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Objectives/Goals: The second highest fear of the aging population is cognitive decline. Diet is associated with brain aging; therefore, the objective is to determine the effects of a Western diet (WD) on cognitive decline and the efficacy of a Mediterranean diet (MeDi) fecal microbiota transplant (FMT) in WD-induced cognitive deficit progression in aged rats. Methods/Study Population: For Study 1, 12-month-old Fischer344 rats (NIA Aging Colony) will be randomly assigned to a WD, MeDi, or control (positive control) for 6 or 12 months. Microbiota composition, blood pressure, and body composition (DXA Scan) will be longitudinally assessed. Groups will undergo a battery of neurobehavioral assessments to measure cognitive performance. At the end of the study, mitochondria bioenergetic assays in isolated cerebral microvessels will be used to determine changes in cerebrovascular function. For Study 2, 18-month-old Fischer344 rats (NIA Aging Colony) will be randomly assigned to a WD, MeDi, or control for 6 months. At month 4, the WD+ MeDi-FMT group will receive once weekly MeDi-FMT for two months. Assessments will be performed as described in Study 1. Results/Anticipated Results: It is anticipated that the WD-related gut dysbiosis will increase blood pressure, fat-free mass, neurovascular dysfunction, and induce cognitive impairment relative to a MeDi. When using a MeDi-FMT as an intervention, it is anticipated that there will be measurable improvements in cognitive function relative to a WD through the regulation of gut dysbiosis, blood pressure, fat-free mass, and neurovascular dysfunction. Discussion/Significance of Impact: These results are expected to have an important positive impact because they will provide insights into the WD-induced gut dysbiosis-associated cognitive impairments, and evaluate the roles and mechanisms of MeDi-FMT in the therapeutic intervention of aged rats.
Objectives/Goals: The timing of neurosurgery is highly variable for post-hemorrhagic hydrocephalus (PHH) of prematurity. We sought to utilize microvascular imaging (MVI) in ultrasound (US) to identify biomarkers to discern the opportune time for intervention and to analyze the cerebrospinal fluid (CSF) characteristics as they pertain to neurosurgical outcome. Methods/Study Population: The inclusion criteria for the study are admission to the neonatal intensive care unit (NICU) with a diagnosis of Papile grade III or IV. Exclusion criteria are congenital hydrocephalus and hydrocephalus secondary to myelomeningocele/brain tumor/vascular malformation. We are a level IV tertiary referral center. Our current clinical care pathway utilizes brain US at admission and at weekly intervals. Patients who meet certain clinical and radiographic parameters undergo temporary or permanent CSF diversion. Results/Anticipated Results: NEL was implemented at our institution for PHH of prematurity in fall 2022. To date, we have had 20 patients who were diagnosed with grade III or IV IVH, of which 12 qualified for NEL. Our preliminary safety and feasibility results as well as the innovative bedside technique pioneered at our institution are currently in revision stages for publication. Preliminary results of the MVI data have yielded that hyperemia may confer venous congestion in the germinal matrix, which should then alert the neurosurgeon to delay any intervention to avoid progression of intraventricular blood. With regard to CSF characteristics, we anticipate that protein, cell count, hemoglobin, iron, and ferritin will decrease with NEL. Discussion/Significance of Impact: The timing of PHH of prematurity is highly variable. We expect that MVI will offer radiographic biomarkers to guide optimal timing of neurosurgical intervention. A better understanding of CSF characteristics could potentially educate the neurosurgeon with regard to optimal timing of permanent CSF diversion based on specific CSF parameters.
The fossil record of dinosaurs in Scotland mostly comprises isolated highly fragmentary bones from the Great Estuarine Group in the Inner Hebrides (Bajocian–Bathonian). Here we report the first definite dinosaur body fossil ever found in Scotland (historically), having been discovered in 1973, but not collected until 45 years later. It is the first and most complete partial dinosaur skeleton currently known from Scotland. NMS G.2023.19.1 was recovered from a challenging foreshore location in the Isle of Skye, and transported to harbour in a semi-rigid inflatable boat towed by a motor boat. After manual preparation, micro-CT scanning was carried out, but this did not aid in identification. Among many unidentifiable elements, a neural arch, two ribs and part of the ilium are described herein, and their features indicate that this was a cerapodan or ornithopod dinosaur. Histological thin sections of one of the ribs support this identification, indicating an individual at least eight years of age, growing slowly at the time of death. If ornithopodan, as our data suggest, it could represent the world's oldest body fossil of this clade.
Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.
Methods
Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.
Results
k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.
Conclusions
Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.
Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.
Aims
To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.
Method
The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).
Results
In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).
Conclusion
Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.
This study aimed to understand the current landscape of USA-based disaster medicine (DM) programs through the lens of alumni and program directors (PDs). The data obtained from this study will provide valuable information to future learners as they ponder careers in disaster medicine and allow PDs to refine curricular offerings.
