We provide an assessment of the Infinity Two Fusion Pilot Plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio A = 10, quasi-isodynamic stellarator with improved confinement appealing to a max-J approach, elevated plasma density and high magnetic fields (⟨B⟩ = 9 T). At the envisioned operating point [800 MW deuterium-tritium (DT) fusion], the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current (|Ibootstrap| ∼ 2 kA). Calculations of collisional alpha particle confinement in a DT FPP scenario show small energy losses to the first wall (< 1.5%) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the Pfus = 800 MW operating point is attainable with high fusion gain (Q = 40) at volume-averaged electron densities ne ≈ 2×1020 m−3, below the Sudo density limit. Additional transport calculations show that an ignited (Q = ∞) solution is available at slightly higher density (2.2×1020 m−3) with Pfus = 1.5 GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed Helium Cooled Pebble Bed is TBR ∼ 1.3. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body’s natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

The primary purpose of this statement is to improve neuroprognostication after devastating brain injury (DBI), with a secondary benefit of potential organ and tissue donation.

Iron-rich meteorites are significantly underrepresented in collection statistics from Antarctica. This has led to a hypothesis that there is a sparse layer of iron-rich meteorites hidden below the surface of the ice, thereby explaining the apparent shortfall. As standard Antarctic meteorite collecting techniques rely upon a visual surface search approach, the need has thus arisen to develop a system that can detect iron objects under a few tens of centimetres of ice, where the expected number density is of the order one per square kilometre. To help answer this hypothesis, a large-scale pulse induction metal detector array has been constructed for deployment in Antarctica. The metal detector array is 6 m wide, able to travel at 15 km h-1 and can scan 1 km2 in ~11 hours. This paper details the construction of the metal detector system with respect to design criteria, notably the ruggedization of the system for Antarctic deployment. Some preliminary results from UK and Antarctic testing are presented. We show that the system performs as specified and should reach the pre-agreed target of the detection of a 100 g iron meteorite at 300 mm when deployed in Antarctica.

OBJECTIVES/SPECIFIC AIMS: Background: Delirium is a well described form of acute brain organ dysfunction characterized by decreased or increased movement, changes in attention and concentration as well as perceptual disturbances (i.e., hallucinations) and delusions. Catatonia, a neuropsychiatric syndrome traditionally described in patients with severe psychiatric illness, can present as phenotypically similar to delirium and is characterized by increased, decreased and/or abnormal movements, staring, rigidity, and mutism. Delirium and catatonia can co-occur in the setting of medical illness, but no studies have explored this relationship by age. Our objective was to assess whether advancing age and the presence of catatonia are associated with delirium. METHODS/STUDY POPULATION: Methods: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Measures of association (OR) were assessed with a simple logistic regression model with catatonia as the independent variable and delirium as the dependent variable. Effect measure modification by age was assessed using a Likelihood ratio test. RESULTS/ANTICIPATED RESULTS: Results: We enrolled 136 medical and surgical critically ill patients with 452 matched (concomitant) delirium and catatonia assessments. Median age was 59 years (IQR: 52–68). In our cohort of 136 patients, 58 patients (43%) had delirium only, 4 (3%) had catatonia only, 42 (31%) had both delirium and catatonia, and 32 (24%) had neither. Age was significantly associated with prevalent delirium (i.e., increasing age associated with decreased risk for delirium) (p=0.04) after adjusting for catatonia severity. Catatonia was significantly associated with prevalent delirium (p<0.0001) after adjusting for age. Peak delirium risk was for patients aged 55 years with 3 or more catatonic signs, who had 53.4 times the odds of delirium (95% CI: 16.06, 176.75) than those with no catatonic signs. Patients 70 years and older with 3 or more catatonia features had half this risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Catatonia is significantly associated with prevalent delirium even after controlling for age. These data support an inverted U-shape risk of delirium after adjusting for catatonia. This relationship and its clinical ramifications need to be examined in a larger sample, including patients with dementia. Additionally, we need to assess which acute brain syndrome (delirium or catatonia) develops first.

