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Between 2014 and 2018, the National Oceanic and Atmospheric Administration conducted the NOAA Satellite Observing System Architecture (NSOSA) study to plan for the next generation of operational environmental satellites. The study generated some important questions that could be addressed by observing system simulation experiments (OSSEs). This paper describes a series of OSSEs in which benefits to numerical weather prediction from existing observing systems are combined with enhancements from potential future capabilities. Assessments include the relative value of the quantity of different types of thermodynamic soundings for global numerical weather applications. We compare the relative impact of several sounding configuration scenarios for infrared (IR), microwave (MW), and radio occultation (RO) observing capabilities. The main results are 1) increasing the revisit rate for satellite radiance soundings produces the largest benefits but at a significant cost by requiring an increase in the number of polar-orbiting satellites from 2 to 12; 2) a large positive impact is found when the number of RO soundings per day is increased well beyond current values and other observations are held at current levels of performance; 3) RO can be used as a mitigation strategy for lower MW/IR sounding revisit rates, particularly in the tropics; and 4) smaller benefits result from increasing the horizontal resolution along the track of the satellites of MW/IR satellite radiances. Furthermore, disaggregating IR and MW instruments into six evenly distributed sun-synchronous orbits is slightly more beneficial than when the same instruments are combined and collocated on three separate orbits. SIGNIFICANCE STATEMENT: The results of this paper are significant because they inform decision-makers about the future configuration of the NOAA's environmental satellite constellation, which serves millions of diverse users. KEYWORDS: Remote sensing; Satellite observations; Sensitivity studies; Data assimilation; Numerical weather prediction/ forecasting, 1. Introduction As planning for future satellite systems takes a long time, in 2014, the National Oceanic and Atmospheric Administration (NOAA) began evaluating existing and new opportunities for the design [...]

Background Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization. Methods This study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received 3 randomized treatments: (1) 100 mg buccal harmine with 100 mg intranasal DMT, (2) 100 mg buccal harmine with intranasal placebo, and (3) full placebo, using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes. Results N,N-dimethyltryptamine produced consistent PK profiles with Cmax values of 22.1 ng/mL and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2–3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/mL but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation's suitability for clinical applications. Conclusions This study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders. Clinical trial registration number Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335 [ABSTRACT FROM AUTHOR]

BackgroundDiabetic forefoot joint deformities are a known risk factor for skin breakdown and amputation, but the causes of deformity are not well understood. The purposes of this study were to determine the effects of intrinsic foot muscle deterioration and limited ankle joint mobility on the severity of metatarsophalangeal joint (MTPJ) deformity, and determine the relationships between these potential contributing factors and indicators of diabetic complications (peripheral neuropathy and advanced glycation end products).MethodsA total of 34 participants with diabetic neuropathy (average age, 59 years; range 41-73) were studied. MTPJ angle and intrinsic foot muscle deterioration were measured with computed tomography and magnetic resonance imaging, respectively. Maximum ankle dorsiflexion was measured using kinematics. Skin intrinsic fluorescence served as a proxy measure for advanced glycation end product accumulation.ResultsTotal forefoot lean muscle volume (r = -0.52, P < .01) and maximum ankle dorsiflexion (r = -0.42, P < .05) were correlated with severity of MTPJ deformity. Together they explained 35% of the variance of MTPJ angle. Neuropathy was correlated with forefoot muscle deterioration (ρ = 0.53, P < .01). Skin intrinsic fluorescence was correlated to severity of neuropathy (r = 0.50, P < .01) but not maximum ankle dorsiflexion, or forefoot deterioration when controlling for neuropathy.ConclusionThese results suggest that the interplay of intrinsic foot muscle deterioration and limited ankle mobility may be the primary contributor to the development of MTPJ deformity. Identifying these muscle and ankle motion impairments as risk factors for MTPJ deformity supports the need for targeted interventions early in the disease process to slow, or possibly stop the progression of deformity over time and reduce the risk of amputation.Level of evidenceLevel IV, case series.