Methods
Two separate surveys were sent to USA-based DM program directors and alumni. The surveys gathered information regarding current training characteristics, career trajectories, and the outlook of DM training.
Results
The study had a 57% response rate among PDs, and 42% response rate from alumni. Most programs are 1-year and accept 1-2 fellows per class. More than 60% of the programs offer additional advanced degrees. Half of the respondents accept international medical graduates (IMGs). Only 25% accept non-MD/DO/MBBs trained applicants. Most of the alumni hold academic and governmental positions post-training. Furthermore, many alumni report that fellowship training offered an advantage in the job market and allowed them to expand their clinical practice.
Conclusions
The field of disaster medicine is continuously evolving owing to the increased recognition of the important roles DM specialists play in healthcare. The fellowship training programs are experiencing a similar evolution with an increasing trend toward standardization. Furthermore, graduates from these programs see their training as a worthwhile investment in career opportunities.
To understand healthcare workers’ (HCWs) beliefs and practices toward blood culture (BCx) use.
Design:
Cross-sectional electronic survey and semi-structured interviews.
Setting:
Academic hospitals in the United States.
Participants:
HCWs involved in BCx ordering and collection in adult intensive care units (ICU) and wards.
Methods:
We administered an anonymous electronic survey to HCWs and conducted semi-structured interviews with unit staff and quality improvement (QI) leaders in these institutions to understand their perspectives regarding BCx stewardship between February and November 2023.
Results:
Of 314 HCWs who responded to the survey, most (67.4%) were physicians and were involved in BCx ordering (82.3%). Most survey respondents reported that clinicians had a low threshold to culture patients for fever (84.4%) and agreed they could safely reduce the number of BCx obtained in their units (65%). However, only half of them believed BCx was overused. Although most made BCx decisions as a team (74.1%), a minority reported these team discussions occurred daily (42.4%). A third of respondents reported not usually collecting the correct volume per BCx bottle, half were unaware of the improved sensitivity of 2 BCx sets, and most were unsure of the nationally recommended BCx contamination threshold (87.5%). Knowledge regarding the utility of BCx for common infections was limited.
Conclusions:
HCWs’ understanding of best collection practices and yield of BCx was limited.
Several organizations including the Environmental Protection Agency, World Health Organization and American Academy of Pediatrics recommend that hospital sound levels not exceed 45 decibels. Yet, several studies across multiple age groups have observed higher than recommended levels in the intensive care setting. Elevated sound levels in hospitals have been associated with disturbances in sleep, patient discomfort, delayed recovery, and delirium.
Methods:
We measured sound levels in a pediatric cardiac intensive care unit and collected vital signs data, sedation dosing and delirium scores. During a 5-week study period, sound levels for 68 patients in 22 private and 4 semi-private rooms were monitored.
Results:
Sound levels were consistently above stated recommendations with an average daytime level of 50.6 decibels (maximum, 76.9 decibels) and an average nighttime level of 49.5 decibels (maximum, 69.6 decibels). An increase in average and maximum sound levels increased the probability of sedation administration the following hour (p-value < 0.001 and 0.01, respectively) and was predictive of an increase in heart rate and blood pressure (p-value < 0.001).
Conclusion:
Sound levels in the CICU were consistently higher than recommended. An increase in heart rate, blood pressure and sedation utilization may suggest a stress response to persistent and sudden loud sounds. Given known negative impacts of excessive noise on stress, sleep, and brain development, as well as the similar adverse effects from the related use of sedative medications, reducing excessive and sudden noise may provide an opportunity to improve short- and long-term hemodynamic and neurodevelopmental outcomes in the pediatric cardiac intensive care unit.
Involuntary celibates (“incels”) are men who desire romantic or sexual partners but purportedly cannot attain them. Their ideology – the Blackpill – holds that their exclusion from successful romantic and sexual relationships is due almost entirely to their relative unattractiveness. Furthermore, the consequences of being an unattractive man bleed over into other aspects of their lives, marring their interpersonal relationships, job prospects, and overall well-being. Blaming women as the chief architects of their unhappiness, incels sometimes commit mass acts of violent retribution. In this chapter, we explicate the incel ideology; explore the interrelated phenomena of social exclusion, self-verification, and identity fusion among incels; describe who incels are; and provide a framework for de-fusing incels from the group.
Since the turn of the century, astronomers have been exploiting the rich information afforded by combining stellar kinematic maps and imaging in an attempt to recover the intrinsic, three-dimensional (3D) shape of a galaxy. A common intrinsic shape recovery method relies on an expected monotonic relationship between the intrinsic misalignment of the kinematic and morphological axes and the triaxiality parameter. Recent studies have, however, cast doubt about underlying assumptions relating shape and intrinsic kinematic misalignment. In this work, we aim to recover the 3D shape of individual galaxies using their projected stellar kinematic and flux distributions using a supervised machine learning approach with mixture density network (MDN). Using a mock dataset of the EAGLE hydrodynamical cosmological simulation, we train the MDN model for a carefully selected set of common kinematic and photometric parameters. Compared to previous methods, we demonstrate potential improvements achieved with the MDN model to retrieve the 3D galaxy shape along with the uncertainties, especially for prolate and triaxial systems. We make specific recommendations for recovering galaxy intrinsic shapes relevant for current and future integral field spectroscopic galaxy surveys.
