Local impact of perivascular plaques on cerebral blood flow dynamics in a transgenic mouse model of Alzheimer's disease.

Cerebrovascular pathology is closely coupled to cognitive function decline, as indicated by numerous studies at the system level. To better understand the mechanisms of this cognitive decline it is important to resolve how pathological changes in the vasculature - such as perivascular plaques - affect local cerebral blood flow dynamics. This issue is ideally studied in the intact brain at very high spatial resolution. Here, we describe initial results obtained by an approach based on in vivo observation by multi-photon microscopy of vascular plaques and local blood flow measurements in a transgenic mouse model engineered to express the human amyloid precursor protein with the Swedish and Arctic mutations. These mice exhibit a striking abundance of perivascular plaques in the cerebral cortex and are well suited to investigate vascular pathology in Alzheimer's disease

Fair domestic allocation of monkeypox virus countermeasures

Countermeasures for mpox (formerly known as monkeypox), primarily vaccines, have been in limited supply in many countries during outbreaks. Equitable allocation of scarce resources during public health emergencies is a complex challenge. Identifying the objectives and core values for the allocation of mpox countermeasures, using those values to provide guidance for priority groups and prioritisation tiers, and optimising allocation implementation are important. The fundamental values for the allocation of mpox countermeasures are: preventing death and illness; reducing the association between death or illness and unjust disparities; prioritising those who prevent harm or mitigate disparities; recognising contributions to combating an outbreak; and treating similar individuals similarly. Ethically and equitably marshalling available countermeasures requires articulating these fundamental objectives, identifying priority tiers, and recognising trade-offs between prioritising the people at the highest risk of infection and the people at the highest risk of harm if infected. These five values can provide guidance on preferable priority categories for a more ethically sound response and suggest methods for optimising allocation of countermeasures for mpox and other diseases for which countermeasures are in short supply. Properly marshalling available countermeasures will be crucial for future effective and equitable national responses to outbreaks

Developments in cell biology for quantitative immunoelectron microscopy based on thin sections: a review

Quantitative immunoelectron microscopy uses ultrathin sections and gold particle labelling to determine distributions of molecules across cell compartments. Here, we review a portfolio of new methods for comparing labelling distributions between different compartments in one study group (method 1) and between the same compartments in two or more groups (method 2). Specimen samples are selected unbiasedly and then observed and expected distributions of gold particles are estimated and compared by appropriate statistical procedures. The methods can be used to analyse gold label distributed between volume-occupying (organelle) and surface-occupying (membrane) compartments, but in method 1, membranes must be treated as organelles. With method 1, gold counts are combined with stereological estimators of compartment size to determine labelling density (LD). For volume-occupiers, LD can be expressed simply as golds per test point and, for surface-occupiers, as golds per test line intersection. Expected distributions are generated by randomly assigning gold particles to compartments and expressing observed/expected counts as a relative labelling index (RLI). Preferentially-labelled compartments are identified from their RLI values and by Chi-squared analysis of observed and expected distributions. For method 2, the raw gold particle counts distributed between compartments are simply compared across groups by contingency table and Chi-squared analysis. This identifies the main compartments responsible for the differences between group distributions. Finally, we discuss labelling efficiency (the number of gold particles per target molecule) and describe how it can be estimated for volume- or surface-occupiers by combining stereological data with biochemical determinations

An ethical framework for global vaccine allocation

In this article, we propose the Fair Priority Model for COVID-19 vaccine distribution, and emphasize three fundamental values we believe should be considered when distributing a COVID-19 vaccine among countries: Benefiting people and limiting harm, prioritizing the disadvantaged, and equal moral concern for all individuals. The Priority Model addresses these values by focusing on mitigating three types of harms caused by COVID-19: death and permanent organ damage, indirect health consequences, such as health care system strain and stress, as well as economic destruction. It proposes proceeding in three phases: the first addresses premature death, the second long-term health issues and economic harms, and the third aims to contain viral transmission fully and restore pre-pandemic activity. To those who may deem an ethical framework irrelevant because of the belief that many countries will pursue "vaccine nationalism," we argue such a framework still has broad relevance. Reasonable national partiality would permit countries to focus on vaccine distribution within their borders up until the rate of transmission is below 1, at which point there would not be sufficient vaccine-preventable harm to justify retaining a vaccine. When a government reaches the limit of national partiality, it should release vaccines for other countries. We also argue against two other recent proposals. Distributing a vaccine proportional to a country's population mistakenly assumes that equality requires treating differently situated countries identically. Prioritizing countries according to the number of front-line health care workers, the proportion of the population over 65, and the number of people with comorbidities within each country may exacerbate disadvantage and end up giving the vaccine in large part to wealthy nations