BackgroundDiabetes mellitus related medial column foot deformity is a major contributor to ulceration and amputation. However, little is known about the relationship between medial column alignment and function and the integrity of the soft tissues that support and move the medial column. The purposes of this study were to determine the predictors of medial column alignment and function in people with diabetes and peripheral neuropathy.Methods23 participants with diabetes and neuropathy had radiographs, heel rise kinematics, magnetic resonance imaging and isokinetic muscle testing to measure: 1) medial column alignment (Meary's angle--the angle between the 1st metatarsal longitudinal axis and the talar head and neck), 2) medial column function (forefoot relative to hindfoot plantarflexion during heel rise), 3) intrinsic foot muscle and fat volume, ratio of posterior tibialis to flexor digitorum tendon volume, 4) plantar fascia function (Meary's angle change from toes flat to extended) and 5) plantarflexor peak torque. Predictors of medial column alignment and function were determined using simultaneous entry multiple regression.FindingsPosterior tibialis to flexor digitorum tendon volume ratio and intrinsic foot muscle volume were significant predictors of medial column alignment (P

PurposeTo describe a semi-automated program that will segment subcutaneous fat, muscle, and adipose tissue in the foot using MR imaging, determine the reliability of the program between and within raters, and determine the validity of the program using MR phantoms.Materials and methodsMR images were acquired from 19 subjects with and without diabetes and peripheral neuropathy. Two raters segmented and measured volumes from single MR slices at the forefoot, midfoot, and hindfoot at two different times. Intra- and inter-rater correlation coefficients were determined. Muscle and fat MR phantoms of known volumes were measured by the program.ResultsMost ICC reliability values were over 0.950. Validity estimates comparing MR estimates and known volumes resulted in r(2) values above 0.970 for all phantoms. The root mean square error was less than 5% for all phantoms.ConclusionSubcutaneous fat, lean muscle, and adipose tissue volumes in the foot can be quantified in a reliable and valid way. This program can be applied in future studies investigating the relationship of these foot structures to functions in important pathologies, including the neuropathic foot or other musculoskeletal problems.

BackgroundMetatarsophalangeal joint deformity is associated with skin breakdown and amputation. The aims of this study were to compare intrinsic foot muscle deterioration ratios (ratio of adipose to muscle volume), and physical performance in subjects with diabetic neuropathy to controls, and determine their associations with 1) metatarsophalangeal joint angle and 2) history of foot ulcer.Methods23 diabetic, neuropathic subjects [59 (SD 10) years] and 12 age-matched controls [57 (SD 14) years] were studied. Radiographs and MRI were used to measure metatarsophalangeal joint angle and intrinsic foot muscle deterioration through tissue segmentation by image signal intensity. The Foot and Ankle Ability Measure evaluated physical performance.FindingsThe diabetic, neuropathic group had a higher muscle deterioration ratio [1.6 (SD 1.2) vs. 0.3 (SD 0.2), P1.0 were included. Muscle deterioration ratios in individuals with diabetic neuropathy were higher for those with a history of ulcers.InterpretationIndividuals with diabetic neuropathy had increased intrinsic foot muscle deterioration, which was associated with second metatarsophalangeal joint angle and history of ulceration. Additional research is required to understand how foot muscle deterioration interacts with other impairments leading to forefoot deformity and skin breakdown.

Background: There is growing scientific evidence for the therapeutic benefits of the Amazonian plant-based psychedelic "ayahuasca" for neuropsychiatric disorders such as depression and anxiety. However, there are certain challenges when incorporating botanical ayahuasca into biomedical research and clinical therapy environments. Formulations inspired by ayahuasca, which contain specific and standardized active components, are a potential remedy. Methods: We investigated subjective acute and persisting effects of a novel formulation containing the reversible monoamine oxidase inhibitor harmine (orodispersible tablet containing 100 mg MAO-I) and N,N-dimethyltryptamine (incremental intranasal dosing of up to 100 mg DMT), compared with two other conditions, namely harmine alone and placebo, in a crossover RCT in 31 healthy male subjects. Results: DMT + harmine, but not harmine alone, induced a psychedelic experience assessed with the 5D-ASC rating scale [global score: F(2,60) = 80.21, p < 0.001] and acute experience sampling items over time, characterized by psychological insights [PIQ, F(2,58.5) = 28.514, p < 0.001], emotional breakthroughs [EBI, F(2,60) = 26.509, p < 0.001], and low scores on the challenging experience questionnaire [CEQ, F(2,60) = 12.84, p < 0.001]. Participants attributed personal and spiritual significance to the experience (GSR) with mainly positive persisting effects (PEQ) at 1- and 4-months follow-up. Acute drug effects correlated positively with persisting effects. We found no changes in trait measures of personality, psychological flexibility, or general well-being, and no increases in psychopathology (SCL-90-R) were reported. Discussion and Conclusion: Our results suggest that the experience induced by the standardized DMT + harmine formulation induces a phenomenologically rich psychedelic experience, demonstrates good psychological safety and tolerability, is well tolerated, and induces beneficial psychological processes that could possibly support psychotherapy. Further studies are required to investigate the psychotherapeutic potential in patients. [ABSTRACT FROM AUTHOR]