Auditory system plasticity is a promising target for neuromodulation, cognitive rehabilitation and therapeutic development in schizophrenia (SZ). Auditory-based targeted cognitive training (TCT) is a ‘bottom up’ intervention designed to enhance the speed and accuracy of auditory information processing, which has been shown to improve neurocognition in certain SZ patients. However, the dynamics of TCT learning as a function of training exercises and their impact on neurocognitive functioning and therapeutic outcomes are unknown.
Methods
Forty subjects (SZ, n = 21; healthy subjects (HS), n = 19) underwent comprehensive clinical, cognitive, and auditory assessments, including measurements of auditory processing speed (APS) at baseline and after 1-h of TCT. SZ patients additionally completed 30-hours of TCT and repeated assessments ~10–12 weeks later.
Results
SZ patients were deficient in APS at baseline (d = 0.96, p < 0.005) relative to HS. After 1-h of TCT, analyses revealed significant main effects of diagnosis (d = 1.75, p = 0.002) and time (d = 1.04, p < 0.001), and a diagnosis × time interaction (d = 0.85, p = 0.02) on APS. APS learning effects were robust after 1-h in SZ patients (d = 1.47, p < 0.001) and persisted throughout the 30-h of training. Baseline APS was associated with verbal learning gains after 30-h of TCT (r = 0.51, p = 0.02) in SZ.
Conclusions
TCT learning metrics may have prognostic utility and aid in the prospective identification of individuals likely to benefit from TCT. Future experimental medicine studies may advance predictive algorithms that enhance TCT-related clinical, cognitive and functional outcomes.
To evaluate the economic costs of reducing the University of Virginia Hospital’s present “3-negative” policy, which continues methicillin-resistant Staphylococcus aureus (MRSA) contact precautions until patients receive 3 consecutive negative test results, to either 2 or 1 negative.
Design:
Cost-effective analysis.
Settings:
The University of Virginia Hospital.
Patients:
The study included data from 41,216 patients from 2015 to 2019.
Methods:
We developed a model for MRSA transmission in the University of Virginia Hospital, accounting for both environmental contamination and interactions between patients and providers, which were derived from electronic health record (EHR) data. The model was fit to MRSA incidence over the study period under the current 3-negative clearance policy. A counterfactual simulation was used to estimate outcomes and costs for 2- and 1-negative policies compared with the current 3-negative policy.
Results:
Our findings suggest that 2-negative and 1-negative policies would have led to 6 (95% CI, −30 to 44; P < .001) and 17 (95% CI, −23 to 59; −10.1% to 25.8%; P < .001) more MRSA cases, respectively, at the hospital over the study period. Overall, the 1-negative policy has statistically significantly lower costs ($628,452; 95% CI, $513,592–$752,148) annually (P < .001) in US dollars, inflation-adjusted for 2023) than the 2-negative policy ($687,946; 95% CI, $562,522–$812,662) and 3-negative ($702,823; 95% CI, $577,277–$846,605).
Conclusions:
A single negative MRSA nares PCR test may provide sufficient evidence to discontinue MRSA contact precautions, and it may be the most cost-effective option.
This chapter discusses the role that fiscal policy can play in the transition to a carbon-neutral economy. In other words, it discusses how to design fiscal policy, both on the revenue and on the expenditure side, to reach net zero emissions by mid-century in a credible, growth- and distribution-friendly way. Furthermore, the chapter discusses how decarbonisation is likely to impact public finances, shedding light on what change might be required in tax revenues/expenditures, and if debt sustainability risks might arise from the green transition.
This chapter explains the consequences on the labour market of the structural changes induced by decarbonisation policies. These policies are indeed likely going to have consequences on labour income distribution given existing rigidities in the labour markets and their different impacts on sectors and job categories. The chapter notably discusses whether decarbonisation can be a net job creator or destroyer, illustrating how job losses can be managed in a fair manner and how green jobs creation can be incentivised.
This chapter first illustrates the risk of decarbonisation impacting low-income households more than high-income ones, as they devote a larger share of their income to energy consumption and as they face more difficulties in switching to green alternatives. It then discusses which kind of policies can be adopted in order to avoid such risks and to ensure a fair transition with no social and political backlash.
The Conclusion closes the book by going back to the opening question: given all the complexities entailed in the process, is it realistic to expect the world to be able to decouple economic growth from GHG emissions in time to save the planet, and by avoiding negative repercussions on our economies and societies? The Conclusion first discusses how the economic literature has so far tackled this question – namely presenting degrowth and green growth theories – and then illustrates the authors’ views on this.