Urban Air Mobility Market Study

The Booz Allen Team explored market size and potential barriers to Urban Air Mobility (UAM) by focusing on three potential markets – Airport Shuttle, Air Taxi, and Air Ambulance. We found that the Airport Shuttle and Air Taxi markets are viable, with a significant total available market value in the U.S. of $500 billion, for a fully unconstrained scenario. In this unconstrained best-case scenario, passengers would have the ability to access and fly a UAM at any time, from any location to any destination, without being hindered by constraints such as weather, infrastructure, or traffic volume. Significant legal and regulatory, weather, certification, public perception, and infrastructure constraints exist, which reduce the market potential for these applications to only about 0.5$2.5 billion, in the near term. However, we determined that these constraints can be addressed through ongoing intra-governmental partnerships, government and industry collaboration, strong industry commitment, and existing legal and regulatory enablers. We found that the Air Ambulance market is not a viable market if served by electric vertical takeoff and landing (eVTOL) vehicles due to technology constraints but may potentially be viable if a hybrid VTOL aircraft are utilized

Unified Entrainment and Detrainment Closures for Extended Eddy-Diffusivity Mass-Flux Schemes

We demonstrate that an extended eddy‐diffusivity mass‐flux (EDMF) scheme can be used as a unified parameterization of subgrid‐scale turbulence and convection across a range of dynamical regimes, from dry convective boundary layers, through shallow convection, to deep convection. Central to achieving this unified representation of subgrid‐scale motions are entrainment and detrainment closures. We model entrainment and detrainment rates as a combination of turbulent and dynamical processes. Turbulent entrainment/detrainment is represented as downgradient diffusion between plumes and their environment. Dynamical entrainment/detrainment is proportional to a ratio of a relative buoyancy of a plume and a vertical velocity scale, that is modulated by heuristic nondimensional functions which represent their relative magnitudes and the enhanced detrainment due to evaporation from clouds in drier environment. We first evaluate the closures off‐line against entrainment and detrainment rates diagnosed from large eddy simulations (LESs) in which tracers are used to identify plumes, their turbulent environment, and mass and tracer exchanges between them. The LES are of canonical test cases of a dry convective boundary layer, shallow convection, and deep convection, thus spanning a broad rangeof regimes. We then compare the LES with the full EDMF scheme, including the new closures, in a single‐column model (SCM). The results show good agreement between the SCM and LES in quantities that are key for climate models, including thermodynamic profiles, cloud liquid water profiles, and profiles of higher moments of turbulent statistics. The SCM also captures well the diurnal cycle of convection and the onset of precipitation

An Extended Eddy-Diffusivity Mass-Flux Scheme for Unified Representation of Subgrid-Scale Turbulence and Convection

Large-scale weather forecasting and climate models are beginning to reach horizontal resolutions of kilometers, at which common assumptions made in existing parameterization schemes of subgrid-scale turbulence and convection—such as that they adjust instantaneously to changes in resolved-scale dynamics—cease to be justifiable. Additionally, the common practice of representing boundary-layer turbulence, shallow convection, and deep convection by discontinuously different parameterizations schemes, each with its own set of parameters, has contributed to the proliferation of adjustable parameters in large-scale models. Here we lay the theoretical foundations for an extended eddy-diffusivity mass flux (EDMF) scheme that has explicit time-dependence and memory of subgrid-scale variables and is designed to represent all subgrid-scale turbulence and convection, from boundary layer dynamics to deep convection, in a unified manner. Coherent up- and downdrafts in the scheme are represented as prognostic plumes that interact with their environment and potentially with each other through entrainment and detrainment. The more isotropic turbulence in their environment is represented through diffusive fluxes, with diffusivities obtained from a turbulence kinetic energy budget that consistently partitions turbulence kinetic energy between plumes and environment. The cross-sectional area of up- and downdrafts satisfies a prognostic continuity equation, which allows the plumes to cover variable and arbitrarily large fractions of a large-scale grid box and to have life cycles governed by their own internal dynamics. Relatively simple preliminary proposals for closure parameters are presented and are shown to lead to a successful simulation of shallow convection, including a time-dependent life cycle

Pediatric Feeding Disorder: Consensus Definition and Conceptual Framework

Pediatric feeding disorders (PFDs) lack a universally accepted definition. Feeding disorders require comprehensive assessment and treatment of 4 closely related, complementary domains (medical, psychosocial, and feeding skill-based systems and associated nutritional complications). Previous diagnostic paradigms have, however, typically defined feeding disorders using the lens of a single professional discipline and fail to characterize associated functional limitations that are critical to plan appropriate interventions and improve quality of life. Using the framework of the World Health Organization International Classification of Functioning, Disability, and Health, a unifying diagnostic term is proposed: “Pediatric Feeding Disorder” (PFD), defined as impaired oral intake that is not age-appropriate, and is associated with medical, nutritional, feeding skill, and/or psychosocial dysfunction. By incorporating associated functional limitations, the proposed diagnostic criteria for PFD should enable practitioners and researchers to better characterize the needs of heterogeneous patient populations, facilitate inclusion of all relevant disciplines in treatment planning, and promote the use of common, precise, terminology necessary to advance clinical practice, research, and health-care policy

