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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.
Methods
We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality.
Results
Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain.
Conclusions
Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.
Background: Facial diplegia with paresthesias (FDP) is a rare Guillain-Barré Syndrome (GBS) variant, characterized by subacute onset of bilateral facial palsy with no other motor weakness, absent reflexes and distal paresthesias, that may be associated with anti-ganglioside autoantibodies. Methods: Patient chart, including medical notes, radiologic, electrophysiological and laboratory testing during the patient’s hospitalization in December 2024 were reviewed. Results: We report the case of a 24-year-old woman, who presented one-week post-partum with a history of tongue and progressive distal extremity paresthesias, headache and gait instability. During hospitalization patient progressively developed bilateral lower limbs areflexia and facial diplegia. Imaging was negative for a central cause but lumbar puncture and clinical examination guided the diagnosis of FDP. Patient responded to a course of intravenous immunoglobulins (IVIg) and was discharged home without any weakness. Conclusions: This case illustrates the rarer FDP presentation of GBS, which can be more frequent in the postpartum period, and explores the differential diagnosis of subacute facial diplegia.
Ketamine exerts potent but transient antidepressant effects in treatment-resistant depression (TRD). Combinations of ketamine and psychotherapy have attracted interest, but no trial has investigated a psychedelic model of ketamine–psychotherapy for TRD to our knowledge.
Aims
This secondary analysis of a randomised clinical trial (RCT) explores the therapeutic effects and experiential mechanisms of the Montreal Model of ketamine–psychotherapy for TRD, with or without music.
Method
A two-centre, single-blinded, RCT conducted in Montreal, Canada, between January 2021 and August 2022 (NCT04701866). Participants received ketamine–psychotherapy for TRD – six subanaesthetic infusions over 4 weeks and psychological support – with either music or matched non-music support during ketamine doses, as per random group assignments. The primary therapeutic outcome was the Montgomery–Åsberg Depression Rating Scale, assessed by blinded raters. Psychedelic-like experiences, evaluated by the Mystical Experience Questionnaire and Emotional Breakthrough Inventory, and their session-by-session relationships with depression were explored with multilevel, time-lagged covariate models with autoregressive residuals.
Results
Thirty-two participants with severe and highly comorbid TRD, including high rates of personality disorder and suicidality, received 181 ketamine infusions. Therapeutic outcomes and psychedelic experiences did not differ between music (n = 15) and non-music (n = 17) interventions. Both groups experienced significant reductions in clinician-rated and self-reported depression (d = 1.2 and d = 0.87, respectively; p < 0.001), anxiety (d = 0.8, p < 0.001) and suicidality (d = 0.4, p < 0.05) at 4 weeks, fully maintained at 8-week follow-up. Ketamine experiences were highly emotional and mystical. Converging analyses supported mystical-like ketamine experiences as mechanisms of its antidepressant effects.
Conclusions
This trial found large and notably sustained benefits of ketamine–psychotherapy for severe TRD, with or without music, and psychedelic experiences of comparable intensity to those observed with psilocybin. Mystical-like experiences may particularly contribute to ketamine’s immediate and persistent psychiatric benefits.
Outbreaks of Pseudomonas aeruginosa infections have been linked to water-related sources. We describe the investigation of a suspected outbreak of five P. aeruginosa infections in pediatric oncology patients in 2021 that triggered a retrospective review and prospective monitoring of additional cases, environmental sampling, and bacterial genomic analysis.
Setting and patients:
Pediatric oncology center.
Methods:
Medical records of patients with P. aeruginosa were reviewed and staff were interviewed to identify common exposures. Environmental samples were cultured for P. aeruginosa. Patient and environmental isolates underwent whole genome sequencing and core genome multi-locus sequence typing (cgMLST) and sequences were added to a previously existing library of P. aeruginosa clinical isolates collected in 2017 and onwards to determine strain relatedness.
Findings:
During 2019–2022, 82 patients with 110 episodes of P. aeruginosa infections were identified and 132 isolates of P. aeruginosa were sequenced. Twenty-three environmental samples were collected, of which two grew P. aeruginosa in culture. CgMLST demonstrated four multi-patient isolate clusters but no genetic relatedness among the isolates from the patients in the suspected outbreak. Two sink-derived isolates from 2021 were genetically related to patient-derived isolates from 2018 and 2017.
Conclusions:
Sequencing revealed there is no common source or linkage between the isolates of the suspected P. aeruginosa outbreak in 2021. However, it revealed genetic relatedness of previous patient strains to later strains collected from hospital sinks, suggesting persistent colonization of a reservoir with P. aeruginosa.
Ecological restoration has traditionally had a bottom-up focus on plants and vegetation, but rewilding has been the opposite, and the impacts of rewilding carnivores and large herbivores on plant species and vegetation are largely unknown. The aim of this perspective, therefore, is to clarify what rewilding means for plants and vegetation, to assess progress in achieving this, to identify research needs and to make recommendations for rewilding practice. Land-use legacies and dispersal limitation are major challenges for plant rewilding, and the slowness of vegetation recovery makes success hard to evaluate on a human timescale. On the other hand, wild vegetation develops spontaneously wherever human pressures are released, regardless of the state of the site. For plant conservation, the key issue is ensuring that all plant species that can be restored are present, including rare and threatened species. Long-term species-level monitoring and, where necessary, continued intervention should be part of all projects that aim to rewild plants and vegetation.
