of conservation practices in agroecosystems.

In 2022, highly pathogenic avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b became enzootic and caused mass mortality in Sandwich Tern Thalasseus sandvicensis and other seabird species across north-western Europe. We present data on the characteristics of the spread of the virus between and within breeding colonies and the number of dead adult Sandwich Terns recorded at breeding sites throughout north-western Europe. Within two months of the first reported mortalities, 20,531 adult Sandwich Terns were found dead, which is >17% of the total north-western European breeding population. This is probably an under-representation of total mortality, as many carcasses are likely to have gone unnoticed and unreported. Within affected colonies, almost all chicks died. After the peak of the outbreak, in a colony established by late breeders, 25.7% of tested adults showed immunity to HPAI subtype H5. Removal of carcasses was associated with lower levels of mortality at affected colonies. More research on the sources and modes of transmission, incubation times, effective containment, and immunity is urgently needed to combat this major threat for colonial seabirds.

Attention-deficit/hyperactivity disorder (ADHD) symptoms are associated with myriad adverse outcomes, including interpersonal difficulties, but factors that moderate the developmental course and functional impact of ADHD over time are not well understood. The present study evaluated developmental contributions of the triarchic neurobehavioral traits (boldness, meanness, and disinhibition) to ADHD symptomatology and its subdimensions from adolescence to young adulthood. Participants were twins and triplets assessed at ages 14, 17, and 19 (initial N = 1,185, 51.2% female). Path analyses using negative binomial regression revealed that boldness at age 14 was associated with more ADHD symptoms cross-sectionally (especially hyperactivity/impulsivity), but fewer symptoms (especially inattention) at age 19 in the prospective analysis. Notably, inclusion of interpersonal problems at ages 14 and 17 as covariates reduced the latter effect to nonsignificant. Disinhibition concurrently and prospectively predicted higher levels of ADHD symptoms, including both subdimensions, and the prospective effects were partially mediated by greater social impairment at age 17. Meanness prospectively (but not concurrently) predicted higher levels of hyperactivity/impulsivity symptoms. Sex moderated certain associations of meanness and disinhibition with ADHD symptoms. These findings highlight how fundamental neurobehavioral traits shape both psychopathology and adaptive outcomes in the developmental course of ADHD.

Loss of local biodiversity resulting from abrupt environmental change is a significant environmental problem throughout the world. Extinctions of plants are particularly important yet are often overlooked. Drawing from a case in Hawai‘i, a global hotspot for plant and other extinctions, we demonstrate an effort to better understand and determine priorities for the management of an endangered plant (‘Ihi makole or Portulaca sclerocarpa) in the face of rapid and extreme environmental change. Volcanic heat emissions and biological invasions have anecdotally been suggested as possible threats to the species. We integrated P. sclerocarpa outplanting with efforts to collect geological and ecological data to gauge the role of elevated soil temperatures and invasive grasses in driving P. sclerocarpa mortality and population decline. We measured soil temperature, soil depth, surrounding cover and P. sclerocarpa survivorship over three decades. The abundance of wild P. sclerocarpa decreased by 99.7% from the 1990s to 2021. Only 51% of outplantings persisted through 3–4 years. Binomial regression and structural equation modelling revealed that, among the variables we analysed, high soil temperatures were most strongly associated with population decline. Finding the niche where soil temperatures are low enough to allow P. sclerocarpa survival but high enough to limit other agents of P. sclerocarpa mortality may be necessary to increase population growth of this species.

Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.

Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:

1. – high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;

2. – putative fossils on Mars will likely be ambiguous biomarkers for life;

3. – microbial contamination resulting from human habitation is unavoidable; and

4. – based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.

Some of the outstanding questions are:

1. – which interpretation of the hemispheric dichotomy of the planet is correct;

2. – to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;

3. – in what abundance are carbonates formed by atmospheric processes;

4. – what properties of martian meteorites could be used to constrain their source locations;

5. – the origin(s) of organic macromolecules;

6. – was/is Mars inhabited;

7. – how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;

8. – how can we ensure that humans and microbes form a stable and benign biosphere; and

9. – should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?

Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.

The leopard Panthera pardus is in range-wide decline, and many populations are highly threatened. Prey depletion is a major cause of global carnivore declines, but the response of leopard survival and density to this threat is unclear: by reducing the density of a dominant competitor (the lion Panthera leo) prey depletion could create both costs and benefits for subordinate competitors. We used capture–recapture models fitted to data from a 7-year camera-trap study in Kafue National Park, Zambia, to obtain baseline estimates of leopard population density and sex-specific apparent survival rates. Kafue is affected by prey depletion, and densities of large herbivores preferred by lions have declined more than the densities of smaller herbivores preferred by leopards. Lion density is consequently low. Estimates of leopard density were comparable to ecosystems with more intensive protection and favourable prey densities. However, our study site is located in an area with good ecological conditions and high levels of protection relative to other portions of the ecosystem, so extrapolating our estimates across the Park or into adjacent Game Management Areas would not be valid. Our results show that leopard density and survival within north-central Kafue remain good despite prey depletion, perhaps because (1) prey depletion has had weaker effects on preferred leopard prey compared to larger prey preferred by lions, and (2) the density of dominant competitors is consequently low. Our results show that the effects of prey depletion can be more complex than uniform decline of all large carnivore species, and warrant further investigation.

Our objective was to determine the content of the bioactive protein osteopontin (OPN) in bovine milk and identify factors influencing its concentration. OPN is expressed in many tissues and body fluids, with by far the highest concentrations in milk. OPN plays a role in immunological and developmental processes and it has been associated with several milk production traits and lactation persistency in cows. In the present study, we report the development of an enzyme linked immunosorbent assay (ELISA) for measurement of OPN in bovine milk. The method was used to determine the concentration of OPN in milk from 661 individual Danish Holstein cows. The median OPN level was determined to 21.9 mg/l with a pronounced level of individual variation ranging from 0.4 mg/l to 67.8 mg/l. Breeding for increased OPN in cow's milk is of significant interest, however, the heritability of OPN in milk was found to be relatively low, with an estimated value of 0.19 in the current dataset. The variation explained by the herd was also found to be low suggesting that OPN levels are not affected by farm management or feeding. Interestingly, the concentration of OPN was found to increase with days in milk and to decrease with parity.

This paper deals with the problem of navigating semi-autonomous mobile robots without global localization systems in unknown environments. We propose a planning-based obstacle avoidance strategy that relies on local maps and a series of short-time coordinate frames. With this approach, simple odometry and range information are sufficient to make the robot to safely follow the user commands. Different from reactive obstacle avoidance strategies, the proposed approach chooses a good and smooth local path for the robot. The methodology is evaluated using a mobile service robot moving in an unknown corridor environment populated with obstacles and people.