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Changes in Adult Alcohol Use and Consequences During the COVID-19 Pandemic in the US
This survey study examines individual-level changes in alcohol use in US adults and associated negative consequences, from before to during the coronavirus disease 2019 (COVID-19) pandemic.
Journal Article
Austerity and political choice in Britain
This is a comprehensive study of the 2015 general election in Britain designed not only for students and scholars of British politics, but also for the interested reader. It looks at the record of the Coalition government both in terms of its plans and performance, particularly in relation to the economy, as the starting point for understanding what happened. The authors go on to examine the campaign during the run-up to polling day and to explain why people voted the way they did. They also take a close look at the various constituency battlegrounds across the country showing how and why voting patterns varied across Britain. Finally, they discuss the implications of the election outcome for the future of the party system and British politics more generally. This book provides important insights into an election which has permanently changed the political geography of Britain.
Book
From Volume To Value: Better Ways To Pay For Health Care
Payment systems for health care today are based on rewarding volume, not value for the money spent. Two proposed methods of payment, \"episode-of-care payment\" and \"comprehensive care payment\" (condition-adjusted capitation), could facilitate higher quality and lower cost by avoiding the problems of both fee-for-service payment and traditional capitation. The most appropriate payment systems for different types of patient conditions and some methods of addressing design and implementation issues are discussed. Although the new payment systems are desirable, many providers are not organized to accept or use them, so transitional approaches such as \"virtual bundling,\" described in this paper, will be needed. [PUBLICATION ABSTRACT]
Journal Article
mGluR5 is transiently confined in perisynaptic nanodomains to shape synaptic function
The unique perisynaptic distribution of postsynaptic metabotropic glutamate receptors (mGluRs) at excitatory synapses is predicted to directly shape synaptic function, but mechanistic insight into how this distribution is regulated and impacts synaptic signaling is lacking. We used live-cell and super-resolution imaging approaches, and developed molecular tools to resolve and acutely manipulate the dynamic nanoscale distribution of mGluR5. Here we show that mGluR5 is dynamically organized in perisynaptic nanodomains that localize close to, but not in the synapse. The C-terminal domain of mGluR5 critically controlled perisynaptic confinement and prevented synaptic entry. We developed an inducible interaction system to overcome synaptic exclusion of mGluR5 and investigate the impact on synaptic function. We found that mGluR5 recruitment to the synapse acutely increased synaptic calcium responses. Altogether, we propose that transient confinement of mGluR5 in perisynaptic nanodomains allows flexible modulation of synaptic function.
The subsynaptic organization of group I mGluRs modulates their activation and downstream signaling, essential for synaptic transmission and plasticity. Here, the authors describe how the C-terminal domain of mGluR5 controls its dynamic organization in perisynaptic nanodomains, and prevents mGluR5 form entering the synapse, allowing mGluR5 to finely tune synaptic signalling.
Journal Article
Who has mental health problems? Comparing individual, social and psychiatric constructions of mental health
Purpose
The persistent gap between population indicators of poor mental health and the uptake of services raises questions about similarities and differences between social and medical/psychiatric constructions. Rarely do studies have assessments from different perspectives to examine whether and how lay individuals and professionals diverge.
Methods
Data from the Person-to-Person Health Interview Study (P2P), a representative U.S. state sample (N ~ 2700) are used to examine the overlap and correlates of three diverse perspectives—self-reported mental health, a self/other problem recognition, and the CAT-MH™ a validated, computer adaptive test for psychopathology screening. Descriptive and multinominal logit analyses compare the presence of mental health problems across stakeholders and their association with respondents’ sociodemographic characteristics.
Results
Analyses reveal a set of socially constructed patterns. Two convergent patterns indicate whether there is (6.9%, The “Sick”) or is not (64.6%, The “Well”) a problem. The “Unmet Needers” (8.7%) indicates that neither respondents nor those around them recognize a problem identified by the screener. Two patterns indicate clinical need where either respondents (The “Self Deniers”, 2.9%) or others (The “Network Deniers”, 6.0%) do not. Patterns where the diagnostic indicator does not suggest a problem include The “Worried Well” (4.9%) where only the respondent does, The “Network Coerced” (4.6%) where only others do, and The “Prodromal” (1.4%) where both self and others do. Education, gender, race, and age are associated with social constructions of mental health problems.
Conclusions
The implications of these results hold the potential to improve our understanding of unmet need, mental health literacy, stigma, and treatment resistance.
Journal Article
A trans-synaptic nanocolumn aligns neurotransmitter release to receptors
Synaptic vesicle fusion, as evoked by action potentials, is confined to presynaptic protein nanoclusters, which are closely aligned with concentrated postsynaptic receptors and their scaffolding proteins—an organization termed a ‘nanocolumn’.
Molecular organization in a single synapse
Efficient neurotransmission has long been suspected to require precise alignment between pre-synaptic vesicle release sites and post-synaptic receptors, but direct observations have been hampered by the physics of light-microscopy. Thomas Blanpied and colleagues use hyper-resolution microscopy — which overcomes the diffraction barrier — to reveal that vesicular fusion at single synapses, as evoked by action potentials, is confined to pre-synaptic protein nanoclusters. The nanoclusters are closely aligned with concentrated post-synaptic receptors and their scaffolding proteins. The resulting molecular 'nanocolumns' are reorganized during NMDA receptor-dependent plasticity, and the authors suggest that they may contribute to the maintenance and regulation of synaptic efficiency.
Synaptic transmission is maintained by a delicate, sub-synaptic molecular architecture, and even mild alterations in synapse structure drive functional changes during experience-dependent plasticity and pathological disorders
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. Key to this architecture is how the distribution of presynaptic vesicle fusion sites corresponds to the position of receptors in the postsynaptic density. However, while it has long been recognized that this spatial relationship modulates synaptic strength
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, it has not been precisely described, owing in part to the limited resolution of light microscopy. Using localization microscopy, here we show that key proteins mediating vesicle priming and fusion are mutually co-enriched within nanometre-scale subregions of the presynaptic active zone. Through development of a new method to map vesicle fusion positions within single synapses in cultured rat hippocampal neurons, we find that action-potential-evoked fusion is guided by this protein gradient and occurs preferentially in confined areas with higher local density of Rab3-interacting molecule (RIM) within the active zones. These presynaptic RIM nanoclusters closely align with concentrated postsynaptic receptors and scaffolding proteins
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, suggesting the existence of a trans-synaptic molecular ‘nanocolumn’. Thus, we propose that the nanoarchitecture of the active zone directs action-potential-evoked vesicle fusion to occur preferentially at sites directly opposing postsynaptic receptor–scaffold ensembles. Remarkably, NMDA receptor activation triggered distinct phases of plasticity in which postsynaptic reorganization was followed by trans-synaptic nanoscale realignment. This architecture suggests a simple organizational principle of central nervous system synapses to maintain and modulate synaptic efficiency.
Journal Article