Volunteer corn can affect dry bean by reducing yields; expanding the life cycle of insects, mites, and pathogens; interfering with harvest; and contaminating bean seed. Field studies were conducted at Lingle, WY, and Scottsbluff, NE, to determine the relationship between volunteer corn density and dry bean yield, establish the proper time of volunteer corn removal, and determine whether dry bean yield was affected by the method used to remove volunteer corn. Volunteer corn reduced dry bean yields, as recorded in other crops. Growing conditions for each location were different, as indicated by the accumulated growing degree days (GDD): Lingle 2008 (990), Lingle 2009 (780), and Scottsbluff 2009 (957). No difference in dry bean yields was observed between hand removal of volunteer corn and herbicide application. Dry bean yield loss increased with longer periods of volunteer corn competition and ranged from 1.2 to 1.8% yield loss for every 100 GDD that control was delayed. Control measures should be implemented 15 to 20 d after planting when volunteer corn densities are close to 1 plant m−2. Dry bean yield losses also increased as volunteer corn densities increased, with losses from 6.5 to 19.3% for 1 volunteer corn plant m−2. Based on 2015 prices, the cost of controlling volunteer corn would be the equivalent of 102 kg ha−1 of dry bean, and potential losses above 4% would justify control and should not be delayed beyond 15 to 20 d after planting.

Field experiments were conducted in Alabama during 1999 and 2000 to test the hypothesis that any glyphosate-induced yield suppression in glyphosate-resistant cotton would be less with irrigation than without irrigation. Yield compensation was monitored by observing alterations in plant growth and fruiting patterns. Glyphosate treatments included a nontreated control, 1.12 kg ai/ha applied POST at the 4-leaf stage, 1.12 kg/ha applied DIR at the prebloom stage, and 1.12 kg/ha applied POST at 4-leaf and postemergence directed (DIR) at the prebloom cotton stages. The second variable, irrigation treatment, was established by irrigating plots individually with overhead sprinklers or maintaining them under dryland, nonirrigated conditions. Cotton yield and all measured parameters including lint quality were positively affected by irrigation. Irrigation increased yield 52% compared to nonirrigated cotton. Yield and fiber quality effects were independent of glyphosate treatments. Neither yield nor any of the measured variables that reflected whole plant response were influenced by glyphosate treatment or by a glyphosate by irrigation interaction.

Objectives: The Medical Services Advisory Committee (MSAC) makes recommendations to the Australian Government for funding health technologies under the Medicare Benefits Schedule (MBS). Differences in public, clinical, commercial, and political opinions on health expenditure emphasize the importance of defensible funding decisions. We aimed to evaluate the quality of health technology assessment (HTA) reports over time and among health technologies assessed for MSAC.

Main Outcome Measures: A cohort study was performed of HTA reports prepared for MSAC between 1998 and 2013. We measured the quality of HTA reports using reporting guidelines proposed by the European Collaboration for Assessment of Health Interventions. Individual component scores across eleven domains were calculated, and summed for an overall aggregate score. We used linear regression to investigate any change in quality over time and among the types of technologies assessed.

Results: We included 110 HTA reports. The safety (80 percent), effectiveness (84 percent), economic (74 percent), and organizational (99 percent) domains were better reported than the psychological, social, and ethical considerations (34 percent). The basic (75 percent), methodological (62 percent), background (82 percent), contextual (46 percent), status quo (54 percent), and technical information (66 percent) that framed each assessment were inconsistently reported. On average, overall quality scores increased by 2 percent (p < 0.001) per year, from approximately 60 percent to 80 percent over the 15-year period, with no significant difference among surgical, diagnostic or other nonpharmaceutical health technologies (p = 0.22).

Conclusions: HTA reports prepared for MSAC are a key tool in allocating scarce health resources. The overall quality of these reports has improved, but the reporting of specific domains and subthemes therein could be better addressed.