The organization of human brain networks can be measured by capturing correlated brain activity with fMRI. There is considerable interest in understanding how brain networks vary across individuals ...or neuropsychiatric populations or are altered during the performance of specific behaviors. However, the plausibility and validity of such measurements is dependent on the extent to which functional networks are stable over time or are state dependent. We analyzed data from nine high-quality, highly sampled individuals to parse the magnitude and anatomical distribution of network variability across subjects, sessions, and tasks. Critically, we find that functional networks are dominated by common organizational principles and stable individual features, with substantially more modest contributions from task-state and day-to-day variability. Sources of variation were differentially distributed across the brain and differentially linked to intrinsic and task-evoked sources. We conclude that functional networks are suited to measuring stable individual characteristics, suggesting utility in personalized medicine.
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•Functional networks are dominated by common group and stable individual features•Task state only modestly influences brain networks, largely varying by individual•With substantial data, day-to-day variability is minimal•Variance sources show distinct topography and links to intrinsic and evoked factors
Gratton et al. comprehensively measure individual, day-to-day, and task variance in functional brain networks, revealing that networks are dominated by stable individual factors, not cognitive content. These findings suggest utility of functional network measurements in personalized medicine.
The basal ganglia, thalamus, and cerebral cortex form an interconnected network implicated in many neurological and psychiatric illnesses. A better understanding of cortico-subcortical circuits in ...individuals will aid in development of personalized treatments. Using precision functional mapping—individual-specific analysis of highly sampled human participants—we investigated individual-specific functional connectivity between subcortical structures and cortical functional networks. This approach revealed distinct subcortical zones of network specificity and multi-network integration. Integration zones were systematic, with convergence of cingulo-opercular control and somatomotor networks in the ventral intermediate thalamus (motor integration zones), dorsal attention and visual networks in the pulvinar, and default mode and multiple control networks in the caudate nucleus. The motor integration zones were present in every individual and correspond to consistently successful sites of deep brain stimulation (DBS; essential tremor). Individually variable subcortical zones correspond to DBS sites with less consistent treatment effects, highlighting the importance of PFM for neurosurgery, neurology, and psychiatry.
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•Precision functional mapping identifies subcortical integration zones in individuals•Systematic connectivity reveals motor, cognitive, and visual attention integration zones•Subcortical functional organization has individually variable and conserved features•Integration zones map onto variably effective DBS sites, suggesting clinical utility
Individual functional mapping of the human subcortex revealed network integration zones (motor, cognitive, visual attention) that were variable and consistent across people. These individualized maps of cortico-subcortical circuits may have immediate clinical translation for invasive personalized treatments (e.g., deep brain stimulation).
Measles virus is directly responsible for more than 100,000 deaths yearly. Epidemiological studies have associated measles with increased morbidity and mortality for years after infection, but the ...reasons why are poorly understood. Measles virus infects immune cells, causing acute immune suppression. To identify and quantify long-term effects of measles on the immune system, we used VirScan, an assay that tracks antibodies to thousands of pathogen epitopes in blood. We studied 77 unvaccinated children before and 2 months after natural measles virus infection. Measles caused elimination of 11 to 73% of the antibody repertoire across individuals. Recovery of antibodies was detected after natural reexposure to pathogens. Notably, these immune system effects were not observed in infants vaccinated against MMR (measles, mumps, and rubella), but were confirmed in measles-infected macaques. The reduction in humoral immune memory after measles infection generates potential vulnerability to future infections, underscoring the need for widespread vaccination.
Extravaginal torsion (EVT) is a rare type of testicular torsion that usually occurs in neonates. The primary type of testicular torsion that occurs in adolescents is intravaginal torsion. In this ...case report, we describe the first case of EVT reported in a 16-year-old male with a contralateral bell clapper deformity and subsequent surgical management using a tunica vaginalis flap and bilateral orchiopexy. In discussion of this case, we examine possible anatomical causes of EVT and suggestions for appropriate surgical management.
Measles virus (MV) is a highly contagious member of the Morbillivirus genus that remains a major cause of childhood mortality worldwide. Although infection induces a strong MV-specific immune ...response that clears viral load and confers lifelong immunity, transient immunosuppression can also occur, leaving the host vulnerable to colonization from secondary pathogens. This apparent contradiction of viral clearance in the face of immunosuppression underlies what is often referred to as the 'measles paradox', and remains poorly understood. To explore the mechanistic basis underlying the measles paradox, and identify key factors driving viral clearance, we return to a previously published dataset of MV infection in rhesus macaques. These data include virological and immunological information that enable us to fit a mathematical model describing how the virus interacts with the host immune system. In particular, our model incorporates target cell depletion through infection of host immune cells-a hallmark of MV pathology that has been neglected from previous models. We find the model captures the data well, and that both target cell depletion and immune activation are required to explain the overall dynamics. Furthermore, by simulating conditions of increased target cell availability and suppressed cellular immunity, we show that the latter causes greater increases in viral load and delays to MV clearance. Overall, this signals a more dominant role for cellular immunity in resolving acute MV infection. Interestingly, we find contrasting dynamics dominated by target cell depletion when viral fitness is increased. This may have wider implications for animal morbilliviruses, such as canine distemper virus (CDV), that cause fatal target cell depletion in their natural hosts. To our knowledge this work represents the first fully calibrated within-host model of MV dynamics and, more broadly, provides a new platform from which to explore the complex mechanisms underlying Morbillivirus infection.
Progressive supranuclear palsy (PSP) is a rare neurodegenerative brain disease with rapid progression and currently limited treatment options. A comprehensive understanding of disease progression, ...management, and healthcare resource utilization is limited, and further research is challenging due to the small population of patients. To address these challenges in conducting PSP research, individuals with PSP were recruited using a multichannel approach tailored specifically to the PSP community. We performed a retrospective observational study using data abstracted from participant medical records collected from multiple patient care centers.