During the COVID-19 pandemic, virtual physician visits rapidly increased among community-dwelling older persons living with dementia (PLWD) in Ontario. Rural residents often have less access to medical care compared to their urban counterparts, and it is unclear whether access to virtual care was equitable between PLWD in urban versus rural locations.
Methods:
Using population-based health administrative data and a repeated cross-sectional study design, we identified and described community-dwelling PLWD between March 2020 and August 2022 in Ontario, Canada. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals comparing rates of virtual visits between rural and urban PLWD by key physician specialties: family physicians, neurologists and psychiatrists/geriatricians.
Results:
Of 122,751 PLWD in our cohort, 9.2% (n = 11,304) resided in rural areas. Rural PLWD were slightly younger compared to their urban counterparts (mean age = 81 vs. 82 years; standardized difference = 0.16). There were no differences across areas by sex or income quintile. In adjusted models, rates of virtual visits were significantly lower for rural compared to urban PLWD across all specialties: family physicians (RR = 0.71 [0.69–0.73]), neurologists (RR = 0.79 [0.75–0.83]) and psychiatrists/geriatricians (RR = 0.72 [0.68–0.76]).
Conclusions:
PLWD in rural areas had significantly lower rates of virtual family physician, neurologist and psychiatrist/geriatrician visits compared to urban dwellers during the study period. This finding raises important issues regarding access to primary and specialist healthcare services for rural PLWD. Future work should explore barriers to care to improve health care access among PLWD in rural communities.
These are all very practical decisions, and the methods of analyzing them make use of Principle 1:A dollar today is not worth the same as a dollar tomorrow. Economists have considered the management of personal financial resources over a lifetime to be a central issue worthy of serious study, and several Nobel Prizes in economics have been awarded for contributions in this area. And, as Box 3.1 shows, financial literacy for a nation’s people is a goal being pursued by countries all over the world.
Most financial decisions boil down to figuring out how much an asset is worth. For example, in deciding whether to invest in a security such as a stock or a bond or in a business opportunity, you have to determine whether the price being asked is high or low relative to other investment opportunities available to you. In addition to investment decisions, there are many other situations in which one needs to determine the value of an asset. For example, suppose that the tax assessor in your town has assessed your house at $500,000 for property tax purposes. Is this value too high or too low? Or suppose you and your siblings inherit some property, and you decide to sell it and share the proceeds equally among yourselves. How do you decide how much it is worth?
In the previous chapters we introduced the concept of valuation, which involved converting cash flows that are expected to happen in the future into today’s terms, and we learned about the returns on various assets and how to analyze the past performance of financial instruments to inform investment decisions. However, the future is not known for sure. The cash flows that occur may be different from what we initially expect, and the value (and rates of return) of financial instruments change over time. In this chapter, we introduce a fundamental concept in finance: Uncertainty about the future can affect valuation and decision making.
We begin by defining what risk is in finance, and how it affects financial decisions. We then dive into how risk can be managed, which includes identifying relevant risks, assessing how they can affect one’s financial situation, and then determining appropriate techniques that can be used to reduce these risks.
Before proceeding with our first steps in valuation, we need to introduce some tools and define some notation that will be used here and throughout the book when valuing assets.
At a fundamental level, the value of an asset comes from the cash flows that are associated with it—that is, from the amounts of money that the owner either receives or pays at various points in time. An essential tool in analyzing cash flows from any financial decision is a diagram known as a timeline, a linear representation of cash outflows and inflows over a period of time. A negative sign in front of a cash flow means that you are paying that amount of money (it’s a cash outflow from you). No sign means that you are receiving an amount of money (it’s a cash inflow to you).
In the last few chapters we have considered financial and strategic decisions made within companies, and whether they improve the value of the company. In this chapter we continue examining company decisions, and focus on a particular financial decision—the payout decision, which considers whether a company keeps the cash it holds or gives it back to investors. As we will show, this decision is important because firms can potentially increase their value—and benefit their investors—through their choice of whether to pay out cash to investors. Furthermore, as we discussed in the previous chapter, agency problems may arise when companies hold onto large amounts of cash due to managerial conflicts of interest. Thus, payout can serve an important role in corporate governance.
In previous chapters we explored how to calculate the value of a company, given decisions that it had already made. In subsequent chapters we then focused on decisions that a manager within a company could make, and how they affect company value, such as project investment decisions. In this chapter we continue to examine decisions made by companies, and focus on a particularly important decision—the financing decision. Capital structure is the mix of financing sources that a firm uses to fund its operations, growth, and investment projects. A firm may choose to use internal funding from operations, or use external funding from issuing debt (bonds) or equity (stock), or other financing instruments.