Pressure cooker ownership and food security in Aurangabad, India

Objective: To explore associations between household food security and home gardening, use of soya and pressure cooker ownership in low-income households affected by HIV/AIDS in Aurangabad, India. Design: Cross-sectional pilot study which assessed household food security using the validated US Department of Agriculture’s food security core-module questionnaire. Questions were added to explore household environment, education, occupation, home gardening, use of soya and pressure cooker ownership. Households with very low v. low food security were compared using logistic regression analysis, controlling for confounding by socio-economic status. Setting: Aurangabad is an urban setting situated in a primarily agricultural dependent area. The study was carried out in 2008, at the peak of the global food crisis. Subjects: Adult caregivers of children affiliated with the Network of People Living with HIV/AIDS in Aurangabad. Results: All except for one of 133 households were identified as food insecure (99?2 %). Of these households, 35?6% had to cut size or skip a meal in the past 30 d. Households that cut meal size due to cooking fuel shortages were more likely to have very low food security (OR54?67; 95% CI 1?62, 13?44) compared with households having no cooking fuel shortages. Owning a pressure cooker was shown to be protective against very low food security after controlling for confounding by socio-economic status (OR50?27; 95% CI 0?11, 0?64). Conclusions: Only pressure cooker ownership showed a protective association with low household food security. Pressure cookers save household fuel costs. Therefore, future interventions should explore pressure cookers as a sustainable means of improving household food securit

Effects of Metal Compounds with Distinct Physicochemical Properties on Iron Homeostasis and Antibacterial Activity in the Lungs: Chromium and Vanadium

In situ reactions of metal ions or their compounds are important mechanisms by which particles alter lung immune responses. The authors hypothesized that major determinants of the immunomodulatory effect of any metal include its redox behavior/properties, oxidation state, and/or solubility, and that the toxicities arising from differences in physicochemical parameters are manifest, in part, via differential shifts in lung iron (Fe) homeostasis. To test the hypotheses, immunomodulatory potentials for both pentavalent vanadium (V(V); as soluble metavanadate or insoluble vanadium pentoxide) and hexavalent chromium (Cr(VI); as soluble sodium chromate or insoluble calcium chromate) were quantified in rats after inhalation (5 h/day for 5 days) of each at 100 mu g metal/m(3). Differences in effects on local bacterial resistance between the two V(V), and between each Cr(VI), agents suggested that solubility might be a determinant of in situ immunotoxicity. For the soluble forms, V(V) had a greater impact on resistance than Cr(VI), indicating that redox behavior/properties was likely also a determinant. The soluble V(V) agent was the strongest immunomodulant. Regarding Fe homeostasis, both V(V) agents had dramatic effects on airway Fe levels. Both also impacted local immune/airway epithelial cell Fe levels in that there were significant increases in production of select cytokines/chemokines whose genes are subject to regulation by HIF-1 (whose intracellular longevity is related to cell Fe status). Our findings contribute to a better understanding of the role that metal compound properties play in respiratory disease pathogenesis and provide a rationale for differing pulmonary immunotoxicities of commonly encountered ambient metal pollutants

Designing for Dissemination: Lessons in Message Design from 1-2-3 Pap

Despite a large number of evidence-based health communication interventions tested in private, public, and community health settings, there is a dearth of research on successful secondary dissemination of these interventions to other audiences. This article presents the case study of 1-2-3 Pap, a health communication intervention to improve human papillomavirus (HPV) vaccination uptake and Pap testing outcomes in Eastern Kentucky, and explores strategies used to disseminate this intervention to other populations in Kentucky, North Carolina, and West Virginia. Through this dissemination project, we identified several health communication intervention design considerations that facilitated our successful dissemination to these other audiences; these intervention design considerations include (a) developing strategies for reaching other potential audiences, (b) identifying intervention message adaptations that might be needed, and (c) determining the most appropriate means or channels by which to reach these potential future audiences. Using 1-2-3 Pap as an illustrative case study, we describe how careful planning and partnership development early in the intervention development process can improve the potential success of enhancing the reach and effectiveness of an intervention to other audiences beyond the audience for whom the intervention messages were originally designed

An Extended Eddy-Diffusivity Mass-Flux Scheme for Unified Representation of Subgrid-Scale Turbulence and Convection

Large-scale weather forecasting and climate models are beginning to reach horizontal resolutions of kilometers, at which common assumptions made in existing parameterization schemes of subgrid-scale turbulence and convection—such as that they adjust instantaneously to changes in resolved-scale dynamics—cease to be justifiable. Additionally, the common practice of representing boundary-layer turbulence, shallow convection, and deep convection by discontinuously different parameterizations schemes, each with its own set of parameters, has contributed to the proliferation of adjustable parameters in large-scale models. Here we lay the theoretical foundations for an extended eddy-diffusivity mass flux (EDMF) scheme that has explicit time-dependence and memory of subgrid-scale variables and is designed to represent all subgrid-scale turbulence and convection, from boundary layer dynamics to deep convection, in a unified manner. Coherent up- and downdrafts in the scheme are represented as prognostic plumes that interact with their environment and potentially with each other through entrainment and detrainment. The more isotropic turbulence in their environment is represented through diffusive fluxes, with diffusivities obtained from a turbulence kinetic energy budget that consistently partitions turbulence kinetic energy between plumes and environment. The cross-sectional area of up- and downdrafts satisfies a prognostic continuity equation, which allows the plumes to cover variable and arbitrarily large fractions of a large-scale grid box and to have life cycles governed by their own internal dynamics. Relatively simple preliminary proposals for closure parameters are presented and are shown to lead to a successful simulation of shallow convection, including a time-dependent life cycle

DNM1 encephalopathy: A new disease of vesicle fission.

ObjectiveTo evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.MethodsWe reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.ResultsWe identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function.ConclusionsThe phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial

IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. INTERVENTIONS: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. MAIN OUTCOMES AND MEASURES: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. RESULTS: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). CONCLUSIONS AND RELEVANCE: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03183141