Seventy-two individuals with PSP were eligible for inclusion. On average, 144 medical documents per participant were collected from an average of 2.9 healthcare centers per participant, with a mean study period of 7.9 years. Among participants with a date of symptom onset documented in the medical records, the median time for the onset of the first fall was 2.0 years (IQR 3.2) before diagnosis, the median onset of unsteady gait or gait impairment was 1.2 years (IQR 1.8) before diagnosis, and the median onset of mobility problems was 0.8 years (IQR 1.8) before diagnosis. The most widely utilized healthcare resources, with at least 85% of participants using each of these resources at some point during the disease course, were medications (100%), imaging (99%), assistive devices (90%), supportive care (86%), and surgeries and procedures (85%).
This retrospective study adds to the current understanding of PSP symptoms, comorbidities, and healthcare resource utilization (HRU) across the disease journey. By involving individuals with PSP and their caregivers or legally authorized representatives in the research process, this study was unique in its approach to participant recruitment and enabled individuals to participate in research without the need for travel. We collected medical documents from multiple healthcare centers, allowing for broad data collection covering the entire disease journey. This approach to the collection of real-world data may be used to generate valuable insights into many aspects of disease progression and management in PSP and many other rare diseases.
•Optimization models for pollution reducing activities for the Chesapeake Bay.•Nonlinear and approximate linear optimization models developed and analyzed.•Low divergence between linear model and ...nonlinear model for optimal solutions.•Propose and test strategies to restrict problem size of linear model.•Restrictions provide high quality solutions to a variety of problem instances.
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Implementing management practices in a cost-efficient manner is critical for regional efforts to reduce the amount of pollutants entering the Chesapeake Bay. We study the problem of selecting a subset of practices that minimizes pollutant load—subject to budgetary and environmental constraints—as simulated in a widely used regulatory watershed model. Mimicking the computation of pollutant load in the regulatory model, we formulate this problem as a continuous optimization model with a linear multiplicative objective function and linear constraints. To lay the groundwork for incorporating additional stakeholder requirements in the future, especially those that would require integer variables, we present and study a continuous linear optimization model that approximates the nonlinear model. The linear model, which requires an exponential number of variables, arises naturally as an alternative model for the same underlying physical process. We examine the theoretical behavior of these optimization models and investigate restrictions of the linear model to handle its large number of variables. Through extensive computational tests on real and randomly generated instances, we demonstrate that the linear model and its restrictions provide optimal solutions close to those of the nonlinear model in practice, despite poor approximation properties in the worst case. We conclude that the linear model—together with our approach to handling its large number of variables—provides a viable framework from which to extend the optimization model to better meet the needs of the Chesapeake Bay watershed management stakeholders.
Not All Nitrogen Is Created Equal BOWEN, JENNIFER L.; GIBLIN, ANNE E.; MURPHY, ANNA E. ...
BioScience/Bioscience,
12/2020, Letnik:
70, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Excess reactive nitrogen (N) flows from agricultural, suburban, and urban systems to coasts, where it causes eutrophication. Coastal wetlands take up some of this N, thereby ameliorating the impacts ...on nearshore waters. Although the consequences of N on coastal wetlands have been extensively studied, the effect of the specific form of N is not often considered. Both oxidized N forms (nitrate, NO₃⁻) and reduced forms (ammonium, NH₄⁺) can relieve nutrient limitation and increase primary production. However, unlike NH₄⁺, NO₃⁻ can also be used as an electron acceptor for microbial respiration. We present results demonstrating that, in salt marshes, microbes use NO₃⁻ to support organic matter decomposition and primary production is less stimulated than when enriched with reduced N. Understanding how different forms of N mediate the balance between primary production and decomposition is essential for managing coastal wetlands as N enrichment and sea level rise continue to assail our coasts.
...elicitation of bNabs is a major goal for an efficacious HIV vaccine. An HIV vaccine administered at birth with successive boosting during infancy will induce anti-HIV neutralizing and ...non-neutralizing antibody responses and HIV-specific cellular immunity that will reduce the risk of HIV infection via breastfeeding. ...immunization started at birth and boosted during infancy, childhood and preadolescence will provide those neutralizing antibodies sufficient time to mature, undergo extensive affinity maturation, and SHM and enhance their breadth and strength prior to sexual debut. ...it is increasingly recognized that qualitative and quantitative differences between infant and adult immune system are critical for the adaptation of early-life immune system to the ex utero environment reviewed in 16. ...the concept of vaccination at birth to protect through infancy and adolescence was highlighted by a study demonstrating that immunization of neonatal rhesus macaques (RM) with poxvirus-based SIV vaccines early after birth provided partial protection against multiple low-dose SIV challenges not only during infancy but also during adolescence 20.
Measles is an acute viral disease associated both with immune suppression and development of life-long immunity. Clearance of measles virus (MeV) involves rapid elimination of infectious virus during ...the rash followed by slow elimination of viral RNA. To characterize cellular immune responses during recovery, we analyzed the appearance, specificity and function of MeV-specific T cells for 6 months after respiratory infection of rhesus macaques with wild type MeV. IFN-γ and IL-17-producing cells specific for the hemagglutinin and nucleocapsid proteins appeared in circulation in multiple waves approximately 2-3, 8 and 18-24 weeks after infection. IFN-γ-secreting cells were most abundant early and IL-17-secreting cells late. Both CD4
and CD8
T cells were sources of IFN-γ and IL-17, and IL-17-producing cells expressed RORγt. Therefore, the cellular immune response evolves during MeV clearance to produce functionally distinct subsets of MeV-specific CD4
and CD8
T cells at different times after infection.
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