Environmental benefits of leaving offshore infrastructure in the ocean

© The Ecological Society of America The removal of thousands of structures associated with oil and gas development from the world's oceans is well underway, yet the environmental impacts of this decommissioning practice remain unknown. Similar impacts will be associated with the eventual removal of offshore wind turbines. We conducted a global survey of environmental experts to guide best decommissioning practices in the North Sea, a region with a substantial removal burden. In contrast to current regulations, 94.7% of experts (36 out of 38) agreed that a more flexible case-by-case approach to decommissioning could benefit the North Sea environment. Partial removal options were considered to deliver better environmental outcomes than complete removal for platforms, but both approaches were equally supported for wind turbines. Key considerations identified for decommissioning were biodiversity enhancement, provision of reef habitat, and protection from bottom trawling, all of which are negatively affected by complete removal. We provide recommendations to guide the revision of offshore decommissioning policy, including a temporary suspension of obligatory removal

Density‐ and size‐dependent mortality in fish early life stages

The importance of survival and growth variations early in life for population dynamics depends on the degrees of compensatory density dependence and size dependence in survival at later life stages. Quantifying density‐ and size‐dependent mortality at different juvenile stages is therefore important to understand and potentially predict the recruitment to the population. We applied a statistical state‐space modelling approach to analyse time series of abundance and mean body size of larval and juvenile fish. The focus was to identify the importance of abundance and body size for growth and survival through successive larval and juvenile age intervals, and to quantify how the dynamics propagate through the early life to influence recruitment. We thus identified both relevant ages and mechanisms (i.e. density dependence and size dependence in survival and growth) linking recruitment variability to early life dynamics. The analysis was conducted on six economically and ecologically important fish populations from cold temperate and sub‐arctic marine ecosystems. Our results underscore the importance of size for survival early in life. The comparative analysis suggests that size‐dependent mortality and density‐dependent growth frequently occur at a transition from pelagic to demersal habitats, which may be linked to competition for suitable habitat. The generality of this hypothesis warrants testing in future research.publishedVersio

Recruitment Variability in North Atlantic Cod and Match-Mismatch Dynamics

Background Fisheries exploitation, habitat destruction, and climate are important drivers of variability in recruitment success. Understanding variability in recruitment can reveal mechanisms behind widespread decline in the abundance of key species in marine and terrestrial ecosystems. For fish populations, the match-mismatch theory hypothesizes that successful recruitment is a function of the timing and duration of larval fish abundance and prey availability. However, the underlying mechanisms of match-mismatch dynamics and the factors driving spatial differences between high and low recruitment remain poorly understood. Methodology/Principal Findings We used empirical observations of larval fish abundance, a mechanistic individual-based model, and a reanalysis of ocean temperature data from 1960 to 2002 to estimate the survival of larval cod (Gadus morhua). From the model, we quantified how survival rates changed during the warmest and coldest years at four important cod spawning sites in the North Atlantic. The modeled difference in survival probability was not large for any given month between cold or warm years. However, the cumulative effect of higher growth rates and survival through the entire spawning season in warm years was substantial with 308%, 385%, 154%, and 175% increases in survival for Georges Bank, Iceland, North Sea, and Lofoten cod stocks, respectively. We also found that the importance of match-mismatch dynamics generally increased with latitude. Conclusions/Significance Our analyses indicate that a key factor for enhancing survival is the duration of the overlap between larval and prey abundance and not the actual timing of the peak abundance. During warm years, the duration of the overlap between larval fish and their prey is prolonged due to an early onset of the spring bloom. This prolonged season enhances cumulative growth and survival, leading to a greater number of large individuals with enhanced potential for survival to recruitment

Predicting the Impact of Long-Term Temperature Changes on the Epidemiology and Control of Schistosomiasis: A Mechanistic Model

, the causative agent of schistosomiasis in humans.The model showed that the impact of temperature on disease prevalence and abundance is not straightforward; the mean infection burden in humans increases up to 30°C, but then crashes at 35°C, primarily due to increased mortalities of the snail intermediate host. In addition, increased temperatures changed the dynamics of disease from stable, endemic infection to unstable, epidemic cycles at 35°C. However, the prevalence of infection was largely unchanged by increasing temperatures. Temperature increases also affected the response of the model to changes in each parameter, indicating certain control strategies may become less effective with local temperature changes. At lower temperatures, the most effective single control strategy is to target the adult parasites through chemotherapy. However, as temperatures increase, targeting the snail intermediate hosts, for example through molluscicide use, becomes more effective. will not respond to increased temperatures in a linear fashion, and the optimal control strategy is likely to change as temperatures change. It is only through a mechanistic approach, incorporating the combined effects of temperature on all stages of the life-cycle, that we can begin to predict the consequences of climate change on the incidence and severity of such diseases