Context: The authors hypothesized that in people with hip-related groin pain, less static ankle dorsiflexion could lead to compensatory hip adduction and contralateral pelvic drop during step-down. Ankle dorsiflexion may be a modifiable factor to improve ability in those with hip-related groin pain to decrease hip/pelvic motion during functional tasks and improve function. Objective: To determine whether smaller static ankle dorsiflexion angles were associated with altered ankle, hip, and pelvis kinematics during step-down in people with hip-related groin pain. Design: Cross-sectional Setting: Academic medical center. Patients: A total of 30 people with hip-related groin pain (12 males and 18 females; 28.7 [5.3] y) participated. Intervention: None. Main Outcome Measures: Weight-bearing static ankle dorsiflexion with knee flexed and knee extended were measured via digital inclinometer. Pelvis, hip, and ankle kinematics during forward step-down were measured via 3D motion capture. Static ankle dorsiflexion and kinematics were compared with bivariate correlations. Results: Smaller static ankle dorsiflexion angles were associated with smaller ankle dorsiflexion angles during the step-down for both the knee flexed and knee extended static measures. Among the total sample, smaller static ankle dorsiflexion angle with knee flexed was associated with greater anterior pelvic tilt and greater contralateral pelvic drop during the step-down. Among only those who did not require a lowered step for safety, smaller static ankle dorsiflexion angles with knee flexed and knee extended were associated with greater anterior pelvic tilt, greater contralateral pelvic drop, and greater hip flexion. Conclusions: Among those with hip-related groin pain, smaller static ankle dorsiflexion angles are associated with less ankle dorsiflexion motion and altered pelvis and hip kinematics during a step-down. Future research is needed to assess the effect of treating restricted ankle dorsiflexion on quality of motion and symptoms in patients with hip-related groin pain. [ABSTRACT FROM AUTHOR]

Quantitative magnetic resonance imaging (qMRI) measures have provided insights into the composition, quality, and structure‐function of musculoskeletal tissues. Low signal‐to‐noise ratio has limited application to tendon. Advances in scanning sequences and sample positioning have improved signal from tendon allowing for evaluation of structure and function. The purpose of this study was to elucidate relationships between tendon qMRI metrics (T1, T2, T1ρ and diffusion tensor imaging [DTI] metrics) with tendon tissue mechanics, collagen concentration and organization. Sixteen human Achilles tendon specimens were collected, imaged with qMRI, and subjected to mechanical testing with quantitative polarized light imaging. T2 values were related to tendon mechanics [peak stress (rsp = 0.51, p = 0.044), equilibrium stress (rsp = 0.54, p = 0.033), percent relaxation (rsp = −0.55, p = 0.027), hysteresis (rsp = −0.64, p = 0.007), linear modulus (rsp = 0.67, p = 0.009)]. T1ρ had a statistically significant relationship with percent relaxation (r = 0.50, p = 0.048). Collagen content was significantly related to DTI measures (range of r = 0.56–0.62). T2 values from a single slice of the midportion of human Achilles tendons were strongest predictors of tendon tensile mechanical metrics. DTI diffusivity indices (mean diffusivity, axial diffusivity, radial diffusivity) were strongly correlated with collagen content. These findings build on a growing body of literature supporting the feasibility of qMRI to characterize tendon tissue and noninvasively measure tendon structure and function. Statement of Clinical Significance: Quantitative MRI can be applied to characterize tendon tissue and is a noninvasive measure that relates to tendon composition and mechanical behavior. [ABSTRACT FROM AUTHOR]